curcumin and Acute-Disease

The aim of this review has been to describe the current state of the therapeutic potential of curcumin in acute and chronic lung injuries. Occupational and environmental exposures to mineral dusts, airborne pollutants, cigarette smoke, chemotherapy, and radiotherapy injure the lungs, resulting in acute and chronic inflammatory lung diseases. Despite major advances in treating lung diseases, until now disease-modifying efficacy has not been demonstrated for any of the existing drugs. Current medical therapy offers only marginal benefit; therefore, there is an essential need to develop new drugs that might be of effective benefit in clinical settings. Over the years, there has been increasing evidence that curcumin, a phytochemical present in turmeric (Curcuma longa), has a wide spectrum of therapeutic properties and a remarkable range of protective effects in various diseases. Several experimental animal models have tested curcumin on lung fibrosis and these studies demonstrate that curcumin attenuates lung injury and fibrosis caused by radiation, chemotherapeutic drugs, and toxicants. The growing amount of data from pharmacological and animal studies also supports the notion that curcumin plays a protective role in chronic obstructive pulmonary disease, acute lung injury, acute respiratory distress syndrome, and allergic asthma, its therapeutic action being on the prevention or modulation of inflammation and oxidative stress. These findings give substance to the possibility of testing curcumin in patients with lung diseases.

Topics: Acute Disease; Animals; Chronic Disease; Curcumin; Disease Models, Animal; Humans; Lung Diseases; Models, Biological; Phytotherapy; Protective Agents

An effective therapy to reduce the number and severity of HLA-B27-related acute anterior uveitis (AAU) recurrences represents a clinical need. Curcumin is a promising therapeutic option in various inflammatory eye diseases. To enhance its absorption and eye tissue selectivity, a phospholipidic-curcumin complex (PHBC) has been formulated (Iphytoone®, Eye Pharma S.p.A.).. This study investigates if PHBC is effective and safe to decrease the number and intensity of HLA-B27-related AAU relapses.. HLA-B27-related AAU patients were randomly divided to receive PHBC or placebo for 12 months (NCT03584724).. Compared with the previous year, the number of relapses decreased in both groups. The proportion of responders was significantly higher in the PBHC group. The severity of attacks was comparable. The study drug was well tolerated.. A beneficial effect of PHBC treatment is suggested because the proportion of responders was significantly higher in this group of patients.

Topics: Acute Disease; Anti-Inflammatory Agents; Curcumin; HLA-B27 Antigen; Humans; Recurrence; Uveitis; Uveitis, Anterior

We aimed to investigate whether nano-curcumin as an anti-inflammatory agent is effective in patients with mild and moderate AP. This study was a double-blind, parallel-arm randomized controlled trial conducted at Taleghani hospital, Tehran, Iran. Eligible subjects with a diagnosis of mild and moderate AP were randomly assigned to receive either two doses of nano-curcumin (40 mg) or placebo (control) daily for 2 weeks. The primary endpoint was gastrointestinal (GI) ward length of stay (LOS). A total of 42 patients were randomly assigned to receive either nano-curcumin (n = 21) or placebo (n = 21). Compared with placebo, nano-curcumin supplementation decreased hospital LOS (RR = 0.67, 95% CI: 0.502-0.894; p = 0.006), reduced the need for analgesics over time (OR = 0.576, 95% CI: 0.421-0.790; p = 0.001), and increased overall appetite score over the study period (β = 0.104, SE: 0.053; p = 0.049). No adverse effects or mortality were reported and there was no withdrawal during the study period. The results indicate that nano-curcumin as an adjuvant therapy is safe and may reduce GI ward LOS, analgesics requirement, and improve the overall appetite in patients with mild and moderate AP. Future multi-center trials with larger sample sizes are required to verify these findings. Clinical trial registration: www.ClinicalTrials.gov NCT04989166.

Topics: Acute Disease; Analgesics; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Iran; Pancreatitis

Acute pancreatitis (AP) is a pathology characterized by activated digestive enzymes to digest pancreatic tissue and inflammation. This study aimed to investigate the effect of curcumin, which has antioxidant and anti-inflammatory properties, on AP and its effectiveness at different doses.. Forty Sprague Dawley albino male rats, 12 weeks old, weighing 285-320 g, were used in the study. The rats were divided into control, curcumin, AP, low (100 mg/kg), and high (200mg/kg) dose curcumin groups. An experimental pancreatitis model was created with 5 g/kg L-arginine and samples (amylase, lipase, IL-1β, IL-6, TNF-alpha, CRP, histopathological) were taken after 72 hours.. There was no difference between the groups in terms of the weight of the rats (p=0.76). In the AP group, it was observed that the experimental pancreatitis model was successfully created after examination. Laboratory and histopathological examination results in the curcumin-administered groups were regressed compared to the AP group. The decrease in laboratory values was higher in the high-dose curcumin group than in the low-dose (p<0.001).. Laboratory and histopathological changes occur in AP according to clinical severity. The antioxidant and anti-inflammatory effects of curcumin are known. In the light of this information and according to the results of our study, it has been shown that curcumin is effective in the treatment of AP, and the effect of curcumin increases with the dose increase. Curcumin is effective in treating AP. However, while high-dose curcumin was more effective in inflammatory response than low-dose, it showed similar histopathological results.. Acute, Curcumin, Cytokines, Inflammation, Pancreatitis.. La pancreatite acuta (AP) è una patologia caratterizzata dall’attivazione di enzimi digestivi pancreatici in grado di determinare la digestione del tessuto pancreatico e l’infiammazione. Questo studio era finalizzato a studiare l’effetto della curcumina, che ha proprietà antiossidanti e antinfiammatorie, sull’AP e la sua efficacia a diverse dosi. Nello studio sperimentale sono stati utilizzati quaranta ratti maschi albini Sprague Dawley, di 12 settimane di età, del peso di 285-320 g. I ratti sono stati divisi in cinque gruppi: 1) di controllo; 2) trattati con curcumina; 3) grupp AP (pancreatite acuta) provocata sperimentalmente; 4) AP, trattata con curcumina a basso dosaggio (100 mg/kg); 5) AP trattata con curcumina ad alto dosaggio (200 mg/kg). È stato creato un modello sperimentale di pancreatite con 5 g/kg di L-arginina e sono stati prelevati campioni (amilasi, lipasi, IL-1β, IL- 6, TNF-alfa, CRP, istopatologico) dopo 72 ore. RISULTATI: Non c’era differenza tra i gruppi in termini di peso dei ratti (p=0,76). Nel gruppo 3 (AP), è stato osservato dopo l’esame che il modello sperimentale di pancreatite era stato creato con successo. I risultati degli esami di laboratorio e istopatologici nei gruppi trattati con curcumina sono risultati regrediti rispetto a quelli del gruppo AP. La diminuzione dei valori di laboratorio è stata maggiore nel gruppo trattato con curcumina ad alto dosaggio rispetto a quello a basso dosaggio (p<0,001). CONCLUSIONE: Cmbiamenti dei dati di laboratorio e quelli istopatologici si verificano in AP in base alla gravità clinica. Sono noti gli effetti antiossidanti e antinfiammatori della curcumina. Alla luce di queste informazioni e in base ai risultati del nostro studio, è stato dimostrato che la curcumina è efficace nel trattamento dell’AP e l’effetto della curcumina aumenta con l’aumento della dose. La curcumina è efficace nel trattamento dell’AP. Tuttavia, sebbene la curcumina ad alte dosi fosse più efficace nella risposta infiammatoria rispetto a quelle a basse dosi, ha mostrato risultati istopatologici simili.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Antioxidants; Arginine; Curcumin; Disease Models, Animal; Inflammation; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley

