curcumin and Reperfusion-Injury

Accumulating evidence has suggested that curcumin may protect against cerebral ischemia-reperfusion injury (CIRI). However, biological mechanisms vary across studies, limiting the clinical applicability of these findings. We performed a meta-analysis on publications evaluating curcumin administration in rat models of CIRI. Furthermore, we sought to test the hypothesis that curcumin alleviates CIRI through diminishing oxidation and inflammation. We searched PubMed, Embase, Web of Science, and Cochrane from the starting date of each database to May 2022 for experimental rat studies exploring the use of curcumin after ischemia reperfusion. Included articles were assessed for bias using SYRCLE's risk of bias tool. Data were aggregated by a random effects model. Curcumin administration significantly reduced neurological deficit score (20 studies; pooled mean difference [MD] = -1.57; 95% CI, -1.78 to -1.36, P < .00001), infarct volume (18 studies; pooled MD = -17.56%; 95% CI, -20.92% to -14.20%; P < 0.00001), and brain water content (8 studies, pooled MD = -11.29%, 95% CI: -16.48%, -6.11%, P < .00001). Compared with control, the levels of superoxide dismutase, glutathione, and glutathione peroxidase were significantly higher, whereas the levels of reactive oxygen species, malondialdehyde, interleukin-1β, interleukin-6, interleukin-8, and nuclear factor kappa B were significantly lower (P < .05). Subgroup analysis raised the possibility that intervention affections differed by curcumin's dose. To our knowledge, this is the first meta-analysis of curcumin's neuroprotection and mechanisms in rat CIRI models. Our analysis suggests the neuroprotective potential of curcumin in CIRI via antioxidant activity and anti-inflammatory effect. More research is required to further confirm the effectiveness and safety of curcumin on ischemic stroke therapy.

Topics: Animals; Antioxidants; Brain Ischemia; Curcumin; Inflammation; Ischemia; Neuroprotective Agents; Oxidative Stress; Rats; Reperfusion Injury

Cerebral ischemia/reperfusion (I/R) injury can result in different levels of cerebral impairment, and in severe cases, death. Curcumin, an essential bioactive component of turmeric, has a rich history as a traditional medicine for various ailments in numerous countries. Experimental and clinical research has established that curcumin offers a protective effect against cerebral I/R injury. Curcumin exerts its protective effects by acting on specific mechanisms such as antioxidant, anti-inflammatory, inhibition of ferroptosis and pyroptosis, protection of mitochondrial function and structure, reduction of excessive autophagy, and improvement of endoplasmic reticulum (ER) stress, which ultimately help to preserve the blood-brain barrier (BBB) and reducing apoptosis. There is currently a shortage of drugs undergoing clinical trials for the treatment of cerebral I/R injury, highlighting the pressing need for research and development of novel treatments to address this injury. The primary objective of this study is to establish a theoretical basis for future clinical applications of curcumin by delineating the mechanisms and protective effects of curcumin against cerebral I/R injury. Adapted with permission from [1].

Topics: Apoptosis; Brain Ischemia; Curcumin; Humans; Neuroprotective Agents; Reperfusion Injury

To review the role of curcumin in retinal diseases, COVID era, modification of the molecule to improve bioavailability and its future scope.. PubMed and MEDLINE searches were pertaining to curcumin, properties of curcumin, curcumin in retinal diseases, curcumin in diabetic retinopathy, curcumin in age-related macular degeneration, curcumin in retinal and choroidal diseases, curcumin in retinitis pigmentosa, curcumin in retinal ischemia reperfusion injury, curcumin in proliferative vitreoretinopathy and curcumin in current COVID era.. In experimental models, curcumin showed its pleiotropic effects in retinal diseases like diabetic retinopathy by increasing anti-oxidant enzymes, upregulating HO-1, nrf2 and reducing or inhibiting inflammatory mediators, growth factors and by inhibiting proliferation and migration of retinal endothelial cells in a dose-dependent manner in HRPC, HREC and ARPE-19 cells. In age-related macular degeneration, curcumin acts by reducing ROS and inhibiting apoptosis inducing proteins and cellular inflammatory genes and upregulating HO-1, thioredoxin and NQO1. In retinitis pigmentosa, curcumin has been shown to delay structural defects of P23H gene in P23H-rhodopsin transgenic rats. In proliferative vitreoretinopathy, curcumin inhibited the action of EGF in a dose- and time-dependent manner. In retinal ischemia reperfusion injury, curcumin downregulates IL-17, IL-23, NF. Curcumin is an easily available spice used traditionally in Indian cooking. The benefits of curcumin are manifold, and large randomized controlled trials are required to study its effects not only in treating retinal diseases in humans but in their prevention too.

Topics: Animals; COVID-19; Curcumin; Diabetic Retinopathy; Endothelial Cells; Humans; Macular Degeneration; Rats; Reperfusion Injury; Retinal Diseases; Retinal Neoplasms; Retinitis Pigmentosa; Vitreoretinopathy, Proliferative

Ischemia/reperfusion (I/R) injury is a term used to describe phenomena connected to the dysfunction of various tissue damage due to reperfusion after ischemic injury. While I/R may result in systemic inflammatory response syndrome or multiple organ dysfunction syndrome, there is still a long way to improve therapeutic outcomes. A number of cellular metabolic and ultrastructural alterations occur by prolonged ischemia. Ischemia increases the expression of proinflammatory gene products and bioactive substances within the endothelium, such as cytokines, leukocytes, and adhesion molecules, even as suppressing the expression of other "protective" gene products and substances, such as thrombomodulin and constitutive nitric oxide synthase (e.g., prostacyclin, nitric oxide [NO]). Curcumin is the primary phenolic pigment derived from turmeric, the powdered rhizome of Curcuma longa. Numerous studies have shown that curcumin has strong antiinflammatory and antioxidant characteristics. It also prevents lipid peroxidation and scavenges free radicals like superoxide anion, singlet oxygen, NO, and hydroxyl. In our study, we highlight the mechanisms of protective effects of curcumin against I/R injury in various organs.

Topics: Curcumin; Humans; Ischemia; Reperfusion Injury

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

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Renal ischemia-reperfusion injury (RIRI) refers to a phenomenon associated with dysfunction of the kidney and tissue damage. Unfortunately, no specific drugs have been found that effectively prevent and treat RIRI. Curcumin (Cur), a polyphenol extracted from turmeric, possesses a variety of biological activities involving antioxidation, inhibition of apoptosis, inhibition of inflammation, and reduction of lipid peroxidation. Eight frequently used databases were searched using prespecified search strategies. The CAMARADES 10-item quality checklist was used to evaluate the risk of bias of included studies, and the RevMan 5.3 software was used to analyze the data. The risk of bias score of included studies ranged from 3 to 6 with an average score of 5.22. Compared with the control group, Cur significantly alleviated renal pathology, reduced blood urea nitrogen and serum creatinine levels, and improved inflammatory indexes, oxidant, and apoptosis in RIRI animal models. Despite the heterogeneity of the response to Cur in terms of serum creatinine, BUN, TNF-alpha, and SOD, its effectiveness for improving the injury of RIRI was remarkable. In the mouse model subgroup of serum creatinine, the effect size of the method of unilateral renal artery ligation with contralateral nephrectomy and shorter ischemic time showed a greater effect than that of the control group. No difference was seen in the methods of model establishment, mode administration, or medication times. The preclinical systematic review provided preliminary evidence that Cur partially improved RIRI in animal models, probably via anti-inflammatory, antioxidant, antiapoptosis, and antifibrosis activities and via improving microperfusion. ARRIVE guidelines are recommended; blinding and sample size calculation should be focused on in future studies. These data suggest that Cur is a potential renoprotective candidate for further clinical trials of RIRI.

Topics: Animals; Curcumin; Disease Models, Animal; Drug Evaluation, Preclinical; Kidney Diseases; Reperfusion Injury

Ischemia-reperfusion injury (I/R injury) is a common feature of ischemic stroke which occurs when blood supply is restored after a period of ischemia. Although stroke is an important cause of death in the world, effective therapeutic strategies aiming at improving neurological outcomes in this disease are lacking. Various studies have suggested the involvement of different mechanisms in the pathogenesis of I/R injury in the nervous system. These mechanisms include oxidative stress, platelet adhesion and aggregation, leukocyte infiltration, complement activation, blood-brain barrier (BBB) disruption, and mitochondria-mediated mechanisms. Curcumin, an active ingredient of turmeric, can affect all these pathways and exert neuroprotective activity culminating in the amelioration of I/R injury in the nervous system. In this review, we discuss the protective effects of curcumin against I/R injury in the nervous system and highlight the studies that have linked biological functions of curcumin and I/R injury improvement.

Topics: Animals; Brain Ischemia; Curcumin; Disease Models, Animal; Humans; Nervous System; Neuroprotective Agents; Reperfusion Injury

Liver ischemia/reperfusion (I/R) injury is a major complication of hepatic surgery and transplantation. It is one of the leading causes of morbidity and mortality because of post-surgery hepatic dysfunction. Several studies have suggested different mechanisms are involved in the pathogenesis of I/R injury in the liver that includes oxidative stress, inflammation, mitochondria dysfunction, liver Kupffer cells (KCs) activation, vascular cell adhesion molecule overexpression, and facilitation of polymorphonuclear neutrophil injury. Curcumin is a natural product extracted from Curcuma longa that is known to suppress these pathways and as a result reduces liver ischemia-reperfusion injury. This paper gives an overview of the protective effects of curcumin against I/R injury in the liver and discusses the studies that have linked biological functions of curcumin with liver I/R injury improvement.

Topics: Animals; Curcumin; Disease Models, Animal; Humans; Liver Diseases; Liver Transplantation; Protective Agents; Reperfusion Injury

Coronary artery disease (CAD) is a well-known pathological condition that is characterized by high morbidity and mortality. The main pathological manifestation of CAD is myocardial injury due to ischemia-reperfusion (I-R). Currently, no efficacious treatment of protecting the heart against myocardial I-R exists. Hence, it is necessary to discover or develop novel strategies to prevent myocardial-reperfusion injury to improve clinical outcomes in patients with CAD. A large body of experimental evidence supports cardioprotective properties of curcumin and the ability of this phytochemical to modify some cardiovascular risk factors. However, the detailed effects of curcumin in myocardial I-R injury are still unclear and there is a lack of evidence concerning which curcumin regimen may be ideal for myocardial I-R injury. This paper presents a brief review of the pathophysiology of myocardial I-R injury and the mechanisms of action of curcumin in reducing myocardial I-R injury.

Topics: Curcumin; Heart; Humans; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Oxidative Stress; Protective Agents; Reperfusion Injury

Curcumin is a bioactive phytochemical that modulates several physiological and cellular processes leading to therapeutic effects against different diseases. Sirtuins are highly conserved nicotine adenine dinucleotide-dependent proteins that regulate the activity of target enzymes and transcription factors by deacetylation. Curcumin possesses both antioxidant and anti-inflammatory properties and has been shown to increase sirtuin-1 (SIRT1) by activating small molecules. Upregulation of SIRT1 by curcumin has been reported to confer protective effects against a range of neurological disorders including glutamate excitotoxicity, β-amyloid-induced cell death in cortical neurons, cerebral ischemic damage, and stroke. Activation of AMPK and SIRT1 by curcumin has also been noted to mediate the protective effects of curcumin against ischemia/reperfusion injury, cardiac fibrosis, diabetes, and lipid metabolism abnormalities. These protective effects of SIRT1 activation are partly mediated by the deacetylation of p53 and reduction of apoptosis. In this review, we summarize the role of SIRT1 in mediating the pharmacological effects of curcumin in several diseases.

Topics: AMP-Activated Protein Kinase Kinases; Amyloid beta-Peptides; Antioxidants; Apoptosis; Curcumin; Gene Expression Regulation; Glutamic Acid; Humans; Neurons; Protein Kinases; Reperfusion Injury; Sirtuin 1; Tumor Suppressor Protein p53

Chronic kidney disease (CKD) and acute kidney injury (AKI) are global health problems that affect over 850 million people, twice the number of diabetic individuals around the world. Diabetes mellitus (DM) is known to increase the susceptibility to AKI. Plants and foods, such as curcumin, are traditionally used as treatments for various diseases due to its wide range of bioactive compounds that exert antioxidative, anti-inflammatory, antimicrobial and anticancer properties. The aim of this study is to evaluate the effect of curcumin in diabetic rats with AKI. Adult male Wistar rats, weighing between 250 and 290 g, were randomized into four groups: Citrate (citrate buffer, i.v., single dose, on Day 1 of the protocol); DM (streptozotocin (STZ), 65 mg/k, single dose, i.v., on Day 1); DM + I/R (DM rats that, on Day 26, had the renal pedicle clamped for 30 min on both sides); DM + I/R + Curcumin (DM + I/R rats submitted to curcumin treatment). Results showed that IR worsened renal function and oxidative stress in DM rats, but the DM + IR + Curcumin group showed an increase in inulin clearance and a decrease in serum creatinine and in NGAL, in addition to an improvement in renal hemodynamics. These effects were accompanied by a reduction in oxidative and nitrosative metabolites and an increase in the thiol antioxidant reserve when curcumin was administered to the DM + IR group.

Topics: Acute Kidney Injury; Animals; Antioxidants; Citrates; Curcumin; Diabetes Mellitus, Experimental; Humans; Ischemia; Kidney; Male; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; 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Inflammation Mediators; Infrared Rays; Inhibitory Concentration 50; Injections, Intravenous; Interferon-gamma; Interleukin-23; Interleukin-4; Interleukin-6; Intermediate Filaments; Intermittent Claudication; Intestine, Small; Iridoid Glucosides; Iridoids; Iron; Isomerism; Isotope Labeling; Isoxazoles; Itraconazole; Kelch-Like ECH-Associated Protein 1; Ketoprofen; Kidney Failure, Chronic; Kinetics; Klebsiella pneumoniae; Lactams, Macrocyclic; Lactobacillus; Lactulose; Lakes; Lamivudine; Laparoscopy; Laparotomy; Laryngoscopy; Leucine; Limit of Detection; Linear Models; Lipid A; Lipopolysaccharides; Listeria monocytogenes; Liver; Liver Cirrhosis; Logistic Models; Longitudinal Studies; Losartan; Low Back Pain; Lung; Lupinus; Lupus Erythematosus, Systemic; Machine Learning; Macular Degeneration; Madin Darby Canine Kidney Cells; Magnetic Phenomena; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetics; Malaria, Falciparum; Male; Mannans; MAP Kinase Signaling System; Mass Spectrometry; 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Plant Oils; Plants, Medicinal; Plasmodium berghei; Plasmodium falciparum; Platelet Activation; Platelet Function Tests; Pneumonia, Viral; Poaceae; Pogostemon; Poloxamer; Poly I; Poly(ADP-ribose) Polymerase Inhibitors; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Polycyclic Compounds; Polyethylene Glycols; Polylysine; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Population Dynamics; Portasystemic Shunt, Transjugular Intrahepatic; Positron Emission Tomography Computed Tomography; Postoperative Complications; Postprandial Period; Potassium Cyanide; Predictive Value of Tests; Prefrontal Cortex; Pregnancy; Prepulse Inhibition; Prevalence; Procalcitonin; Prodrugs; Prognosis; Progression-Free Survival; Proline; Proof of Concept Study; Prospective Studies; Protein Binding; Protein Conformation; Protein Domains; Protein Folding; Protein Multimerization; Protein Sorting Signals; Protein Structure, Secondary; Proton Pump Inhibitors; Protozoan Proteins; Psychometrics; Pulse Wave Analysis; Pyridines; Pyrrolidines; Quality of Life; Quantum Dots; Quinoxalines; Quorum Sensing; Radiopharmaceuticals; Rain; Random Allocation; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Rats, Wistar; RAW 264.7 Cells; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, PAR-1; Receptors, CXCR4; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Interleukin-1; Receptors, Interleukin-17; Receptors, Notch; Recombinant Fusion Proteins; Recombinant Proteins; Reducing Agents; Reflex, Startle; Regional Blood Flow; Regression Analysis; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Tract Diseases; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Risk Assessment; Risk Factors; Rituximab; RNA, Messenger; RNA, Ribosomal, 16S; ROC Curve; Rosmarinic Acid; Running; Ruthenium; Rutin; Sarcolemma; Sarcoma; Sarcopenia; Sarcoplasmic Reticulum; SARS-CoV-2; Scavenger Receptors, Class A; Schools; Seasons; Seeds; Sequence Analysis, DNA; Severity of Illness Index; Sex Factors; Shock, Cardiogenic; Short Chain Dehydrogenase-Reductases; Signal Transduction; Silver; Singlet Oxygen; Sinusitis; Skin; Skin Absorption; Small Molecule Libraries; Smoke; Socioeconomic Factors; Soil; Soil Microbiology; Solid Phase Extraction; Solubility; Solvents; Spain; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Speech; Speech Perception; Spindle Poles; Spleen; Sporothrix; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Stomach Neoplasms; Stress, Physiological; Stroke Volume; Structure-Activity Relationship; Substrate Specificity; Sulfonamides; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Rate; T-Lymphocytes, Cytotoxic; Tandem Mass Spectrometry; Temperature; Tenofovir; Terpenes; Tetracycline; Tetrapleura; Textiles; Thermodynamics; Thiobarbituric Acid Reactive Substances; Thrombin; Thyroid Hormones; Thyroid Neoplasms; Tibial Meniscus Injuries; Time Factors; Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea

Cardiopulmonary bypass during tetralogy of Fallot corrective surgery is associated with oxidative stress, and contributes to peri-operative problems. Curcumin has been known as a potent scavenger of reactive oxygen species, which enhances the activity of antioxidants and suppresses phosphorylation of transcription factors involved in inflamation and apoptosis.. To evaluate the effects of curcumin as an antioxidant by evaluating the concentrations of malondialdehyde and glutathione, activity of nuclear factor-kappa B, c-Jun N-terminal kinase, caspase-3, and post-operative clinical outcomes.. Tetralogy of Fallot patients for corrective surgery were randomised to receive curcumin (45 mg/day) or placebo orally for 14 days before surgery. Malondialdehyde and glutathione concentrations were evaluated during the pre-ischaemia, ischaemia, re-perfusion phases, and 6 hours after aortic clamping-off. Nuclear factor-kappa B, c-Jun N-terminal kinase, and caspase-3, taken from the infundibulum, were assessed during the pre-ischaemia, ischaemia, and re-perfusion phases. Haemodynamic parameters were monitored until day 5 after surgery.. In all the observation phases, malondialdehyde and glutathione concentrations were similar between groups. There was no significant difference in nuclear factor-kappa B activity between the groups for three observations; however, in the curcumin group, c-Jun N-terminal kinase significantly decreased from the pre-ischaemia to the re-perfusion phases, and caspase-3 expression was lower in the ischaemia phase. Patients in the curcumin group had lower temperature and better ventricular functions, but no significant differences were found in mechanical ventilation day or length of hospital stay in the two groups.. Cardioprotective effects of curcumin may include inhibition of the c-Jun N-terminal kinase pathway and caspase-3 in cardiomyocytes, particularly in the ischaemia phase.

Topics: Antioxidants; Apoptosis; Cardiopulmonary Bypass; Caspase 3; Child; Child, Preschool; Curcumin; Double-Blind Method; Female; Hemodynamics; Humans; Indonesia; JNK Mitogen-Activated Protein Kinases; Male; Myocytes, Cardiac; Oxidative Stress; Reperfusion Injury; Tetralogy of Fallot

Hepatic ischemia-reperfusion injury (IRI) is a common innate immune-mediated sterile inflammatory response in liver transplantation and liver tumor resection. Neutrophil extracellular traps (NETs) can aggravate liver injury and activates innate immune response in the process of liver IRI. However, Curcumin (Cur) can reverse this damage and reduce NETs formation. Nevertheless, the specific regulatory mechanism is still unclear in liver IRI. This study aimed to explore the potential mechanisms that how does Cur alleviate hepatic IRI by inhibits NETs production and develop novel treatment regimens.. We established a hepatic IRI model by subjecting C57BL/6J mice to 60 min of ischemia, followed by reperfusion for 2 h, 6 h, 12 h, and 24 h respectively. Subsequently, we were separated into 5 groups, namely the I/R group, Cur group, DNase-1 group, Cur + DNase1 group and sham operation group. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Hematoxylin-eosin staining, immunofluorescence, and TUNEL analysis were applied to assess liver injury degree and NETs levels. Western blot assay was used to detect the protein levels of apoptosis-related proteins and MEK pathway proteins.. Cur could alleviate hepatic IRI by inhibiting the generation of NETs via suppressing the MEK/ERK pathway. In addition, this study also revealed that DNase-1 is vital for alleviating hepatic IRI by reducing the generation of NETs.. Cur combined with DNase-1 was more effective than the two drugs administered alone in alleviating hepatic IRI by inhibiting the generation of NETs. These results also suggested that curcumin combined with DNase-1 was a potential therapeutic strategy to mitigate hepatic IRI.

Topics: Animals; Curcumin; Deoxyribonucleases; Extracellular Traps; Inflammation; Liver; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase Kinases; Reperfusion Injury

In this study, the effects of the pretreatment of Curcumin and LoxBlock-1 on liver, pancreas, and cardiac dysfunction following Ischemia-Reperfusion-induced (IR) Acute Kidney Injury (AKI) were investigated through the mechanisms of oxidative stress and ferroptosis. Total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) parameters in the tissue were analyzed to investigate the oxidative stress occurring in the liver, pancreas, and heart, and Acyl-Coa synthetase long-chain family member (ACSL4). Glutathione peroxidase 4 (GPx4) enzyme levels were also analyzed by ELISA to investigate the effect on ferroptosis. In addition, hematoxylin-eosin staining was performed for histopathological examination of the tissues. As a result of biochemical analyzes, it was observed that oxidative stress parameters increased significantly in the IR group. In addition, while the ACSL4 enzyme level increased in the IR group in all tissues, the GPx4 enzyme level decreased. In the histopathological examination, it was observed that IR caused serious damage to the heart, liver, and pancreas tissues. The present study shows that Curcumin and LoxBlock-1 have a protective effect on the liver, pancreas, and cardiac ferroptosis following the effect on AKI. In addition, Curcumin was found to be more effective than LoxBlock-1 in I/R injury with its antioxidant property.

Topics: Acute Kidney Injury; Animals; Antioxidants; Curcumin; Ferroptosis; Liver; Oxidative Stress; Pancreas; Rats; Reperfusion; Reperfusion Injury

Diabetes mellitus has been implicated in the exacerbation of cerebral ischemic injuries. Among the most promising therapeutic approaches is the combination of nutraceuticals and nanotechnology. Curcumin has been termed "the magic molecule", and it was proven to exert several therapeutic actions. Therefore, the aim of the presented work was to investigate the therapeutic effects of curcumin nanoemulsion (NC) administered orally on the middle cerebral artery occlusion and reperfusion (MCAO/Re)-induced cerebral damage in rats with streptozotocin-induced diabetes. The cerebral injury was induced in rats by MCAO/Re 6 weeks after single intraperitoneal STZ injection (50 mg/kg; i.p.). MCAO/Re diabetic rats were then treated with NC (50 and 100 mg/kg; bw; p.o.) for two consecutive weeks. The results of the present study showed that oral treatment of MCAO/Re diabetic rats with NC was associated with a marked attenuation of the neurological deficit score as well as the brain imbalance of the redox homeostasis. NC treatment was also associated with decline in the brain expression of tumor necrosis factor, interleukin-1β, COX-2, cleaved caspase-3, and nuclear factor kappa B. In addition, the expression of glucose transporter 1 proteins upon treatment was restored. PRACTICAL APPLICATIONS: From all these results, it can be concluded that oral supplementation of curcumin nanoemulsion (NC) in diabetic rats reduced the brain injury via augmentation of the expression of glucose transporter 1, as well as its antioxidant and anti-inflammatory properties. Therefore, NC could be delineated as a promising treatment option for cerebral ischemia in diabetic patients.

