ubiquinone and 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; 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Ischemia/reperfusion (IR) injury is a central component in the pathogenesis of several diseases and is a leading cause of morbidity and mortality in the western world. Subcellularly, mitochondrial dysfunction, characterized by depletion of ATP, calcium-induced opening of the mitochondrial permeability transition pore, and exacerbated reactive oxygen species (ROS) formation, plays an integral role in the progression of IR injury. Nitric oxide (NO) and more recently nitrite (NO(2)(-)) are known to modulate mitochondrial function, mediate cytoprotection after IR and have been implicated in the signaling of the highly protective ischemic preconditioning (IPC) program. Here, we review what is known about the role of NO and nitrite in cytoprotection after IR and consider the putative role of nitrite in IPC. Focus is placed on the potential cytoprotective mechanisms involving NO and nitrite-dependent modulation of mitochondrial function.

Topics: Animals; Cytochromes c; Cytoprotection; Glutathione; Humans; Ischemic Preconditioning; Mice; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Mitochondrial Proton-Translocating ATPases; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Protein Processing, Post-Translational; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Ubiquinone

Mitochondria have long been known to play a critical role in maintaining the bioenergetic status of cells under physiological conditions. Mitochondria produce large amounts of free radicals, and mitochondrial oxidative damage can contribute to a range of degenerative conditions including cardiovascular diseases (CVDs). Although the molecular mechanisms responsible for mitochondrion-mediated disease processes are not correctly understood, oxidative stress seems to play an important role. Consequently, the selective inhibition of mitochondrial oxidative damage is an obvious therapeutic strategy. This review considers the process of CVD from a mitochondrial perspective and provides a summary of the following areas: reactive oxygen species (ROS) production and its role in pathophysiological processes such as CVD, currently available antioxidants and possible reasons for their efficacy and inefficacy in ameliorating oxidative stress-mediated diseases, and recent developments in mitochondria-targeted antioxidants that concentrate on the matrix-facing surface of the inner mitochondrial membrane. These mitochondrion-targeted antioxidants have been developed by conjugating the lipophilic triphenylphosphonium cation to antioxidant moieties such as ubiquinol. These compounds pass easily through biological membranes and, due to their positive charge, they accumulate several-hundred-fold within mitochondria. In this way they protect against mitochondrial oxidative damage and show potential as a future therapy for CVDs.

Topics: Antioxidants; Cardiovascular Diseases; Diabetes Mellitus; Endothelium, Vascular; Humans; Membrane Potentials; Mitochondria; Mitochondrial Diseases; Nitric Oxide; Organophosphorus Compounds; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Risk Factors; Ubiquinone

The cessation of blood flow followed by a reperfusion period results in severe damages to cell structures. This induces a complex cascade of events involving, more particularly, a loss of energy, an alteration of ionic homeostasis promoting H(+) and Ca(2+) build up and the generation of free radicals. In this context, mitochondria are highly vulnerable and play a predominant role in the cell signaling leading from life to death. This is why, recently, efforts to find an effective therapy for ischemia-reperfusion injury have focused on mitochondria. This review summarizes the pharmacological strategies which are currently developed and the potential mitochondrial targets which could be involved in the protection of cells.

Topics: Acetanilides; Animals; Antioxidants; Coenzymes; Drug Delivery Systems; Enzyme Inhibitors; Humans; Ion Channels; Membrane Proteins; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Piperazines; Potassium Channels; Ranolazine; Reperfusion Injury; Sodium-Calcium Exchanger; Trimetazidine; Ubiquinone; Vasodilator Agents

Astrocytes, the most abundant glial cell type in the brain, are considered to have physiological and pathological roles in neuronal activities. We found that reperfusion of cultured astrocytes after Ca2+ depletion causes Ca2+ overload followed by delayed cell death and the Na(+)-Ca2+ exchanger in the reverse mode is responsible for this Ca(2+)-mediated cell injury (Ca2+ paradox injury). The Ca2+ paradox injury of cultured astrocytes is considered to be an in vitro model of ischemia/reperfusion injury, since a similar paradoxical change in extracellular Ca2+ concentration is reported in ischemic brain tissue. This review summarizes the mechanisms underlying the Ca(2+)-mediated injury of astrocytes and the protective effects of drugs against Ca2+ reperfusion injury. This study shows that Ca2+ reperfusion injury of astrocytes is accompanied by apoptosis as evidenced by DNA fragmentation and nuclear condensation. Calpain, reactive oxygen species, calcineurin, caspase-3, and NF-kappa B are involved in Ca2+ reperfusion-induced delayed apoptosis of astrocytes. Several drugs including CV-2619, T-588 and ibudilast protect astrocytes against the delayed apoptosis. CV-2619 prevents astrocytes from the delayed apoptosis by production of nerve growth factor, resulting in an activation of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3 (PI3) kinase signal pathways. The protective effect of T-588 is mainly mediated by an activation of MAP/ERK signal cascade. Moreover, ibudilast prevents the Ca2+ reperfusion-induced delayed apoptosis of astrocytes via cyclic GMP signaling pathway. Further studies in this system will contribute to the development of new drugs that attenuate ischemia/reperfusion injury via modulation of astrocytes.

Topics: Animals; Apoptosis; Astrocytes; Benzoquinones; Calcium; Cells, Cultured; Diethylamines; Humans; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase Kinases; Reperfusion Injury; Sodium-Calcium Exchanger; Thiophenes; Ubiquinone

The clinical experience in cardiology with CoQ10 includes studies on congestive heart failure, ischemic heart disease, hypertensive heart disease, diastolic dysfunction of the left ventricle, and reperfusion injury as it relates to coronary artery bypass graft surgery. The CoQ10-lowering effect of HMG-CoA reductase inhibitors and the potential adverse consequences are of growing concern. Supplemental CoQ10 alters the natural history of cardiovascular illnesses and has the potential for prevention of cardiovascular disease through the inhibition of LDL cholesterol oxidation and by the maintenance of optimal cellular and mitochondrial function throughout the ravages of time and internal and external stresses. The attainment of higher blood levels of CoQ10 (> 3.5 micrograms/ml) with the use of higher doses of CoQ10 appears to enhance both the magnitude and rate of clinical improvement. In this communication, 34 controlled trials and several open-label and long-term studies on the clinical effects of CoQ10 in cardiovascular diseases are reviewed.

Topics: Antioxidants; Cardiovascular Diseases; Clinical Trials as Topic; Coenzymes; Coronary Artery Bypass; Heart Failure; Humans; Hypertension; Myocardial Ischemia; Reperfusion Injury; Ubiquinone; Ventricular Dysfunction, Left

Incubation of cultured astrocytes in Ca(2+)-containing medium after exposure to Ca(2+)-free medium causes Ca2+ influx followed by delayed cell death. Here, we summarize the mechanisms underlying the Ca(2+)-mediated injury of cultured astrocytes and the protective effects of drugs against Ca(2+)-reperfusion injury. Our results show that Ca(2+)-reperfusion injury of astrocytes appears to be mediated by apoptosis as evidenced by DNA fragmentation and nuclear condensation. Calpain, reactive oxygen species (ROS) production, calcineurin, caspase-3, and NF-kappa B activation are involved in Ca(2+)-reperfusion injury. Several drugs including T-588 and idebenone protect astrocytes against Ca(2+)-reperfusion injury. The protective effect of idebenone is mediated by nerve growth factor production, whereas that of T-588 is mediated mainly by the mitogen-activated protein/extracellular signal-regulated kinase signal cascade.

Topics: Animals; Apoptosis; Astrocytes; Benzoquinones; Calcium; Calpain; Cell Death; Cells, Cultured; Humans; Reperfusion Injury; Ubiquinone

Topics: Allopurinol; Animals; Catalase; Free Radical Scavengers; Glutathione; Humans; Lung Diseases; Molecular Weight; Oxygen; Reperfusion Injury; Superoxide Dismutase; Ubiquinone; Vitamin E; Xanthine Oxidase