2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA-challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.

Topics: Acute Disease; Animals; Asthma; Bronchial Hyperreactivity; Curcumin; Cyclohexanones; Cytokines; Goblet Cells; Immunoglobulin E; Leukocytes; Male; Mice; Mice, Inbred BALB C; Ovalbumin

Multiple sclerosis (MS) is an autoimmune disease, associated with central nervous system (CNS) inflammation, demyelination, and axonal loss. Myelin, a multilayer membranous that covers nerve fibers, is essential for rapid impulse conduction. Oligodendrocytes that are generated either from CNS-resident oligodendrocyte progenitor cells (OPCs) or subventricular zone-derived neural stem cells (NSCs) are the myelinating cells of the CNS. The adult CNS maintains a certain endogenous potential to repair myelin damage. However, this process often fails as MS progresses. The origin of this failure is not fully understood, but it is likely to relate to progenitors/stem cells' arrestment in a quiescent state, incapable of generating new oligodendrocyte. Current treatments for MS are immunomodulatory or immunosuppressive medications, with little to no effect on myelin restoration. Recent studies have provided proof-of-principle that CNS remyelination can be promoted either via enhancing endogenous remyelination or by transplanting myelinating cells. Curcumin, a natural polyphenolic compound, has been shown to have therapeutic properties in several neurodegenerative diseases. Here, we investigated the effect of a curcumin nanoformulation, dendrosomal nanoparticles (DNC) on oligodendrogenesis and remyelination, both in vitro and in animal model of demyelination. We indicated that DNC enhanced oligodendrogenesis from NSCs and OPCs, in vitro in dose dependent manner. DNC also induced in vivo remyelination via promotion of oligodendrogenesis. Furthermore, DNC enhanced remyelination capacity of transplanted NSCs through promoting their survival and oligodendrogenesis capacity. Our findings suggest that DNC has significant beneficial effects in demyelinating conditions, either as mono-therapy or as being paired with transplantation approaches.

Topics: Acute Disease; Animals; Astrocytes; Cell Differentiation; Cell Lineage; Cell Proliferation; Cell Survival; Cells, Cultured; Chronic Disease; Cuprizone; Curcumin; Demyelinating Diseases; Disease Models, Animal; Embryo, Mammalian; Male; Mice, Inbred C57BL; Nanoparticles; Neural Stem Cells; Neurogenesis; Oligodendroglia; Remyelination

Curcumin was used to interfere with acute pancreatitis model rats to explore its possible mechanism. One hundred and twenty rats were randomly divided into blank group, model group, model+curcumin group, model+mock+curcumin group, model+antagonist+curcumin group and model+curcumin+LY294002 group, with 20 rats in each group. The wet/dry weight ratio of pancreatic tissue was measured and the pathological changes of pancreas were observed by HE staining. The apoptosis was detected by TUNEL staining; the levels of serum amylase, lipase, Bcl-2 and Bax were detected by ELISA, and the levels of PI3 K, Akt and p-Akt in pancreatic tissue were measured by Western blot. HE staining showed that curcumin could improve the pathological changes of pancreas and reduce the pathological score of pancreas, while ELISA results showed that curcumin could decrease the levels of amylase, lipase and Bax in peripheral serum and increase the concentration of Bcl-2. Western blot results showed that the expression levels of PI3 K and p-Akt in pancreatic tissue of model rats were up-regulated after the intervention of curcumin, and the apoptosis rate of pancreatic cells decreased in TUNEL staining. The above effects could be weakened by miR-198 antagonist and PI3 K-Akt signal pathway inhibitor LY294002. In conclusion, curcumin has an ideal effect on acute pancreatitis, and its mechanism may be mediated by miR-198-PI3 K-Akt axis.