Topics: Animals; Brain Injuries; Curcumin; Diabetes Mellitus, Experimental; Glucose Transporter Type 1; Infarction, Middle Cerebral Artery; Rats; Reperfusion Injury

Medical improvements are needed to prevent ischemia-reperfusion injury in thoracoabdominal aortic surgery. The aim of this study was to determine the antioxidant effects of thymoquinone, silymarin, and curcumin against ischemia-reperfusion injury associated with abdominal aorta.. Twenty-five Wistar albino rats were included in the study. Sham, control, and treatment (thymoquinone, silymarin, and curcumin) groups were set in equal numbers. Ischemia-reperfusion was applied by clamping (120 minutes) and de-clamping (60 minutes) the infrarenal aorta of all groups, except the sham group. Before reperfusion, thymoquinone, silymarin, and curcumin were given intraperitoneally to the treatment groups. After reperfusion, blood samples were taken from the right ventricle. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were studied in serum samples and histopathological examination was performed on the gastrocnemius muscle.. There was a significant difference in TOS and OSI values between the control and sham groups. Both values were found higher in the control group than in the sham group (P<0.05). OSI values were found to be lower in the thymoquinone group compared to the control group (P<0.05). All three parameters were found to be lower in the silymarin group than in the control group (P<0.05). TAS and TOS levels were found to be higher in the curcumin group than in the control group (P<0.05). There was no histopathological difference between the groups.. Silymarin and thymoquinone administration decreases oxidative stress in experimental aortic ischemia-reperfusion injury. Antioxidant effect of curcumin was lower than silymarin and thymoquinone.

Topics: Animals; Antioxidants; Aorta, Abdominal; Curcumin; Ischemia; Rats; Rats, Wistar; Reperfusion; Reperfusion Injury; Silymarin

Oxidative stress and inflammation are two key pathophysiological mechanisms that lead to neuronal apoptosis and brain damage following ischemia/reperfusion (I/R) injury. Because of their complex pathological mechanisms and the presence of the blood-brain barrier, the treatment of I/R is severely limited. Inspired by the fact that Macrophage membranes (MM) can cross the blood-brain barrier, we have developed a new multifunctional bionic particle (MSAOR@Cur). The modification of Sialic acid (SA) on the surface of Angelica polysaccharides (APS), the attachment of Resveratrol (Res) using the ROS-responsive bond oxalate bond as a linker arm, constitutes amphiphilic nanoparticles with an inner core encapsulated with curcumin (SAOR@Cur), and finally the use of MM camouflage to integrate the neuroprotection of APS, the free radical scavenging of Res, and the anti-inflammation of curcumin (Cur) in one strategy. Interestingly, the experimental results show that MSAOR@Cur can successfully deliver curcumin to the area of ischemia-reperfusion injury.

Topics: Curcumin; Humans; N-Acetylneuraminic Acid; Nanoparticles; Oxidative Stress; Polysaccharides; Reperfusion Injury; Resveratrol; Stroke

Oxidative stress-induced neuronal damage is a main cause of ischemia/reperfusion injury. Curcumin (Cur), the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric), exhibits excellent antioxidant effects. Previous studies have indicated that miR-1287-5p was downregulated in patients with ischemic stroke. Additionally, we predicted that Lon Peptidase 2, Peroxisomal (LONP2), which is involved in oxidative stress regulation, is targeted by miR-1287-5p. The aim of the current study is to investigate the effect of Cur on ischemia/reperfusion damage and its underlying mechanism. To mimic ischemia/reperfusion damage environment, SH-SY5Y cells were subjected to oxygen-glucose-deprivation/reperfusion (OGD/R). OGD/R treatment downregulated miR-1287-5p and upregulated LONP2 in SH-SY5Y cells, but Cur alleviated OGD/R-induced oxidative damage and reversed the effect of OGD/R on the expression of miR-1287-5p and LONP2. Furthermore, we confirmed the interactive relationship between miR-1287-5p and LONP2 (negative regulation). We revealed that miR-1287-5p overexpression alleviated OGD/R-induced oxidative damage alleviation, similar to the effect of Cur. MiR-1287-5p inhibition accentuated OGD/R-induced oxidative damage in SH-SY5Y cells, which was reversed by Cur. The expression of LONP2 in OGD/R-treated SH-SY5Y cells was decreased by miR-1287-5p overexpression and increased by miR-1287-5p inhibition, and Cur counteracted the increase in LONP2 expression induced by miR-1287-5p inhibition. In conclusion, we suggest that Cur alleviates OGD/R-induced oxidative damage in SH-SY5Y cells by regulating the miR-1287-5p/LONP2 axis. The findings provide a theoretical basis for the clinical application of curcumin.

Topics: Antioxidants; Apoptosis; Brain; Cell Hypoxia; Cell Line, Tumor; Curcumin; Glucose; Humans; Ischemic Stroke; MicroRNAs; Neurons; Neuroprotective Agents; Oxidative Stress; Reperfusion Injury; Signal Transduction

Epidemic modeling has been a key tool for understanding the impact of global viral outbreaks for over two decades. Recent developments of the COVID-19 pandemic have accelerated research using compartmental models, like SI, SIR, SEIR, with their appropriate modifications. However, there is a large body of recent research consolidated on homogeneous population mixing models, which are known to offer reduced tractability, and render conclusions hard to quantify. As such, based on our recent work, introducing the heterogeneous geo-spatial mobility population model (GPM), we adapt a modified SIR-V (susceptible-infected-recovered-vaccinated) epidemic model which embodies the idea of patient relapse from R back to S, vaccination of R and S patients (reducing their infectiousness), thus altering the infectiousness of V patients (from

Topics: Acute Lung Injury; Adherens Junctions; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antigens, CD; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; beta Catenin; Brain Ischemia; Cadherins; Carcinogenesis; Catalysis; Cell Line; Cells, Cultured; Curcuma; Curcumin; Dioxoles; Disease Models, Animal; Endothelial Cells; Epithelial Cells; Heme Oxygenase (Decyclizing); Humans; Inflammasomes; Intestinal Diseases; Intestinal Mucosa; Ischemic Stroke; Kidney Neoplasms; Lignans; Lung; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; NAD(P)H Dehydrogenase (Quinone); Nanostructures; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phytotherapy; Plant Extracts; Pneumonia; PPAR gamma; Proto-Oncogene Proteins c-akt; Pyroptosis; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reperfusion Injury; Respiratory Distress Syndrome; Sepsis; Sesamum; Signal Transduction; Silybin; Silybum marianum; Silymarin; Sirtuin 3; Titanium; Transfection; Treatment Outcome; White Matter

Ischemia-reperfusion injury (IRI) is an important factor limiting the success of cardiac reperfusion therapy. Curcumin has a significant cardioprotective effect against IRI, can inhibit ventricular remodeling induced by pressure load or MI, and improve cardiac function. However, the poor water solubility and low bioavailability of curcumin restrict its clinical application.. In this study, we prepared and evaluated a curcumin-hydrogel (cur-hydrogel) to reduce cardiomyocyte apoptosis and reactive oxygen species formation induced by hypoxia-reoxygenation injury, promote autophagy, and reduce mitochondrial damage by maintaining the phosphorylation of Cx43.. Meanwhile, cur-hydrogel can restore cardiac function, inhibit myocardial collagen deposition and apoptosis, and activate JAK2/STAT3 pathway to alleviate myocardial ischemia-reperfusion injury in rats.. The purpose of this study is to elucidate the protective effects of cur-hydrogel on myocardial ischemia-reperfusion injury by regulating apoptosis, autophagy, and mitochondrial injury in vitro and in vivo, which lays a new theoretical and experimental foundation for the prevention and reduction of IRI.

Topics: Animals; Apoptosis; Autophagy; Curcumin; Hydrogels; Mitochondria; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats; Reperfusion Injury

Liver ischemia-reperfusion (I/R) injury is a common clinical pathological phenomenon, which is accompanied by the occurrence in liver transplantation. However, the underlying mechanism is not yet fully understood. MicroRNAs (miRNAs) play an important role in liver I/R injury. Therefore, the study of miRNAs function will contribute a new biological marker diagnosis of liver I/R injury. This study aims to evaluate effects of miR-497-5p in liver I/R injury in mice. The related regulatory factors of miR-497-5p in liver I/R injury were predicted by bioinformatics analysis. Vascular occlusion was performed to establish the liver I/R injury animal models. Hypoxia/reoxygenation (H/R) was performed to establish the in vitro models. Hematoxylin-eosin (HE) staining was conducted to assess liver injury. The inflammatory factors were evaluated by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was adopted to assess the cell apoptosis. The expression of miR-497b-5p was increased in liver I/R injury. Knockdown of miR-497b-5p inhibited the production of inflammatory factors and cell apoptosis. Overexpression of mediator complex subunit 1 (MED1) and tissue inhibitor of metalloproteinase 2 (TIMP2) inhibited cell apoptosis to alleviate liver I/R injury. miR-497b-5p could activate the nuclear factor kappa-B (NF-κB) pathway by inhibiting the MED1/TIMP-2 axis to promote liver I/R injury. This study may provide a new strategy for the treatment of liver I/R injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Gene Expression Regulation; Hepatocytes; Kupffer Cells; Liver Diseases; Male; Mediator Complex Subunit 1; Mice; Mice, Inbred C57BL; MicroRNAs; NF-kappa B; Oxygen; Reperfusion Injury; Tissue Inhibitor of Metalloproteinase-2

Cerebral ischemia-reperfusion injury is caused by a blood reperfusion injury in the ischemic brain and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury.. Curcumin was reported to exert a good therapeutic effect on neural cells against ischemia- reperfusion injury, However, the mechanism is not clear.. In this study, Oxygen-Glucose Deprivation (OGD) model of fetal rat cerebral cortical neurons and the Middle Cerebral Artery Occlusion (MCAO) model of rats were employed to mimic cerebral ischemia-reperfusion injury in vitro and in vivo, respectively.. We confirmed that curcumin has a promotive effect on neuronal proliferation and an inhibitory effect on neuronal pyroptosis. Furthermore, we found that curcumin could improve cerebral infarction. The results of western blotting showed that curcumin down-regulated the expression of nucleotide-binding oligomerization domain-containing protein-, leucine-rich repeats-, and pyrin domain-containing protein 1 (NLRP1), cysteinyl aspartate-specific protease 1 (caspase-1), gasdermin D (GSDMD), IL-1β, IL-6, TNF-α, and iNOS proteins in OGD and MCAO models. NLRP1- dependent neuronal pyroptosis played an important role in cerebral ischemia-reperfusion injury.. Curcumin could effectively inhibit NLRP1-dependent neuronal pyroptosis by suppressing the p38 MAPK pathway and therefore exerted neuroprotective effects against cerebral ischemia- reperfusion injury.

Topics: Animals; Brain Ischemia; Cell Proliferation; Cerebral Cortex; Curcumin; Male; Nerve Tissue Proteins; Neurons; Pyroptosis; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Topics: Animals; Antioxidants; Cells, Cultured; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; Drug Evaluation, Preclinical; Green Chemistry Technology; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Oxidative Stress; PC12 Cells; Protective Agents; Rats; Reperfusion Injury; Structure-Activity Relationship

To investigate the influence of curcumin on the Notch2/Hes-1 pathway after pulmonary injury induction via limb ischemia-reperfusion (I/R).. Curcumin post-treatment reduced I/R-induced lung injury in rats. Its mechanism may be related to the inhibition of Notch2/Hes-1 signaling pathway and the release of inflammatory factors.

Topics: Animals; Curcumin; Lung; Lung Injury; Male; Rats; Rats, Sprague-Dawley; Receptor, Notch2; Reperfusion; Reperfusion Injury; Tumor Necrosis Factor-alpha

Hepatic ischemia/reperfusion (I/R) injury occurs in different clinical settings as hepatic transplantation, and different types of shock. I/R injury is the main cause of hepatic damage and failure due to the production of reactive oxygen species (ROS) and inflammatory cytokines. Dimethyl fumarate (DMF), an immunomodulatory drug, activates cellularantioxidantsignaling pathways exerting cytoprotective properties. Curcumin (CUR), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties.. To study potential protective effects of DMF with CUR against hepatic I/R injury in rats, animals were randomly allocated into seven groups as follows: (1) Sham; (2) DMF (25 mg/Kg, p.o); (3) CUR (400 mg/Kg, p.o.); (4) I/R; (5) DMF + I/R; (6) CUR + I/R; and combination (COM) therapy + I/R. Drugs were given for 14 days before I/R.. Compared with I/R group, COM group showed the best amelioration in hepatic injury induced by I/R insult. This was confirmed by a significant reduction in serum ALT and AST activity with improved histopathological results when compared to every single treatment. Hepatic protection afforded by DMF was mediated by activating Nrf2/HO-1 signaling and increasing GSH and TAC contents. CUR treatment improved the inflammatory markers (TNF-α, IL-1β, Il-6 and iNOS) as well as neutrophilic infiltration assessed as MPO. Moreover, CUR potentiated Nrf2/HO-1 signaling induced by DMF with significant suppression in lipid peroxidation.. We concluded that combining DMF and CUR has more efficient hepatoprotective effects against hepatic-induced IRI via potentiating antioxidant and anti-inflammatory properties mediated by Nrf2/HO-1 pathway.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Curcumin; Dimethyl Fumarate; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Heme Oxygenase (Decyclizing); Humans; Immunosuppressive Agents; Liver Failure, Acute; Male; NF-E2-Related Factor 2; Rats; Reperfusion Injury; Signal Transduction

Hexahydrocurcumin (HHC), a major metabolite of curcumin, has been reported to have protective effects against ischemic and reperfusion damage. The goal of the present research was to examine whether HHC could alleviate brain damage and ameliorate functional outcomes by diminishing the blood-brain barrier (BBB) damage that follows cerebral ischemia/reperfusion.. Middle cerebral artery occlusion was induced for 2 h in rats followed by reperfusion. The rats were divided into three groups: sham-operated, vehicle-treated, and HHC-treated groups. At the onset of reperfusion, the rats were immediately intraperitoneally injected with 40 mg/kg HHC. At 48 h after reperfusion, the rats were evaluated for neurological deficits and TTC staining. At 24 h and 48 h after reperfusion, animals were sacrificed, and their brains were extracted.. Treatment with HHC reduced neurological scores, infarct volume, morphological changes, Evans blue leakage and immunoglobulin G extravasation. Moreover, HHC treatment reduced BBB damage and neutrophil infiltration, downregulated myeloperoxidase, ICAM-1, and VCAM-1, upregulated tight junction proteins (TJPs), and reduced aquaporin 4 expression and brain water content.. These results revealed that HHC treatment preserved the BBB from cerebral ischemia/reperfusion injury by regulating TJPs, attenuating neutrophil infiltration, and reducing brain edema formation.

Topics: Animals; Aquaporin 4; Blood-Brain Barrier; Brain; Brain Edema; Brain Ischemia; Curcumin; Infarction; Infarction, Middle Cerebral Artery; Male; Rats; Rats, Wistar; Reperfusion Injury; Zonula Occludens-1 Protein

Curcumin, the complex extracted from the traditional edible herb, has a wide range of pharmacological effects. A great deal of studies has demonstrated that curcumin could protect against cerebral ischemia-reperfusion (I/R) injury. In the present study, we aimed to test the hypothesis that curcumin reduces brain damage via regulating mitophagy and preserving mitochondrial function. To clarify the potential effect and mechanism of curcumin on cerebral I/R, we utilize MCAO followed by reperfusion rats and OGD/R neurons as cerebral I/R in vivo and in vitro, respectively.. We determined the cellular ROS levels and mitochondrial function, including mitochondrial membrane potential (MMP), ATP levels, state 3 respiration and state 4 respiration. We also detected the levels of mitophagy by immunofluorescent staining and western blotting.. Results found that curcumin decreased neurological deficit scores, infarct volume and morphological changes of neurons in rats after brain I/R injury. Curcumin also reduced the levels of ROS while increased MMP, ATP levels and state 3 respiration to prevent the impairment of mitochondrial function from cerebral I/R. Furthermore, curcumin enhanced the co-localization of LC3B and mitochondrial marker VDAC1, the ratio of LC3-II to LC3-I, improving cerebral I/Rinduced mitophagy.. In conclusion, our results suggest that curcumin protects against cerebral I/R injury by improving mitophagy and preserving mitochondrial function.

Topics: Animals; Apoptosis; Curcumin; Disease Models, Animal; Male; Membrane Potential, Mitochondrial; Mitochondria; Mitophagy; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury

BACKGROUND Cerebral ischemia/reperfusion (I/R) injury contributes to mortality and morbidity in preterm infants. Curcumin has been shown to exert neuro-protective effects in the central nervous system (CNS). The aim of this study was to investigate the neuro-protective activity of curcumin and the possible underlying molecular mechanisms. MATERIAL AND METHODS A hypoxia/reoxygenation (H/R) protocol was used to simulate I/R injury in vitro. Isolated neonatal neurons were pre-treated with curcumin at serially diluted concentrations and exposed to H/R injury. Cell viability and apoptosis were assessed by MTT and flow cytometry, respectively. Contents of TNFa and IL6 in supernatant of cell culture medium were detected by ELISA. Protein expression, phosphorylation, and nuclear translocation levels were studied by Western blotting. RESULTS H/R reduced cell viability and increased apoptosis of neurons. H/R significantly increased Wnt5a expression, JNK1 phosphorylation, and NF-kappaB nuclear translocation. Moreover, expression levels of cleaved caspase3, TNFalpha, and IL6 were elevated in H/R-exposed neurons. Curcumin pre-treatment significantly increased cell viability and inhibited apoptosis of neurons exposed to H/R, in a concentration-dependent manner. Moreover, curcumin pre-treatment significantly decreased expression levels of Wnt5a, IL6, TNFalpha, and phosphorylation level of JNK1, as well as the nuclear translocation level of NF-kappaB in H/R-exposed neurons, in a concentration-dependent manner. CONCLUSIONS Curcumin exerted neuro-protective effects against H/R-induced neuron apoptosis and inflammation by inhibiting activation of the Wnt/JNK1 signaling pathway.

Topics: Animals; Apoptosis; Cell Line; Cell Survival; Curcumin; Female; Fetus; Hypoxia; Inflammation; Neurons; Neuroprotective Agents; Pregnancy; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Wnt Signaling Pathway

Curcumin, a polyphenolic compound extracted from the plant Curcuma longa, has been reported to exert neuroprotective effects against cerebral ischemia reperfusion (I/R) injury. However, the mechanisms underlying these effects remain to be fully elucidated. Emerging evidence indicated that apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional enzyme, participates in neuronal survival against I/R injury. Therefore, the aim of the present study was to investigate whether curcumin alleviates oxygen‑glucose deprivation/reperfusion (OGD/R)‑induced SH‑SY5Y cell injury, which serves as an in vitro model of cerebral I/R injury, by regulating APE1. The results revealed that curcumin increased cell viability, decreased LDH activity, reduced apoptosis and caspase‑3 activity, downregulated the pro‑apoptotic protein Bax expression and upregulated the anti‑apoptotic protein Bcl‑2 expression in SH‑SY5Y cells subjected to OGD/R. Simultaneously, curcumin eliminated the OGD/R‑induced decreases in APE1 protein and mRNA expression, as well as 8‑hydroxy‑2'‑deoxyguanosine (8‑OHdG) level and AP sites in SH‑SY5Y cells. However, APE1 knockdown by siRNA transfection markedly abrogated the protective effects of curcumin against OGD/R‑induced cytotoxicity, apoptosis and oxidative stress, as illustrated by the decreases in reactive oxygen species production and NADPH oxidase 2 expression, and the increase in superoxide dismutase activity and glutathione levels in SH‑SY5Y cells. Furthermore, curcumin mitigated the OGD/R‑induced activation of phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway. Treatment with LY294002, an inhibitor of PI3K/AKT pathway activity, attenuated the protective effects of curcumin on cytotoxicity and apoptosis, and reversed the curcumin‑induced upregulation of APE1 protein expression in SH‑SY5Y cells subjected to OGD/R. Taken together, these results demonstrated that curcumin protects SH‑SY5Y cells against OGD/R injury by inhibiting apoptosis and oxidative stress, and via enhancing the APE1 level and activity, promoting PI3K/AKT pathway activation.

Topics: Cell Line, Tumor; Curcumin; DNA-(Apurinic or Apyrimidinic Site) Lyase; Humans; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reperfusion Injury; Signal Transduction

Curcumin presents some therapeutic effects including anti-cancer and anti-inflammation. Herein, we centred on the functional role of curcumin in cerebral ischaemia injury and its potential molecular mechanisms.. Microarray analysis was used for excavating crucial genes in cerebral ischaemia. PC12 cells were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) to imitate cerebral ischaemia/reperfusion (I/R) injury in vitro. Cell viability and apoptosis abilities were evaluated by Cell Counting Kit-8 and flow cytometry assays. qRT-PCR, Western blot and enzyme-linked immunosorbent assays were performed to assess the concentrations of related genes.. By enquiring GEO dataset, C-C motif chemokine ligand 3 (CCL3) was profoundly upregulated in cerebral I/R injury model. And CCL3 was found to be highly expressed in PC12 cells suffered from OGD/R. Moreover, we found that CCL3 was a potential target of curcumin in cerebral I/R injury. More importantly, the following experiments illustrated that curcumin inhibited the expression of CCL3 in OGD/R model and reduced cell apoptosis and inflammation. Moreover, high expression levels of TLR4, MyD88, p-NF-κB P65, p-P38 MAPK and p-IκBα in OGD/R model were inhibited by curcumin.. Our study manifested that curcumin might be a meritorious drug for the treatment of cerebral ischaemia by acting on CCL3.