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; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; Enterobacteriaceae; Enterococcus faecalis; Enterotoxigenic Escherichia coli; Environmental Monitoring; Enzyme Inhibitors; Epidemiologic Factors; Epigenesis, Genetic; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Esterases; Esterification; Ethanol; Ethiopia; Ethnicity; Eucalyptus; Evidence-Based Practice; Exercise; Exercise Tolerance; Extracorporeal Membrane Oxygenation; Family; Fatty Acids; Feedback; Female; Ferric Compounds; Fibrin Fibrinogen Degradation Products; Filtration; Fish Diseases; Flavonoids; Flavonols; Fluorodeoxyglucose F18; Follow-Up Studies; Food Microbiology; Food Preservation; Forests; Fossils; Free Radical Scavengers; Freund's Adjuvant; Fruit; Fungi; Gallium; Gender Identity; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Genes, Bacterial; Genes, Plant; Genetic Predisposition to Disease; Genitalia; Genotype; Glomerulonephritis, IGA; Glottis; Glucocorticoids; Glucose; Glucuronides; Glutathione Transferase; Glycogen Synthase Kinase 3 beta; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Grassland; Guinea Pigs; Half-Life; Head Kidney; Heart Atria; Heart Rate; Heart Septum; HEK293 Cells; Hematopoietic Stem Cells; Hemodynamics; Hep G2 Cells; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatocytes; Hesperidin; High-Frequency Ventilation; High-Temperature Requirement A Serine Peptidase 1; Hippocampus; Hirudins; History, 20th Century; History, 21st Century; HIV Infections; Homeostasis; Hominidae; Housing, Animal; Humans; Hydrocarbons, Brominated; Hydrogen Bonding; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxybutyrates; Hydroxyl Radical; Hypertension; Hypothyroidism; Image Interpretation, Computer-Assisted; Immunoconjugates; Immunogenic Cell Death; Indoles; Infant, Newborn; Infant, Premature; Infarction, Middle Cerebral Artery; Inflammation; 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; Melatonin; Membrane Glycoproteins; Membrane Proteins; Meniscectomy; Menisci, Tibial; Mephenytoin; Mesenchymal Stem Cells; Metal Nanoparticles; Metal-Organic Frameworks; Methionine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Mice, Obese; Mice, Transgenic; Microbial Sensitivity Tests; Microcirculation; MicroRNAs; Microscopy, Video; Microtubules; Microvascular Density; Microwaves; Middle Aged; Minimally Invasive Surgical Procedures; Models, Animal; Models, Biological; Models, Molecular; Models, Theoretical; Molecular Docking Simulation; Molecular Structure; Molecular Weight; Morus; Mouth Floor; Multicenter Studies as Topic; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Muscle, Skeletal; Myocardial Ischemia; Myocardium; NAD; NADP; Nanocomposites; Nanoparticles; Naphthols; Nasal Lavage Fluid; Nasal Mucosa; Neisseria meningitidis; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms, Experimental; Neural Stem Cells; Neuroblastoma; Neurofilament Proteins; Neurogenesis; Neurons; New York; NF-E2-Related Factor 2; NF-kappa B; Nicotine; Nitriles; Nitrogen; Nitrogen Fixation; North America; Observer Variation; Occupational Exposure; Ochrobactrum; Oils, Volatile; Olea; Oligosaccharides; Omeprazole; Open Field Test; Optimism; Oregon; Oryzias; Osmolar Concentration; Osteoarthritis; Osteoblasts; Osteogenesis; Ovarian Neoplasms; Ovariectomy; Oxadiazoles; Oxidation-Reduction; Oxidative Stress; Oxygen; Ozone; p38 Mitogen-Activated Protein Kinases; Pakistan; Pandemics; Particle Size; Particulate Matter; Patient-Centered Care; Pelargonium; Peptides; Perception; Peripheral Arterial Disease; Peroxides; Pets; Pharmaceutical Preparations; Pharmacogenetics; Phenobarbital; Phenols; Phenotype; Phosphates; Phosphatidylethanolamines; Phosphines; Phospholipids; Phosphorus; Phosphorylation; Photoacoustic Techniques; Photochemotherapy; Photosensitizing Agents; Phylogeny; Phytoestrogens; Pilot Projects; Plant Components, Aerial; Plant Extracts; Plant Immunity; Plant Leaves; 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

To evaluate the effect of coenzyme Q10 in reducing the skeletal muscle reperfusion injury following clamping and declamping the abdominal aorta.. 30 patients undergoing elective vascular surgery for abdominal aortic aneurysm or obstructive aorto-iliac disease were randomly divided into two groups: patients in group I were treated with coenzyme Q10 (150 mg/day) for seven days before operation, and those in group II received a placebo. We studied the hemodynamic profile in each patient during clamping and declamping of the abdominal aorta. The plasma concentrations of thiobarbituric acid reactive substances (malondialdhehyde), conjugated dienes, creatine kinase and lactate dehydrogenase were measured in samples from both arterial and inferior vena cava sites. Serial sampling was performed after induction of anesthesia, 5 and 30 minutes after abdominal aortic cross clamping, 5 and 30 minutes after aortic cross-clamp removal.. The concentrations of malondialdehyde, conjugated dienes, creatine kinase and lactate dehydrogenase in patients who received CoQ10 were significantly lower than in the placebo group. Decrease of plasma malondialdehyde concentrations correlated positively (p < 0.01) with decrease of both creatine kinase and lactate dehydrogenase release in samples from the inferior vena cava. The hemodynamic profile during clamping and declamping the abdominal aorta was similar in both groups.. Our findings suggest that pre-treatment with coenzyme Q10 may play a protective role during routine vascular procedures requiring abdominal aortic cross clamping by attenuating the degree of peroxidative damage.

Topics: Aortic Aneurysm, Abdominal; Aortic Diseases; Arterial Occlusive Diseases; Coenzymes; Constriction; Double-Blind Method; Female; Hemodynamics; Humans; Male; Middle Aged; Muscle, Skeletal; Premedication; Reperfusion Injury; Thiobarbituric Acid Reactive Substances; Ubiquinone

Retinal ischemia-reperfusion injury (RIRI) is an important pathological process of many ocular diseases. Mitoquinone (MitoQ), a mitochondrial targeted antioxidant, is a potential compound for therapeutic development of RIRI. This study observed the effect of MitoQ on RIRI, and further explored its possible molecular mechanism. Temporary increase in intraocular pressure was used to establish rat model of RIRI to observe the effect of MitoQ treatment on retinal function, pathological injury, oxidative stress, inflammation and apoptosis. Immunohistochemistry and Western blot were used to detect expressions of cleaved caspase 3, B cell leukemia/lymphoma 2 associated X (Bax), nicotinamide adenine dinucleotide phosphate oxidase (NOX1), NOX4, cleaved-Notch 1, hairy and enhancer of split 1 (Hes1), and sirtuin 1 (SIRT 1) in retina were detected by immunohistochemistry and Western blot. MitoQ treatment significantly improved retinal function and pathological injury, inhibited the over-production of reactive oxygen species, increased the expression of superoxide dismutase 1 (SOD 1), suppressed the releases of inflammatory cytokines, and inhibited retinal cells apoptosis. MitoQ also down-regulated the expressions of cleaved caspase 3, Bax, NOX 1, NOX 4, cleaved-Notch 1, and Hes 1, increased the expression of SIRT 1 protein and its activity. These effects were significantly reversed by SIRT1 inhibitor EX527. Our data suggests that MitoQ, as a potentially effective drug for improving RIRI, may act through the SIRT1/Notch1/NADPH signal axis.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Intravitreal Injections; NADP; Organophosphorus Compounds; Oxidative Stress; Rats; Receptor, Notch1; Reperfusion Injury; Retina; Sirtuin 1; Ubiquinone

Mitochondrial dysfunction is a critical factor contributing to oxidative stress and apoptosis in ischemia-reperfusion (I/R) diseases. Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant whose potent anti-I/R injury capacity has been demonstrated in organs such as the heart and the intestine. In the present study, we explored the role of MitoQ in maintaining mitochondrial homeostasis and attenuating oxidative damage in renal I/R injury. We discovered that the decreased renal function and pathological damage caused by renal I/R injury were significantly ameliorated by MitoQ. MitoQ markedly reversed mitochondrial damage after I/R injury and inhibited renal reactive oxygen species production. In vitro, hypoxia/reoxygenation resulted in increased mitochondrial fission and decreased mitochondrial fusion in human renal tubular epithelial cells (HK-2), which were partially prevented by MitoQ. MitoQ treatment inhibited oxidative stress and reduced apoptosis in HK-2 cells by restoring mitochondrial membrane potential, promoting ATP production, and facilitating mitochondrial fusion. Deeply, renal I/R injury led to a decreased expression of sirtuin-3 (Sirt3), which was recovered by MitoQ. Moreover, the inhibition of Sirt3 partially eliminated the protective effect of MitoQ on mitochondria and increased oxidative damage. Overall, our data demonstrate a mitochondrial protective effect of MitoQ, which raises the possibility of MitoQ as a novel therapy for renal I/R.