Topics: Acute Disease; Animals; Apoptosis; Curcumin; MicroRNAs; Pancreatitis; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

Topics: Acetylcysteine; Acute Disease; Child, Preschool; Curcumin; Female; Humans; Neurodevelopmental Disorders; Obsessive-Compulsive Disorder; Syndrome; Treatment Outcome

BACKGROUND Inflammation plays an important role in initiation and development of severe acute pancreatitis (SAP). Curcumin exerts potent anti-inflammatory effects in many diseases, including acute pancreatitis. However, the specific molecular mechanisms are not clear. MATERIAL AND METHODS Intra-biliopancreatic duct injection of taurocholate was used to establish an animal model of SAP. Curcumin was administrated to animals as pre-treatments. Concentrations of cytokines in serum and ascites were measured by enzyme-linked immunosorbent assay (ELISA). A colorimetric method was used to determine the amylase activity. Western blotting was used to examine the expression levels and phosphorylation levels of proteins. Immunoprecipitation was used to assess the molecular association between apoptosis signal- regulating kinase 1 (ASK1) and thioredoxin (Trx). RESULTS Pre-treatment with curcumin reduced the concentrations of interleukin (IL6) and tumor necrosis factor (TNFα) in serum and ascites, as well as the ascites volume and amylase activity in SAP rats. Pre-treatment with curcumin reduced the expression level of TNF receptor-associated factor 1 (TRAF1), IL6, and TNFa in pancreas in SAP rats. Moreover, the phosphorylation levels of mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), MKK7, and c-Jun NH(2)-terminal protein kinase (JNK) were reduced by curcumin pre-treatment. The molecular association between ASK1 and Trx was recovered by curcumin pre-treatment. As a result, the nuclear translocation of nuclear factor kappa B (NF-κB) was suppressed in pancreases from SAP rats. CONCLUSIONS Activation of the TRAF1/ASK1/JNK/NF-κB signaling pathway is involved in the inflammation of SAP. Curcumin exerts anti-inflammatory effects by suppressing this proinflammatory pathway.

Topics: Acute Disease; Amylases; Animals; Ascites; Curcumin; Cytokines; Disease Models, Animal; Male; MAP Kinase Kinase 4; MAP Kinase Kinase Kinase 5; NF-kappa B; Pancreatitis; Rats; Rats, Sprague-Dawley; Signal Transduction; Taurocholic Acid; Thioredoxins; TNF Receptor-Associated Factor 1

Increasing the intestinal dissolution of orally administered poorly water-soluble drugs that have poor oral bioavailability to a therapeutically effective level has long been an elusive goal. In this work, an approach that can greatly enhance the oral bioavailability of a poorly water-soluble drug such as curcumin (CUR) is developed, using a "Transformers"-like nanocarrier system (TLNS) that can self-emulsify the drug molecules in the intestinal lumen to form nanoemulsions. Owing to its known anti-inflammation activity, the use of CUR in treating pancreatitis is evaluated herein. Structural changes of the TLNS in the intestinal environment to form the CUR-laden nanoemulsions are confirmed in vitro. The therapeutic efficacy of this TLNS is evaluated in rats with experimentally induced acute pancreatitis (AP). Notably, the CUR-laden nanoemulsions that are obtained using the proposed TLNS can passively target intestinal M cells, in which they are transcytosed and then transported into the pancreatic tissues via the intestinal lymphatic system. The pancreases in rats that are treated with the TLNS yield approximately 12 times stronger CUR signals than their counterparts receiving free CUR, potentially improving the recovery of AP. These findings demonstrate that the proposed TLNS can markedly increase the intestinal drug dissolution, making oral delivery a favorable noninvasive means of administering poorly water-soluble drugs.

Topics: Acute Disease; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Curcumin; Drug Carriers; Drug Liberation; Emulsions; Humans; Intestinal Absorption; Nanostructures; Pancreatitis; Rats, Wistar; Solubility; Water

The anti-inflammatory and cardioprotective properties of curcumin (Cur), a natural polyphenolic flavonoid isolated from the rhizomes of Curcuma longa, are increasingly considered to have beneficial effects on the progression of Chagas heart disease, caused by the protozoan parasite Trypanosoma cruzi.. To evaluate the effects of oral therapy with Cur on T. cruzi-mediated cardiovasculopathy in acutely infected mice and analyse the in vitro response of parasite-infected human microvascular endothelial cells treated with this phytochemical.. Inflammation of heart vessels from Cur-treated and untreated infected mice were analysed by histology, with benznidazole (Bz) as the reference compound. Parasitaemia was monitored by the direct method. Capillary permeability was visualised by Evans-blue assay. Myocardial ET-1, IL-6, and TNF-α mRNA expressions were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Microvascular endothelial HMEC-1 cells were infected in vitro with or without addition of Cur or Bz. Induction of the Ca2+/NFAT pathway was assessed by fluorometry, immunoblotting, and reporter assay.. Oral Cur therapy of recently infected mice reduced inflammatory cell infiltration of myocardial arteries without lowering parasite levels. Compared to that of the phosphate-buffered saline-receiving group, hearts from Cur-treated mice showed significantly decreased vessel inflammation scores (p < 0.001), vascular permeabilities (p < 0.001), and levels of IL-6/TNF-α (p < 0.01) and ET-1 (p < 0.05) mRNA. Moreover, Cur significantly (p < 0.05 for transcript; p < 0.01 for peptide) downregulated ET-1 secretion from infected HMEC-1 cells. Remarkably, Cur addition significantly (p < 0.05 at 27.0 μM) interfered with T. cruzi-dependent activation of the Ca2+/NFATc1 signalling pathway that promotes generation of inflammatory agents in HMEC-1 cells.. Oral treatment with Cur dampens cardiovasculopathy in acute Chagas mice. Cur impairs the Ca2+/NFATc1-regulated release of ET-1 from T. cruzi-infected vascular endothelium. These findings identify new perspectives for exploring the potential of Cur-based interventions to ameliorate Chagas heart disease.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Capillary Permeability; Cells, Cultured; Chagas Cardiomyopathy; Curcumin; Disease Progression; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Fluorescent Dyes; Interleukin-6; Male; Mice, Inbred C57BL; NFATC Transcription Factors; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Trypanosoma cruzi; Tumor Necrosis Factor-alpha