Topics: Animals; Apoptosis; Brain Ischemia; Chemokine CCL3; Curcumin; Gene Expression Regulation; Glucose; Inflammation; Myeloid Differentiation Factor 88; Oxygen; p38 Mitogen-Activated Protein Kinases; PC12 Cells; Rats; Reperfusion Injury; Toll-Like Receptor 4; Transcription Factor RelA

Ischemia/reperfusion (I/R) is one of the most important causes of acute kidney injury (AKI), a clinical syndrome with kidney dysfunction and high mortality rates. New diagnostic biomarkers need to be defined to better illuminate the pathophysiology of AKI. For the first time, we aim to investigate the protective effects of Curcumin which is known for its antioxidant and anti-inflammatory properties and 12/15 lipoxygenase inhibitor LOXblock-1 on I/R induced AKI by modulating inflammatory processes, oxidative stress, apoptosis and semaphorin-plexin pathway.. The rats were divided into five groups, with eight animals per group: Sham, I/R, I/R + DMSO (1%, i.p.), I/R + Curcumin (100 mg/kg, i.p.), I/R + LOXblock-1 (2 μg/kg, i.p.).. The renal function biomarkers (BUN, CREA and UA) in serum were significantly increased in the I/R group. The inflammatory (TNF-α, IL-6 and MCP-1), apoptotic (CYCS and CASP3) and oxidative stress parameters (MDA, MPO, TAS and TOS) measured by ELISA were significantly increased in the I/R group. In histopathological analysis, it was observed that I/R caused serious damage to kidney tissue. SEMA3A was found to increase both serum level and mRNA expression in I/R group. It was observed that curcumin and LOXblock-1 reduce inflammatory processes, oxidative stress and apoptosis via the semaphorin-plexin pathway by both measurements and histopathological analysis. Curcumin was proved more effective than LOXblock-1 with its antioxidant feature in I/R injury.. The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Benzene Derivatives; Cell Adhesion Molecules; Curcumin; Inflammation; Lipoxygenase Inhibitors; Nerve Tissue Proteins; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Semaphorin-3A; Semaphorins

The pathogenesis of ischemic cerebrovascular disease has revealed that ischemia-reperfusion (I/R) injury often leads to aggravation of metabolic oxidative stress and blood-brain barrier (BBB) destruction, eventually causing secondary brain tissue damage. Accumulated reactive oxygen species (ROS) in focal ischemia activate mitochondria-mediated apoptosis and damage the BBB by degrading tight junction proteins (TJPs). Herein, we report macrophage-derived exosomes (Ex) loaded with curcumin (cur) as a multifunctional biomimetic delivery vehicle (Ex-cur) for targeting ischemic brain tissue and alleviating cerebral I/R injury by inhibiting ROS-mediated mitochondrial apoptosis in a transient cerebral ischemia rat model. The design principle relies on unique features of macrophage-derived exosomes and the natural ingredient cur. Specifically, cur can be entrapped within exosomes when incubated with murine macrophage RAW264.7 cells, and its stability is subsequently significantly improved. The resultant Ex-cur can target ischemic regions by leveraging the targeting migration capability of Ex driven by inflammation. Accumulated Ex-cur in ischemic regions is experimentally proven to be highly effective at reducing ROS accumulation by virtue of the antioxidant properties of cur. Using Ex-cur to down-regulate ROS accumulation in lesions, we alleviate BBB damage and suppress mitochondria-mediated neuronal apoptosis, which is confirmed by a series of relevant protein analysis. These findings demonstrate good therapeutic efficacy of Ex-cur for treating I/R injury, providing experimental evidence for the potential clinical benefits of Ex-cur for other modes of neuroprotection.

Topics: Animals; Apoptosis; Brain; Curcumin; Exosomes; Ischemia; Mice; Mitochondria; Rats; Reactive Oxygen Species; Reperfusion Injury

This study was to investigate the potential protective effects of curcumin in cerebral ischemia-reperfusion (CIR) and its regulation of miR-7.. Rats were occluded by middle cerebral artery occlusion (MCAO) for 1.5 h and reperfused for 2 h to establish a local CIR model. After 24 hours of model establishment, MCAO rats were given curcumin for 3 days by intragastric administration. PC12 cells were cultured for 6 h in oxygen-glucose deprivation medium and then reoxygenated for 24 h to establish an oxygenglucose deprivation/reoxygenation (OGD/R) model. The OGD/R model cells were treated with curcumin for 48 h.. Curcumin inhibited the decrease of miR-7-5p expression and an increase of RelA p65 expression induced by CIR and ODG/R. RelA p65 was a target of miR-7-5p. MiR-7-5p antagonists were able to counteract the effect of curcumin on the expression of RelA p65 in ischemic brain tissue of MCAO rats and OGD/R model cells. Curcumin improved OGD/R-induced inhibition of cell activity, necrosis and apoptosis. Curcumin significantly reduced the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the activity of superoxide dismutases (SOD) and catalase (CAT) in OGD/R-induced cells. Curcumin may inhibit OGD/R-induced cell damage by regulating miR-7-5p. Curcumin improved cerebral infarction, nerve damage and cognitive dysfunction in rats with CIR, which may be related to the regulation of miR-7-5p/RelA p65 axis.. Curcumin exerts cerebral protection by attenuating cell necrosis and apoptosis, inflammatory response and oxidative stress following CIR, which may be related to its regulation of the miR-7/RELA p65 axis.

Topics: Animals; Apoptosis; Cognition Disorders; Curcumin; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Male; MicroRNAs; Neuroprotective Agents; Oxidative Stress; Rats; Reactive Oxygen Species; Reperfusion Injury

Cerebral ischemia-reperfusion (CIR) accelerates the progression of neurodegeneration by causing mitochondrial dysfunction to overproduce reactive oxygen species (ROS). Curcumin shows protective effects against CIR-induced oxidative damage. Free curcumin (FC) is effective at high doses due to its poor bioavailability. Also the blood-brain barrier (BBB) limits the passage of substances from circulation into the cerebral region. Thus, formulation of curcumin within polyethylene glycol (PEG)-ylated polylactide-co-glycolide (PLGA) nanoparticles (NC) was applied orally to aged rats to explore its role against CIR injury. Mitochondrial damage was evaluated. The levels of pro-inflammatory cytokines and components of apoptotic pathway were studied. Unlike FC, NC pre-treatment exerted better neuro-protection by ameliorating ROS-mediated oxidative damage and prevented CIR-induced neuronal apoptosis. Therefore, curcumin incorporated PEGylated PLGA nanoparticles may be used as a suitable delivery vehicle to the brain as they can increase curcumin bioavalability and the released curcumin may confer protection to the neurons against CIR-induced oxidative damage.

Topics: Animals; Apoptosis; Brain; Curcumin; Female; Lipid Peroxidation; Nanocapsules; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury

Topics: Animals; Blood-Brain Barrier; Brain; Brain Ischemia; Curcumin; Infarction, Middle Cerebral Artery; Male; Mice, Inbred C57BL; Mitochondria; Reperfusion Injury; Stroke

Oxidative stress and inflammation are two important pathophysiological mechanisms that arouse neuronal apoptosis and cerebral damage after ischemia/reperfusion (I/R) injury. Here, we hypothesized that curcumin-encapsulated nanoparticles (NPcurcumin) could reduce oxidative stress and inflammation in the ischemic penumbra via protecting the blood-brain barrier (BBB) and inhibiting M1-microglial activation. Under oxidative stress conditions in vitro, we found that NPcurcumin protected microvascular endothelial cells against oxidative stress and reduced BBB permeability. In vivo, NPcurcumin could cross the BBB and accumulate in the ischemic penumbra. At 3 d after I/R injury, NPcurcumin inhibited the increase in MMP-9, attenuated the decrease in occludin and zona occluden-1, and maintained BBB integrity. NPcurcumin effectively reduced the number of activated M1 microglia and weakened the increase in TNF-α and IL-1β. Furthermore, NPcurcumin also reduced the infarct size and improved function recovery.

Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Curcumin; Humans; Interleukin-1beta; Macrophage Activation; Matrix Metalloproteinase 9; Occludin; Oxidative Stress; Reperfusion Injury; Tumor Necrosis Factor-alpha; Zonula Occludens-1 Protein

The aim of the present study was to investigate the effects of curcumin on lung damage following ischemia/reperfusion (I/R) injury after hind limb ligation.. Forty Wistar rats were divided into four groups: sham (G1), I/R (G2), curcumin plus sham (G3), and curcumin plus I/R (G4). Curcumin was administered (200 mg/kg) daily for 2 weeks before the study. I/R was induced by placement of rubber tourniquets at the greater trochanters for 2 h, followed by reperfusion for 4 h.. Curcumin pretreatment had significantly lower level of malondialdehydes and higher level of superoxide dismutase in the lung tissues (p<0.05) than the I/R group. Glutathione peroxidase activity was not significantly different among the groups (p>0.05). I/R caused severe histopathological injury (p<0.05), including inflammatory cell infiltration and intra-alveolar hemorrhage.. These results suggest that curcumin pretreatment has protective effects against lung injury induced by muscle I/R.

Topics: Animals; Curcumin; Disease Models, Animal; Lung; Lung Injury; Muscle, Skeletal; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury

The aim of the present study was to investigate the protective effects of curcumin and its effect on the methyl ethyl ketone/extracellular signal regulated kinase/cAMP‑response element binding protein (MEK/ERK/CREB) pathway. The study was conducted in vivo and in vitro as follows: In vivo: Focal cerebral ischemia‑reperfusion (IR) models of rats were made with the plug‑line method. Adult male Sprague‑Dawley rats were divided into four groups: Sham operation control group, IR and curcumin‑treatment groups (100 mg/kg and IC, 300 mg/kg). The effects of curcumin on neurological deficit scores, brain water content and infarct volumes were identified. Transmission electron microscope was utilized to observe morphological changes of hippocampal neurons; hematoxylin and eosin staining was used to observe morphological changes of brain tissue; and the terminal deoxynucleotidyl transferase (TdT)‑mediated dUTP nick end labeling method detected neurons apoptosis of hippocampal CA1. Finally, western blot analysis detected the expression of phosphorylated (p)‑MEK, p‑ERK, p‑CREB, B‑cell lymphoma‑2 (Bcl‑2) and Bcl‑2 associated X protein (Bax). In vitro: An oxygen‑glucose deprivation/reoxygenation method was used on primary cultured astrocytes to make cerebral ischemia‑reperfusion models in vitro. Astrocytes were randomly divided into five groups: Normoxia, oxygen‑glucose deprivation/reoxygenation (OGD/Reoxy), OGD/Reoxy + curcumin (5, 10, 20 µmol/l). The cell viability and toxicity were assessed by MTT and lactate dehydrogenase release assay, and levels of p‑MEK, p‑ERK and p‑CREB proteins were analyzed by the western blotting method. Curcumin was demonstrated to improve nerve damage symptoms and infarct volume, reduce brain water content, relieve neuronal apoptosis and also increase the expression of p‑MEK, p‑ERK, p‑CREB, Bcl‑2 and reduce Bax levels in vivo and in vitro. In conclusion curcumin can mitigate focal cerebral ischemia‑reperfusion injuries and this effect may be carried out through the MEK/ERK/CREB pathway.

Topics: Animals; Apoptosis; Astrocytes; Brain Ischemia; Cell Survival; Curcumin; Hippocampus; L-Lactate Dehydrogenase; Male; Nerve Tissue Proteins; Neurons; Neuroprotective Agents; Organ Size; Phosphorylation; Rats, Sprague-Dawley; Reperfusion Injury; Water

The beneficial, neuroprotective effects of curcumin against ischemia-reperfusion injury have been demonstrated. In the present study, whether curcumin exerts neuroprotective effects associated with the inhibition of autophagy and hypoxia inducible factor-1α (HIF-1α) was investigated.. PC12 cellular model of oxygen glucose deprivation/reperfusion (OGD/R) has been developed to mimic cerebral ischemia-reperfusion injury. Cell viability was evaluated using the CellTiter 96. In this study, curcumin decreased the death and apoptosis of cells, and inhibited autophagy and HIF-1α under OGD/R conditions, consistent with 3-MA treatment or HIF-1α downregulation. Moreover, inhibition of autophagy caused a decrease in HIF-1α, and the attenuation of HIF-1α induced autophagy suppression under OGD/R conditions.. The results of this study showed that curcumin exerts neuroprotective effects against ischemia-reperfusion, which is associated with the regulation of the reciprocal function between autophagy and HIF-1α.

Topics: Animals; Autophagy; Cell Survival; Cells, Cultured; Curcumin; Dose-Response Relationship, Drug; Hypoxia-Inducible Factor 1, alpha Subunit; Neuroprotective Agents; Optical Imaging; PC12 Cells; Rats; Reperfusion Injury; Structure-Activity Relationship

In this study, we provided evidence that curcumin could be a promising therapeutic agent for ischemic stroke by activating neuroprotective signaling pathways. Post oxygen and glucose deprivation/reoxygenation (OGD/R), primary mouse cortical neurons treated with curcumin exhibited a significant decrease in cell death, LDH release and enzyme caspase-3 activity under OGD/R circumstances, which were abolished by flotillin-1 downregulation or extracellular signal-regulated kinase (ERK) inhibitor. Moreover, flotillin-1 knockdown led to suppression of curcumin-mediated ERK phosphorylation under OGD/R condition. Based on these findings, we concluded that curcumin could confer neuroprotection against OGD/R injury through a novel flotillin-1 and ERK1/2 pathway.

Topics: Animals; Brain Ischemia; Cells, Cultured; Cerebellar Cortex; Curcumin; Female; Glucose; Male; MAP Kinase Signaling System; Membrane Proteins; Mice, Inbred BALB C; Neurons; Neuroprotective Agents; Oxygen; Reperfusion Injury

Curcumin, a natural antioxidant isolated from Curcuma longa, has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying mechanism is still not fully understood. The purpose of this study was to investigate the effect of curcumin treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury and in mouse N2a cells after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and its underlying mechanism.. The cerebral I/R injury was established by 1-hr middle cerebral artery occlusion (MCAO) and reperfusion in mice. Infarct volume was determined by TTC staining, and neurological score was evaluated by mNSS. Cell morphology in the ischemic boundary zone were detected by HE staining. The number and apoptotic rate of neurons in ischemic boundary zone were assayed by immunohistochemistry and TUNEL, respectively. Mouse neuroblastoma N2a cells were subjected to OGD/R. Cell viability was assessed with CCK-8. The mitochondrial membrane potential was measured using JC-1 staining. The expression of Bax, Bcl-2, and caspase-3 was detected using Western blotting. Besides, cellular distribution of Bax was determined by immunofluorescence assays.. Curcumin promotes neuron survival

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Brain Ischemia; Caspase 3; Cell Line, Tumor; Cell Survival; Cells, Cultured; Curcumin; Disease Models, Animal; Mice; Neurons; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Stroke

Ovarian torsion must be diagnosed and treated as early as possible. The aim of the present study was to investigate the effects of intraperitoneal administration of nanocurcumin on ischemia-reperfusion injury in ovaries.. Thirty-five (35) healthy female Wistar rats weighing approximately 250 g were randomized into seven experimental groups (n=5): Group SSG - The rats underwent only laparotomy. Group I: A 3-hour ischemia only. Group I/R: A 3-hour ischemia and 3-hour reperfusion. Group I/C: A 3-hour ischemia only, and 1 mg/kg intraperitoneal administration of curcumin 2.5 hours after induction of ischemia. Group I/R/C: A 3-hour ischemia, 3-hour reperfusion, and 1 mg/kg intraperitoneal administration of curcumin 2.5 hours after induction of ischemia. Group I/NC: A 3-hour ischemia only and 1 mg/kg intraperitoneal administration of nanocurcumin 2.5 hours after induction of ischemia. Group I/R/C: A 3-hour ischemia, 3-hour reperfusion and 1 mg/kg intraperitoneal administration of nanocurcumin 2.5 hours after induction of ischemia.. Nanocurcumin-treated animals showed significantly improved development of ischemia and reperfusion tissue injury compared to those in the other groups (p<0.05). Significant higher values of SOD, tGSH, GPO, GSHRd and GST were observed in I/R/NC animals compared to those in the other groups (p<0.05). The damage indicators (NOS, MDA, MPO and DNA damage level) were significantly lower in I/R/NC animal compared to those of other groups (p<0.05).. Intraperitoneal administration of nanocurcumin can be helpful in minimizing ischemia-reperfusion injury in ovarian tissue exposed to ischemia.

Topics: Administration, Cutaneous; Animals; Antioxidants; Curcumin; Disease Models, Animal; Female; Humans; Injections, Intraperitoneal; Ischemia; Nanoparticles; Ovary; Rats; Rats, Wistar; Reperfusion Injury

Previous studies indicated that cerebral ischemia/reperfusion injury (CI/RI) could induce behavioral deficits. Single treatment of vagus nerve stimulation (VNS) or curcumin is reported to restore CI/RI-induced behavioral deficits. However, the synergic effect remains unclear.. Rats were divided into 6 groups: sham, CI/RI, VNS, CI/RI + VNS, VNS + curcumin and CI/RI + VNS + curcumin groups. Each group was further divided into three or four subgroups for further assessments. In specific, Morris water maze task and shuttle box test were used to evaluate cognitive capacity. Rota-rod test, neurological deficits scores, 2,3,5-triphenyltetrazolium chloride staining, TUNEL staining were performed to estimate motor capacity, neurological deficits, the size of infarct volume and neural apoptosis, respectively. Finally, the expressions of apoptosis-associated proteins and key kinases in the AKT/extracellular signal-regulated kinase-2 (ERK2) pathway were measured by Western blot analysis.. Combination of curcumin and VNS significantly restored the CI/RI-induced cognitive and motor impairments compared with the CI/RI + VNS group (P < 0.05 and P < 0.01). Moreover, combination of curcumin and VNS significantly lowered CI/RI-induced neurological deficits, infract volume, neural apoptosis (all P < 0.05) and inflammatory cytokines release (P < 0.05 and P < 0.01) when compared to the CI/RI + VNS group. Additionally, the phosphorylation levels of AKT and ERK2 were both increased by combination of curcumin and VNS compared with the CI/RI + VNS group.. Combination of curcumin and VNS restored CI/RI-induced behavioral deficits by inhibiting apoptosis and inflammatory response. Besides, the AKT/ERK2 pathway might be implicated.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain Ischemia; Combined Modality Therapy; Curcumin; Inflammation Mediators; Maze Learning; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Vagus Nerve Stimulation

As a major cause of renal failure, transient renal ischemia and reperfusion induce both acute kidney injury and late fibrosis, which are the common pathological manifestations of end-stage renal disease. Curcumin is a biologically active polyphenolic compound found in turmeric. Increasing evidence has demonstrated that curcumin has a protective action against renal fibrosis, whereas mechanisms underlying the anti-fibrosis role of curcumin remain poorly defined. Here, we found that APPL1, an important intracellular binding partner for AdipoR, was involved in the pathogenesis of acute injury or fibrosis and was significantly upregulated by curcumin in a mouse model of ischemia reperfusion-induced late kidney fibrosis. Moreover, Akt signaling was the specific signaling pathway identified downstream of APPL1 in the pathogenesis of fibrosis. Our in vitro experiment demonstrated that curcumin alleviates ischemia reperfusion-induced late kidney fibrosis via the APPL1/Akt pathway. These data are helpful for understanding the anti-fibrosis mechanism of curcumin in the pathogenesis of AKI-induced late fibrosis.

Topics: Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Animals; Curcumin; Disease Models, Animal; Fibrosis; Humans; Kidney; Mice; Proto-Oncogene Proteins c-akt; Receptors, Adiponectin; Reperfusion Injury; Signal Transduction

The present study assessed whether the protective effects of curcumin against cerebral ischemia injury were due to the suppression of overactivated autophagy. Curcumin is a well-known natural polyphenolic compound that effectively counteracts oxidation, inflammation, and various types of cancer. Several studies have demonstrated the protective effects of curcumin against ischemia-reperfusion injury in tissues from the lungs, cardiomyocytes, and liver. The present study employed brain injury models induced by middle cerebral artery occlusion (MCAO) in rats and PC12 oxygen-glucose-deprived (OGD) cells. Infarct area, neurological score, lactate dehydrogenase (LDH) activity, autophagy expression, cell apoptosis, and mRNA and protein expressions of caspase-3 were determined following curcumin supplementation. Compared to MCAO rats, curcumin-treated MCAO rats exhibited substantial reductions in neurological score, infarct area, and LDH activity. MCAO also increased LC3 II/I protein expression and decreased p62 protein expression, but curcumin supplementation significantly reversed these altered protein expressions. Caspase-3 protein expression increased by 46.2% in the MCAO group, but curcumin supplementation significantly reduced this expression. Similarly, apoptosis increased by 33.1% in OGD cells, but curcumin supplementation significantly reduced apoptosis to 21.6% and 9.3% at doses of 100 and 200 mg/kg, respectively. The mRNA and protein expressions of caspase-3 exhibited substantial increases in OGD cells but these expressions were significantly decreased following curcumin supplementation. Taken together, the present results indicate that curcumin represents a natural bioactive substance that can protect against cerebral ischemia via the suppression of overactivated autophagy.

Topics: Animals; Autophagy; Curcumin; Disease Models, Animal; Neuroprotective Agents; PC12 Cells; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Curcumin shows protective effects on various diseases due to its anti-inflammatory and anti-oxidative functions; however, its effect on organ transplantation has not been fully elucidated. To understand its role in liver ischemia/reperfusion (I/R) injury, we studied its impact on orthotopic liver transplantation (OLT) and Kupffer cells (KCs) polarization and its underlying mechanisms. We first investigated the reactive oxygen species (ROS) accumulation and cytokines profile of KCs, intracellular ROS and the mRNA level of pro-inflammatory cytokines were downregulated while the mRNA level of anti-inflammatory cytokine was upregulated by the pretreatment of Curcumin; Then the liver injury was detected by histopathological examination and liver function. Pretreatment with Curcumin significantly alleviated liver injury while improving liver function and overall post-transplantation survival compared with the control groups. The Western blotting showed that Curcumin inhibited the function of KCs via down-regulating the nuclear factor κb (NF-κb) signaling pathway by activating peroxisome proliferator-activated receptor γ (PPARγ) and flow cytometry revealed that Curcumin suppressed pro-inflammatory phenotype (M1) of KCs while promoting its anti-inflammatory phenotype (M2) polarization. These results showed that Curcumin may exert positive effects on I/R injury after OLT through activating PPARγ by inhibiting the activation of NF-κb pathway and remodeling the polarization of KCs. This may reveal a potential therapy for I/R injury after liver transplantation.