Topics: Adenosine Triphosphate; Antioxidants; Homeostasis; Humans; Ischemia; Kidney Diseases; Mitochondria; Organophosphorus Compounds; Oxidative Stress; Reactive Oxygen Species; Reperfusion; Reperfusion Injury; Sirtuin 3; Ubiquinone

To evaluate the efficacy of antioxidants in cellular-level post-ischemia/reperfusion injury of the testis and to validate these effects with. Fifty-six adult male rats were randomly divided into seven groups-Group 1: sham; Group 2: ischemia/reperfusion only group; Group 3: ischemia was induced and vitamin E (100 mg/kg) was administered intraperitoneally 30 min before reperfusion; Group 4: vitamin E was given intraperitoneally without ischemia/reperfusion; Group 5: ischemia was induced and coenzyme Q10 (10 mg/body weight) was administered intraperitoneally 30 min before reperfusion; Group 6: coenzyme Q10 was administered intraperitoneally without ischemia/reperfusion; Group 7: ischemia was induced and coenzyme Q10 + vitamin E was administered intraperitoneally 30 min before reperfusion. After detorsion, fluorodeoxyglucose was applied to all groups according to the animals' weight and fluorodeoxyglucose positron emission tomography was performed after 1 h. In pursuit of imaging, orchiectomy was performed for histopathological and biochemical evaluations.. A significant effect of group on catalase, maximum standardized uptake value, and seminiferous tubule diameters (p < 0.005) was observed. According to this, combining ischemia/reperfusion with vitamin E increased the maximum standardized uptake value significantly higher than in all other groups; in addition, catalase was significantly higher than in Groups 4-6. Histopathological outcomes revealed that "sham" had significantly larger seminiferous tubule diameter than Groups 2-4. Also, "ischemia/reperfusion" was the only group which had significantly smaller seminiferous tubule diameters than Groups 6 and 7.. In contrast to vitamin E, coenzyme Q10 provided remarkable regression of oxidative stress-induced enzymes and revealed consistent effects on histopathological outcomes, which were validated with fluorodeoxyglucose positron emission tomography imaging.

Topics: Animals; Disease Models, Animal; Fluorodeoxyglucose F18; Glucose; Male; Positron-Emission Tomography; Radiopharmaceuticals; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Testis; Ubiquinone; Vitamin E; Vitamins

Topics: Animals; Cytokines; Ischemia; Male; Malondialdehyde; Matrix Metalloproteinase 2; Matrix Metalloproteinases; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Spermatic Cord Torsion; Testis; Ubiquinone

Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation. Oxidative damage to mitochondria is an early event in IR injury. Therefore, the uptake, safety, and efficacy of the mitochondria-targeted antioxidant MitoQ were investigated in models of transplant IR injury.. MitoQ uptake by warm and cooled pairs of pig and declined human kidneys was measured when preserved in cold static storage or by hypothermic machine perfusion. Pairs of pigs' kidneys were exposed to defined periods of warm and cold ischaemia, flushed and stored at 4°C with or without MitoQ (50 nmol/l to 250 µmol/l), followed by reperfusion with oxygenated autologous blood in an ex vivo normothermic perfusion (EVNP). Pairs of declined human kidneys were flushed and stored with or without MitoQ (5-100 µmol/l) at 4°C for 6 h and underwent EVNP with ABO group-matched blood.. Stable and concentration-dependent uptake of MitoQ was demonstrated for up to 24 h in pig and human kidneys. Total blood flow and urine output were significantly greater in pig kidneys treated with 50 µmol/l MitoQ compared with controls (P = 0.006 and P = 0.007 respectively). In proof-of-concept experiments, blood flow after 1 h of EVNP was significantly greater in human kidneys treated with 50 µmol/l MitoQ than in controls (P ≤ 0.001). Total urine output was numerically higher in the 50-µmol/l MitoQ group compared with the control, but the difference did not reach statistical significance (P = 0.054).. Mitochondria-targeted antioxidant MitoQ can be administered to ischaemic kidneys simply and effectively during cold storage, and may improve outcomes after transplantation.

Topics: Animals; Antioxidants; Disease Models, Animal; Humans; Kidney; Kidney Transplantation; Organ Preservation; Organophosphorus Compounds; Reperfusion Injury; Swine; Ubiquinone

To examine the changes of coenzyme Q10 (CoQ10) and β. Fifty SD rats were randomly divided into 5 groups (. The infarct volume percentage after TTC staining was zero in the sham group. With the progress of disease and USW therapy, the infarct volume percentage was decreased in the experimental groups (all. Non-caloric USW therapy may upregulate the expression of CoQ10 to suppress the expression of C1GALT1C1 in rats, leading to alleviating cerebral ischemic reperfusion injury.

Topics: Animals; Brain; Brain Ischemia; Molecular Chaperones; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ubiquinone

Idebenone is a well-appreciated mitochondrial protectant while the mechanisms underlying the neuroprotection in cerebral ischemia and reperfusion (I/R) remain elusive. It has been manifested NLRP3 inflammasom activation contributed to I/R induced damage. It raises questions how exactly NLRP3 inflammasom was activated in microglia and neuron and whether idebenone reverses the process in I/R.. I/R rat model was utilized and BV2, primary microglia and PC12 cells were subjected to oxygen-glucose deprivation (OGD). Then, western-blotting, q-PCR, immunofluorescence staining, ELISA, flow cytometry and immunoprecipitation analysis were performed.. We found ROS-NLRP3 singaling was activated in BV2 cells at OGD/R 24 h. Importantly, microglial NLRP3 activation was essential for NLRP3 activation in PC12 cells under microglial-neuronal co-culture circumstance, which has been confirmed to induced neuronal apoptosis. Further, we found mitochondrial dysfunction in OGD/R led to mt-DNA translocation as well as generation of mt-ROS, resulting cytosolic accumulation of oxidized mt-DNA. Ultimately, oxidized mt-DNA binding to NLRP3 contributed to further activation of NLRP3 and dramatically augmented inflammation in BV2 and PC12 cells. Furthermore, idebenone treatment inhibited the process, thus suppressing the NLRP3-mediated inflammatory injury after OGD/R. In vivo, NLRP3 was activated in microglia of I/R rats and inhibition of NLRP3 was observed in idebenone treatment group, which had less neurological deficit and less infarct volume.. Our data revealed the anti-inflammatory effects of idebenone via suppressing activation of NLRP3 and ameliorating NLRP3-mediating damage in I/R, which may provide new insight in therapeutic strategy for ischemic stroke.

Topics: Animals; Animals, Newborn; Brain Ischemia; Cells, Cultured; Encephalitis; Inflammasomes; Male; Mice; Mice, Inbred C57BL; Neuroprotection; NLR Family, Pyrin Domain-Containing 3 Protein; PC12 Cells; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Stroke; Ubiquinone

Activation of sterile inflammation after hepatic ischemia/reperfusion (I/R) culminates in liver injury. The route to liver damage starts with mitochondrial oxidative stress and cell death during early reperfusion. The link between mitochondrial oxidative stress, damage-associate molecular pattern (DAMP) release, and sterile immune signaling is incompletely understood and lacks clinical validation. The aim of the study was to validate this relation in a clinical liver I/R cohort and to limit DAMP release using a mitochondria-targeted antioxidant in I/R-subjected mice.. Plasma levels of the DAMPs high-mobility group box 1 (HMGB1), mitochondrial DNA, and nucleosomes were measured in 39 patients enrolled in an observational study who underwent a major liver resection with (N = 29) or without (N = 13) intraoperative liver ischemia. Circulating cytokine and neutrophil activation markers were also determined. In mice, the mitochondria-targeted antioxidant MitoQ was intravenously infused in an attempt to limit DAMP release, reduce sterile inflammation, and suppress I/R injury.. In patients, HMGB1 was elevated following liver resection with I/R compared to liver resection without I/R. HMGB1 levels correlated positively with ischemia duration and peak post-operative transaminase (ALT) levels. There were no differences in mitochondrial DNA, nucleosome, or cytokine levels between the two groups. In mice, MitoQ neutralized hepatic oxidative stress and decreased HMGB1 release by ±50%. MitoQ suppressed transaminase release, hepatocellular necrosis, and cytokine production. Reconstituting disulfide HMGB1 during reperfusion reversed these protective effects.. HMGB1 seems the most pertinent DAMP in clinical hepatic I/R injury. Neutralizing mitochondrial oxidative stress may limit DAMP release after hepatic I/R and reduce liver damage.

Topics: Aged; Alarmins; Antioxidants; Cytokines; DNA, Mitochondrial; Female; HMGB1 Protein; Humans; Liver; Male; Middle Aged; Mitochondria; Organophosphorus Compounds; Oxidative Stress; Reperfusion Injury; Ubiquinone

Renal ischemia-reperfusion injury (RIRI) may occur secondary to several reasons leading to renal failure. Coenzyme-Q10 (CoQ10) is a well-known antioxidant. However, the effects CoQ10 against RIRI have not been evaluated. Our aim was to evaluate protective effects of CoQ10 to renal ischemia-reperfusion by biochemical, immunohistochemical and scintigraphic findings.. Thirty Wistar-albino rats were randomly separated into groups of 10; Group Sham; Group ischemia-reperfusion (IR) had left renal pedicle clamping; Group CoQ10+IR had IR and CoQ10. Twenty-four hours later after reperfusion, scintigraphy was performed and after that, rats were sacrificed. To demonstrate effects of RIRI, serum urea and creatinine levels and tissue levels oxidative stress markers were evaluated. Both kidneys were subjected to histopathological evaluation and to confirm RIRI-induced immunohistochemical aspects of apoptosis, terminal-deoxynucleotidyl-transferase mediated-deoxyuridine-triphosphate-nick-end-labeling assay and caspase-3 were assessed.. Tissue oxidative stress, histopathologic changes, apoptosis scores and quantitative scintigraphic parameters were significantly higher in Group IR compared with Group Sham. Although tissue oxidative stress levels and histopathologic changes were not significant, quantitative scintigraphic parameters of contralateral kidney of Group IR were significantly increased. Compared with Group IR, Group CoQ10+IR presented decreased tissue oxidative stress levels; decreased scores of histopathology and apoptosis; and decreased quantitative scintigraphic parameters with increased split renal function in ischemic kidney.. Our results suggest that other than its antioxidant properties, CoQ10 shows antiperoxidative, antiapoptotic and antiinflammatory potential in protecting renal functioning of ischemic kidney. Furthermore, our results show that renal scintigraphy is a feasible method to detect early changes in renal functioning after RIRI.