Acute pancreatitis (AP) is a serious inflammatory disorder of the pancreas with considerable mortality. The clinical therapy is hampered due to lack of any approved drug for AP. In this study, we developed curcumin (cur)-loaded poly (lactic-co-glycolic acid) cur microparticles (CuMPs) for sustained release. CuMPs were prepared by emulsion solvent evaporation method and characterized for shape, size, compatibility, and entrapment efficiency. The in vitro drug release and in vivo pharmacokinetic studies confirmed sustained release pattern of cur from CuMPs. The pharmacodynamic study was conducted in cerulein induced AP model. Prophylactic treatment was planned with single dose of CuMPs (equivalent to 7.5 mg/kg of cur) and compared with free cur given orally (100 mg/kg) and intraperitoneally (7.5 mg/kg) daily for 7 days. Interestingly, the effects of CuMPs were superior compared to the free drug administered either orally or intraperitoneally through repeated administrations. CuMPs showed significant decrease of serum amylase and lipase levels, oxidative and nitrosative stress was also significantly decreased. Moreover, CuMPs impressively decreased inflammatory cytokines. Our results may pave a way to propose similar strategy for many of promising natural products to combat several oxidative stress-mediated disorders via sustained release microparticle approaches.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Ceruletide; Curcumin; Cytokines; Delayed-Action Preparations; Drug Liberation; Male; Mice; Oxidative Stress; Pancreas; Pancreatitis; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley

The aim of this study was to prepare curcumin nanoemulsion (CR-NE) to solve the problems associated with poor water solubility and low bioavailability of CR and to test its efficiency in the treatment of acute and chronic toxoplasmosis in mouse models.. The mean particle size and zeta potential of CR-NE included 215.66±16.8 nm and -29.46±2.65 mV, respectively, and were stable in particle size after a three freeze-thaw cycle. In acute phase experiment, the survival time of mice infected with RH strain of. Results from the current study showed the potential of CR-S and CR-NE in treatment of acute and chronic toxoplasmosis in mouse models for the first time. However, CR-NE was more efficient than CR-S, and it seems that CR-NE has a potential formula for the treatment of acute and chronic toxoplasmosis, especially in those with latent bradyzoites in brain.

Topics: Acute Disease; Animals; Brain; Chronic Disease; Curcumin; Disease Models, Animal; Emulsions; Female; Gene Expression Regulation; Mice, Inbred BALB C; Nanoparticles; Toxicity Tests; Toxoplasma; Toxoplasmosis

Substantial evidence supports the neurochemical vulnerability to lead (Pb) as one of the most potent neurotoxic heavy metals. In the present study, we aimed to assess: (i) The subcommissural organ (SCO) responsiveness as a secretory circumventricular organ to chronic and acute Pb intoxication together with its serotoninergic innervation. (ii) The possible restorative effect of curcumin against Pb intoxication under the same pathological conditions. We used immunohistochemistry with antibodies against Reissner's fiber and serotonin [5-hydroxytryptophan (5-HT)] in Wistar rats following chronic as well as acute Pb administration, respectively, at 25 mg/kg intraperitoneally for 3 days and 0.3% in drinking water from the intrauterine stage until 2 months of adult age. Our data showed a significant decrease in Reissner's fiber material immunoreactivity concomitant with an overall increased 5-HT innervation of the SCO and the ventricular borders. Coadministration of curcumin (50 mg/kg body weight) restores this impairment by reversing the effect of chronic and acute Pb on the secretory activity and the 5-HTergic innervation of the SCO. The investigation showed, on the one hand, the involvement of the SCO in the response to heavy metals, especially Pb, and on the other, the beneficial corrector role of curcumin. As a part of the circumventricular organ, known as a privileged area of brain-blood exchanges, the SCO may play a key role in the mechanism of brain defense against heavy metal neurotoxicity in rats.

Topics: Acute Disease; Animals; Chronic Disease; Curcumin; Disease Models, Animal; Female; Immunohistochemistry; Lead Poisoning, Nervous System; Male; Neuroprotective Agents; Rats, Wistar; Serotonin; Subcommissural Organ

Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.

Topics: Acute Disease; Animals; Chagas Disease; Curcumin; Cytokines; Female; Liver; Mice; Myocardium; Nitroimidazoles; Parasitemia; Transaminases; Trypanocidal Agents; Trypanosoma cruzi

We investigated the possible beneficial effects of curcumin (CMN) in the treatment of sinusitis. An experimentally induced sinusitis model was created in rats, and the results were evaluated histologically. Thirty-two healthy, female Sprague Dawley rats weighing 270 to 310 g each, were randomly divided into four groups. Group 1 was the control group. In Groups 2 to 4, experimentally induced acute sinusitis was developed, and the rats in those groups were given saline, sulbactam-ampicillin, and CMN, respectively, for 10 days. Then all rats were dissected, and samples of sinus mucosa were taken. Histologic examination was performed via light microscopy. In the sinusitis + antibiotic group, values of inflammation, vascular congestion, vascular dilatation, and subepithelial glandular atrophy were significantly higher; and values of mucosal damage and cilia loss, and hyperplasia of goblet cells, were not significantly different from those in the control group. In the sinusitis + CMN group, values of inflammation, vascular congestion, and vascular dilatation were significantly higher; and values of mucosal damage and cilia loss, hyperplasia of goblet cells, and subepithelial glandular atrophy were not significantly different from those of the control group. Histologic examination revealed that in the sinusitis + CMN group, a nearly normal appearance of the epithelial tissue and reduced cellular inflammation in connective tissue were observed. Minimal vascular congestion in connective tissue remained. The efficacy of CMN in acute sinusitis may be related to its potent anti-inflammatory effects on modulation of various inflammatory cytokines. When low side effects are taken into account, CMN therapy may be a promising option in the treatment of acute sinusitis.