Topics: Animals; Apoptosis; Curcumin; Kupffer Cells; Liver; Liver Transplantation; Male; Mice, Inbred C57BL; PPAR gamma; Protective Agents; Reperfusion Injury; Transplants

The present study aimed to explore the protective mechanism of curcumin-precondition in renal ischemia-reperfusion (I/R) injury. Thirty male SD rats were randomly equally divided into Sham, IRI, and Curcumin groups (n = 10). The model of IRI was induced by clamping the left renal artery for 45 min followed by 24 h reperfusion with the contralateral nephrectomy. ELISA was used to examine the expression of Cr, BUN, IL-8, TNF-α, and IL-6 in the serum; RT-PCR was used to detect the mRNA level of IL-8,TNF-α, and IL-6 in the kidney; The morphology of kidney was examined by Periodic Acid-Schiff stain (PAS). The expression of JAK2, p-JAK2, STAT3, p-STAT3, p65, and p-p65 in kidney were detected by Western blotting. The result displayed that Curcumin pretreatment can significantly increase the expression of p-JAK2 and p-STAT3 and reduce the expression of Cr, BUN, IL-8, TNF-α, IL-6, and p-p65. In addition, Curcumin can attenuate the kidney pathological injury and have no effect on the expression of JAK2, STAT3, and p65. Our findings showed the protective effect of Curcumin in I/R injury is associated with suppressing NF-κB mediating inflammation by activating JAK2/STAT3 signal pathway.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Disease Models, Animal; Humans; Janus Kinase 2; Kidney; Male; NF-kappa B; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; STAT3 Transcription Factor

The purpose of this study is to investigate the neurological, biochemical, and histopathologic effects of both the acute and maintenance treatment of curcumin on an experimental spinal cord ischemia-reperfusion injury model in rats.. The animals were randomly divided into 4 groups: (1) Sham, (2) ischemia-reperfusion (IR), (3) curcumin, and (4) solvent. Spinal cord ischemia was induced by clamping the aorta with minivascular clamps at a position just below the left renal artery and just proximal to the aortic bifurcation for 45 min. After 72 hr of reperfusion, neurological function was evaluated with a modified Tarlov score. In spinal cords, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and nitric oxide (NO) levels were detected biochemically. Immunohistochemical staining was performed by antibodies against interleukin-6 (IL-6) and myeloperoxidase. Histopathologic changes were examined with hematoxylin and eosin staining.. Although MDA tissue levels were elevated significantly in the IR group compared with the sham group, SOD and GPx levels decreased. After the administration of curcumin, MDA levels in the spinal cord decreased, and SOD and GPx levels increased. Those changes were statistically significant. There was no significance at NO levels. Among all groups, there was no difference in IL-6 and myeloperoxidase immunostaining. Histopathological analysis showed that histopathological changes in the IR group were improved by curcumin treatment. In the curcumin group, neurological outcome scores were significantly better statistically when compared with the IR group.. We believe that curcumin possesses antioxidant, antiproliferative, and anticarcinogenic properties and may be an effective drug for the prevention of spinal cord IR injury in light of the neurologic, biochemical, and histopathological data of this study and published scientific literature.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; Glutathione Peroxidase; Interleukin-6; Malondialdehyde; Neuroprotective Agents; Nitric Oxide; Peroxidase; Rats, Wistar; Reperfusion Injury; Spinal Cord; Spinal Cord Ischemia; Superoxide Dismutase; Time Factors

The pathogenesis of visual dysfunction in stroke remains unclear. The objective of this study was to explore retinal damage in stroke spontaneously hypertensive rats (SHR) and evaluate the role of curcumin in the retinal injury after stroke. Mature male SHR were used as the animal model for hypertension and age-matched male Wistar-Kyoto (WKY) rats as the normotensive controls. The rat model of stroke was made by bilateral vertebral artery electrocoagulation combined with transient bilateral common carotid artery ligation. The animals were randomly divided into sham group, ischemia/reperfusion group, solvent control group, and curcumin treatment group. Each group was subdivided into 2 h, 6 h, 24 h, 72 h, and 7 day after reperfusion. Blood pressure was measured in SHR and WKY rats. Eye fundus was examined in living animals, and then, tissue specimens were collected for histologic examination, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling, and immunohistochemistry. Retinopathy, induced by I/R, was more serious in rats with hypertension than that in normotensive rats (retinal thickness index, p = 0.004). The number of apoptosis in retinal capillary cells and neurons reduced significantly in the curcumin-treated groups. Curcumin treatment inhibited phosphorylated c-Jun N-terminal kinase (JNK) expression in SHR after retinal I/R injury. Thus, hypertension aggravated retinal I/R injury after stroke. Curcumin, a specific inhibitor of JNK, can prevent the development of hypertensive retinopathy after I/R injury by inhibiting apoptosis in retinal capillary cells and neurons.

Topics: Animals; Apoptosis; Blood Pressure; Brain Ischemia; Capillaries; Curcumin; Disease Models, Animal; Enzyme Inhibitors; Hypertension; Hypertensive Retinopathy; JNK Mitogen-Activated Protein Kinases; Male; Neurons; Protective Agents; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reperfusion Injury; Retina; Stroke

Reperfusion is the only approved therapy for acute ischemic stroke; however, it can cause excessive inflammation responses and aggravate brain damage. Therefore, supplementary treatment against inflammation caused by reperfusion is required. In a previous study from our group, curcumin was demonstrated to decrease infarction volume, brain edema and blood‑brain barrier (BBB) disruption against cerebral ischemia/reperfusion (I/R) injury. However, the underlying mechanisms remain unclear. The present study was conducted to understand whether curcumin protects against cerebral I/R injury through anti‑inflammatory and antiapoptotic properties. Ischemia for 1 h was induced in vivo in Wistar rats by middle cerebral artery occlusion (MCAO), followed by reperfusion for 24 h, and curcumin was injected intraperitoneally at 30 min prior to reperfusion. Immunohistochemistry was performed to analyze the expression levels of nuclear factor (NF)‑κB, intercellular adhesion molecule (ICAM)‑1, matrix metalloproteinase (MMP)‑9 and caspase‑3. The findings revealed that inflammation (NF‑κB, ICAM‑1 and MMP‑9) and apoptosis (caspase‑3)‑related markers were significantly downregulated in the curcumin‑treated MCAO group compared with the vehicle‑treated MCAO group. Furthermore, brain infarction size, brain edema and neurological dysfunction were attenuated in the curcumin‑treated MCAO group compared with the vehicle‑treated MCAO group. Taken together, the present results provided evidence that the protective effect of curcumin against cerebral I/R injury might be mediated by anti‑inflammatory and anti‑apoptotic properties. Therefore, curcumin may be a promising supplementary agent against cerebral I/R injury in the future.

Topics: Animals; Caspase 3; Curcumin; Disease Models, Animal; Gene Expression; Intercellular Adhesion Molecule-1; Male; Matrix Metalloproteinase 9; NF-kappa B; Protective Agents; Rats; Reperfusion Injury

To explore the protective effect of curcumin on renal ischemia-reperfusion injury (RIRI) in rats, and its influence on nephridial tissue's NO and cGMP levels as well as downstream signaling pathway, to elucidate the possible mechanism of curcumin on RIRI.. 36 Sprague Dawley rats (SD rats) were randomly divided into Sham group, Model group, curcumin (CUR +) Model group, 12 rats per group. They were all given RIRI model preparation by unilateral artery occlusion method. All groups' β2-MG in urine in 24h, serum Cr and BUN were compared, and UAER were calculated. Nitric oxide synthase (NOS), cGMP-dependent protein kinase (PKG), Caspase-3 expression were all determined by western blot. Nitric oxide (NO), NOS and cGMP levels were also examined by using ELISA. All groups' nephridial histomorphology and kidney tubules score were evaluated and compared.. β2-MG and UAER in urine, serum Cr and BUN, in renal tissue were all elevated in Model of RIRI, indicating the success of animal model of RIRI establishment, and above index in CUR + Model group were all lower than those in Model group. Furthermore, iNOS, NO, cGMP, PKG and Caspase-3 in renal tissue were all increased in Model of RIRI, indicating the NO signaling pathway was activated, which is one of the pathogenesis of RIRI, and above index in CUR + Model group were all lower than those in Model group, suggesting that inactivation of iNOS/NO/cGMP/PKG signaling pathway is one of the reasons that explain the protective effect of curcumin in RIRI.. The activation of iNOS/NO/cGMP/PKG signaling pathway and the consequent promoted apoptosis of renal tubules are significantly involved in the pathogenesis of development of RIRI, and curcumin treatment could protect renal tubules against RIRI, at least partially, by suppressing the activated iNOS/NO/cGMP/PKG signaling pathway.

Topics: Animals; beta 2-Microglobulin; Blood Urea Nitrogen; Caspase 3; Cell Line; Creatinine; Curcumin; Cyclic GMP; Disease Models, Animal; Humans; Kidney Tubules; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Phosphoglycerate Kinase; Protective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction

The purpose of the present experiment was to investigate whether hexahydrocurcumin (HHC) attenuates brain damage and improves functional outcome via the activation of antioxidative activities, anti-inflammation, and anti-apoptosis following cerebral ischemia/reperfusion (I/R). In this study, rats with cerebral I/R injury were induced by a transient middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. The male Wistar rats were randomly divided into five groups, including the sham-operated, vehicle-treated, 10 mg/kg HHC-treated, 20 mg/kg HHC-treated, and 40 mg/kg HHC-treated I/R groups. The animals were immediately injected with HHC by an intraperitoneal administration at the onset of cerebral reperfusion. After 24 h of reperfusion, the rats were tested for neurological deficits, and the pathology of the brain was studied by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyltransferase UTP nick end labeling (TUNEL) staining. In addition, the brain tissues were prepared for protein extraction for Western blot analysis, a malondialdehyde (MDA) assay, a nitric oxide (NO) assay, a superoxide dismutase (SOD) assay, a glutathione (GSH) assay, and a glutathione peroxidase (GSH-Px) assay. The data revealed that the neurological deficit scores and the infarct volume were significantly reduced in the HHC-treated rats at all doses compared to the vehicle group. Treatment with HHC significantly attenuated oxidative stress and inflammation, with a decreased level of MDA and NO and a decreased expression of NF-κB (p65) and cyclooxygenase-2 (COX-2) in the I/R rats. HHC also evidently increased Nrf2 (nucleus) protein expression, heme oxygenase-1 (HO-1) protein expression, the antioxidative enzymes, and the superoxide dismutase (SOD) activity. Moreover, the HHC treatment also significantly decreased apoptosis, with a decrease in Bax and cleaved caspase-3 and an increase in Bcl-XL, which was in accordance with a decrease in the apoptotic neuronal cells. Therefore, the HHC treatment protects the brain from cerebral I/R injury by diminishing oxidative stress, inflammation, and apoptosis. The antioxidant properties of HHC may play an important role in improving functional outcomes and may offer significant neuroprotection against I/R damage.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; Inflammation; Rats; Reperfusion Injury; Stroke

To determine the protective effect of curcumin on ovarian reserve in a rat ischemia model.. Thirty female Albino rats were randomly divided into two groups by time of unilateral, left ovary ischemia/reperfusion (group 1: two-hour ischemia / two-hour reperfusion; group 2: four-hour ischemia / four-hour reperfusion). Each group was subdivided into three subgroups, sham, control, and curcumin (intraperitoneal curcumin (200 mg/kg) simultaneously with reperfusion). Histological grading of ischemic indices of paraffin-embedded ovarian tissue using hematoxylin and eosin (H&E), and anti-Mulerian hormone (AMH) levels by enzyme-linked immunosorbent assay (ELISA), were measured 40 days later.. No difference was found between groups 1 and 2 or among subgroups within either group for right and left ovary grades. AMH levels were significantly higher in the curcumin subgroup compared to sham and control within group 2 and in group 2 versus group 1 curcumin subgroups.. Curcumin maintains and protects ovarian functions in an ischemia-reperfusion rat model.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Curcumin; Disease Models, Animal; Female; Ovarian Reserve; Ovary; Rats; Rats, Wistar; Reperfusion Injury

To investigate the neuroprotective effect of chronic curcumin supplementation on the rat forebrain prior to ischemia and reperfusion.. Forebrain ischemia was induced by bilateral common carotid artery occlusion for 1/2 hour, followed by reperfusion for 72 hours. Older rats were divided into five groups: Group I received 300 mg/kg oral curcumin for 21 days before ischemia and 300 mg/kg intraperitoneal curcumin after ischemia; Group II received 300 mg/kg intraperitoneal curcumin after ischemia; Group III received 300 mg/kg oral curcumin for 21 days before ischemia; Group IV had only ischemia; Group V was the sham-operated group. The forebrain was rapidly dissected for biochemical parameter assessment and histopathological examination.. In forebrain tissue, enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase were significantly higher in Group I than Groups II or III (p < 0.05) while xanthine dehydrogenase and malondialdehyde enzyme activities and concentrations of interleukin-6 and TNF-alpha were significantly lower in Group I when compared to Groups II and III (p < 0.05). A significant reduction in neurological score was observed after 24 and 72 hours in the curcumin-treated groups compared with the ischemic group. We also found a marked reduction in apoptotic index after 72 hours in the groups receiving curcumin. Significantly more TUNEL-positive cells were observed in the ischemic group compared to those treated with curcumin.. We demonstrated the neuroprotective effect of chronic curcumin supplement on biochemical parameters, neurological scores and apoptosis following ischemia and reperfusion injury in rats.

Topics: Animals; Apoptosis; Catalase; Curcumin; Glutathione Peroxidase; Interleukin-6; Ischemia; Male; Malondialdehyde; Neuroprotective Agents; Prosencephalon; Rats; Reperfusion Injury; Stroke; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Xanthine Dehydrogenase

The relationship between the chemistry characteristic and the hepatoprotective effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione (DDD), a curcumin analogue, in operative liver injury rats was investigated to reveal the mechanism of hepatic protection effects of DDD. DDD (1.2-4.8mmol/kg) was administrated 10min before reperfusion phase in hepatic ischemia-reperfusion injury (IRI) rats. DDD (4.8mmol/kg) administrated 10min before ischemia and N-acetylcysteine (NAC) (4.8mmol/kg) administrated 10min before reperfusion were included for comparative studies. The plasma liver enzyme activities, histopathological indices and markers of lipid peroxide were determined to evaluate the hepatic protection effects. Effects of DDD on succinate dehydrogenase (SDH) activity were also investigated. DDD showed dose-dependent hepatocyte protections when administrated 10min before reperfusion stages in hepatic IRI rats. DDD showed almost equivalent hepatoprotective effects when administrated 10min before ischemia phase demonstrating that DDD acted on the reperfusion stages selectively against the hepatic IRI, instead of ischemia phase. NAC was not effective against hepatic IRI when treated 10min before reperfusion because of the higher pKa of NAC. In additional, DDD had no effect on the SDH both in hepatic IRI rats and in mitochondria. In conclusion, DDD had dose-dependent hepatocyte protections in the reperfusion stages in hepatic IRI rats, while the observed hepatocyte protections of DDD did not involve SDH activities. β-Diketone structures of DDD were crucial for the hepatocyte protections. The abilities of DDD to clear up the unsaturated aldehydes related with the enolate nucleophilicity and the pKa. DDD might be a promising candidate to treat hepatic IRI.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Curcumin; Glutathione; Glutathione Disulfide; Liver; Male; Protective Agents; Rats, Sprague-Dawley; Reperfusion Injury; Succinate Dehydrogenase

The effects of curcumin (CCM) on cerebral ischemia/reperfusion injury are not well understood. The aim of this study was to investigate whether CCM attenuates inflammation and mitochondrial dysfunction in a rat model of cerebral ischemia/reperfusion injury and whether Sirt1 is involved in these potential protective effects. Sirtinol, a Sirt1 inhibitor, was used to elucidate the underlying mechanism. Rats were subjected to 2h of transient middle cerebral artery occlusion (MCAO), followed by reperfusion for 24h. Brain magnetic resonance imaging (MRI) was used to detect infarct volumes. Neurological scores and brain water content were also assessed. Levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in the brain were detected using commercial enzyme-linked immunosorbent assay (ELISA) kits. Expression of SIRT1, acetylated p53 (Ac-p53), Bcl-2, and Bax was measured by western blotting. Our results suggested that CCM exerted a neuroprotective effect, as shown by reduced infarct volumes and brain edema and improved neurological scores. CCM also exerted anti-inflammatory effects, as indicated by decreased TNF-α and IL-6 levels in the brain. CCM elevated mitochondrial membrane potential, mitochondrial complex I activity, and mitochondrial cytochrome c levels, but reduced cytosolic cytochrome c levels. Moreover, CCM upregulated SIRT1 and Bcl-2 expression and downregulated Ac-p53 and Bax expression. These effects of CCM were abolished by sirtinol. In conclusion, our results demonstrate that CCM treatment attenuates ischemic stroke-induced brain injury via activation of SIRT1.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain Edema; Curcumin; Disease Models, Animal; Drug Administration Schedule; Gene Expression Regulation; Histocompatibility Antigens Class I; Infarction, Middle Cerebral Artery; Inflammation; Male; Membrane Potential, Mitochondrial; Mitochondrial Diseases; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Sirtuin 1

Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) injury. Curcumin exhibits substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptotic effects; however, the molecular mechanism underlying the effects of curcumin against cerebral I/R injury remains unclear.. To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, and the expression of nuclear factor-kappa-B (NF-κB) and nuclear factor-erythroid-related factor-2 (Nrf2).. Middle cerebral artery occlusion (MCAO, 1-hour occlusion and 24-hour reperfusion) was performed in male Wistar rats (n=64) as a cerebral I/R injury model. In the MCAO+CUR group, the rats were administered curcumin (300mg/kg BW, i.p.) at 30min after occlusion. The same surgical procedures were performed in SHAM rats without MCAO occlusion. At 24h post-operation, the parameters, including neurological deficit scores, blood brain barrier (BBB) disruption, water content, and infarction volume, were determined. Brain tissue NF-κB and Nrf2 expression levels were assayed through immunohistochemistry.. Compared with the SHAM group, BBB disruption, neurological deficit, and increased brain water content and infarction volume were markedly demonstrated in the MCAO group. NF-κB expression was enhanced in the MCAO group. However, in the MCAO+CUR group, the upregulation of Nrf2, an anti-oxidation related protein, was consistent with a significant decline in the water content, infarction volume, and NF-κB expression.. The protective effects of curcumin against cerebral I/R injury reflect anti-oxidation, anti-inflammation and anti-apoptotic activities, resulting in the elevation of Nrf2 and down-regulation of NF-κB.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Blood-Brain Barrier; Brain Edema; Capillary Permeability; Curcumin; Disease Models, Animal; Down-Regulation; Infarction, Middle Cerebral Artery; Male; Motor Activity; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; Rats, Wistar; Reperfusion Injury; Signal Transduction; Time Factors; Transcription Factor RelA; Up-Regulation

Curcumin is a molecule found in turmeric root that possesses anti-inflammatory and antioxidant properties and has been widely used to treat neurodegenerative diseases. We investigated whether curcumin stimulates the neurorepair process and improves locomotor function in a rat model of spinal cord ischemia-reperfusion injury.. Thirty-two Wistar albino rats (190-220 g) were randomly allocated into 4 groups of 8 rats each: 1 sham-operated group and 3 ischemia-reperfusion injury groups that received intraperitoneal injections of saline vehicle, methylprednisolone (MP, 30 mg/kg following induction of ischemia-reperfusion [IR] injury), or curcumin (200 mg/kg for 7 days before induction of IR injury). Spinal cord IR injury was induced by occlusion of the abdominal aorta for 30 minutes. After 24 hours of reperfusion, locomotor function was assessed using the Basso, Beattie, and Bresnahan scale. All animals were sacrificed. Spinal cord tissues were harvested to evaluate histopathological and ultrastructural alterations and to analyze levels of malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta, nitric oxide, and caspase-3, as well as enzyme activities of superoxide dismutase and glutathione peroxidase.. Intraperitoneal administration of curcumin significantly reduced inflammatory cytokine expression, attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in comparison to treatment with MP or saline. Histopathological and ultrastructural abnormalities were significantly reduced in curcumin-treated rats compared to the MP- and saline-treated groups. Furthermore, curcumin significantly improved locomotor function.. Curcumin treatment preserves neuronal viability against inflammation, oxidative stress, and apoptosis associated with ischemia-reperfusion injury.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Biomarkers; Curcumin; Cytoprotection; Disease Models, Animal; Inflammation Mediators; Lipid Peroxidation; Locomotion; Male; Motor Activity; Neuroprotective Agents; Oxidative Stress; Rats, Wistar; Reperfusion Injury; Spinal Cord; Spinal Cord Ischemia; Time Factors

Curcumin and dexmedetomidine have been shown to have protective effects in ischemia-reperfusion injury on various organs. However, their protective effects on kidney tissue against ischemia-reperfusion injury remain unclear. We aimed to determine whether curcumin or dexmedetomidine prevents renal tissue from injury that was induced by hind limb ischemia-reperfusion in rats. Fifty rats were divided into five groups: sham, control, curcumin (CUR) group (200 mg/kg curcumin, n = 10), dexmedetomidine (DEX) group (25 μg/kg dexmedetomidine, n = 10), and curcumin-dexmedetomidine (CUR-DEX) group (200 mg/kg curcumin and 25 μg/kg dexmedetomidine). Curcumin and dexmedetomidine were administered intraperitoneally immediately after the end of 4 h ischemia, just 5 min before reperfusion. The extremity re-perfused for 2 h and then blood samples were taken and total antioxidant capacity (TAC), total oxidative status (TOS) levels, and oxidative stress index (OSI) were measured, and renal tissue samples were histopathologically examined. The TAC activity levels in blood samples were significantly lower in the control than the other groups (p < 0.01 for all comparisons). The TOS activity levels in blood samples were significantly higher in Control group and than the other groups (p <  0.01 for all comparison). The OSI were found to be significantly increased in the control group compared to others groups (p < 0.001 for all comparisons). Histopathological examination revealed less severe lesions in the sham, CUR, DEX, and CUR-DEX groups, compared with the control group (p < 0.01). Rat hind limb ischemia-reperfusion causes histopathological changes in the kidneys. Curcumin and dexmedetomidine administered intraperitoneally was effective in reducing oxidative stress and renal histopathologic injury in an acute hind limb I/R rat model.

Topics: Acute Kidney Injury; Animals; Antioxidants; Curcumin; Dexmedetomidine; Disease Models, Animal; Extremities; Kidney; Kidney Function Tests; Oxidative Stress; Rats; Reperfusion Injury; Treatment Outcome

We describe several novel curcumin analogues that possess both anti-inflammatory antioxidant properties and thrombolytic activities. The therapeutic efficacy of these curcumin analogues was verified in a mouse ear edema model, a rat arterial thrombosis assay, a free radical scavenging assay performed in PC12 cells, and in both in vitro and in vivo ischemia/reperfusion models. Our findings suggest that their protective effects partially reside in maintenance of optimal mitochondrial function.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytochromes c; Disease Models, Animal; Edema; Enzyme-Linked Immunosorbent Assay; Free Radical Scavengers; Human Umbilical Vein Endothelial Cells; Interleukin-6; Mice; Microscopy, Fluorescence; Mitochondria; Muscle, Skeletal; Oxidative Stress; PC12 Cells; Quantum Theory; Rats; Reactive Oxygen Species; Reperfusion Injury; Tumor Necrosis Factor-alpha

The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats.. Rats were subjected to bilateral renal I/R (40 min I, 24 hours R) to induce AKI. Kidney injury was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium level, fractional excretion of sodium, and macroproteinuria. Oxidative stress in renal tissues was assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione content. Hematoxylin & eosin staining was done to assess histological changes in renal tissues. Curcumin (30 and 60 mg/kg) was administered one hour before subjecting rats to AKI. In separate groups, NMDA receptor agonists, glutamic acid (200 mg/kg), and spermidine (20 mg/kg) were administered prior to curcumin treatment in rats followed by AKI.. I/R-induced AKI was demonstrated by significant change in plasma and urine parameters along with marked increase in oxidative stress and histological changes in renal tissues that were aggravated with pretreatment of glutamic acid and spermidine in rats. Administration of curcumin resulted in significant protection against AKI. However, glutamic acid and spermidine pretreatments prevented curcumin-mediated renoprotection.. It is concluded that NMDA receptor antagonism significantly contributes towards curcumin-mediated protection against I/R-induced AKI.

Topics: Acute Kidney Injury; Animals; Blood Urea Nitrogen; Creatinine; Curcumin; Disease Models, Animal; Enzyme Inhibitors; Female; Kidney; Oxidative Stress; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Reperfusion Injury; Uric Acid

We tested whether the combined nano-formulation, prepared with curcumin (anti-inflammatory and neuroprotective molecule) and embryonic stem cell exosomes (MESC-exo

Topics: Animals; Astrocytes; Cell Adhesion Molecules; Curcumin; Drug Compounding; Embryonic Stem Cells; Endothelial Cells; Exosomes; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Neurons; Neuroprotective Agents; Reperfusion Injury; Tight Junction Proteins

The aim of the present study was to assess the neuroprotective effects of tetrahydrocurcumin (THC) in a mouse model of cerebral ischemia/reperfusion (I/R) injury, and to investigate the involvement of Golgi reassembly and stacking protein 65 (GRASP65) and the extracellular signal‑regulated kinase (ERK) signaling pathway. Cerebral I/R injury was induced using the Pulsinelli four‑vessel occlusion method. After 5 min of reperfusion, mice received THC (5, 10 or 25 mg/kg) or saline by intraperitoneal injection. After 24 h of reperfusion, mice underwent neurological evaluation. Infarct volumes were determined by triphenyltetrazolium chloride staining, and levels of superoxide dismutase and malondialdehyde were measured in brain tissue homogenates. Expression of GRASP65, phosphorylated‑GRASP65, ERK and phosphorylated‑ERK was determined by western blotting. THC induced a dose‑dependent decrease in the phosphorylation of ERK and GRASP65. Thus, THC attenuated I/R injury‑induced activation of the ERK signaling pathway and reduced the phosphorylation of GRASP65. THC exhibited a dose‑dependent protective effect against cerebral I/R injury, mediated by suppression of the ERK signaling pathway and a subsequent reduction in GRASP65 phosphorylation. The current study provided new information in the research of the cerebral ischemia‑reperfusion injury mechanism.