Topics: Animals; Caspase 3; Cytoprotection; Female; Kidney; Rats; Rats, Wistar; Reperfusion Injury; Ubiquinone

To investigate the effect of mitochondria-targeted antioxidant MitoQ in reducing the severity of renal ischemia-reperfusion injury (IRI) in rats using T. Ischemia-reperfusion injury was induced by temporarily clamping the left renal artery. Rats were pretreated with MitoQ or saline. The MRI examination was performed before and after IRI (days 2, 5, 7, and 14). The T. The standardized signal intensity of the OSOM on IRI kidneys with MitoQ were lower than those with saline on days 5 and 7 (P = 0.004, P < 0.001, respectively). K. These findings demonstrate that MitoQ can reduce the severity of renal damage in rodent IRI models using T

Topics: Acute Kidney Injury; Animals; Contrast Media; Kidney; Magnetic Resonance Imaging; Male; Organophosphorus Compounds; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ubiquinone

Disruption of the mucosal barrier following intestinal ischemia reperfusion (I/R) is life threatening in clinical practice. Mitochondrial dysfunction and oxidative stress significantly contribute to the early phase of I/R injury and amplify the inflammatory response. MitoQ is a mitochondrially targeted antioxidant that exerts protective effects following I/R injury. In the present study, we aimed to determine whether and how MitoQ protects intestinal epithelial cells (IECs) from I/R injury. In both in vivo and in vitro studies, we found that MitoQ pretreatment downregulated I/R-induced oxidative stress and stabilized the intestinal barrier, as evidenced by MitoQ-treated I/R mice exhibiting attenuated intestinal hyperpermeability, inflammatory response, epithelial apoptosis, and tight junction damage compared to controls. Mechanistically, I/R elevated mitochondrial 8-hydroxyguanine content, reduced mitochondrial DNA (mtDNA) copy number and mRNA transcription levels, and induced mitochondrial disruption in IECs. However, MitoQ pretreatment dramatically inhibited these deleterious effects. mtDNA depletion alone was sufficient to induce apoptosis and mitochondrial dysfunction of IECs. Mitochondrial transcription factor A (TFAM), a key activator of mitochondrial transcription, was significantly reduced during I/R injury, a phenomenon that was prevented by MitoQ treatment. Furthermore, we observed that thee protective properties of MitoQ were affected by upregulation of cellular antioxidant genes, including HO-1, NQO-1, and γ-GCLC. Transfection with Nrf2 siRNA in IECs exposed to hypoxia/reperfusion conditions partially blocked the effects of MitoQ on mtDNA damage and mitochondrial oxidative stress. In conclusion, our data suggest that MitoQ exerts protective effect on I/R-induced intestinal barrier dysfunction.

Topics: Animals; Antioxidant Response Elements; Antioxidants; Apoptosis; DNA Damage; DNA-Binding Proteins; DNA, Mitochondrial; Humans; Intestinal Mucosa; Intestines; Male; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondrial Proteins; NF-E2-Related Factor 2; Organophosphorus Compounds; Oxidative Stress; Protective Agents; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Transcription Factors; Ubiquinone

Topics: Animals; Antioxidants; Apoptosis; Astrocytes; bcl-2-Associated X Protein; bcl-Associated Death Protein; bcl-X Protein; Caspase 3; Cell Survival; Disease Models, Animal; Female; Gene Expression Regulation; Intraocular Pressure; Mice; Mice, Inbred C57BL; Microglia; Oxidative Stress; Phosphorylation; Reactive Oxygen Species; Reperfusion Injury; Retinal Degeneration; Retinal Ganglion Cells; Signal Transduction; Ubiquinone

Coenzyme Q10 (CoQ10) has antioxidant and anti-inflammatory activity. The aim of this study was to investigate the effects of CoQ10 on the inhibition of nuclear factor-kappa B (NF-κB) activation during ischemia-reperfusion (I/R) of skeletal muscle.. For ischemia induction, the animals were anesthetized and the external iliac vessels blocked for three hours. CoQ10 or vehicle was given intraperitoneally during ischemia, just before reperfusion. Four groups received 3,7,14 and 28 days' reperfusion, respectively, after the intraperitoneal injection of CoQ10 and four corresponding groups received vehicle only. After reperfusion, the gastrocnemius muscles were removed, fixed and stained for the analysis of edema and mast cell infiltration.. Immuno-histochemistry staining was performed for the detection of tumor necrosis factor alpha (TNF-α) and NF-κB. CoQ10-treated groups showed a significant decrease of mast cell infiltration in the gastrocnemius muscle and edema as compared with the corresponding non-treated groups. Also, CoQ10-treated groups showed a significant TNF-α and NF-κB expression decrease when compared to the corresponding non-treated controls. The results of this study showed CoQ10 administration with ischemia decreased interstitial edema, degeneration of muscle fibers and infiltration of mast cells.. It seems that CoQ10 has inhibitory effects on NF-κB and TNF-α activation.

Topics: Animals; Edema; Gene Expression Regulation; Male; Muscle, Skeletal; NF-kappa B; Rats; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha; Ubiquinone

The purpose of this study is to investigate the effect of coenzyme Q10 (CoQ10) on focal cerebral ischemia/reperfusion (I/R) injury in hyperglycemic rats and the possible involved mechanisms. In this study, we established the transient middle cerebral artery occlusion (MCAO) for 30min in the rats with diabetic hyperglycemia. The neurological deficit score, 2,3,5-triphenyltetrazolium chloride (TTC) staining and pathohistology are applied to detect the extent of the damage. The expression of Fis1, Mfn2 and Lc3 in the brain is investigated by immunohistochemical and Western blotting techniques. The results showed that the streptozotocin-induced diabetic hyperglycemia and MCAO-induced focal cerebral ischemia were successfully prepared in rats. In the hyperglycemic group, the neurological deficit scores, infarct volumes, and number of pyknotic cells were higher than that in the normalglycemic group at 24h and/or 72h reperfusion. Pretreated with CoQ10 (10mg/kg) for four weeks could significantly reduce the neurological scores, infarct volume, and pyknotic cells at 24h and/or 72h reperfusion of the hyperglycemic rats compared with non-CoQ10 pretreated hyperglycemic animals. Immunohistochemistry and Western blotting showed that pretreatment with CoQ10 or insulin could significantly reduce the expression of Fis1 protein in the brain at 24h and 72h reperfusion. Inversely, a significantly increased expression of Mfn2 was observed in the rats CoQ10 or insulin pretreated at 24h and/or 72h reperfusion when compared with matched hyperglycemic rats. These results demonstrated that hyperglycemia could aggravate ischemic brain injury. Pretreatment with CoQ10 might ameliorate the diabetic hyperglycemia aggravated I/R brain damage in the MCAO rats by maintain the balance between mitochondrial fission and fusion.

Topics: Animals; Brain; Brain Ischemia; Diabetes Mellitus, Experimental; Hyperglycemia; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ubiquinone

Coenzyme Q10 (CoQ10) is a lipid-soluble benzoquinone with antioxidant features that make it important in the treatment of ischemia reperfusion injury. In this study, we aimed to investigate the beneficial effect of CoQ10 in the treatment of venous ischemia/reperfusion injury.. Eighteen Sprague-Dawley male rats were randomly divided into two equal groups: the control group and an experimental group (n = 9 rats). The experimental group received CoQ10 orally, and the control group received a control diet for 8 wk. An inferior epigastric island flap was raised, and the inferior epigastric vein was clamped for 9 h; the flap was then reperfused. All rats were sacrificed on postoperative day 5. The flap survival rate and levels of CoQ10, malondialdehyde, glutathione, and superoxide dismutase were assessed, and flap tissues were examined under a light microscope (×200 magnification) after being stained with Hematoxylin & Eosin.. The flap survival rate and levels of CoQ10, glutathione, and superoxide dismutase were significantly higher, but level of malondialdehyde was lower in the experimental group. The mean flap survival rates and plasma levels of CoQ10 were 51% ± 24% and 251 ± 11 ng/mL in the control group, whereas they were 88% ± 7% and 692.8 ± 79.7 ng/mL in the experimental group with statistically significant differences (P < 0.001). Polymorphonuclear leukocyte infiltration was higher, and surface epithelial integrity was more impaired in the control group.. We concluded that CoQ10 supplementation has a beneficial effect on venous ischemia and/or reperfusion injury and improves flap survival rate.