Topics: Acute Disease; Ampicillin; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Female; Nasal Mucosa; Random Allocation; Rats; Rats, Sprague-Dawley; Sinusitis; Sulbactam; Treatment Outcome

Curcumin is a phenolic product isolated from the rhizome of Curcuma longa and has protective effects on inflammatory diseases. Here we investigated the protective effect of curcumin in acute Propionibacterium acnes (P. acnes)-induced inflammatory liver injury. C57BL/6 mice were primed with P. acnes followed by LPS challenge to induce fulminant hepatitis. Curcumin or vehicle control was administered perorally by gavage once daily starting 2days before P. acnes priming. We found that curcumin significantly improved mouse mortality. Then, to investigate the underlying mechanisms of curcumin in this acute inflammatory liver injury model, we primed C57BL/6 mice with P. acnes only. We found that curcumin treatment attenuated P. acnes-induced liver injury as evidenced by decreased production of ALT. In addition, curcumin treatment reduced the production of proinflammatory cytokines such as TNF-α and IFN-γ, accompanied by reduced hepatocyte apoptosis. Furthermore, curcumin treatment significantly reduced HMGB1 cytoplasmic translocation and expression by down-regulating acetylation of lysine. Taken together, our results suggest that curcumin protects mice from P. acnes-induced liver injury through reduction of HMGB1 cytoplasmic translocation and expression.

Topics: Acetylation; Acute Disease; Animals; Apoptosis; Curcuma; Curcumin; Gram-Positive Bacterial Infections; Hepatocytes; HMGB1 Protein; Interferon-gamma; Liver; Liver Failure, Acute; Mice; Mice, Inbred C57BL; Propionibacterium acnes; Protein Transport; Rhizome; Tumor Necrosis Factor-alpha

The purpose of this study was investigating the effects of curcumin on the histological changes and functional recovery following spinal cord injury (SCI) in a rat model. Following either sham operation or SCI, 36 male Sprague-Dawley rats were distributed into three groups: sham group, curcumin-treated group, and vehicle-injected group. Locomotor function was assessed according to the Basso, Beattie, and Bresnahan (BBB) scale in rats who had received daily intraperitoneal injections of 200 mg/kg curcumin or an equivalent volume of vehicle for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation. BBB scores were significantly higher in rats receiving curcumin than receiving vehicle (P < 0.05). The cavity volume was significantly reduced in the curcumin group as compared to the control group (P = 0.039). Superoxide dismutase (SOD) activity was significantly elevated in the curcumin group as compared to the vehicle group but was not significantly different from the sham group (P < 0.05, P > 0.05, respectively) at one and two weeks after SCI. Malondialdehyde (MDA) levels were significantly elevated in the vehicle group as compared to the sham group (P < 0.05 at 1 and 2 weeks). MDA activity was significantly reduced in the curcumin group at 2 weeks after SCI when compared to the vehicle group (P = 0.004). The numbers of macrophage were significantly decreased in the curcumin group (P = 0.001). This study demonstrated that curcumin enhances early functional recovery after SCI by diminishing cavitation volume, anti-inflammatory reactions, and antioxidant activity.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Drug Evaluation, Preclinical; Injections, Intraperitoneal; Lipid Peroxidation; Locomotion; Male; Malondialdehyde; Neuroprotective Agents; Phytotherapy; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Superoxide Dismutase

We investigated the effect of curcumin (CMN) in the treatment of experimentally induced acute otitis media (AOM) in rats.. Thirty-two Sprague-Dawley female rats were used, yielding 64 temporal bones. Group 1 was the control group. For groups 2 to 4, AOM was induced experimentally, and saline, antibiotics (sulbactam-ampicillin), or CMN were administered for 14 days to groups 2, 3, and 4, respectively. During the histological examination, thickening of the tympanic membrane, damage to the epithelium, inflammation, and sclerosis were evaluated.. The AOM+antibiotic and AOM+CMN groups exhibited reduced histological damage compared with the AOM+saline group. No significant differences in thickening of the tympanic membrane or damage to the epithelium or inflammation were observed between the AOM+antibiotic and the AOM+CMN groups. However, the sclerosis values of the AOM+CMN group were significantly lower than those of the AOM+antibiotic group.. CMN treatment resulted in similar effects on the experimentally induced AOM model as did the antibiotic treatment. The efficacy of this treatment may be related to its effects on the production of various inflammatory cytokines. In light of the worldwide increase in antibiotic resistance and the mild side effects of CMN, we suggest that CMN therapy may be a promising option in AOM treatment.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Curcumin; Female; Otitis Media; Rats; Rats, Sprague-Dawley; Tympanic Membrane

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

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

After acute spinal cord injury (SCI), a large number of axons are lost by a cascade of pathophysiological events known as a secondary injury. The main aim of the current study was to investigate the potential neuroprotective effects of curcumin on lipid peroxidation (LPO), neurological function, and ultrastructural findings after SCI.. Forty adult Wistar albino rats were randomized into five groups: control, SCI alone (50 g/cm weight drop), methylprednisolone sodium succinate (MPSS) (30 mg/kg), curcumin + dimethyl sulfoxide (DMSO) (300 mg/kg), and DMSO alone (0.1 mg/kg).. Administration of curcumin significantly decreased LPO in first 24 hours. However, there were no differences in the neurological scores of injured rats between the medication groups and the control group. Curcumin was more effective than DMSO and MPSS in reducing LPO, whereas DMSO was more effective than curcumin and MPSS in minimizing ultrastuctural changes. The results of this study indicate that curcumin exerts a beneficial effect by decreasing LPO and may reduce tissue damage.. Since ultrastructural and neurological findings does not support biochemical finding, our findings do not exclude the possibility that curcumin has a protective effect on the spinal cord ultrastructure and neurological recovery after SCI. A combination of curcumin with other vehicle may also have a considerable synergy in protecting spinal cord.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Female; Lipid Peroxidation; Malondialdehyde; Methylprednisolone Hemisuccinate; Mitochondria; Nerve Fibers, Myelinated; Neuroprotective Agents; Rats; Rats, Wistar; Recovery of Function; Spinal Cord; Spinal Cord Injuries