Topics: Animals; Apoptosis; Brain Infarction; Brain Ischemia; Carrier Proteins; Curcumin; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Intracellular Signaling Peptides and Proteins; Male; Malondialdehyde; Membrane Proteins; Mice; Neurons; Neuroprotective Agents; Reperfusion Injury; Signal Transduction; Superoxide Dismutase

Renal ischemia/reperfusion (I/R) damage may arise due to nephron sparing surgery in patient with a solitary kidney of restricted renal parenchymas. Apoptosis, inflammation and oxidative stress play a significant role in the expansion of renal dysfunction following renal I/R. The aim of the current investigation was to particularize the potential effect of curcumin against hypoxia induced renal injury. The albino Wistar rats divided into groups and each group contains six rats. They groups are normal control; disease control; curcumin (5 mg/kg per day) and another group orally treated with curcumin (10 mg/kg per day) for two weeks before induction of renal I/R. The renal and serum samples were collected and used for the biochemical estimation. The renal tissue was further used for the histopathological estimation. The result of the current investigation demonstrated that the curcumin significantly (P<0.01) attenuated I/R induced renal injury in a dose-dependent way. It also causes significant (P<0.01) reduction in the serum creatinine, blood urea nitrogen level and also suppressed the kidney injury molecules-1. Additionally, it also causes significant inhibition of the malonaldehyde, caspase-3, myeloperoxide, lactose dehydrogenase and interferon-gamma together with enhanced interlukin-10 content.

Topics: Animals; Antioxidants; Blood Urea Nitrogen; Caspase 3; Caspase Inhibitors; Cell Adhesion Molecules; Creatinine; Curcumin; Disease Models, Animal; Inflammation Mediators; Kidney; Kidney Function Tests; Lactose; Male; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury

Renal ischemia-reperfusion injury (IRI) is a major complication in clinical practice. However, despite its frequency, effective preventive/treatment strategies for this condition are scarce. Curcumin possesses antioxidant properties and is a promising potential protective agent against renal IRI, but its poor water solubility restricts its application. In this study, we constructed curcumin-carrying distearoylphosphatidylethanolamine-polyethylene glycol nanoparticles (Cur-NPs), and their effect on HK-2 cells exposed to IRI was examined in vitro. Curcumin encapsulated in NPs demonstrated improved water solubility and slowed release. Compared with the IRI and Curcumin groups, Cur-NP groups displayed significantly improved cell viability, downregulated protein expression levels of caspase-3 and Bax, upregulated expression of Bcl-2 protein, increased antioxidant superoxide dismutase level, and reduced apoptotic rate, reactive oxygen species level, and malondialdehyde content. Results clearly showed that Cur-NPs demonstrated good water solubility and slow release, as well as exerted protective effects against oxidative stress in cultured HK-2 cells exposed to IRI.

Topics: Apoptosis; Caspase 3; Cell Proliferation; Cells, Cultured; Curcumin; Humans; Kidney; Nanoparticles; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Reperfusion Injury; Solubility

To investigate the anti-inflammatory and antioxidant effect of curcumin on lung lesion induced by intestinal ischemia reperfusion injury (IIR).. Rats were divided into four groups: sham, intestinal IIR (IIR), 1 mg/kg of curcumin treatment group (1 mg/kg), and 5 mg/kg of curcumin treatment group (5 mg/kg). Curcumin was given respectively (1 mg/kg and 5 mg/kg) following the above doses. IIR was produced by 1 h of intestinal ischemia followed by 2 h of reperfusion. Rats were sacrificed at the end of reperfusion and lung tissues were collected for biochemical and histopathological examination in 4 groups. Lung tissues histology and bronchoalveolar lavage fluid (BALF) protein were assayed. Serum IL-6, lung superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The expression level of NF-κB and ICAM-1 (including immunohistochemical analysis and western blot analysis) were also measured.. Lung tissue injury induced by IIR was obviously observed through pathology and BALF protein. MPO activity, IL-6 level and ICAM-1 expression were significantly increased with the elevation of NF-κB, simultaneously, SOD activity was decreased. With Treatment of curcumin, pathology and BALF protein of lung tissue were improved clearly. Inflammatory indexes (MPO activity, IL-6 level and ICAM-1) were improved and antioxidant index (SOD activity) was enhanced paralleled with NF-κB.. Using curcumin effectively prevented IIR-induced lung injury. Anti-inflammatory and antioxidant effects of curcumin could be observed by inhibiting the pathway of NF-κB.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Bronchoalveolar Lavage Fluid; Curcumin; Humans; Intestines; Lung; Male; Models, Animal; NF-kappa B; Rats; Rats, Wistar; Reperfusion Injury

The aim of this study was to investigate the role of curcumin in remote testicular injury caused by hindlimb ischemia reperfusion (IR).. Forty male Wistar rats were allocated to four groups: sham (G1), sham + curcumin (G2), IR (G3) and IR + curcumin (G4). Curcumin 200 mg/kg was administered intraperitoneally 2 h prior to IR induction. Lower extremities were subjected to IR induced by infrarenal aortic occlusion for 2 h, followed by 6 h of reperfusion. The rats were euthanized and the testes were removed. Glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and myeloperoxidase (MPO) activities and histopathological damage scores were determined in right testicular tissues. Left testes were used for wet/dry weight ratio measurement.. Activities of SOD and CAT in testicular tissues were significantly decreased by IR, but curcumin pretreatment increased these levels (P < 0.05). MPO activity in testicular tissues in the G3 was significantly higher than in the G4 (P < 0.05). Significantly increased MDA levels in testicular tissues by IR were decreased by curcumin pretreatment (P < 0.05). Testis tissues showed a significant increase in GPx activity compared to the IR group when curcumin was applied. The wet/dry weight ratio of testicular tissues in the G3 was significantly higher than in the other groups (P < 0.05). In addition, specimens from the G3 had a significantly greater histological injury than those from the G4 (P < 0.05). There were no significant differences in tissue MDA, MPO, SOD, CAT and GPx activities, histological changes and wet/dry weight ratio between the G1, G2 and G4.. According to the findings, we conclude that curcumin has preventive effects in the testicular injury induced by hindlimb IR in rats.

Topics: Animals; Antioxidants; Catalase; Curcumin; Glutathione Peroxidase; Hindlimb; Male; Malondialdehyde; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury; Superoxide Dismutase; Testis

To investigate the effect of curcumin on cerebral ischemia-reperfusion injury in rats and its mechanism.. 250 male SD rats were randomly divided into five groups:sham group (Sham group), ischemia-reperfusion group (I/R group), curcumin groups with dosage of 30 mg/kg (Cur30 group), 100 mg/kg (Cur100 group) and 300 mg/kg (Cur300 group). The brain tissue damage degree, leukocyte cells infiltration, levels of TNF-α and MMP-9 expressions, and blood-brain barrier permeability were detected.. At the same time point,the score of brain tissue injury,number of leukocyte, expression of MMP-9 and TNF-α, and Evans blue dye of I/R group and Curs group were higher than those of Sham group (P < 0.05). The score of brain tissue damage degree, number of leukocyte, expression of MMP-9 and TNF-α, and Evans blue dye of Cur groups were lower than those of I/R group (P < 0.05). The Cur100 group had the best effect.. Curcumin can decrease cerebral ischemia reperfusion pathological damage significantly and suppressed the expression of MMP-9 and TNF-α, and Evans blue dye, brain tissue damage, leukocyte infiltration, which may be involved in protective mechanisms of curcumin.

Topics: Animals; Blood-Brain Barrier; Brain; Brain Ischemia; Curcumin; Leukocytes; Male; Matrix Metalloproteinase 9; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha

This study aimed to investigate the effect of curcumin on the retinal structure and the expressions of interleukin-23 (IL-23) and IL-17 in the rat retina after retinal ischemia-reperfusion injury (RIRI).. 150 Sprague-Dawley rats were randomly divided into RIRI group (MG), low-dose curcumin group (LDCG) and high-dose curcumin group (HDCG), (n = 50 per group). RIRI was generated by anterior chamber perfusion of normal saline to the right eye. The left eye served as a normal control group (NCG). Rats in LDCG and HDCG received an intraperitoneal injection of 20 mg/kg/d and 100 mg/kg/d curcumin respectively, at 30 min before RIRI and once daily after RIRI.. The morphological changes in HDCG group were improved as compared to MG and LDCG groups. Immunohistochemistry showed that IL-23 and IL-17 were mainly expressed in the ganglion cell layer and the inner nuclear layer of the retina. Low IL-23 and IL-17 expressions were observed in NCG, but increased significantly in MG and LDCG groups. Western blot assay and ELISA also showed that IL-23 and IL-17 expressions increased significantly after RIRI (vs. NCG, P<0.01). Moreover, the IL-23 expression reached a peak at 24 h, whereas IL-17 expression peaked at 72 h after RIRI. Curcumin reduced IL-23 and IL-17 expressions significantly in a dose-dependent manner (vs. MG, P<0.01).. The IL-23 and IL-17 expressions increase after RIRI and curcumin significantly reduces retinal IL-23 and IL-17 expressions in a dose-dependent manner and is able to prevent the RIRI induced damage to the retina.

Topics: Animals; Curcumin; Dose-Response Relationship, Drug; Interleukin-17; Interleukin-23; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Retina; Retinal Vessels

We aimed to identify the oxidative stress effects of the ischemic priapism on cavernosal tissues and to assess the biochemical and histopathological effects of curcumin in rats.. 26 adult male Sprague Dawley rats were randomly divided into three groups. Group 1 (Control, n = 8): only penectomy was performed and 3 ml blood samples were obtained from the vena cava inferior (VCI). Group 2 (ischemia-reperfusion group; n= 8): penectomy was performed after 1 hour ischemic priapism + 30 min reperfusion and 3 ml blood samples were obtained from the VCI. Group III (IR + CURC group, n = 10): 200 mg/kg/day curcumin per orally before surgery for 7 days + penectomy after 1 hour ischemic priapism + 30 min reperfusion and 3 ml blood samples from the VCI. Total oxidant status (TAS), total antioxidant status (TAS) and paraoxonase (PON1) levels were measured. Tissue samples were investigated and scored histopathologically in terms of bleeding, edema and necrosis.. TOS levels were higher (p = 0.002), and TAS levels were lower (p = 0.001) in the IR group compared to the control group. As a result of curcumin treatment, TAS levels were increased (p = 0.003), and TOS levels were decreased (p = 0.004) in the IR + CURC group compared to the IR group. In the treatment group (IR + CURC) TAS and TOS levels were similar to levels in the control group. PON1 levels were increased with ischemia-reperfusion (p = 0.21) and decreased with curcumin treatment (p = 0.53), however these changes were not statistically significant. There was no significant difference in the effects of curcumin on histopathological changes.. This study showed that curcumin has preventive effects on oxidative stress parameters against ischemia-reperfusion injury.

Topics: Animals; Antioxidants; Aryldialkylphosphatase; Curcumin; Male; Oxidative Stress; Penis; Priapism; Rats; Rats, Sprague-Dawley; Reperfusion Injury

The object of this study was to conduct a prospective, randomized, laboratory investigation of the neuroprotective effects of curcumin functionally, biochemically, and histologically in an experimental acute spinal cord ischemia-reperfusion injury on rabbits.. Eighteen rabbits were randomly assigned to 1 of 3 groups: the sham group, the ischemia-reperfusion group, or the curcumin group. Spinal cord ischemia was induced by applying an infrarenal aortic cross-clamp for 30 minutes. At 48 hours after ischemia, neurological function was evaluated with modified Tarlov criteria. Biochemical changes in the spinal cord and plasma were observed by measuring levels of malondialdehyde (MDA), advanced oxidation protein products (AOPP), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), nitrite/nitrate, and tumor necrosis factor-α (TNF-α). Histological changes were examined with H & E staining. Immunohistochemical staining with antibodies against caspase-3 was performed to evaluate cell apoptosis after ischemia.. In the curcumin group, neurological outcome scores were statistically significantly better compared with the ischemia-reperfusion group. In the ischemia-reperfusion group, MDA, AOPP, and nitrite/nitrate levels were significantly elevated in the spinal cord tissue and the plasma by the induction of ischemia-reperfusion. The curcumin treatment significantly prevented the ischemia-reperfusion-induced elevation of nitrite/nitrate and TNF-α. In addition, the spinal cord tissue and the plasma SOD, GSH, and CAT levels were found to be preserved in the curcumin group and not statistically different from those of the sham group. Histological evaluation of the tissues also demonstrated a decrease in axonal damage, neuronal degeneration, and glial cell infiltration after curcumin administration.. Although further studies including different dose regimens and time intervals are required, curcumin could attenuate a spinal cord ischemia-reperfusion injury in rabbits via reducing oxidative products and proinflammatory cytokines, as well as increasing activities of antioxidant enzymes and preventing apoptotic cell death.

Topics: Animals; Antioxidants; Curcumin; Glutathione; Male; Malondialdehyde; Neuroprotective Agents; Prospective Studies; Rabbits; Reperfusion Injury; Spinal Cord; Spinal Cord Ischemia; Superoxide Dismutase; Treatment Outcome

Decreasing organ quality is prompting research toward new methods to alleviate ischemia reperfusion injury (IRI). Oxidative stress and nuclear factor kappa beta (NF-κB) activation are well-described elements of IRI. We added cyclodextrin-complexed curcumin (CDC), a potent antioxidant and NF-κB inhibitor, to University of Wisconsin (UW) solution (Belzer's Solution, Viaspan), one of the most effective clinically approved preservative solutions. The effects of CDC were evaluated on pig endothelial cells and in an autologous donation after circulatory death (DCD) kidney transplantation model in large white pigs. CDC allowed rapid and lasting uptake of curcumin into cells. In vitro, CDC decreased mitochondrial loss of function, improved viability and lowered endothelial activation. In vivo, CDC improved function recovery, lowered histological injury and doubled animal survival (83.3% vs. 41.7%). At 3 months, immunohistochemical staining for epithelial-to-mesenchymal transition (EMT) and fibrosis markers was intense in UW grafts while it remained limited in the UW + CDC group. Transcriptional analysis showed that CDC treatment protected against up-regulation of several pathophysiological pathways leading to inflammation, EMT and fibrosis. Thus, use of CDC in a preclinical transplantation model with stringent IRI rescued kidney grafts from an unfavorable prognosis. As curcumin has proved well tolerated and nontoxic, this strategy shows promise for translation to the clinic.

Topics: Adenosine; Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Cells, Cultured; Chemistry, Pharmaceutical; Curcumin; Cyclodextrins; Disease Models, Animal; Fibrosis; Flow Cytometry; Glutathione; Graft Rejection; Humans; Inflammation; Insulin; Kidney Transplantation; Kidney Tubules; Male; Organ Preservation Solutions; Oxidative Stress; Prostate; Raffinose; Real-Time Polymerase Chain Reaction; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Swine

Curcumin is known to have neuroprotective properties in cerebral ischemia reperfusion (I/R) injury. However, the underlying molecular mechanisms remain largely unknown. Recently, emerging evidences suggested that increased mitochondrial biogenesis enabled preventing I/R injury. Here, we sought to determinate whether curcumin alleviates I/R damage through regulation of mitochondrial biogenesis. Sprague-Dawley rats were subjected to a 2-h period of right middle cerebral artery occlusion followed by 24 h of reperfusion. Prior to onset of occlusion, rats had been pretreated with either low (50 mg/kg, intraperitoneal injection) or high (100 mg/kg, intraperitoneal injection) dose of curcumin for 5 days. Consequently, we found that curcumin pretreatment enabled improving neurological deficit, diminishing infarct volume and increasing the number of NeuN-labeled neurons in the I/R rats. Accordingly, the index of mitochondrial biogenesis including nuclear respiratory factor-1, mitochondrial transcription factor A and mitochondrial number significantly down-regulated in I/R rats were reversed by curcumin pretreatment in a dose-dependent manner, and the mitochondrial uncoupling protein 2 presented the similar change. Taken together, our findings provided novel evidence that curcumin may exert neuroprotective effects by increasing mitochondrial biogenesis.

Topics: Animals; Brain Ischemia; Curcumin; Male; Mitochondria; Mitochondrial Turnover; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Previous studies have demonstrated that curcumin (CUR) has protective effects against ischemia reperfusion injury to various organs. We aimed to determine whether CUR has favorable effects on tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury.. Thirty rats were divided into three groups as sham, control and treatment (CUR) group. Control and CUR groups underwent abdominal aorta ischemia for 60 min followed by a 120 min period of reperfusion. In the CUR group, CUR was given 5 min before reperfusion at a dose of 200 mg/kg via an intraperitoneal route. Total antioxidant capacity (TAC), total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured, and lung, renal and heart tissue histopathology were evaluated with light microscopy.. TOS and OSI activity in blood samples were statistically decreased in sham and CUR groups compared to the control group (p < 0.001 for TOS and OSI). Renal, lung, heart injury scores of sham and CUR groups were statistically decreased compared to control group (p < 0.001 for all comparisons). Histopathological examination revealed less severe lesions in CUR group than in the control group.. CUR administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta I/R rat model.

Topics: Animals; Antioxidants; Aorta, Abdominal; Coronary Vessels; Curcumin; Disease Models, Animal; Drug Evaluation, Preclinical; Injections, Intraperitoneal; Kidney; Lung; Male; Oxidative Stress; Rats, Wistar; Reperfusion Injury

Acute respiratory distress syndrome (ARDS) is a common scenario associated with hepatic warm ischemia and reperfusion (I/R) injury after shock or hemorrhage. Inflammation of lung parenchyma and increase in matrix metalloprotease 9 (MMP-9) activity have been implicated in ARDS. In this study, we aimed to investigate the protective efficacy of curcumin treatment against hepatic I/R-induced lung function impairment.. Thirty Sprague-Dawley male rats were evenly divided into 3 groups: a sham group, a hepatic I/R group, and a group treated with curcumin (15 mg/kg/d) 15 minutes before ischemia and every 24 hours for the next 48 hours. Ischemia was induced by occluding the hepatic artery and portal vein for 30 minutes. The clamps were then released and the abdominal incision was closed. Pulmonary function test was conducted after 48 hours of reperfusion. We also examined serum alanine transaminase (ALT) level and degrees of tumor necrosis factor α (TNF-α) and MMP-9 activity in the lung tissue.. Hepatic I/R injury decreased the ratio of residual volume to total lung capacity (RV/TLC), chord compliance (Cchord), and maximum midexpiratory flow (MMEF; P < .05), and increased inspiratory resistance (RI; P < .05), characterized as combined obstructive and restrictive lung disease. Treatment with curcumin markedly improved RV/TLC, Cchord, and MMEF and decreased RI (P < .05). In addition, curcumin treatment reduced serum ALT level and degrees of TNF-α level and MMP-9 activity in the lungs.. Curcumin attenuated hepatic I/R-induced combined restrictive and obstructive lung disease by reducing lung inflammation and MMP-9 activity.

Topics: Alanine Transaminase; Animals; Biomarkers; Curcumin; Cytoprotection; Disease Models, Animal; Liver; Liver Diseases; Lung; Lung Diseases, Obstructive; Lung Injury; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors; Tumor Necrosis Factor-alpha; Warm Ischemia

To investigate the ameliorative effect of curcumin pretreatment against impaired spatial working memory on global cerebral ischemia-reperfusion rats and to explore its mechanism.. After trained on a modified T-maze, 120 adult SD rats were randomly divided into 5 groups: sham group (S group), cerebral ischemia-reperfusion group (IR group), curcumin group (C group), LPS group (L group) and curcumin+LPS group (C+L group). Rats were treated with drugs or vehicles 1 h before 10 min global cerebral ischemia. Six rats in each group 7 days after reperfusion were tested in T-maze. Six rats in each group were sacrificed at 2 h, 1, 3 and 7 d after reperfusion and their serum or brains were harvested. Brain sections were stained with HE or toluidine blue and neuronal damage was quantified by the average neuronal density of CA1 area. Immunohistochemical staining for hippocampal IL-1β and TNF-α was carried out, levels of serum IL-1β and TNF-α was detected using ELISA procedure.. Compared with S group, percentage of T-maze correct responses was decreased (88% ± 12% vs 69% ± 8%, P < 0.05), an extensive pyramidal neurons loss in CA1 area was observed, level of IL-1β (0.26 ± 0.04 vs 0.53 ± 0.06, P < 0.05;48 ± 13 vs 161 ± 31, P < 0.05) and TNF-α (40.244 ± 0.025 vs 0.418 ± 0.036, P < 0.05; 33 ± 4 vs 85 ± 15, P < 0.05) in hippocampi or serum was increased in IR group. Compared with IR group, percentage of T-maze correct responses was increased (78% ± 13%) and average pyramidal neuronal density in CA1 area was increased with an decrease in hippocampi or serum IL-1β (0.44 ± 0.09, 72 ± 19) and TNF-α (0.307 ± 0.047, 57 ± 14) in C group(P < 0.05). Compared with IR group, percentage of T-maze correct responses (61% ± 6%) was decreased with IL-1β (0.86 ± 0.13, 331 ± 51), TNF-α (0.735 ± 0.059, 185 ± 20) in hippocampi and serum was increased in L group (P < 0.05). Compared with L group, percentage of T-maze correct responses (69% ± 12%) and average pyramidal neuronal density in CA1 area was increased with IL-1β (0.69 ± 0.09, 246 ± 24), TNF-α(0.586 ± 0.047, 105 ± 25) in hippocampi and serum was decreased in C+L group (P < 0.05).. Curcumin pretreatment improves the impaired spatial working memory in global cerebral ischemia-reperfusion rats by inhibiting proinflammatory cytokines.

Topics: Animals; Brain Ischemia; CA1 Region, Hippocampal; Curcumin; Interleukin-1beta; Male; Memory, Short-Term; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha

In this study, we investigated the protective effect and mechanism of curcumin on a rat model of intestinal ischemia/reperfusion (I/R), which induces an acute liver lesion.. Curcumin was injected into rats in the curcumin groups through left femoral vein. The same volume of vehicle (0.9% normal saline) was injected into sham and I/R groups. Blood and liver tissue were gathered for serological and histopathological determination.. Intestinal I/R led to severe liver injury manifested as a significant increase in serum AST and ALT levels; all of those were reduced by treatment with curcumin. Simultaneously, the activity of SOD in liver decreased after intestinal I/R, which was increased by curcumin treatment. On the other hand, curcumin reduced MPO activity of liver tissue, as well as serum IL-6 and TNF-α levels observably. This is in parallel with the decreased level of liver intercellular cell adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) expression.. Our findings suggest that curcumin treatment attenuates liver lesion induced by intestinal I/R, attributable to the antioxidative and anti-inflammatory effect via inhibition of the NF-κB pathway.