Topics: Animals; Drug Evaluation, Preclinical; Male; Random Allocation; Rats, Sprague-Dawley; Reperfusion Injury; Surgical Flaps; Ubiquinone; Vascular System Injuries; Vitamins

Spinal cord ischemia remains a serious complication of thoracoabdominal aortic aneurysm surgery. Coenzyme Q10, a potent antioxidant, has been reported to exert a neuroprotective effect. In the present study, we evaluated the effect of coenzyme Q10 pretreatment on spinal cord ischemia-reperfusion injury.. Male Sprague-Dawley rats were treated with either 300 mg/kg coenzyme Q10 (CoQ10 group, n = 12) or saline (control and sham groups, n = 12 for each group) for 5 days before ischemia. Spinal cord ischemia was induced in the control and CoQ10 groups. Neurological function was assessed using the Basso-Beattie-Bresnahan (BBB) motor rating scale until 7 days after reperfusion, and then the spinal cord was harvested for histopathological examinations and an evaluation of malondialdehyde level.. On post-reperfusion Day 1, the CoQ10 group showed higher BBB scores compared with those in the control group, although the difference was not significant. However, on Day 2, the CoQ10 group showed a significantly higher BBB score than the control group (14.0 [10.3-15.0] vs 8.0 [5.0-9.8], median [IQR], respectively; p = 0.021), and this trend was maintained until Day 7 (17.5 [16.0-18.0] vs 9.0 [6.5-12.8], respectively; p < 0.001). Compared with the control group, the CoQ10 group had more normal motor neurons (p = 0.003), fewer apoptotic changes (p = 0.003) and a lower level of tissue malondialdehyde (p = 0.024).. Pretreatment with 300 mg/kg coenzyme Q10 resulted in significantly improved neurological function and preservation of more normal motor neurons.

Topics: Animals; Disease Models, Animal; Neurologic Examination; Premedication; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Spinal Cord; Ubiquinone

Ischemia-reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury.

Topics: Animals; Antioxidants; Creatinine; Kidney; Male; Mice; Mice, Inbred C57BL; Mitochondria; Organophosphorus Compounds; Oxidative Stress; Reperfusion Injury; Ubiquinone

Free radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction. We therefore assessed the efficacy of the mitochondria-targeted anti-oxidant MitoQ in reducing IR injury in a murine heterotopic cardiac transplant model.. Hearts from C57BL/6 donor mice were flushed with storage solution alone, solution containing the anti-oxidant MitoQ, or solution containing the non-anti-oxidant decyltriphenylphosphonium control and exposed to short (30 minutes) or prolonged (4 hour) cold preservation before transplantation. Grafts were transplanted into C57BL/6 recipients and analyzed for mitochondrial reactive oxygen species production, oxidative damage, serum troponin, beating score, and inflammatory markers 120 minutes or 24 hours post-transplant.. MitoQ was taken up by the heart during cold storage. Prolonged cold preservation of donor hearts before IR increased IR injury (troponin I, beating score) and mitochondrial reactive oxygen species, mitochondrial DNA damage, protein carbonyls, and pro-inflammatory cytokine release 24 hours after transplant. Administration of MitoQ to the donor heart in the storage solution protected against this IR injury by blocking graft oxidative damage and dampening the early pro-inflammatory response in the recipient.. IR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury.

Topics: Animals; Antioxidants; Disease Models, Animal; Female; Free Radical Scavengers; Heart Transplantation; Male; Mice; Mice, Inbred C57BL; Micronutrients; Mitochondria, Heart; Organ Preservation; Organophosphorus Compounds; Oxidative Stress; Primary Graft Dysfunction; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Ubiquinone

We herein report on a mitochondrial therapeutic effect based on the delivery of coenzyme Q10 (CoQ10), an anti-oxidant, to in vivo mitochondria using a MITO-Porter, a liposome-based mitochondrial delivery system that functions via membrane fusion. To evaluate the effects, we used a mouse liver ischemia/reperfusion injury (I/R injury) model, in which mitochondrial reactive oxygen species are overexpressed. We packaged CoQ10 in the lipid phase of a MITO-Porter and optimized the mitochondrial fusogenic activities to produce the CoQ10-MITO-Porter. A histological observation of the carriers in the liver by confocal laser scanning microscopy was done and the accumulation of the carrier labeled with a radio isotope in the liver confirmed that the CoQ10-MITO-Porter was delivered to liver mitochondria via systemic injection. These analytical results permitted us to optimize the compositions of the CoQ10-MITO-Porter so as to permit it to efficiently accumulate in mouse liver mitochondria. Finally, we applied the optimized CoQ10-MITO-Porter to mice via tail vein injection, and hepatic I/R injury was then induced, followed by measuring serum alanine aminotransferase (ALT) levels, a marker of liver injury. We confirmed that the use of the CoQ10-MITO-Porter resulted in a significant decrease in serum ALT levels, indicating that in vivo mitochondrial delivery of the CoQ10 via MITO-Porter prevents I/R injury in mice livers. This provides a demonstration of the potential use of such a delivery system in mitochondrial therapies.

Topics: Animals; Antioxidants; Drug Delivery Systems; Liposomes; Liver; Male; Mice; Mice, Inbred C57BL; Mitochondria; Reperfusion Injury; Ubiquinone

Generation of toxic oxygen metabolites followed by oxidant- and inflammatory-mediated tissue injury plays a crucial role in the pathogenesis of ischemia and reperfusion (IR). Ubiquinol, the reduced form of coenzyme Q10, is recognized for its potent antioxidant and anti-inflammatory properties in biological membranes. The present study was established to examine the possible protective effect of ubiquinol against renal IR injury. Groups of male Wistar rats were assigned into sham, ubiquinol, IR (45-min bilateral renal ischemia followed by 24-h reperfusion), and ubiquinol+ IR (ubiquinol 300 mg/kg given orally for 7 consecutive days before IR induction). Renal morphology, function, oxidative stress, and inflammatory markers were evaluated at the end of reperfusion. IR caused renal dysfunction as shown by significant increases in blood urea nitrogen, plasma creatinine, and a decrease in creatinine clearance. Light and electron microscopic examinations exhibited severe tubular damages and abnormal mitochondrial structure. IR-induced renal injuries were associated with significant increases in malondialdehyde, nitric oxide, tumor necrosis factor-α, but decreases in antioxidant thiols and superoxide dismutase. Pretreatment with ubiquinol obviously attenuated all the changes caused by IR, whereas it had no considerable effect in the sham-operated rats. These findings indicate that supplementation of ubiquinol prior to IR incidence confers functional and morphological protection to the ischemic kidney by maintaining the redox balance and regulating the generation of inflammatory mediator. The outcomes suggest that ubiquinol may be a potential candidate to counteract organ dysfunction in conditions involving IR injury.

Topics: Animals; Antioxidants; Blood Urea Nitrogen; Dietary Supplements; Drug Evaluation, Preclinical; Ischemia; Kidney; Male; Malondialdehyde; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Sulfhydryl Compounds; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Ubiquinone

Haemorrhagic shock (HS) and fluid resuscitation can lead to increased reactive oxygen species (ROS), contributing to ischaemia-reperfusion injury and organ damage. Ubiquinol is a potent antioxidant that decreases ROS. This study examined the effects of ubiquinol administered with fluid resuscitation following controlled HS. Adult male Sprague-Dawley rats were randomly assigned to treatment [ubiquinol, 1 mg (100 g body weight)(-1)] or control groups. Rats were subjected to 60 min of HS by removing 40% of the total blood volume to a mean arterial pressure ∼45-55 mmHg. The animals were resuscitated with blood and lactated Ringer solution, with or without ubiquinol, and monitored for 120 min. At the end of the experiments, the rats were killed and the lungs, diaphragm, heart and kidneys harvested. Leucocytes were analysed for mitochondrial superoxide at baseline, end of shock and 120 min following fluid resuscitation using MitoSOX Red. Diaphragms were examined for hydrogen peroxide using dihydrofluorescein diacetate and confocal microscopy. The apoptosis in lungs, diaphragm, heart and kidneys was measured using fluorescence microscopy with acridine orange and ethidium bromide. Leucocyte mitochondrial superoxide levels were significantly lower in rats that received ubiquinol than in the control animals. Production of hydrogen peroxide and apoptosis were significantly reduced in the organs of rats treated with ubiquinol. These findings suggest that ubiquinol, administered with fluid resuscitation after HS, attenuates ROS production and apoptosis. Thus, ubiquinol is a potent antioxidant that may be used as a potential treatment to reduce organ injury following haemorrhagic events.