Both fish oil (FO) and curcumin have potential as anti-tumour and anti-inflammatory agents. To further explore their combined effects on dextran sodium sulphate (DSS)-induced colitis, C57BL/6 mice were randomised to four diets (2 × 2 design) differing in fatty acid content with or without curcumin supplementation (FO, FO+2 % curcumin, maize oil (control, MO) or MO+2 % curcumin). Mice were exposed to one or two cycles of DSS in the drinking-water to induce either acute or chronic intestinal inflammation, respectively. FO-fed mice exposed to the single-cycle DSS treatment exhibited the highest mortality (40 %, seventeen of forty-three) compared with MO with the lowest mortality (3 %, one of twenty-nine) (P = 0·0008). Addition of curcumin to MO increased (P = 0·003) mortality to 37 % compared with the control. Consistent with animal survival data, following the one- or two-cycle DSS treatment, both dietary FO and curcumin promoted mucosal injury/ulceration compared with MO. In contrast, compared with other diets, combined FO and curcumin feeding enhanced the resolution of chronic inflammation and suppressed (P < 0·05) a key inflammatory mediator, NF-κB, in the colon mucosa. Mucosal microarray analysis revealed that dietary FO, curcumin and FO plus curcumin combination differentially modulated the expression of genes induced by DSS treatment. These results suggest that dietary lipids and curcumin interact to regulate mucosal homeostasis and the resolution of chronic inflammation in the colon.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Colitis; Colon; Curcumin; Cytokines; Dextran Sulfate; Dietary Supplements; Fish Oils; Gene Expression Profiling; Gene Expression Regulation; Intestinal Mucosa; Irritants; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Oligonucleotide Array Sequence Analysis; Random Allocation; Survival Analysis

Curcumin is used anecdotally as an herb in traditional Indian and Chinese medicine. In the present study, the effects and possible mechanism of curcumin in experimental autoimmune myocarditis (EAM) rats were further investigated. They were divided randomly into a treatment and vehicle group, and orally administrated curcumin (50 mg/kg/day) and 1% gum arabic, respectively, for 3 weeks after myosin injection. The results showed that curcumin significantly suppressed the myocardial protein expression of inducible nitric oxide synthase (iNOS) and the catalytic subunit of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase. In addition, curcumin significantly decreased myocardial endoplasmic reticulum (ER) stress signaling proteins and improved cardiac function. Furthermore, curcumin significantly decreased the key regulators or inducers of apoptosis. In summary, our results indicate that curcumin has the potential to protect EAM by modulating cardiac oxidative and ER stress-mediated apoptosis, and provides a novel therapeutic strategy for autoimmune myocarditis.

Topics: Acute Disease; Animals; Apoptosis; Autoimmune Diseases; Curcumin; Disease Models, Animal; Endoplasmic Reticulum Stress; Male; Myocarditis; Myocardium; Oxidative Stress; Random Allocation; Rats; Rats, Inbred Lew

Curcuma longa (CL) has been reported to possess a variety of pharmacological activities. However, the effects of CL on acute pancreatitis (AP) have not yet been determined. To this end, we examined the effects of CL on cerulein-induced AP. Cell viability and cytokine productions were measured in pancreatic acini. Mice were divided into 3 groups: i) Normal group, ii) normal saline-treated group, iii) group treated with CL at a dose of 0.05, 0.1, 0.5 and 1 g/kg. CL was administered orally to mice for 7 days. The mice were intraperitoneally injected with the stable cholecystokinin analogue, cerulein (50 μg/kg), every hour for a total of 6 h. The mice were sacrificed 6 h after the completion of the cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphological examination, measurement of tissue myeloperoxidase activity, as well as the level of cytokines and heme oxygenase-1 (HO-1). The CL treatment reduced cerulein-induced cell death and cytokine production in pancreatic acini. The administration of CL significantly ameliorated the severity of pancreatitis and pancreatitis-associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization, necrosis, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as interleukin (IL)-1ß and -6 and tumor necrosis factor (TNF)-α. In order to identify the regulatory mechanism of CL on cerulein-induced pancreatitis, we examined the level of HO-1 in the pancreas. We found that the administration of CL induced HO-1. Our results suggest that CL plays a protective role in the development of AP and pancreatitis-associated lung injury.

Topics: Acute Disease; Animals; Ceruletide; Curcuma; Cytokines; Female; Heme Oxygenase-1; Lung Injury; Mice; Mice, Inbred C57BL; Pancreas; Pancreatitis; Peroxidase; Plant Extracts

In this study, we assessed the immunosuppressive potential of curcumin, a pharmacologically safe and cost-effective naturally occurring polyphenolic phytochemical, on the induction of Th1 cytokines that are frequently overexpressed in patients experiencing rejection after renal transplant.. Peripheral blood lymphocytes obtained from 68 renal transplant recipients and 17 healthy controls were treated with curcumin before stimulation with phorbol myristate acetate and were analyzed with flow cytometry for interferon-alpha and interleukin 4 positive cells.. Patients experiencing acute rejection exhibited a high level of interferon-alpha (38.3% +/- 11.2%) and a low level of interleukin 4 (4.2% +/- 2.0%) in their activated peripheral blood lymphocytes. The use of curcumin dose-dependently decreased interferon-alpha induction in cultures from healthy controls (28.1% +/- 4.8%-10.7% +/- 5.3%, P < .001), patients experiencing acute rejection (38.3%-18.3%, P < .001), and those experiencing chronic rejection (40.6%-12.9%, P = .01) when compared with corresponding untreated cultures. In contrast, curcumin exerted only a marginal effect on interleukin 4 expression. Interestingly, curcumin was found to inhibit nuclear factor kappa beta activation by blocking the degradation of the inhibitory unit I kappa B alpha. We also noted the synergistic inhibitory effect of in vitro treatment with curcumin in combination with cyclosporine on the peripheral blood lymphocytes of patients experiencing acute rejection.. These data provide a rationale for the use of curcumin as an affordable, pharmacologically safe, adjuvant immunosuppressant when used with cyclosporine and suggest that curcumin can effectively suppress Th1 cytokine induction after renal transplant.