Topics: Acute Disease; Alanine Transaminase; Animals; Aspartate Aminotransferases; Curcumin; Disease Models, Animal; Intercellular Adhesion Molecule-1; Interleukin-6; Liver; Liver Diseases; Male; NF-kappa B; Peroxidase; Protective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Superoxide Dismutase

To investigate the effect of curcumin on the injury in hippocampal neurons and the expression of regulated upon activation nonnal T-cell expressed and secreted (RANTES) in hippocamp during cerebral ischemia/reperfusion (I/R) in rats with spontaneous hypertension (SH).. Male Wistar-Kyoto (WKY) rats and spontaneous hypertension rats (SHR) were randomly divided into five groups (n = 6): sham group (W-Sham and S-Sham group), ischemia/reperfusion group (W-/R and S/R group), curcumin group (S-Cur group) . Each group was splitted into 5 subgroups of 3 h,12 h, 1 d, 3 d and 7 d according to the time interval before reperfusion. Global brain ischemia/reperfusion model was established by 4-VO method. Hematoxylin-eosin staining (HE staining) was used to observe the vertebral cell morphology in hippocampal CA1 region. Nissl staining was applied to detect the average density of cone cells in hippocampal CA1 region. The expression of RANTES in hippocamp was determined by ELISA. The behavior of the rats was evaluated at 7 days after reperfusion. Results: Compared with the sham group rats, the ability of learning and memory was significantly decreased in ischemia/reperfusion group rats, the number of injured neurons were greatly elevated , the protein expression levels of RANTES was significantly increased (P < 0.05). Compared with W-I/R group rats, the ability of learning and memory in S-I/R group rats was greatly reduced, the number of injured neurons increased extremely, the protein expression level of RANTES was significantly enhanced( P <0.05). The number of injured neurons declined significantly in S-Cur group rats, the ability to learn and remember of these rats was improved and the RANTES protein content decreased significantly (P < 0.05).. SHR are more susceptible to ischemia/reperfusion induced hippocampal neuronal injury which may be improved by curcu min. Its underlying mechanism is possibly associated with the inhibition of RANTES protein expression level.

Topics: Animals; Brain Ischemia; Chemokine CCL5; Cognition; Curcumin; Hippocampus; Hypertension; Male; Neurons; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reperfusion Injury

To explore the effect of curcumin (CUR) on cycteinyl aspirate specific protease-12 (Caspase-12) and pneumocyte apoptosis in pulmonary ischemia/reperfusion (I/R) injury mice.. The in vivo unilateral in situ pulmonary I/R injury mouse model was established in C57BL/6J mice. Sixty experimental mice were randomly divided into six groups by random digit table, i. e., the sham-operation group (Sham), the I/R group, the I/R + dimethyl sulfoxide group (I/R + DMSO), the I/R + low dose CUR pre-treated group (I/R + CUR-100), the I/R + middle dose CUR pre-treated group (I/R + CUR-150), the I/R + high dose CUR pre-treated group (I/R + CUR-200), 10 in each group. Mice were euthanized and their left lungs were excised. Wet lung weight to dry lung weight (W/D) and the total lung water content (TLW) were tested. The morphological changes of the lung tissue were observed and index of quantitative evaluation for alveolar damage (IQA) detected under light microscope. The ultra-microstructure of the lung tissue was observed under electron microscope. The mRNA and protein expression levels of Caspase-12 and glucose regulated protein (GRP78) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Apoptosis index (AI) of the lung tissue was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method.. Compared with the Sham group, expression levels of Caspase-12, GRP78 mRNA and protein all significantly increased in the I/R group (P < 0.05); W/D, TLW, IQA, and AI were all notably higher (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were notably observed in I/R group. Compared with the I/R + DMSO group, expression levels of GRP78 mRNA and protein were increasingly higher in the I/R + CUR-100 group, the I/R + CUR-150 group, and the I/R +CUR-200 group (P < 0.05), expression levels of Caspase-12 mRNA and protein were lower (P < 0.05); W/D, TLW, IQA, and AI also decreased (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were gradually alleviated in the I/R + CUR groups.. CUR had better effect on the lung protection against I/R injury, which might be related to inhibition for pneumocyte apoptosis associated with Caspase-12 in excessive unfolded protein response (UPR).

Topics: Animals; Apoptosis; Caspase 12; Curcumin; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Lung; Male; Mice; Mice, Inbred C57BL; Reperfusion Injury

To evaluate curcumin loaded solid lipid nanoparticles (C-SLNs) in the experimental paradigm of cerebral ischemia (BCCAO model) in rats.. Oral administration of free curcumin and C-SLNs (25 and 50 mg/kg) was started 5 days prior and continued for 3 days after BCCAO. Alleviation in behavioral, oxidative and nitrosative stress, acetylcholinesterase, mitochondrial enzyme complexes, and physiological parameters were assessed. Confirmation of effective brain delivery of C-SLNs (p.o) was done using biodistribution studies in mice and confocal microscopy of rat brain section. There was an improvement of 90% in cognition and 52% inhibition of acetylcholinesterase versus cerebral ischemic group (I/R). Neurological scoring improved by 79%. Levels of superoxide dismutase, catalase, glutathione, and mitochondrial complex enzyme activities were significantly increased, while lipid peroxidation, nitrite, and acetylcholinesterase levels decreased (p<0.05) after C-SLNs administration. It is noteworthy to report the restoration of SOD, GSH, catalase, and mitochondrial complex enzyme levels equivalent to sham control values. Gamma-scintigraphic studies show 16.4 and 30 times improvement in brain bioavailability (AUC) upon oral and i.v administration of C-SLNs versus solubilized curcumin (C-S).. Study indicates protective role of curcumin against cerebral ischemic insult; provided it is packaged suitably for improved brain delivery.

Topics: Administration, Intravenous; Administration, Oral; Animals; Antioxidants; Area Under Curve; Brain; Brain Ischemia; Curcumin; Dose-Response Relationship, Drug; Lipid Peroxidation; Lipids; Male; Mice; Microscopy, Confocal; Mitochondria; Nanoparticles; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Tissue Distribution

We sought to test the hypothesis that turmeric-derived curcuminoids limit reperfusion brain injury in an experimental model of stroke via blockade of early microvascular inflammation during reperfusion.. Male Sprague Dawley rats subjected to MCAO/R were treated with turmeric-derived curcuminoids (vs. vehicle) 1 hour prior to reperfusion (300 mg/kg ip). Neutrophil adhesion to the cerebral microcirculation and measures of neutrophil and endothelial activation were assayed during early reperfusion (0-4 hours); cerebral infarct size, edema, and neurological function were assessed at 24 hours. Curcuminoid effects on TNFα-stimulated human brain microvascular endothelial cell (HBMVEC) were assessed.. Early during reperfusion following MCAO, curcuminoid treatment decreased neutrophil rolling and adhesion to the cerebrovascular endothelium by 76% and 67% and prevented >50% of the fall in shear rate. The increased number and activation state (CD11b and ROS) of neutrophils were unchanged by curcuminoid treatment, while increased cerebral expression of TNFα and ICAM-1, a marker of endothelial activation, were blocked by >30%. Curcuminoids inhibited NF-κB activation and subsequent ICAM-1 gene expression in HBMVEC.. Turmeric-derived curcuminoids limit reperfusion injury in stroke by preventing neutrophil adhesion to the cerebrovascular microcirculation and improving shear rate by targeting the endothelium.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; CD11b Antigen; Cells, Cultured; Curcumin; Endothelial Cells; Endothelium, Vascular; Humans; Leukocyte Rolling; Male; Neutrophil Activation; Neutrophils; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Stroke

We aimed to investigate the effects of curcumin on ischemia/ reperfusion (IR) injury of the liver and distant organs resulting from liver blood flow arrest.. Totally 40 rats, divided into four groups, each included 10 rats were used. Group I as only laparatomy, Group II laparatomy and curcumin application, Group III hepatic IR; and Group IV as hepatic IR and curcumin application group. Ischemia was generated by hepatoduedonal ligament clamping for 30 minutes and then reperfusion is started. Curcumin capsules were opened and appropriate dose had been created within weighing scales. After calculations, the powder was diluted with saline. Fifteen minutes before the ischemia, curcumin was applied via oral gavage. Blood samples were taken from the animals for biochemical analysis at 60th minutes of the experiment in the first and second groups; 30 minutes after beginning reperfusion in the third and forth groups. Simultaneously, liver, lung and kidney tissues were sampled for biochemical and histopathological examinations.. Plasma malondialdehyde levels were found to be higher (p < 0.001), but total antioxidant activity values were not different in IR group compared with IR + curcumin group (p > 0.05). Biochemical and histopathological evaluation of tissue samples revealed that there were no differences in total antioxidant activity, total oxidant activity and histopathologic scores in IR + curcumin group compared with values of IR group (p > 0.05).. Curcumin did not reduce the effects of hepatic ischemia reperfusion injury on the liver and distant organs including kidneys and lungs significantly.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; Ischemia; Kidney; Lipid Peroxidation; Liver; Lung; Male; Malondialdehyde; Organ Specificity; Rats; Rats, Wistar; Reperfusion Injury

Previous studies have demonstrated that both curcumin and leptin are protective factors against acute injuries. Here, we investigated whether leptin and its signaling pathway mediate the protective effects of curcumin.. A solid dispersion of curcumin-polyvinylpyrrolidone K30 was prepared and administered intraperitoneally. In vivo intestinal ischemia/reperfusion (I/R) injury in mice determined the effects of curcumin administration on inflammation, oxygen radical production, and leptin expression. In vitro studies using the venous epithelial cell line ECV-304 examined hypoxia/reoxygenation-induced leptin expression and release after curcumin administration. Furthermore, the effects on the leptin-regulated ERK1/2 and p38 MAPK signaling pathways were also explored.. Intestinal I/R induced marked bowel injuries. Curcumin treatment significantly improved animal survival and reduced the pathologic injuries in the intestines. Furthermore, the elevated intestinal water content and levels of malondialdehyde, interleukin 1β (IL-1β) and IL-6 were significantly decreased, but levels of superoxide dismutase increased. Interestingly, we found that the decreased leptin and its receptor Ob-Rb were restored by curcumin administration. In addition, in vitro studies showed that curcumin increased leptin expression and release after hypoxia/reoxygenation-induced cell injuries. Moreover, curcumin treatment restored decreased ERK1/2 phosphorylation (p-ERK1/2) and inhibited overactive p38 (p-p38) after injuries, and the effect was reversed by a leptin-specific antibody or Ob-R blocker.. These data suggest that leptin and Ob-Rb-dependent ERK and p38 MAPK signaling pathways may be involved in curcumin protection against intestinal I/R injury, and leptin may be a potential target of curcumin in intestinal I/R injury and other related acute diseases.

Topics: Acute Disease; Animals; Curcumin; Disease Models, Animal; Enzyme Inhibitors; Epithelial Cells; Intestines; Leptin; Male; Mice; Phosphorylation; Reperfusion Injury; Signal Transduction

To investigate the effects of curcumin on the apoptosis of ischemia/reperfusion (I/R) induced H9c2 myocardial cells and the expression of glycogen synthase kinase-3 (GSK-3) and its phosphorylation state.. I/R of H9c2 cells in vitro was simulated by an ischemic Tyrode solution. Cells were randomly divided into 3 groups, i.e., the model group (exposed to ischemic solution for 90 min followed by 30 min reperfusion with the normal Tyrode solution), the curcumin group (7.5 micromol/L curcumin added at the onset of reperfusion for 30 min), and the control group (exposed to normal Tyrode solution for 120 min). Then, the cell apoptosis was detected in 3 groups by flow cytometry. The expression levels of GSK-3, phosphotyrosine-GSK-3 (pTyr-GSK-3), and phosphoserine-GSK-3 (pSer-GSK-3) were detected by Western blot.. Compared with the control group,the apoptosis rate was obviously enhanced in the model group (t = 10.439, P = 0.000). And the relative expression levels of both pTyr-GSK-3 and pSer-GSK-3 significantly increased in the model group (t = 5.208, P = 0.006; t = 5.854, P = 0.004, respectively). Compared with the model group, the apoptosis rate and the expression of pTyr-GSK-3 significantly decreased in the curcumin group (t = -8.325, P = 0.001; t = -3.607, P = 0.023). Compared with the model group, the rate of viable cells and the expression of pSer-GSK-3 were significantly enhanced in the curcumin group (t = 9.165, P = 0.001; t = 3.747, P = 0.02).. Both pTyr-GSK-3 and pSer-GSK-3 might participate in the IR injured myocardial cells. Curcumin could reduce apoptosis of I/R injured myocardial cells, which might be correlated with GSK-3 inhibition by decreasing tyrosine phosphorylation and increasing serine phosphorylation.

Topics: Animals; Apoptosis; Cell Line; Curcumin; Glycogen Synthase Kinase 3; Myocardial Reperfusion Injury; Myocytes, Cardiac; Phosphorylation; Rats; Reperfusion Injury; Signal Transduction

The aim of this study was to investigate the effects curcumin on inflammation and oxidative stress markers in the intestinal ischemia reperfusion (IIR) injury induced rats. Rats were divided into four groups: sham (S), intestinal IR (IIR), curcumin plus sham (CS), and curcumin plus intestinal IR (CIIR). Curcumin was given 200 mg kg⁻¹ for 20 days. IIR was produced by 45 min of intestinal ischemia followed by a 120 min of reperfusion. Although interleukin-6 levels tended to increase in IIR group tumor necrosis factor-α levels were not different. Intestinal myeloperoxidase activity in CS group was lower than IIR group. In intestine and heart tissues, malondialdehyde levels in CS and CIIR groups were lower than S and IIR groups. Superoxide dismutase activity in CIIR group was higher than IIR group in intestine and lung tissues. Curcumin has a protective role against ischemia reperfusion injury.

Topics: Animals; Curcumin; Disease Models, Animal; Intestinal Diseases; Male; Oxidative Stress; Phytotherapy; Plant Preparations; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury

To evaluate the protective effects of curcumin in experimental ischemia and ischemia/reperfusion (I/R) injury of rat ovaries.. Forty-eight female adult Wistar Albino rats were used. Rats divided into six groups and designed: Sham, Torsion, Detorsion, Sham + Curcumin, Torsion + Curcumin, and Detorsion + Curcumin. Except for the Sham and Sham + Curcumin group, all groups were performed to bilateral adnexal torsion for 3 h. Bilateral adnexal detorsion was implemented in the Detorsion and Detorsion + Curcumin groups. The injection of curcumin was intraperitoneally achieved 30 min before the sham, torsion and detorsion.. Total oxidant status levels (TOS), oxidative stress index (OSI) and histologic scores values of ovarian tissue were higher in the torsion and detorsion groups than the sham group (p < 0.05). There was a strong correlation between the total histologic scores of I/R injury and the OSI (r = 0.809, p < 0.001). By the use of curcumin, a significant decrease was established in the mean levels of oxidant markers and histopathologic scores of the ovarian tissues.. Administration of curcumin is effective in reversing tissue damage induced by ischemia-reperfusion injury in ovarian torsion.

Topics: Animals; Antioxidants; Curcumin; Female; Ovarian Diseases; Ovary; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury

Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery.. To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model.. A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3-L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed.. Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05).. The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; In Situ Nick-End Labeling; Male; Neuroprotective Agents; Rabbits; Recovery of Function; Reperfusion Injury; Spinal Cord Ischemia

To investigate the effects of curcumin (CUR) on pneumocyte apoptosis and CCAAT/enhancer binding protein homologous protein (CHOP) in pulmonary ischemia/reperfusion injury (PIRI) in mice.. Sixty C57BL/6J mice were randomly allocated into six groups (n = 10): Sham operation group (Sham group), ischemia/reperfusion group (I/R group), ischemia/reperfusion + dimethyl sulfoxide group (DMSO group), ischemia/reperfusion + curcumin pre-treated with respectively 100 mg/kg, 150 mg/kg and 200 mg/kg groups (CUR-100 group, CUR-150 group and CUR-200 group). Left lung tissue of each group was excised after reperfusion for 3 h. Wet lung weight to dry lung weight (W/D) and total lung water content (TLW) were tested. The morphological and ultrastructural changes of lung tissue were observed under light microscope and electron microscope, and index of quantitative evaluation for alveolar damage (IQA) was calculated. The expression levels of CHOP and glucose regulated protein 78 (GRP78) were detected by RT-PCR and Western Blot. Apoptosis index (AI) of lung tissue was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method.. Compared with Sham group, the expression levels of CHOP, GRP78 mRNA and protein were all significantly increased (P < 0.05) in I/R group and DMSO group, W/D, TLW, IQA and AI were all notably higher (P < 0.01); morphological and ultrastructural injury in lung tissue were notably observed in I/R group. Compared with DMSO group, the expression levels of GRP78 mRNA and protein were increased higher (P < 0. 05) in CUR-100 group, CUR-150 group, and CUR-200 group, but the expression levels of CHOP mRNA and protein were decreased lower (P < 0.05), W/D, TLW, IQA and AI were also decreased (P < 0.05, P < 0.01); morphological and ultrastructural injury in lung tissue were gradually alleviated in CUR groups.. I/R induces excessive unfolded protein response (UPR) in lung tissue, in which CHOP participates in pneumocyte apoptosis, leading to lung injury; CUR has notable effects on lung protection against I/R injury, which may be related to inhibition of apoptosis mediated by CHOP in excessive UPR.

Topics: Alveolar Epithelial Cells; Animals; Apoptosis; Curcumin; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Lung; Male; Mice; Mice, Inbred C57BL; Reperfusion Injury; Transcription Factor CHOP

Hepatic ischemia-reperfusion (IR) injury is a clinical problem that leads to cellular damage and organ dysfunction mediated mainly via production of reactive oxygen species and inflammatory cytokines. Vinpocetine has long been used in cerebrovascular disorders. This study aimed to explore the protective effect of vinpocetine in IR injury to the liver. Ischemia was induced in rats by clamping the common hepatic artery and portal vein for 30 min followed by 30 min of reperfusion. Serum transaminases and liver lactate dehydrogenase (LDH) activities, liver inflammatory cytokines, oxidative stress biomarkers, and liver histopathology were assessed. IR resulted in marked histopathology changes in liver tissues coupled with elevations in serum transaminases and liver LDH activities. IR also increased the production of liver lipid peroxides, nitric oxide, and inflammatory cytokines interleukin-1β and interleukin-6, in parallel with a reduction in reduced glutathione and interleukin-10 in the liver. Pretreatment with vinpocetine protected against liver IR-induced injury, in a dose-dependent manner, as evidenced by the attenuation of oxidative stress as well as inflammatory and liver injury biomarkers. The effects of vinpocetine were comparable with that of curcumin, a natural antioxidant, and could be attributed to its antioxidant and anti-inflammatory properties.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers, Pharmacological; Curcumin; Cytokines; Glutathione; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-6; L-Lactate Dehydrogenase; Liver; Male; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Transaminases; Vinca Alkaloids

Pulmonary failure, instead of kidney failure, is one of the leading causes of acute kidney injury (AKI)-related death. Volume overload was previously regarded as the primary cause of lung injury, presumably by impaired renal fluid clearance. Recent evidence suggested that proinflammatory cytokines, chemokines, and free radicals released during AKI are playing a crucial role in the lung injury. We aimed to examine the protective efficacy of lung function with curcumin pretreatment.. AKI was induced by 45 minutes of kidney ischemia (bilateral occlusion of renal pedicles) followed by 3 hours of reperfusion. Rats were divided into 3 groups: sham-operated, kidney ischemia and reperfusion (I/R), and a group with 2 days of oral pretreatment with curcumin (12.5 mg/kg/d) before I/R injury. The pulmonary function test (PFT) was conducted at baseline and after 3 hours of reperfusion, yielding parameters of lung volumes, chord compliance (Cchord), inspiratory resistance (RI), and forced expiratory volume at the first 200 millisecond (FEV200). We also examined levels of protein concentration (PC), methylguanidine (MG), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) in the bronchoalveolar lavage (BAL).. Ischemic AKI-induced restrictive lung disease was demonstrated by the decreased Cchord, total lung capacitance (TLC), and FEV200, in addition to the increased lavage PCBAL, MG, TNF-α, and MDA level. Curcumin pretreatment ameliorated lung function impairment and alveolar vascular protein leak and attenuated lung inflammation.. The protective effect of curcumin pretreatment against restrictive lung disease is most likely associated with decreasing hydroxyl radical, lipid peroxidation, and inflammation in the lungs and improving alveolar vascular permeability.

Topics: Acute Kidney Injury; Airway Resistance; Animals; Anti-Inflammatory Agents; Antioxidants; Bronchoalveolar Lavage Fluid; Capillary Permeability; Curcumin; Cytoprotection; Disease Models, Animal; Forced Expiratory Volume; Kidney; Lipid Peroxidation; Lung; Lung Compliance; Malondialdehyde; Methylguanidine; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Respiratory Insufficiency; Total Lung Capacity; Tumor Necrosis Factor-alpha

Renal ischemia and reperfusion (I/R) injury frequently leads to acute renal failure (ARF) and multiple-organ injury with a substantial morbidity rate. The primary cause of ARF-associated death is, however, cardiac failure instead of renal failure itself, and the pathogenesis of renal I/R-induced cardiac injury is still poorly understood. We evaluated the efficacy of curcumin pretreatment on cardioprotection.. Thirty Sprague-Dawley rats were evenly divided into 3 groups of sham-operated control, renal I/R injury, and a curcumin pretreatment group. Renal ischemia was conducted by bilateral occlusions of pedicles for 45 minutes, followed by 3 hours of reperfusion. The cardiac function was assessed by the left ventricular end-systolic-pressure-volume-relation (ESPVR), systolic pressure (SP), ejection fraction (EF), and stroke volume (SV). Myocardial injury was assessed based on creatine kinase muscle brain fraction (CK-MB) and Troponin I (cTnI), and kidney injury was assessed based on blood urea nitrogen (BUN) and creatinine. We also assessed the levels of tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) in the heart tissues.. SV, EF, and SP reduced moderately during the ischemic phase with no major change in ESPVR. During reperfusion, SV, SP, and ESPVR initially increased, and then steadily decreased. Myocardial and kidney injury were marked by the increases in serum CK-MB and cTnI, and creatinine and BUN level. Curcumin pretreatment ameliorated ESPVR and attenuated injuries of both the heart and kidney resulting from I/R insult.. Curcumin pretreatment improved cardiac contractility and attenuated myocardial and renal injury through reducing inflammatory response in the kidney and heart and oxidative stress in the myocardium.

Topics: Acute Kidney Injury; Animals; Biomarkers; Blood Urea Nitrogen; Creatine Kinase, MB Form; Creatinine; Curcumin; Cytoprotection; Disease Models, Animal; Heart; Heart Diseases; Inflammation Mediators; Kidney; Malondialdehyde; Myocardial Contraction; Myocardium; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stroke Volume; Troponin I; Tumor Necrosis Factor-alpha; Ventricular Function, Left; Ventricular Pressure

The aim of this study is to evaluate the role of curcumin on acute lung injury induced by intestinal ischaemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into 3 groups: sham, I/R, and I/R + curcumin; each group contains 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the curcumin group, 3 days before I/R, curcumin (100 mg/kg) was administered by gastric gavage. All animals were killed at the end of reperfusion and lung tissue samples were obtained for biochemical and histopathological investigation in all groups. To date, no more biochemical and histopathological changes on intestinal I/R injury in rats by curcumin treatment have been reported. Curcumin treatment significantly decreased the elevated tissue malondialdehyde levels and increased reduced superoxide dismutase, and glutathione peroxidase enzyme activities in lung tissue samples. Intestinal I/R caused severe histopathological injury including oedema, haemorrhage, increased thickness of the alveolar wall, and infiltration of inflammatory cells into alveolar spaces. Curcumin treatment significantly attenuated the severity of intestinal I/R injury. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase and increase in the expression of surfactant protein D in lung tissue of acute lung injury induced by intestinal I/R with curcumin therapy. It was concluded that curcumin treatment may have beneficial effects in acute lung injury, and therefore has potential for clinical use.