Topics: Animals; Antioxidants; Apoptosis; Diaphragm; Fluid Therapy; Heart; Hydrogen Peroxide; Kidney; Leukocytes; Lung; Male; Mitochondria; Myocardium; Rats, Sprague-Dawley; Reperfusion Injury; Resuscitation; Shock, Hemorrhagic; Superoxides; Ubiquinone

To investigate the effects of coenzyme Q10 pretreatment on the expressions of Bcl-2, Bax and glycogen synthase kinase-3β (GSK-3β) in rats suffering from ischemia/reperfusion injury.. Thirty-six adult male SD rats were randomly assigned into 3 groups: sham-operated group (sham), ischemia/reperfusion group (I/R) and coenzyme Q10 preconditioning group (Q10). Focal cerebral ischemia/reperfusion models were established in experimental rats by blocking middle cerebral artery with suture. Histological changes of hippocampal neurons were observed by HE staining. The expressions of Bcl-2, Bax and GSK-3β were detected by immunohistochemistry and Western blotting.. Immunohistochemistry showed that the percentage of Bcl-2 positive cells increased in the hippocampus, while the percentages of Bax and GSK-3β positive cells decreased in Q10 group compared with I/R group. Western blotting revealed that the expression level of Bcl-2 was higher and the expression levels of Bax and GSK-3β were lower in Q10 group than in I/R group. There were significant differences between the two groups (P<0.05).. Coenzyme Q10 promoted the expression of Bcl-2 and suppressed the expressions of Bax and GSK-3β in the hippocampus of rats exposed to cerebral ischemia/reperfusion.

Topics: Animals; bcl-2-Associated X Protein; Brain Ischemia; CA1 Region, Hippocampal; Disease Models, Animal; Gene Expression Regulation; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Male; Proto-Oncogene Proteins c-bcl-2; Rats; Reperfusion Injury; Ubiquinone

The aim of this study was to investigate the protective effects of coenzyme Q₁₀ (CoQ₁₀) on ovarian ischemia/reperfusion injury in an experimental rat adnexal torsion model.. 48 female adult Wistar albino rats, weighing 220-250 g, were randomly equally divided into six groups (n = 8): sham, torsion, detorsion, sham+CoQ₁₀, torsion+CoQ₁₀, and detorsion+CoQ₁₀ groups. Bilateral adnexal torsion was performed for 3 h in all groups, except the sham and sham+CoQ₁₀ groups. Bilateral adnexal detorsion was performed on the detorsion and detorsion+CoQ₁₀ groups. CoQ₁₀ was injected intraperitoneally 30 min before the sham operation, torsion, and detorsion.. The torsion and detorsion groups had significantly higher histologic evaluation scores, as well as higher MDA levels, TOS values, and oxidative stress index values than the sham group. A strong correlation between total histologic evaluation scores for ischemia/reperfusion injury and the oxidative stress index was found. The mean oxidant marker levels and histopathologic scores for the ovarian tissue significantly decreased after using CoQ₁₀, which is a potent antioxidant.. Conservative surgery (detorsion) was found to provide inadequate protection to ovarian tissue. The results of this study suggest that CoQ₁₀ could be useful for the protection of ovarian tissue before conservative surgery.

Topics: Animals; Aryldialkylphosphatase; Female; Malondialdehyde; Ovary; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Torsion Abnormality; Ubiquinone

Mitochondrial reactive oxygen species generation has been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury; however, its exact role and its spatial-temporal relationship with inflammation are elusive. Herein we explore the spatial-temporal relationship of oxidative/nitrative stress and inflammatory response during the course of hepatic I/R and the possible therapeutic potential of mitochondrial-targeted antioxidants, using a mouse model of segmental hepatic ischemia-reperfusion injury. Hepatic I/R was characterized by early (at 2 h of reperfusion) mitochondrial injury, decreased complex I activity, increased oxidant generation in the liver or liver mitochondria, and profound hepatocellular injury/dysfunction with acute proinflammatory response (TNF-α, MIP-1α/CCL3, MIP-2/CXCL2) without inflammatory cell infiltration, followed by marked neutrophil infiltration and a more pronounced secondary wave of oxidative/nitrative stress in the liver (starting from 6 h of reperfusion and peaking at 24 h). Mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently attenuated I/R-induced liver dysfunction, the early and delayed oxidative and nitrative stress response (HNE/carbonyl adducts, malondialdehyde, 8-OHdG, and 3-nitrotyrosine formation), and mitochondrial and histopathological injury/dysfunction, as well as delayed inflammatory cell infiltration and cell death. Mitochondrially generated oxidants play a central role in triggering the deleterious cascade of events associated with hepatic I/R, which may be targeted by novel antioxidants for therapeutic advantage.

Topics: Animals; Antioxidants; Cyclic N-Oxides; Dose-Response Relationship, Drug; Inflammation; Liver Diseases; Male; Mice; Mice, Inbred C57BL; Mitochondria, Liver; Organophosphorus Compounds; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Ubiquinone

Our previous study has reported that superoxide mediates ischemia-reperfusion (IR)-induced necrosis in mouse skeletal muscle. However, it remains poorly understood whether IR induces apoptosis and what factors are involved in IR-induced apoptosis in skeletal muscle. Using a murine model of tourniquet-induced hindlimb IR, we investigated the relationship between mitochondrial dysfunction and apoptosis in skeletal muscle. Hindlimbs of C57/BL6 mice were subjected to 3 h ischemia and 4 h reperfusion via placement and release of a rubber tourniquet at the greater trochanter. Compared to sham treatment, tourniquet-induced IR significantly elevated mitochondria-derived superoxide production, activated opening of mitochondrial permeability transition pore (mPTP), and caused apoptosis in the gastrocnemius muscles. Pretreatment with a superoxide dismutase mimetic (tempol, 50 mg/kg) or a mitochondrial antioxidant (co-enzyme Q(10), 50 mg/kg) not only decreased mitochondria-derived superoxide production, but also inhibited mPTP opening and apoptosis in the IR gastrocnemius muscles. Additionally, an inhibitor of mPTP (cyclosporine A, 50 mg/kg) also inhibited both mPTP opening and apoptosis in the IR gastrocnemius muscles. These results suggest that mitochondria-derived superoxide overproduction triggers the mPTP opening and subsequently causes apoptosis in tourniquet-induced hindlimb IR.

Topics: Animals; Antioxidants; Apoptosis; Blotting, Western; Caspase 9; Cyclic N-Oxides; Cyclosporine; Electron Transport Complex IV; Hindlimb; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred C57BL; Mitochondria, Muscle; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Muscle, Skeletal; Reperfusion Injury; Spin Labels; Superoxides; Tourniquets; Ubiquinone; Vitamins

Recanalization and secondary prevention are the main therapeutic strategies for acute ischemic stroke. Neuroprotective therapies have also been investigated despite unsuccessful clinical results. Coenzyme Q10 (CoQ10), which is an essential cofactor for electron transport in mitochondria, is known to have an antioxidant effect. We investigated the protective effects of CoQ10 against hypoxia in neural stem cells (NSCs). We measured cell viability and levels of intracellular signaling proteins after treatment with several concentrations of CoQ10 under hypoxia-reperfusion. CoQ10 protected NSCs against hypoxia-reperfusion in a concentration-dependent manner by reducing growth inhibition and inhibiting free radical formation. It increased the expression of a number of survival-related proteins such as phosphorylated Akt (pAkt), phosphorylated glycogen synthase kinase 3-β (pGSK3-β), and B-cell lymphoma 2 (Bcl-2) in NSCs injured by hypoxia-reperfusion and reduced the expression of death-related proteins such as cleaved caspase-3. We conclude that CoQ10 has effects against hypoxia-reperfusion induced damage to NSCs by enhancing survival signals and decreasing death signals.

Topics: Animals; Antioxidants; Blotting, Western; Cell Hypoxia; Cell Survival; Cells, Cultured; Free Radicals; In Situ Nick-End Labeling; Neural Stem Cells; Rats; Reperfusion Injury; Signal Transduction; Ubiquinone

Partial bladder outlet obstruction (PBOO) in rabbits causes free radical production through ischemia and reperfusion within the bladder smooth muscle and mucosa. We had previously shown that pretreatment of rabbits with a combination of α-lipoic acid (αLA) and coenzyme Q10 (CoQ) protected the bladder from contractile and metabolic dysfunctions mediated by PBOO. In this study, we examined the ability of pretreatment with αLA and CoQ combination in rabbits to protect the bladder from contractile damage mediated by either hydrogen peroxide (H(2)O(2)) or in vitro ischemia-reperfusion (I/R) which represents two in vitro models of oxidative damage.. Eight adult male New Zealand white rabbits were pretreated with CoQ and αLA orally for four weeks. Eight adult male control rabbits were given vehicle. Eight full-thickness bladder strips were isolated from each of 4 treated and 4 control rabbit bladders, and a dose-response curve to H(2)O(2) (0.1-0.8%) was generated. Similarly, isolated strips of bladder from the remaining 4 control and 4 treated rabbits were subjected to 1 h of ischemia (no oxygen without glucose) followed by 2 h of incubation in oxygenated buffer with glucose. The effects on the contractile responses to field stimulation (FS) at 2, 8, and 32 Hz, carbachol, and potassium chloride (KCl) were determined.. H(2)O(2) reduced the contractile responses to KCl and carbachol to a significantly greater degree than to FS, whereas I/R reduced the contractile responses to FS to a significantly greater degree than to KCl and carbachol. Pretreatment of the rabbits with the combination of CoQ and αLA significantly protected the bladder from the damaging effects of I/R, but had virtually no effect on the damaging effects of H(2)O(2).. Although both H(2)O(2) and I/R are in vitro models of oxidative free radical damage to bladder smooth muscle, they have significantly different methods of action and different sensitivities to antioxidants.