Topics: Acute Disease; Adult; Case-Control Studies; Cells, Cultured; Chronic Disease; Curcumin; Cyclosporine; Dose-Response Relationship, Drug; Female; Flow Cytometry; Graft Rejection; Humans; Immunosuppressive Agents; India; Interferon-gamma; Interleukin-4; Kidney Transplantation; Living Donors; Lymphocytes; Male; Middle Aged; Mitogens; NF-kappa B; Tetradecanoylphorbol Acetate; Time Factors; Young Adult

Acute myeloid leukaemia (AML) continues to present demanding treatment challenges, as in general the prognosis for long-term survival remains dire for the patients. Natural plant-derived substances with antileukemic properties offer new treatment possibilities or may act as by-stander therapy. Their molecular mechanisms of action are often not entirely clear, limiting theory-directed screening and application strategies. The plant substance curcumin is a known activator of the transcription factor aryl hydrocarbon receptor (AhR), and has well-documented antileukemic effects. The AhR regulates cell processes, including cell cycle and apoptosis. We ask here whether direct AhR-activation by curcumin contributes to its antileukemic/apoptotic potential.. The induction of caspases 3/7, 8, and 9, the breakdown of mitochondrial transmembrane potential, the BCL-2/BAX ratio, and the DNA content of cells were measured as indicators of apoptosis. In addition, the induction of cell cycle inhibitors p21 and p27 were assessed.. While triggering of AhR signalling by curcumin in HL-60 cells was confirmed, induction of the above apoptosis parameters was not blocked by two AhR antagonists, alpha-naphtoflavone (alphaNF) and 3'-methoxy-4'nitroflavone (MNF). Only a moderate (20%) AhR-dependent induction of caspases 3/7 was detectable. Interestingly, transcriptional changes induced by curcumin and by anticarcinogenic 1,25-dihydroxy vitamin D3 overlapped by one third.. We conclude that AhR is only marginally involved in the antileukemic effects of its ligand curcumin.

Topics: Acute Disease; Apoptosis; Benzoflavones; Caspases; Cell Cycle; Curcumin; Enzyme Activation; Flavonoids; HL-60 Cells; Humans; Isoenzymes; Leukemia, Myeloid; Ligands; Receptors, Aryl Hydrocarbon; Reverse Transcriptase Polymerase Chain Reaction

To investigate the effect of curcumine on acute lung injury induced by oleic acid in rat and the possible mechanism of action. The rats were divided into 6 groups randomly: normal group, control group, curcumine groups (5, 10, 20 mg x kg(-1)) and dexamethasone group (1 mg x kg(-1)). During the experiment, acute lung injury was induced by oleic acid in rat. The changes of dynamic lung compliance were recorded by anrise 2005 pulmonary function test apparatus, light microscope was used to examine histological changes and lung index as well as wet to dry weight ratio was calculated by weighting method. Lung vascular permeability and protein level in BALF were detected by ultraviolet spectrophotometry, and the concentrations of TNF-alpha, IL-6 and IL-10 in BALF were measured by enzyme linked immunosorbent assay (ELISA). The result showed that the changes of pulmonary compliance were inhibited and pulmonary function was improved by curcumine. The OA-induced elevation of lung index was restrained, as well as wet to dry weight ratio, lung vascular permeability, protein level, TNF-alpha (250.4 +/- 21.6 vs. 172.53 +/- 14.88, 122.2 +/- 10.98, 108.69 +/- 3.39) ng x L(-1), IL-6 (763.6 +/- 88.33 vs. 207.41 +/- 15.55, 172.13 +/- 21.91, 142.92 +/- 4.32) ng x L(-1) in BALF in curcumine groups, IL-10 (98.90 +/- 2.99 vs. 208.44 +/- 16.30, 218.43 +/- 6.23, 252.70 +/- 20.58) ng x L(-1) in BALF was increased, respectively significantly. Light microscope findings shown that the impairment in curcumine groups was far less severe than that in model groups. Pretreatment of curcumine showed beneficial effect on acute lung injury induced by oleic acid in rats. The mediation of both proinflammatory factor and anti-inflammatory factor by curcumine may be involved in mechanism of action of curcumine effects.

Topics: Acute Disease; Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Drugs, Chinese Herbal; Humans; Male; Oleic Acids; Random Allocation; Rats; Rats, Sprague-Dawley

Summary Inflammatory cytokines have been demonstrated to play an important role in the induction and severity of acute pancreatitis (AP) in the recent studies. The aim of this study was to investigate the effects of curcumin on inflammatory cytokines, such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 in the late phase of AP. The study was conducted on 40 male Wistar Albino rats. The animals were divided randomly into four equal groups. AP was induced by the infusion of 3% sodium taurocholate into the biliopancreatic duct (in groups I and II). Starting on day 20 prior to the induction of AP, rats in group I received daily dose of 100 mg/kg of curcumin, dissolved in 9% ethanol via an intragastric tube. The same procedure was repeated for 6 days following the onset of AP. Group III was infused only on saline solution. Group IV (curcumin control group) received 9% ethanol via an intragastric tube, during the experimental period (totally 26 days). All the animals were sacrificed on day 6 after the collection of blood samples and serum TNF-alpha and IL-6 levels were determined. Tissue samples were taken from pancreas, mesenteric lymph nodes, liver, lungs, spleen and the kidneys for histopathological evaluation. Serum TNF-alpha and IL-6 levels in the group, which received curcumin (group I), were determined to be significantly lower than those of the untreated group (group II) (P<0.05). No statistically significant difference was detected in terms of total histopathological scores in the treatment group versus untreated group. Curcumin has been shown to markedly reduce serum TNF-alpha and IL-6 levels in the late phase of AP, but failed in the prevention of tissue injury.