Topics: Acute Lung Injury; Animals; Curcumin; Immunohistochemistry; Intestines; Lung; Male; Nitric Oxide Synthase Type II; Oxidative Stress; Protective Agents; Pulmonary Surfactant-Associated Protein D; Rats; Rats, Wistar; Reperfusion Injury; Statistics, Nonparametric

Topics: Animals; Antioxidants; Curcumin; Muscle, Skeletal; Regional Blood Flow; Reperfusion Injury

In the present study, we investigated the potential protective effect of selected natural substances in a rat model of heart and mesenteric ischemia-reperfusion (I/R). Experiments were performed on isolated Langendorff-perfused rat hearts, subjected to 30-min global ischemia, followed by 30-min reperfusion. Arbutin, curcumin, rosmarinic acid and extract of Mentha x villosa were applied in the concentration of 1 × 10⁻⁵ mol/l 10 min before the onset of ischemia and during reperfusion, through the perfusion medium. Mesenteric ischemia was induced by clamping the superior mesenteric artery (SMA) for 60 min, subsequent reperfusion lasted 30 min. Production of reactive oxygen species (ROS) by SMA ex vivo was determined by luminol-enhanced chemiluminiscence (CL). The effect of the substances was tested after their incubation with tissue. Curcumin and extract of Mentha x villosa were found to be the most effective in reducing reperfusion-induced dysrhythmias--ventricular tachycardia and fibrillation. This effect was accompanied by bradycardic effect. The mesenteric I/R induced an increase in CL in vascular tissue which was dampened by substances tested. All substances tested were found to have antioxidant properties, as demonstrated by a reduction in ROS production in mesenteric vessels. This effect was confirmed in curcumin and extract of Mentha x villosa which reduced reperfusion dyshythmias.

Topics: Animals; Antioxidants; Arbutin; Cinnamates; Curcumin; Depsides; Male; Mentha; Mesenteric Artery, Superior; Myocardial Reperfusion Injury; Phytotherapy; Plant Preparations; Polyphenols; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Rosmarinic Acid; Tachycardia, Ventricular; Ventricular Fibrillation

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway.. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting.. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein.. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigen-Presenting Cells; Antioxidants; Blotting, Western; Chemokines; Curcumin; Cytokines; Drug Delivery Systems; Epithelial Cells; In Situ Nick-End Labeling; Kidney Tubules; Liposomes; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Oxidative Stress; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; Time Factors

Curcumin has been shown to decrease ischemia-reperfusion (I/R) injury in kidney or brain tissues. In this study, the effects of curcumin were evaluated in skeletal muscle during I/R injury.. Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4 h ischemia, the clamp of the femoral vessels of animals was taken off and the animal underwent 2 h reperfusion. We measured plasma concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) using enzyme-linked immunosorbent assay (ELISA). The right gastrocnemius muscle was harvested and immediately stored at -30°C for the assessment of superoxide dismutase (SOD), catalase (CAT) activities, and measurement of glutathione (GSH), malondialdehyde (MDA), and protein oxidation (PO) levels. Curcumin (100 mg/kg), α-tocopherol, and normal saline (10 mL /kg1) were administered intraperitoneally 1 h prior reperfusion.. Plasma TNF-α or IL-1β levels increased significantly in I/R group. The plasma levels of these proinflammatory cytokines were reduced in curcumin group. Muscle tissues of I/R groups revealed significantly higher antioxidant enzyme (superoxide dismutase, glutathione peroxidase, catalase) activities, and increased levels of malondialdehyde, nitric oxide, and protein carbonyl content compared with the SHAM group. Levels of these parameters in muscle revealed significant reductions in the I/R + curcumin group compared witho the I/R group. Curcumin has more potent antioxidant activity than vitamin E in the skeletal muscle I/R.. In this study, protective effects of curcumin against skeletal muscle ischemia-reperfusion injury have been revealed. We underscore the necessity of human studies with curcumin that would be hypothetically beneficial preventing skeletal muscle I/R injury.

Topics: Animals; Antioxidants; Catalase; Curcumin; Glutathione; Interleukin-1beta; Malondialdehyde; Models, Animal; Muscle, Skeletal; Peptide Fragments; Rats; Rats, Wistar; Regional Blood Flow; Reperfusion Injury; Superoxide Dismutase; Tumor Necrosis Factor-alpha

High levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy), contribute to autophagy and ischemia/reperfusion injury (I/R). Previous studies have shown that I/R injury and HHcy cause increased cerebrovascular permeability; however, the associated mechanism remains obscure. Interestingly, during HHcy, cytochome-c becomes homocysteinylated (Hcy-cyto-c). Cytochrome-c (cyto-c) transports electrons and facilitates bioenergetics in the system. However, its role in autophagy during ischemia/reperfusion injury is unclear. Tetrahydrocurcumin (THC) is a major herbal antioxidant and anti-inflammatory agent. Therefore, the objective of this study was to determine whether THC ameliorates autophagy during ischemia/reperfusion injury by reducing homocysteinylation of cyto-c in hyperhomocysteinemia pathological condition. To test this hypothesis, we employed 8-10-week-old male cystathionine-beta-synthase heterozygote knockout (CBS⁺/⁻) mice (genetically hyperhomocystemic mice). Experimental group was: CBS⁺/⁻, CBS⁺/⁻ + THC (25 mg/kg in 0.1% DMSO dose); CBS ⁺/⁻/I/R, and CBS⁺/⁻/I/R + THC (25 mg/kg in 0.1% DMSO dose). Ischemia was performed for 30 min and reperfusion for 72 h. THC was injected intra-peritoneally (I.P.) once daily for a period of 3 days after 30 min of ischemia. The infarct area was measured using 2,3,5-triphenyltetrazolium chloride staining. Permeability was determined by brain edema and Evans Blue extravasation. The brain tissues were analyzed for oxidative stress, matrix metalloproteinase-9 (MMP-9), damage-regulated autophagy modulator (DRAM), and microtubule-associated protein 1 light chain 3 (LC3) by Western blot. The mRNA levels of S-adenosyl-L-homocysteine hydrolases (SAHH) and methylenetetrahydrofolate reductase (MTHFR) genes were measured by quantitative real-time polymerase chain reaction. Co-immunoprecipitation was used to determine the homocysteinylation of cyto-c. We found that brain edema and Evans Blue leakage were reduced in I/R + THC-treated groups as compared to sham-operated groups along with reduced brain infarct size. THC also decreased oxidative damage and ameliorated the homocysteinylation of cyto-c in-part by MMP-9 activation which leads to autophagy in I/R groups as compared to sham-operated groups. This study suggests a potential therapeutic role of dietary THC in cerebral ischemia.

Topics: Animals; Antioxidants; Autophagy; Brain Ischemia; Curcumin; Cytochromes c; Hyperhomocysteinemia; Male; Mice; Mice, Knockout; Reperfusion Injury

Reperfusion of the ischemic liver results in the generation of oxidative and nitrosative stresses and reaction product of peroxynitrite, which induce rapid cytotoxicity and liver injury. In this study we demonstrated that curcumin, an antioxidant, attenuated ischemia/reperfusion (I/R)-induced liver injury.. Ischemia was induced by clamping the common hepatic artery and portal vein of rats for 30 minutes. Thereafter, flow was restored and the liver was reperfused for 80 minutes. Blood samples collected prior to ischemia and after reperfusion were analyzed for methyl guanidine (MG), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and adenosphate triphosphate (ATP). Blood levels of serum glutamic oxaloacetic transaminase (sGOT), serum glutamate pyruvate transaminase (sGPT), and lactic dehydrogenase (LDH), which served as indexes of liver injury, were measured.. The protocol resulted in elevation of blood NO (P < .001), TNF-α (P < .001), and MG (P < .001). sGOT, sGPT, and LDH were elevated significantly (P < .001), whereas ATP was significantly diminished (P < .001). Pretreatment with curcumin (25 mg/kg) significantly attenuated the reperfusion liver injury, while the ATP content reversed. In addition, MG, TNF-α, and NO release were attenuated.. These results indicated that curcumin exerted potent anti-inflammatory effects in I/R-induced liver injury due to its antioxidant effects.

Topics: Adenosine Triphosphate; Alanine Transaminase; Animals; Anti-Inflammatory Agents; Antioxidants; Aspartate Aminotransferases; Biomarkers; Curcumin; Cytoprotection; Disease Models, Animal; Inflammation Mediators; L-Lactate Dehydrogenase; Liver; Liver Diseases; Male; Methylguanidine; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors; Tumor Necrosis Factor-alpha

Mesenteric ischemia/reperfusion injury induces a systemic response and releases harmful substances that may affect distant organs such as the lung, liver and kidney. We designed this study to determine if curcumin has protective effects against mesenteric ischemia/reperfusion injury and mesenteric ischemia/reperfusion-induced intestinal and distant organ injury.. Forty Wistar-Albino rats were divided into four groups as: sham, control, ischemia/reperfusion, and ischemia/reperfusion+curcumin. The ischemia/reperfusion and ischemia/reperfusion+curcumin groups were subjected to mesenteric arterial ischemia for 30 minutes and reperfusion for 1 hour. The control and ischemia/reperfusion+curcumin groups were administered curcumin (200 mg/kg, single dose) via oral gavage 15 min before the injury insult. Blood and pulmonary, hepatic and kidney tissue specimens were obtained to measure serum malondialdehyde and total antioxidant capacity, tissue levels of total antioxidant capacity, total oxidative status, and oxidative stress index. In addition, intestine, pulmonary, hepatic, and kidney tissue specimens were obtained for the evaluation of histopathological changes.. The histopathological injury scores of the intestine and distant organs were significantly higher in the ischemia/reperfusion group; these injuries were prevented by curcumin in the ischemia/reperfusion+curcumin group. In the ischemia/reperfusion group, a significant increase in serum malondialdehyde levels was determined, which was prevented with curcumin pretreatment in the ischemia/reperfusion+curcumin group. Total antioxidant capacity levels were significantly supported by curcumin pretreatment in the control and ischemia/reperfusion+curcumin groups.. This study demonstrated that curcumin ameliorates histopathological damage in the intestine and distant organs against mesenteric ischemia/reperfusion injury.

Topics: Animals; Antioxidants; Curcumin; Intestines; Ischemia; Kidney; Liver; Lung; Malondialdehyde; Mesentery; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury

Curcumin, a component of the spice turmeric, was shown to have a protective effect on acute kidney injury markers following ischemia-reperfusion injury (IRI). However, its effect on glomerular and tubular renal functions following IRI is not known and this data is probably of more clinical relevance. In this study, curcumin was tested for its effect on renal functional parameters following two different periods of warm IRI in the rat. Groups V-30 (n=10) and C-30 (n=10) underwent ischemia for 30 minutes whereas groups V-45 (n=8) and C-45 (n=8) underwent ischemia for 45 minutes. C-30 and C-45 received oral curcumin (200 mg/kg/day) whereas V-30 and V-45 received a vehicle. The left renal artery blood flow was measured by a flowmeter before and 15 minutes after reperfusion. Serum TNF-alpha was measured before and 2 days after ischemia. The function of both kidneys was measured 2 days following ischemia using clearance technique. IRI caused significant increase in TNF-alpha in all groups. Curcumin significantly ameliorated the ischemia-induced alterations in serum TNF-alpha and associated histological changes but did not affect the alterations in renal artery blood flow, glomerular (glomerular filtration rate, renal blood flow) or tubular (urinary volume, urinary sodium and fractional excretion of sodium) functions following 30 or 45 min of IRI.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Male; Rats; Rats, Wistar; Renal Circulation; Reperfusion Injury; Treatment Outcome

Curcumin is an antioxidant molecule that has been shown to attenuate ischemia/reperfusion (I/R) injury in several organ systems. In the present study, we aimed to evaluate the possible effects of curcumin on contractile response to agonists and histopathological alterations in rat esophagus subjected to mesenteric I/R.. Adult male Wistar albino rats were randomly allocated to 4 groups, namely group I: sham-operated animals (n=10); group II: animals subdued to I/R injury only (n=10) and laparotomy; 45 minutes of superior mesenteric artery ligation were followed by 2 hours of reperfusion, group III: curcumin/sham (n=10); 20 days before I/R, curcumin (200 mg/kg/) was administered by gastric gavage, and group IV: curcumin-I/R (n=10). Mesenteric ischemia/reperfusion model was generated by clamping the superior mesenteric artery for 45 min followed by reperfusion for 2 h. Oral administration of curcumin by gavage at a dose of 200 mg/kg/day lasted 20 days just before inducing the mesenteric ischemia. At the end of reperfusion period, all animals were sacrificed and esophagus samples were collected to assess the contractile response to agonists and histopathological alterations.. Ischemia/reperfusion significantly decreased the contractile responses to carbachol and KCl and this decrease was attenuated by curcumin. Pretreatment with curcumin caused a remarkable decrease in histopathological parameters such as edema, congestion and inflammatory cells.. The results of the present study demonstrate for the first time that curcumin can attenuate the esophageal injury associated with I/R (Tab. 4, Fig. 3, Ref. 32).

Topics: Animals; Carbachol; Curcumin; Dose-Response Relationship, Drug; Esophagus; In Vitro Techniques; Male; Mesentery; Muscle Contraction; Muscle, Smooth; Potassium Chloride; Rats; Rats, Wistar; Reperfusion Injury

Renal ischemia followed by reperfusion results in kidney injury which in turn produces and releases destructive inflammatory cytokines into the circulation causing subsequent distant organ injury. Little data suggest the immune mechanism of curcumin on protection against ischemia/reperfusion induced injury. We investigated the immunomodulatory and anti-apoptotic effects of curcumin on ischemia/reperfusion (I/R) injury in rats. Thirty-six rats were randomly divided into three experimental groups (sham, I/R and curcumin pretreated I/R, n=12 each). Curcumin was administered orally to curcumin pretreated I/R group. Curcumin can significantly decrease both systemic as well as blood levels of cytokines (p<0.05). Treatment with curcumin also resulted in significant reduction in serum and tissue level of TNF-α, IL-1β, IL-12, IL-18 and INF-γ that were increased by renal I/R injury (p<0.05). Curcumin pretreatment reduce pulmonary apoptotic pathway via significant inhibition of TGF-β and caspase-3 in kidney and lung tissues. Given that pulmonary apoptosis is an important complication of acute renal injury, we identified curcumin protective effect against distant organ I/R induced injury. Based on our results, we concluded that curcumin protects the kidneys and other vital organs against I/R injury via immune-mediated and the new identified anti-apoptotic mechanisms.

Topics: Animals; Apoptosis; Caspase 3; Curcumin; Cytokines; Immunologic Factors; Kidney; Kidney Diseases; Lung; Lung Injury; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Transforming Growth Factor beta

To explore the effects of curcumin on the expression of high mobility group box 1 (HMGB1) and apoptotic neurons in hippocampus after global cerebral ischemia/reperfusion in SD rats.. A total of 192 male SD rats were randomly divided into 4 groups: sham group (SH), ischemia-reperfusion group (IR), curcumin group (Cur) and solvent control group (SC). Bilateral vertebrate arteries were electrocauterized and bilateral common carotid arteries liberated in 3 ischemic groups. Isasteric curcumin solutions (200 mg/kg) or menstruum were injected intraperitoneally at 1 hour pre-ischemia in Cur and SC groups. The rats in each group were ligated for 15 minutes and then decapitated at 1, 3, 5 and 7 d post-reperfusion respectively. Cell morphology was observed on hematoxylin & eosin-stained slides. Apoptotic neurons were detected in CA1 region by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Western blot was used to make a semi-determination of HMGB1 expression.. At each time point, the number of apoptotic neurons was much more in IR and SC groups than that in SH group (P < 0.05). And the number of apoptotic neurons at 1, 3, 5, 7 d post-reperfusion was only 41%, 57%, 65% and 70% in Cur group respectively (P < 0.05). The expressional level of HMGB1 in IR and SC groups was significantly lower at 1d post-reperfusion (0.685 ± 0.050; 0.695 ± 0.053 vs 0.977 ± 0.063, P < 0.05). And it was significantly higher at 3, 5, 7 d post-reperfusion in IR and SC groups than that in SH groups (1.360 ± 0.045/1.353 ± 0.045; 1.342 ± 0.046/1.338 ± 0.047; 1.319 ± 0.052/1.322 ± 0.035 vs 0.992 ± 0.031; 0.978 ± 0.090; 0.992 ± 0.075, P < 0.05). The level at 1 d post-reperfusion (0.842 ± 0.063) in Cur group was significantly higher than that in IR and SC groups but lower than that in SH group. And it was lower at 3, 5, 7 d post-reperfusion (1.125 ± 0.023, 1.098 ± 0.073, 1.087 ± 0.089) than those in IR and SC groups (P < 0.05). There was no significant difference of HMGB1expression level between IR and SC groups.. The expression level of HMGB1 in hippocampus is significantly reduced at 1 d post-reperfusion. Then it significantly increases and a high level is maintained until 7 d after global cerebral ischemia/reperfusion. Curcumin can reduce hippocampal neuronal apoptosis and injury. Such an effect may be due to an inhibition of the synthesis and release of HMGB1.

Topics: Animals; Apoptosis; Brain Ischemia; Curcumin; Disease Models, Animal; Hippocampus; HMGB1 Protein; Male; Neurons; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Neuron loss, glial activation and vascular degeneration are common sequelae of ischemia-reperfusion (I/R) injury in ocular diseases. The present study was conducted to explore the ability of curcumin to inhibit retinal I/R injury, and to investigate underlying mechanisms of the drug effects.. Different dosages of curcumin were administered. I/R injury was induced by elevating the intraocular pressure for 60 min followed by reperfusion. Cell bodies, brn3a stained cells and TUNEL positive apoptotic cells in the ganglion cell layer (GCL) were quantitated, and the number of degenerate capillaries was assessed. The activation of glial cells was measured by the expression level of GFAP. Signaling pathways including IKK-IκBα, JAK-STAT1/3, ERK/MAPK and the expression levels of β-tubulin III and MCP-1 were measured by western blot analysis. Pre-treatment using 0.01%-0.25% curcumin in diets significantly inhibited I/R-induced cell loss in GCL. 0.05% curcumin pre-treatment inhibited I/R-induced degeneration of retinal capillaries, TUNEL-positive apoptotic cell death in the GCL, brn3a stained cell loss, the I/R-induced up-regulation of MCP-1, IKKα, p-IκBα and p-STAT3 (Tyr), and down-regulation of β-tubulin III. This dose showed no effect on injury-induced GFAP overexpression. Moreover, 0.05% curcumin administered 2 days after the injury also showed a vaso-protective effect.. Curcumin protects retinal neurons and microvessels against I/R injury. The beneficial effects of curcumin on neurovascular degeneration may occur through its inhibitory effects on injury-induced activation of NF-κB and STAT3, and on over-expression of MCP-1. Curcumin may therefore serve as a promising candidate for retinal ischemic diseases.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Blotting, Western; Chemokine CCL2; Curcumin; Dose-Response Relationship, Drug; Glial Fibrillary Acidic Protein; Male; Neurons; NF-kappa B; Rats; Rats, Wistar; Reperfusion Injury; Retina; Retinal Ganglion Cells; Retinal Vessels; Signal Transduction; STAT3 Transcription Factor; Time Factors; Tubulin; Vascular Diseases

The aim of this study was to demonstrate the role of curcumin on oxidative stress, cell proliferation and apoptosis in the rat intestinal mucosa after ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ curcumin; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the curcumin group, 3 days before I/R, curcumin (100 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and intestinal tissues samples were obtained for biochemical and histopathological investigation in all groups. Curcumin treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in intestinal tissues samples. I/R caused severe histopathological injury including mucosal erosions and villous congestion and hemorrhage. Curcumin treatment significantly attenuated the severity of intestinal I/R injury, with inhibiting of I/R-induced apoptosis and cell proliferation. These results suggest that curcumin treatment has a protective effect against intestinal damage induced by intestinal I/R. This protective effect is possibly due to its ability to inhibit I/R-induced oxidative stress, apoptosis and cell proliferation.

Topics: Animals; Apoptosis; Cell Growth Processes; Curcumin; Glutathione Peroxidase; Intestinal Mucosa; Intestines; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Superoxide Dismutase

Ischemia-reperfusion (I/R) of the rat pancreas induces acute pancreatitis with a systemic inflammatory response. Activated inflammatory cells are sequestered in the lung, and the consequent respiratory burst may increase airway reactivity. In this study, we characterized the effect of the antioxidant curcumin on airway hyperreactivity induced by pancreatic I/R.. Ischemia of the pancreas was induced by clamping the gastroduodenal and the splenic artery for 2 hours followed by reperfusion for 6 hours. The pulmonary function data of Penh, a measurement of airway resistance, were used to show the airway responses to a methacholine challenge. The blood concentration of oxygen radicals, nitric oxide, and tumor necrosis factor-alpha (TNFalpha) were measured after pancreatic I/R. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFalpha in lung tissues were measured after pancreatic I/R. Pretreatment with curcumin (20 mg/kg) was administered by intraperitoneal injection 2 hours before pancreatic I/R.. The protocol resulted in significant elevations of the blood concentrations of amylase, hydroxyl radical, nitric oxide, TNFalpha, and white cells among the I/R group. iNOS and TNFalpha mRNA expressions also significantly increased in lung tissues. Pulmonary function data showed that pancreatic I/R induced significant increases in responses to methacholine challenge: Penh increased significantly in the I/R group when compared with the sham group. Pretreatment with curcumin significantly attenuated the inflammatory, oxidative, and nitrosative responses and lung tissue iNOS and TNFalpha expressions. Curcumin also attenuated airway reactivity to methacholine challenge.. I/R of the pancreas induced systemic inflammatory responses with respiratory burst, nitrosative stress, and hyperresponses in the airways. Curcumin, which has antioxidant and anti-inflammatory effects, significantly attenuated the inflammatory responses and airway hyperreactivity induced by pancreatic I/R.