Topics: Animals; Antioxidants; Disease Models, Animal; Drug Therapy, Combination; Follow-Up Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Muscle Contraction; Muscle, Smooth; Oxidative Stress; Rabbits; Reperfusion Injury; Thioctic Acid; Ubiquinone; Urinary Bladder Neck Obstruction; Vitamins

Although arterial limb tourniquet is one of the first-line treatments to prevent exsanguinating hemorrhage in both civilian pre-hospital and battlefield casualty care, prolonged application of a limb tourniquet can lead to serious ischemia-reperfusion injury. However, the underlying pathomechanisms of tourniquet-induced ischemia-reperfusion injury are still poorly understood. Using a murine model of acute limb ischemia-reperfusion, we investigated if acute limb ischemia-reperfusion injury is mediated by superoxide overproduction and mitochondrial dysfunction. Hind limbs of C57/BL6 mice were subjected to 3h ischemia and 4h reperfusion via placement and release of a rubber tourniquet at the greater trochanter. Approximately 40% of the gastrocnemius muscle suffered infarction in this model. Activities of mitochondrial electron transport chain complexes including complex I, II, III, and IV in the gastrocnemius muscle were decreased in the ischemia-reperfusion group compared to sham. Superoxide production was increased while activity of manganese superoxide dismutase (MnSOD, the mitochondria-targeted SOD isoform) was decreased in the ischemia-reperfusion group compared to the sham group. Pretreatment with tempol (a SOD mimetic, 50mg/kg) or co-enzyme Q(10) (50mg/kg) not only decreased the superoxide production, but also reduced the infarct size and normalized mitochondrial dysfunction in the gastrocnemius muscle. Our results suggest that tourniquet-induced skeletal muscle ischemia-reperfusion injuries including infarct size and mitochondrial dysfunction may be mediated via superoxide overproduction and reduced antioxidant activity. In the future, this murine ischemia-reperfusion model can be adapted to mechanistically evaluate anti-ischemic molecules in tourniquet-induced skeletal muscle injury.

Topics: Animals; Cyclic N-Oxides; Electron Transport Chain Complex Proteins; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Mitochondria; Muscle, Skeletal; Myocardial Infarction; Reperfusion Injury; Spin Labels; Superoxide Dismutase; Superoxides; Tourniquets; Ubiquinone

To evaluate the protective effects of two naturally occurring antioxidants, α-Lipoic acid and coenzyme Q10 on the response to in vitro ischemia of the rabbit urinary bladder. We measured free fatty acid (FFA) content, phospholipid (PL) content, malondialdehyde (MDA) levels, and phospholipase A(2) activity (PLA) of subcellular compartments. Twenty New Zealand White male rabbits were separated into four groups of five rabbits each. The in vitro whole bladders from Groups 1 and 2 received a 3 h incubation under normal oxygenated physiological conditions. The bladders were stimulated by field stimulation at 1 and 3 h. The bladders from groups 3 and 4 underwent 1 h incubation time under normal oxygenated physiological conditions. After 1 h, the bladders were stimulated with field stimulation. After a maximal pressure response was recorded, the stimulation was turned off and the bath medium changed to one equilibrated with 95% nitrogen, 5% oxygen without glucose (ischemic medium) and incubated for 1 h with field stimulations occurring at 5 min intervals during this time. At the end of this hour of ischemia with repetitive stimulation, the bath was changed to an oxygenated medium with glucose for a 1-h reperfusion period after which the stimulation was repeated. The rabbits from groups 2 and 4 received α-Lipoic acid (10 mg/kg/day) + Coenzyme Q10 (3 mg/kg/day) by gavage for 4 weeks before the experiment. At the end of the experimental period, each bladder was opened longitudinally, and the muscle and mucosa separated by blunt dissection, frozen under liquid nitrogen, and stored at -80°C for biochemical analyses. Each tissue was fractionated by differential centrifugation into nuclear, mitochondrial, synaptosomal, and cytosol (supernatant) components. PL, FFA, MDA, and PLA were analyzed using standard biochemical techniques. Post-ischemic contractility only returned to 30% of control of the untreated group. However, post-ischemic contractility of the treated group returned to approximately 70% of control. PL loss in the muscle mitochondria and synaptosomes was prevented by antioxidant treatment, while the mucosal layer showed a significant drop in PL with antioxidants treatment. Administration of CoQ + LA significantly decreased MDA levels in both control and ischemic tissues in both the muscle and mucosal bladder layers, especially substantial in the microsomal and mitochondrial components. Treatment had variable effects on PLA(2) activity. Treatment of bladder d

Topics: Animals; Antioxidants; Fatty Acids, Nonesterified; Ischemia; Lipid Peroxidation; Male; Malondialdehyde; Mucous Membrane; Muscle, Smooth; Organ Size; Phospholipases A2; Phospholipids; Rabbits; Reperfusion Injury; Thioctic Acid; Ubiquinone; Urinary Bladder

In this experimental study, we assessed the preventive effects of coenzyme Q(10) (CoQ(10)) in a rat model of ischemia/reperfusion injury. The results of this study show that CoQ(10) administration before the reperfusion period of testicular torsion provides a significant decrease in testicular lipid peroxidation products and expressions of inducible nitric oxide synthase, endothelial nitric oxide synthase, and germ cell-specific apoptosis.

Topics: Animals; Apoptosis; Disease Models, Animal; Down-Regulation; Lipid Peroxidation; Male; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Rats; Rats, Wistar; Reperfusion Injury; Spermatic Cord Torsion; Testis; Ubiquinone

Ischaemia-reperfusion injury is a life-threatening complication of lung transplantation. Attempts to ameliorate this injury have included optimization of donor management and improving techniques of lung preservation. However, few investigators have sought to pretreat potential recipients. Coenzyme Q(10) (CoQ(10)) is a potent antioxidant and cellular energizer that has been shown to protect the heart against injury. However, its protective effect in the lung is unknown. We therefore set out to study the impact of Coenzyme Q(10) pretreatment in a model of mild and severe lung injury.. We evaluated the impact of CoQ(10) in a two-stage laboratory study. In the first stage, in order to measure the magnitude of increase in tissue and plasma CoQ(10) following oral therapy we administered high-dose oral CoQ(10) to rats (n = 6). In the second stage we evaluated the impact of CoQ(10) in the rat lung (n = 10) that was subjected to 230 min of normoxic lung injury or 90 min of warm ischaemia and 120 min of reperfusion in a model of lung transplantation.. High-dose oral CoQ(10) for 7 days produced a 15-fold increase in plasma and a 3-fold increase in lung CoQ(10). In the normoxic lung, the injury-induced rise in peak airway pressure was reduced by CoQ(10) treatment at 90 min (P = 0.037) and at 120 min (P = 0.005) without any change in arterial oxygen. In the lung subjected to severe ischaemia-reperfusion injury, CoQ(10) did not reduce the injury-induced increase in peak airway pressure (P = 0.599) nor the decrease in arterial oxygen (P = 0.844). However, CoQ(10) markedly reduced the increase in tumour necrosis factor-alpha in ischaemic compared with normoxic lung (P = 0.027).. The effect of CoQ(10) pretreatment is insufficient to protect the lung against severe ischaemia-reperfusion as may occur in lung transplantation. However, in the setting of less severe pulmonary injury as in anaesthesia and non-transplant surgery, CoQ(10) may have a protective role.

Topics: Administration, Oral; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Lung; Lung Injury; Lung Transplantation; Male; Protective Agents; Rats; Reference Values; Reperfusion Injury; Treatment Outcome; Ubiquinone

To investigate the possible role of vitamin E, coenzyme Q10 and rutin in ameliorating the biochemical changes in brain and serum induced by cerebral ischemia/reperfusion (I/R) in whole body γ-irradiated rats.. Cerebral ischemia was induced in male Wistar rats (either irradiated or non-irradiated) followed by reperfusion.. I/R increased brain content of malondialdehyde (MDA) and depleted its glutathione (GSH) content with a compensatory elevation in cytosolic activities of glutathione peroxidase (GPx) and glutathione reductase (GR) enzymes. It also raised brain cytosolic lactate dehydrogenase (LDH) activity and calcium (Ca(2+)) level. Furthermore, I/R provoked an inflammatory response reflected by an increment in serum levels of the proinflammatory cytokines tumour necrosis factor-α (TNF-α) and interlukin-1β (IL-1β). Moreover, induction of I/R in irradiated rats resulted in a further increase in brain oxidative stress and cytosolic LDH activity, disturbed brain Ca(2+) homeostasis and exaggerated the inflammatory reaction. During irradiation, administration of each of vitamin E, coenzyme Q10 (CoQ10) and rutin to irradiated rats before induction of I/R, alleviated the brain oxidative stress. Moreover, these antioxidants caused attenuation of the rise of the cytosolic activities of GPx and GR. A lowering effect of the cytosolic LDH activity and Ca(2+) level were caused by treatment with antioxidants. Each of vitamin E and rutin revealed an anti-inflammatory action of these antioxidants, while CoQ10 had no effect on serum levels of TNF-α and IL-1β.. These findings indicate that supplementation with either vitamin E, CoQ10 or rutin ameliorated most of the biochemical changes induced by I/R in irradiated rat brain and serum.