Topics: Acute Disease; Analysis of Variance; Animals; Curcumin; Immunohistochemistry; Interleukin-6; Male; Pancreas; Pancreatitis, Acute Necrotizing; Random Allocation; Rats; Rats, Wistar; Treatment Outcome; Tumor Necrosis Factor-alpha

When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1(MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CML). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of 10 microM curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.

Topics: Acute Disease; Adolescent; Age Factors; Antineoplastic Agents; Bone Marrow; Cell Survival; Child, Preschool; Curcumin; Female; Gene Expression Regulation, Leukemic; Genes, MDR; Humans; Infant; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

To evaluate the safety of Curcuma aromatica oil gelatin microspheres (CAO-GMS) infused via hepatic artery against primary liver cancer.. The safety of CAO-GMS was evaluated in view of its acute toxicity in rats, long-term toxicity in Beagle dogs and general pharmacology in rats and mongrel dogs.. The 50% lethal dose (LD50) of CAO-GMS infused via the hepatic artery was 17.19 mg/kg, and the serum biochemical indices of dying rats after the administration changed markedly while those of survived rats did not. Subsequent pathological examination of the tissues from the dead rats indicated improper embolism. Similar edema and small necrotic foci in the hepatic lobule were found in the hepatic tissue of rats receiving 10 and 5 mg/kg CAO-GMS and GMS 60 d after the last administration, while not in the rats of the blank control group, indicating that microspheres infused via the hepatic artery may induce irreversible liver damage dose-dependently. General pharmacological study showed that the activities (posture and gait), respiration frequency, blood pressure or heart rate of the dogs were not affected by CAO-GMS, nor were salivation, tremor or pupil changes of the rats observed or their balancing ability compromised, suggesting CAO-GMS infused via the hepatic artery did not significantly affect the nervous, respiratory and cardiovascular systems.. CAO-GMS embolization administered via the hepatic artery is safe but undesired embolization induced by vascular variation should be given due attention in its clinical application. Individualized embolization dosage and super-selective catheterization technique are recommended to avoid undesired embolism and reduce complications.

Topics: Acute Disease; Animals; Blood Pressure; Chemoembolization, Therapeutic; Curcuma; Dogs; Drugs, Chinese Herbal; Female; Gelatin; Heart Rate; Hepatic Artery; Injections, Intra-Arterial; Liver; Liver Neoplasms; Male; Microspheres; Nervous System; Plant Oils; Rats; Rats, Sprague-Dawley; Respiration

We evaluated the radioprotective action of curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] extracted from Curcuma longa LINN against the acute and chronic effects and the mortality induced by exposure to radiation using female rats.. For the assay of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine, a marker for acute effects, Wistar-MS virgin rats were fed the basal diet with exposure at 0 or 3 Gy to gamma-rays from a 60Co source as the control. Rats in the experimental groups received whole-body irradiation with 3 Gy and were fed a diet containing 1% (wt/wt) curcumin for 3 days before and/or 2 days after irradiation. The urine was collected for a 24-h period between 1 and 2 days after irradiation. Urine samples were used to determine the 8-OHdG level using an enzyme-linked immunosorbent assay and the creatinine level by a modified Jaffé reaction. For long-term effects, rats at Day 17 of pregnancy were fed a diet containing curcumin for 3 days before and/or 3 days after irradiation with 1.5 Gy, and received a pellet of diethylstilbestrol as the promoter. The rats were examined for mammary and pituitary tumors for 1 year. To determine survival, virgin rats received whole-body irradiation with 9.6 Gy and were fed a diet containing curcumin for 3 days before and/or 3 days after irradiation. After irradiation, all rats were assessed daily for survival for 30 days.. Acutely in virgin rats irradiated with 3 Gy, the creatinine-corrected concentration and total amount of 8-OHdG in the 24-h urine samples were higher (approximately 1.3-fold) than the corresponding values in the nonirradiated controls. Adding curcumin to the diet for 3 days before and/or 2 days after irradiation reduced the elevated 8-OHdG levels by 50-70%. The evaluation of the protective action of curcumin against the long-term effects revealed that curcumin significantly decreased the incidence of mammary and pituitary tumors. However, the experiments on survival revealed that curcumin was not effective when administered for 3 days before and/or 3 days after irradiation (9.6 Gy).. These findings demonstrate that curcumin can be used as an effective radioprotective agent to inhibit acute and chronic effects, but not mortality, after irradiation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Disease; Animals; Biomarkers; Carcinogens; Creatinine; Curcumin; Deoxyguanosine; Diethylstilbestrol; Drug Evaluation, Preclinical; Female; Mammary Neoplasms, Experimental; Neoplasms, Radiation-Induced; Pituitary Neoplasms; Pregnancy; Radiation-Protective Agents; Rats; Rats, Wistar; Whole-Body Irradiation

Transcription of type 1 human immunodeficiency virus (HIV-1) provirus is governed by the viral long terminal repeat (LTR). Drugs can block HIV-1 replication by inhibiting activity of its LTR. We report that topotecan, beta-lapachone, and curcumin are potent and selective inhibitors of HIV-1 LTR-directed gene expression, at concentrations that have minor effects on cells. At these concentrations, each drug inhibited p24 antigen production in cells either acutely or chronically infected with HIV-1. Their target is transcriptional function of the LTR.

Topics: Acute Disease; Antiviral Agents; Camptothecin; Cells, Cultured; Chronic Disease; Curcumin; Gene Expression Regulation, Viral; HIV Infections; HIV Long Terminal Repeat; HIV-1; In Vitro Techniques; Naphthoquinones; RNA, Viral; Topotecan; Virus Replication