Topics: Amylases; Animals; Anti-Inflammatory Agents; Antioxidants; Bronchial Hyperreactivity; Curcumin; Male; Methylguanidine; Nitric Oxide; Nitric Oxide Synthase Type II; Pancreas; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Respiratory Function Tests; RNA, Messenger; Tumor Necrosis Factor-alpha

Topics: Animals; Coloring Agents; Curcumin; E-Selectin; Humans; Intercellular Adhesion Molecule-1; Lymphocyte Function-Associated Antigen-1; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Models, Animal; Rats; Reactive Oxygen Species; Reperfusion Injury; Spermatic Cord Torsion; Testis

To investigate the diversify of the nuclear pathway of c-Jun NH2-terminal kinases (JNK) during transient brain ischemia/reperfusion injury in hippocampal neuron apoptosis in spontaneously hypertensive rats (SHR) and to test whether the neuroprotection of curcumine on transient brain ischemia/reperfusion injury in SHR is related to the nuclear pathway of JNK.. Male Wistar-Kyoto (WKY) rats and SHR were randomly divided into five groups (n = 6): WKY sham group (W-Sham), WKY ischemia/reperfusion group (W-I/ R), SHR sham group (S-Sham), SHR ischemia/reperfusion group (S-I/R) and SHR curcumine (a chinese traditional medicine)100 mg/kg treatment group (S-Cur), which were sacrificed at 2 h, 6 h, 24 h, 3 d and 7 d after reperfusion. Global brain ischemic model was established by 4-VO method. The TdT-mediated dUTP nick end labeling (TUNEL) method was used to detect the neuron apoptosis in hippocampal CA1 region. The immunohistochemical method was applied to investigate the expressions of c-jun and c-fos in hippocampal CA1 region.. The expressions of apoptosis and c-jun and c-fos in CA1 region in S-Sham group, W-I/R group and S-I/R group were more than those in W-Sham group (P < 0.05), were significantly increased in S-I/R group than those in W-I/R group (P < 0.05), and were significantly decreased in S-Cur group than those in S-I/R group (P < 0.05).. Neuronal apoptosis and the expressions of c-jun and c-fos are more in SHR hippocampal. Global brain ischemia/reperfusion injury induces more expressions of apoptosis in hippocampal neuron in SHR, and the more expressions of c-jun and c-fos may participate in that process. The neuroprotection of curcumine in SHR is related to c-jun and c-fos.

Topics: Animals; Apoptosis; Brain Ischemia; CA1 Region, Hippocampal; Curcumin; JNK Mitogen-Activated Protein Kinases; Male; Neurons; Proto-Oncogene Proteins c-fos; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reperfusion Injury

The present study aimed to investigate potential effects of curcumin (CUR) and dexamethasone (DXM) on ischaemia-reperfusion (I/R) induced lung injury in rats. Experimental rats were pre-treated with a single i.p. dose of vehicle, CUR (50 mg.kg(-1) or 200 mg.kg(-1)) or DXM (5 mg.kg(-1)), 2 h before anaesthesia and subjected to left lung hilus clamping with 90-min ischaemia followed by 4 h of reperfusion. Pre-treatment with CUR (200 mg.kg(-1)) or DXM markedly attenuated I/R-induced barrier disruption, lung oedema, tissue inflammation, hypoxaemia 4 h after reperfusion, and overactivation of nuclear factor-kappaB, inflammatory cytokines, myeloperoxidase and malondialdehyde. It appears that curcumin attenuates acute lung injury, probably through improving oxidative stress and inhibiting nuclear factor-kappaB-mediated expression of inflammatory cytokines. Thus, curcumin may be an alternative therapy for improving the outcomes of ischaemia-reperfusion-induced lung injury.

Topics: Animals; Curcumin; Dexamethasone; Disease Models, Animal; Edema; Glucocorticoids; Lung; Microcirculation; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors; Treatment Outcome

To investigate the effects of curcumin on the expression of nuclear factor-kappaB (NF-kappaB) and intercellular adhesion molecular 1 (ICAM-1) in rats with cerebral ischemia-reperfusion (IR) injury.. A total of 160 SD rats were randomized equally into sham-operated group, IR model group, curcumin treatment group and solvent control group. Global cerebral ischemia/reperfusion injury was induced in the latter 3 groups with subsequent corresponding treatment. At 6 h and 1, 3, and 7 days after the injury, 10 rats from each group were sacrificed, and brain sections were prepare for HE staining, immunohistochemical staining for NF-kappaB, and enzyme-linked immunosorbent assay for ICAM-1 expression.. In the IR model group, the contour of the pyramidal cells in hippocampal CA1 region was almost indistinguishable after the injury, whereas more than 70% of the pyramidal cells retained distinct cell contour and nuclear boundary in curcumin treatment group. At 6 h and 1, 3, and 7 days after the IR injury, the expression of NF-kappaB in curcumin treatment group showed significantly reduction in comparison with that in the IR model and solvent control groups (P<0.05), and the content of ICAM-1 protein was also reduced, which was especially obvious at 1 and 3 days (P<0.05).. Curcumin can ameliorate cerebral pathological changes in the event of IR injury by suppressing the expressions of NF-kappaB and ICAM-1.

Topics: Animals; Brain Ischemia; Curcumin; Down-Regulation; Intercellular Adhesion Molecule-1; Male; NF-kappa B; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Curcumin is an anti-oxidant molecule known to be a potent inhibitor of nuclear factor-kappaB (NF-kappaB). It has been shown to attenuate ischemia/reperfusion (I/R) injury in several organ systems. In this study, we sought to investigate the effects of curcumin on the prevention of superior mesenteric artery I/R injury in rats.. Wistar albino rats were randomly allocated to 3 groups: group I, sham operated (n = 10); group II, I/R injury only (n = 10); group III, curcumin-treated I/R cohort (n = 10). Group I animals underwent laparotomy without I/R injury. After group II animals underwent laparotomy, 60 minutes of superior mesenteric artery ligation were followed by 3 hours of reperfusion. In the curcumin group, 15 days before I/R, curcumin (40 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion. Intestinal tissue samples were obtained to investigate intestinal mucosal injury; in addition we estimated levels of myeloperoxidase (MPO) activity, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha.. There were statistically significant decreases in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, NO, IL-6, and TNF-alpha in group I when compared with groups II and III (P = .01). Curcumin treatment in group III produced a significant increase in GSH levels, as well as a decrease in intestinal mucosal injury scores, MPO activity, MDA, and NO levels when compared with group II (P < .05).. This study showed that curcumin treatment significantly attenuated reperfusion injury in a superior mesenteric artery I/R model in rats.

Topics: Animals; Curcumin; Disease Models, Animal; Gastric Lavage; Glutathione; Interleukin-6; Intestinal Mucosa; Male; Malondialdehyde; Nitric Oxide; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury; Splanchnic Circulation; Tumor Necrosis Factor-alpha

To evaluate the effect of curcumin, a potent antioxidant, on testicular ischemia-reperfusion injury caused by overgeneration of reactive oxygen species (ROS) after testicular torsion-detorsion.. Controlled experimental study using rats.. Research laboratory.. Sixty adult male Sprague-Dawley rats.. Rats in the control group underwent a sham operation of the left testis. In the torsion-detorsion group, the left testis was rotated 720 degrees for 2 hours. Rats in treatment group received the same surgical procedure as the torsion-detorsion group, but curcumin was administered IV at repair of testicular torsion.. Testicular activity of xanthine oxidase, which catalyzes production of ROS; malondialdehyde level (an indicator of ROS content); protein expression level of heme oxygenase-1, which catalyzes antioxidant generation; and spermatogenesis.. Unilateral testicular torsion-detorsion caused significant increases in xanthine oxidase activity, malondialdehyde level, and heme oxygenase-1 protein expression level and caused a significant decrease in testicular spermatogenesis in ipsilateral testes. The rats treated with curcumin had significant decreases in xanthine oxidase activity and malondialdehyde level and had significant increases in heme oxygenase-1 protein expression level and testicular spermatogenesis in ipsilateral testes, compared with the torsion-detorsion group.. The curcumin exerts a protective effect on testicular ischemia-reperfusion injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Male; Malondialdehyde; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Spermatic Cord Torsion; Testis; Xanthine Oxidase

Curcumin (diferuloylmethane), an active ingredient of turmeric, obtained from the powdered rhizomes of Curcuma longa Linn., has been traditionally recognized for treatment of several diseases. To evaluate the potential clinical use of curcumin, we determined the dose dependence of its effects in the therapeutic window and of the neuroprotective efficacy in a cerebral thromboembolic model of the rat. Rats were subjected to occlusion of the middle cerebral artery (MCAo) by a thrombus and treated with different doses of curcumin or the vehicle at 4h after ischemia. The animals were assessed after 24h for motor performance and neurological deficit. The rats were sacrificed immediately afterwards for evaluation of infarct, edema volume, estimation of nitrate and nitrite levels, neutrophil infiltration and levels of GSH and glutathione peroxidase (GSH-Px) in brain tissue. Curcumin reduced in a dose-dependent manner the ischemia-induced cerebral infarct and edema volume and attenuated neurological deficits observed after 24h. Curcumin reduced post-ischemic brain neutrophil infiltration, nitrate and nitrite levels and ameliorated the loss of GSH-Px and tends to increase the GSH levels but not significantly in the brain tissue. Neuronal levels of reactive oxygen species, peroxynitrite, and nitric oxide were lowered and in brain cryosections inducible nitric oxide synthase expression were significantly inhibited after treatment with curcumin. The present study is the first evidence of effectiveness of curcumin when given 4h post-ischemia in the rat thromboembolic stroke models, as it reduces infarct volume, ameliorates the sensory motor function and significantly attenuated the nitrosative stress.

Topics: Animals; Behavior, Animal; Brain Edema; Brain Ischemia; Cerebrovascular Circulation; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione Peroxidase; Immunohistochemistry; Infarction, Middle Cerebral Artery; Male; Motor Activity; Neuroprotective Agents; Nitrates; Nitric Oxide; Nitrites; Peroxidase; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Treatment Outcome

In this study we explored the effects of curcumin in cardiac cells subjected to a protocol simulating ischemia-reperfusion (IR). Curcumin (10 microM) was administered before ischemia (pretreatment) or at the moment of reperfusion (posttreatment) and its effects were compared to those produced by a reference antioxidant (Trolox) with an equal antioxidant capacity. IR cardiac cells showed clear signs of oxidative stress, impaired mitochondrial activity, and a marked development of both necrotic and apoptotic processes; at the same time, increases in NF-kappaB nuclear translocation and JNK phosphorylation were observed. Curcumin pretreatment was revealed to be the most effective in attenuating all these modifications and, in particular, in reducing the death of IR cells. This confirms that the protective effect of curcumin is not related simply to its antioxidant properties but involves other mechanisms, notably interactions in the NF-kappaB and JNK pathways. These findings suggest that curcumin administration, in particular before the hypoxic challenge, represents a promising approach to protecting cardiac cells against IR injury. In this scenario our results point out the importance of the chronology for the outcome of the treatment and provide a differential valuation of the degree of protection that curcumin can exert by its antioxidant activity or by other mechanisms.

Topics: Animals; Blotting, Western; Cell Death; Cell Line; Cell Nucleus; Curcumin; L-Lactate Dehydrogenase; Lipid Peroxidation; MAP Kinase Kinase 4; NF-kappa B; Oxidative Stress; Phosphorylation; Protein Transport; Rats; Reactive Oxygen Species; Reperfusion Injury

Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from the powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Hence, in the present study the neuroprotective potential of curcumin was investigated in middle cerebral artery occlusion (MCAO) induced focal cerebral IR injury. Administration of curcumin 100 and 300 mg/kg i.p. 60 min after MCAO significantly diminished infarct volume, and improved neurological deficit in a dose-dependent manner. Nissl staining showed that the neuronal injury was significantly improved after being treated with curcumin. Curcumin significantly decreased the expression of caspase-3 protein. A higher number of TUNEL-positive cells were found in the vehicle group, but they were significantly decreased in the treated group. Taken together, these results suggest that the neuroprotective potentials of curcumin against focal cerebral ischemic injury are, at least in part, ascribed to its anti-apoptotic effects.

Topics: Analysis of Variance; Animals; Brain Infarction; Caspase 3; Cell Count; Curcumin; Disease Models, Animal; DNA Fragmentation; Dose-Response Relationship, Drug; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Male; Nervous System Diseases; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury

The aim of the study was to determine the protective effect of curcumin on testicular ischemia-reperfusion (I/R) injury.. 32 male rats were divided into four groups (n = 8): group 1: control; group 2: ischemia; group 3: I/R, and group 4: I/R+CUR. Curcumin (150 mg/kg, p.o.) was administered before 30 min of reperfusion in group 4. Malondialdehyde (MDA) levels, Johnsen's testicular biopsy scores, and mean seminiferous tubule diameter measurements were evaluated in testes. In addition, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expressions were evaluated immunohistochemically.. MDA levels in control groups were significantly lower than other groups in ipsilateral and contralateral testes. Johnsen's scores in the control group were significantly higher than in other groups. MDA levels and Johnsen's scores in the I/R+CUR group were similar to the ischemia and I/R groups in ipsilateral and contralateral testes. The immunoreactivity of iNOS and eNOS were increased in I/R ipsilateral testicular groups. After I/R, iNOS and eNOS expression increased slightly in contralateral groups. Additionally, the curcumin treatment decreased iNOS and eNOS immunoreactivity in ipsilateral and contralateral testes.. The results suggest that curcumin did not protect the unilateral nor contralateral testes. This observation may depend on inhibition of iNOS and eNOS due to inhibition of the antioxidant, anti-inflammatory effects of nitric oxide.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Male; Rats; Reperfusion Injury; Spermatic Cord Torsion

Topics: Anesthetics; Animals; Anthocyanins; Antioxidants; Carbon Monoxide; Curcumin; Cytoprotection; Disease Models, Animal; Flavonoids; Glucosides; Heme Oxygenase-1; Hepatocytes; Humans; Isoflurane; Liver; Liver Diseases; Liver Transplantation; Phenols; Polyphenols; Propofol; Reperfusion Injury

Renal ischemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allograft. We investigated the effect of curcumin on ischemia-reperfusion (I/R) injury and the antioxidant effects of curcumin in rats.. Thirty rats were randomly divided into five experimental groups (control, sham, curcumin, I/R and I/R+curcumin, n=6 each). Curcumin was administered (200 mg kg(-1)) orally to curcumin and I/R+curcumin groups for 7 days. Then, the rats were subjected to bilateral renal ischemia for 45 min and followed by reperfusion for 24 h. All rats were killed and kidney function tests, serum and tissue nitric oxide (NO), protein carbonyl (PC), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were determined. Histopathological examinations were also performed.. Curcumin significantly improved the urea and cystatin C levels in I/R+curcumin group compared to I/R group (p<0.05). Reduction of serum GSH-Px was significantly improved by curcumin (p<0.001), but SOD enzyme activity did not alter (p>0.05). Treatment with curcumin also resulted in significant reduction in serum and tissue MDA, NO and PC and for tissue that were increased by renal I/R injury (p<0.001 for serum and p<0.05 for tissue, respectively). In histological examination, the rats treated with curcumin had nearly normal morphology of the kidney.. Based on our results, it can be concluded that curcumin protects the kidneys against I/R injury via its antioxidant effects.

Topics: Administration, Oral; Animals; Antioxidants; Curcumin; Disease Models, Animal; Enzyme Inhibitors; Kidney; Kidney Diseases; Male; Rats; Rats, Wistar; Reperfusion Injury; Treatment Outcome

To explore the relationship between the effects of curcumin on cerebral ischemic/reperfusion injury and immediately genic expressions of Fos, Jun and NF-kappaB in hippocampal CA1 area.. Gerbils were randomly divided into sham group (SH), ischemia/reperfusion group (I/R), curcumin group (CU) and solvent control group (SC). Forebrain ischemia was induced by occlusion of bilateral common carotid arteries. Observations were carried out in each group 15 min, 1 h, 2 h, 6 h, 1 d, 3 d, 5 d and 7 d after ischemia: open field test was used to examine the behavioral change, the apoptosis neurons in hippocampal CA1 region was counted, the expression of Fos, Jun and NF-kappaB in hippocampal CA1 was detected by SABC immunocytochemical technique.. The behavioral mark and the number of apoptosis neurons in hippocampal (CA1 region was much less in CU group than in I/R group (P < 0.01) The expression of Fos was more and the expression of Jun and NF-kappaB was less in CA1 area in CU group than in I/R group (P < 0.01).. Curcumin can significantly protect neurons against cerebral ischemia, increasing the expression Fos and decreasing the expression of Jun and NF-kappaB may be the protective mechanisms.

Topics: Animals; Apoptosis; Brain Ischemia; Curcumin; Gerbillinae; Hippocampus; Male; NF-kappa B; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Reperfusion Injury

Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Disruption of the blood-brain barrier occurs after stroke. Protection of the blood-brain barrier has become an important target of stroke interventions in experimental therapeutic. The objective of the present study was to determine whether curcumin prevents cerebral ischemia/reperfusion injury by protecting blood-brain barrier integrity. We report that a single injection of curcumin (1 and 2 mg/kg, i.v.) 30 min after focal cerebral ischemia/reperfusion in rats significantly diminished infarct volume, improved neurological deficit, decreased mortality, reduced the water content of the brain and the extravasation of Evans blue dye in ipsilateral hemisphere in a dose-dependent manner. In cultured astrocytes, curcumin significantly inhibited inducible nitric oxide synthase (iNOS) expression and NO(x) (Nitrites/nitrates contents) production induced by lipopolysaccharide (LPS)/tumor necrosis factor alpha (TNF(alpha)). Furthermore, curcumin prevented ONOO(-) donor SIN-1-induced cerebral capillaries endothelial cells damage. We concluded that curcumin ameliorates cerebral ischemia/reperfusion injury by preventing ONOO(-) mediated blood-brain barrier damage.

Topics: Animals; Astrocytes; Blood-Brain Barrier; Brain Edema; Brain Ischemia; Capillaries; Curcuma; Curcumin; Dose-Response Relationship, Drug; Endothelial Cells; Lipopolysaccharides; Male; Neuroprotective Agents; Nitrates; Nitric Oxide Synthase Type II; Nitrites; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Rhizome; Tumor Necrosis Factor-alpha

To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion (I/R) injury are associated with increasing heat shock protein 70 (Hsp70) expression and antioxidant enzyme activity.. Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C + I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin (50 mg/kg) was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C + I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver tissue NO(2)(-) + NO(3)(-), malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), nitricoxide synthase (NOS) and myeloperoxidase (MPO) activity, Hsp70 expression and apoptosis ratio.. Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusion-induced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C + I/R group, and a significant increase of MDA, NO(2)(-) + NO(3)(-) and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C + I/R group. Curcumin also decreased the activity of inducible NO synthase (iNOS) in liver after reperfusion, but had no effect on the level of endothelial NO synthase (eNOS) after reperfusion in liver. The 7 d survival rate was significantly higher in C + I/R group than in I/R group.. Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.

Topics: Alanine Transaminase; Animals; Antioxidants; Apoptosis; Aspartate Aminotransferases; Curcumin; Enzyme Activation; Enzyme Inhibitors; Gene Expression Regulation; HSP70 Heat-Shock Proteins; Liver; Male; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Peroxidase; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Warm Ischemia

Preconditioning treatments hold significant potential for improving outcomes in solid organ transplantation. Protective phenotypes can be induced using certain drugs. Curcumin is a biologically active component of turmeric and has been reported to induce stress proteins in certain cell lines, leading to cell protection. This study investigates in detail the effect of curcumin on the stress-response in human hepatocytes, in particular its effect on heme oxygenase 1 (HO-1) and its cytoprotective effect. Pretreatment with curcumin protected hepatocytes in a model of oxidative injury and this protection was mediated through HO-1. In a model of cold preservation injury, curcumin pretreatment resulted in elevation of HO-1 throughout the cold storage and rewarming period, and was cytoprotective against oxidative injury. This is the first study to demonstrate that curcumin induces HO-1 in human hepatocytes, and that the protective effects of curcumin pretreatment may have clinical potential in hepatic transplantation.

Topics: Adenosine; Allopurinol; Curcumin; Gene Expression Regulation, Enzymologic; Glutathione; Heme Oxygenase-1; Hepatocytes; HSP70 Heat-Shock Proteins; Humans; Insulin; Liver Circulation; Liver Transplantation; Organ Preservation Solutions; Polymerase Chain Reaction; Raffinose; Reperfusion Injury; Tissue Preservation; Transplantation Conditioning

Oxidative stress is believed to be implicated in the pathogenesis of postischaemic cerebral injury. Many antioxidants were shown to be neuroprotective in experimental models of cerebral ischaemia/reperfusion (I/R). The present study was designed to investigate the potential protective effects of curcumin (CUR) against I/R insult in rat forebrain. The model adopted was that of surgically-induced forebrain ischaemia, performed by means of bilateral common carotid artery occlusion (BCCAO) for 1 h, followed by reperfusion for another 1h. The effects of a single i.p. dose of CUR (50, 100 or 200 mg kg(-1)), administered 0.5 h after the onset of ischaemia, were investigated by assessing oxidative stress-related biochemical parameters in rat forebrain. CUR, at the highest dose level (200 mg kg(-1)), decreased the I/R-induced elevated xanthine oxidase (XO) activity, superoxide anion (O(2)*(-)) production, malondialdehyde (MDA) level and glutathione peroxidase (GPx), superoxide dismutase (SOD), and lactate dehydrogenase (LDH) activities. On the other hand, CUR did not affect the declined reduced glutathione (GSH) content due to I/R insult. Worth mentioning is that the activity of catalase (CAT) did not change in response to either I/R insult or drug treatment. In conclusion, CUR was found to protect rat forebrain against I/R insult. These protective effects may be attributed to its antioxidant properties and/or its inhibitory effects on xanthine dehydrogenase/xanthine oxidase (XD/XO) conversion and resultant O(2)*(-) production.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Brain Ischemia; Catalase; Curcumin; Glutathione Peroxidase; L-Lactate Dehydrogenase; Male; Malondialdehyde; Neuroprotective Agents; Prosencephalon; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Superoxide Dismutase; Superoxides; Xanthine Oxidase

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Gene Expression Regulation; Kidney; Quercetin; Rats; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; Superoxide Dismutase; Transcription, Genetic

Topics: Animals; Curcumin; Drug Synergism; Flavonoids; Graft Rejection; Immunosuppressive Agents; Ischemia; Kidney; Male; Mycophenolic Acid; Quercetin; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Skin Transplantation

Nonimmune renal injury plays an important role in acute and chronic rejection by triggering an injury response through cytokine and chemokine release. Bioflavonoids are agents with potential immunosuppressive and renoprotective properties. We studied the effects of quercetin and curcumin, two bioflavonoids, on ischemia-reperfusion in the rat.. Rats underwent 30 min of left renal pedicle occlusion with simultaneous right nephrectomy and were pretreated with quercetin or curcumin. Serial serum creatinine was measured, and renal expression of the chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1), and allograft inflammatory factor (AIF) was quantified by polymerase chain reaction.. Pretreatment with quercetin or curcumin resulted in preservation of histological integrity, with a decrease in tubular damage and interstitial inflammation. On day 2 after ischemia-reperfusion, quercetin pretreatment decreased the mean serum creatinine level from 6.5+/-1.4 to 3.3+/-0.5 mg/dl (P=0.06). On day 7, the creatinine level for control animals was 7.5+/-1.5 mg/dl, which was significantly decreased by pretreatment with quercetin, curcumin, or both together (creatinine levels: 1.6+/-1.3, 1.8+/-0.2, and 2.0+/-0.4 mg/dl, respectively; all P<0.05 vs. untreated). By semiquantitative polymerase chain reaction, RANTES, MCP-1, and AIF were detected at high levels in kidneys on day 2 but not in normal kidneys. Pretreatment with quercetin or curcumin strongly attenuated this expression.. Quercetin and curcumin reduce ischemia-reperfusion injury and its inflammatory sequelae. The bioflavonoids hold promise as agents that can reduce immune and nonimmune renal injury, the key risk factors in chronic graft loss.

Topics: Animals; Chemokine CCL2; Chemokine CCL5; Curcumin; Gene Expression; Ischemia; Kidney; Male; Quercetin; Rats; Rats, Inbred F344; Reperfusion Injury