Topics: Animals; Antioxidants; Brain Ischemia; Gamma Rays; Glutathione; Interleukin-1beta; Male; Malondialdehyde; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Rats, Wistar; Reperfusion Injury; Rutin; Tumor Necrosis Factor-alpha; Ubiquinone; Vitamin E

Ischemia/reperfusion (I/R) can significantly change the nerve function of the bladder, thus resulting in detrusor weakness and overactivity. CoQ10 is a lipid-soluble cofactor found naturally in the mitochondria and has been reported to have neuroprotective and antiapoptosis effects. The aim of this study is to determine if CoQ10 can protect bladders subjected to I/R injury.. Four groups of male New Zealand White rabbits (N = 4) were treated with CoQ10 (3 mg/kg body weight/day) (groups 1 and 2) or vehicle (groups 3 and 4). In groups 2 and 4 (I/R groups), bilateral vesicular ischemia was induced for 2 hr and the rabbits allowed to recover for 2 weeks. Groups 1 and 3 were controls and given sham surgery. The cholinergic nerve marker, vesicular acetylcholine transporter (VAChT), was examined by western blotting. Nerve density and cell apoptosis were calculated by immunohistochemistry.. I/R significantly decrease bladder innervation; CoQ10 has significant neuroprotective effects, which are evidenced by increased VAChT expression and neurofilament immunostaining. Detrusor cells apoptosis increase significantly by I/R. CoQ10 control and I/R groups both show significantly lower apoptosis than vehicle groups.. The current study clearly demonstrated that these CoQ10 supplement provides significant bladder protection against I/R injury. This protective effect is in part by protecting damage to cholinergic innervation.

Topics: Animals; Antioxidants; Apoptosis; Blotting, Western; Female; Fluorescent Antibody Technique; Immunohistochemistry; In Situ Nick-End Labeling; In Vitro Techniques; Neurofilament Proteins; Neuroprotective Agents; Peripheral Nerve Injuries; Peripheral Nerves; Rabbits; Reperfusion Injury; Ubiquinone; Urinary Bladder; Vesicular Acetylcholine Transport Proteins

Here we report effect of ischemia-reperfusion on mitochondrial Ca2+ uptake and activity of complexes I and IV in rat hippocampus. By performing 4-vessel occlusion model of global brain ischemia, we observed that 15 min ischemia led to significant decrease of mitochondrial capacity to accumulate Ca2+ to 80.8% of control whereas rate of Ca2+ uptake was not significantly changed. Reperfusion did not significantly change mitochondrial Ca2+ transport. Ischemia induced progressive inhibition of complex I, affecting final electron transfer to decylubiquinone. Minimal activity of complex I was observed 24 h after ischemia (63% of control). Inhibition of complex IV activity to 80.6% of control was observed 1 h after ischemia. To explain the discrepancy between impact of ischemia on rate of Ca2+ uptake and activities of both complexes, we performed titration experiments to study relationship between inhibition of particular complex and generation of mitochondrial transmembrane potential (DeltaPsi(m)). Generation of a threshold curves showed that complex I and IV activities must be decreased by approximately 40, and 60%, respectively, before significant decline in DeltaPsi(m) was documented. Thus, mitochondrial Ca2+ uptake was not significantly affected by ischemia-reperfusion, apparently due to excess capacity of the complexes I and IV. Inhibition of complex I is favourable of reactive oxygen species (ROS) generation. Maximal oxidative modification of membrane proteins was documented 1 h after ischemia. Although enhanced formation of ROS might contribute to neuronal injury, depressed activities of complex I and IV together with unaltered rate of Ca2+ uptake are conditions favourable of initiation of other cell degenerative pathways like opening of mitochondrial permeability transition pore or apoptosis initiation, and might represent important mechanism of ischemic damage to neurones.

Topics: Adaptor Protein Complex 1; Adaptor Protein Complex 4; Animals; Azides; Brain Ischemia; Calcium; Ferricyanides; Hippocampus; Male; Membrane Potentials; Membrane Proteins; Mitochondria; Mitochondrial Diseases; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Rotenone; Spectrometry, Fluorescence; Ubiquinone; Uncoupling Agents

Glaucoma is a worldwide leading cause of irreversible vision loss characterized by progressive death of retinal ganglion cells (RGCs). In the course of glaucoma, RGC death may be the consequence of energy impairment that triggers secondary excitotoxicity and free radical generation. There is substantial evidence also that a number of free radical scavengers and/or agents that improve mitochondrial function may be useful as therapies to ameliorate cell death in various neurological disorders including glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and its protective effect has been attributed in part to its free radical scavenger ability and to a specific regulation of the mitochondrial permeability transition pore. Using an established animal model of transient retinal ischemia, we have conclusively identified a role for abnormal elevation of extracellular glutamate in the mechanisms underlying RGC death that occurs, at least in part, via activation of the apoptotic program. Under these experimental conditions, N-methyl-D-aspartate (NMDA) and non-NMDA subtype of glutamate receptor antagonists, nitric oxide synthase inhibitors, and CoQ10 afford retinal protection supporting an important role for excitotoxicity in the mechanisms underlying RGC death.

Topics: Animals; Calpain; Cell Death; Glaucoma; Glutamic Acid; Humans; Intraocular Pressure; Neuroprotective Agents; Oxidative Stress; Rats; Reperfusion Injury; Retina; Retinal Ganglion Cells; Ubiquinone

Ischemia, reperfusion, and free radical generation have been recently implicated in the progressive bladder dysfunction. Coenzyme Q10 (CoQ10) is a pro-vitamin like substance that appears to be efficient for treatment of neurodegenerative disorders and ischemic heart disease. Our goal was to investigate the potential protective effect of CoQ10 in a rabbit model of in vivo bilateral ischemia and ischemia/reperfusion (I/R).. Six groups of four male New Zealand White rabbits each were treated with CoQ10 (3 mg/kg body weight/day-dissolved in peanut oil) (groups 1-3) or vehicle (peanut oil) (groups 4-6). Groups 1 and 4 (ischemia-alone groups) had clamped bilateral vesical arteries for 2 h; in groups 2 and 5 (I/R groups), bilateral ischemia was similarly induced and the rabbits were allowed to recover for 2 weeks. Groups 3 and 6 were controls (shams) and were exposed to sham surgery. The effects on contractile responses to various stimulations and biochemical studies such as citrate synthase (CS), choline acetyltransferase (ChAT), superoxide dismutase (SOD), and catalase (CAT) were evaluated. The protein peroxidation indicator, carbonyl group, and nitrotyrosine contents were analyzed by Western blotting.. Ischemia resulted in significant reductions in the contractile responses to all forms of stimulation in vehicle-fed rabbits, whereas there were no reductions in CoQ10-treated rabbits. Contractile responses were significantly reduced in vehicle-treated I/R groups, but significantly improved in CoQ10-treated rabbits. Protein carbonylation and nitration increased significantly in ischemia-alone and I/R bladders; CoQ10 treatment significantly attenuated protein carbonylation and nitration. CoQ10 up-regulated SOD and CAT activities in control animals; the few differences in CoQ10-treated animal in SOD and CAT after ischemia and in general increase CAT activities following I/R.. CoQ10 supplementation provides bladder protection against I/R injury. This protection effect improves mitochondrial function during I/R by repleting mitochondrial CoQ10 stores and potentiating their antioxidant properties.

Topics: Animals; Antioxidants; Catalase; Choline O-Acetyltransferase; Citrate (si)-Synthase; Dietary Supplements; Male; Mitochondria; Muscle Contraction; Rabbits; Reperfusion Injury; Superoxide Dismutase; Ubiquinone; Urinary Bladder

N-acetylcysteine, beta-glucan, and coenzyme Q(10) were shown to have antioxidant and anti-inflammatory effects on reperfusion injury. The aim of our study was to determine and evaluate the effects of these agents on ischemia reperfusion injury of limb.. Forty-four New Zealand white rabbits, all female, weighing between 2.3 to 4.2 (mean 3.8) kg, were used in the study. Four study groups were arranged of 11 animals each, by randomization. The first group was the control group (Group C), the other groups were the Group Q, which was medicated with coenzyme Q10, the Group betaG, which was medicated with beta-glucan, and the Group N, medicated with N-acetylcysteine. After baseline measurements, for the ischemia-reperfusion experiments, common iliac artery was clamped and collateral flow was occluded by a rubber arterial tourniquet wrapped around the thigh at the proximal third of the leg. After 60 min of transient ischemic period, the limb was perfused for 180 min. After perfusion, biopsy was taken from the adductor magnus muscle. Second blood sampling was done after reperfusion period. Blood and tissue analysis were done and evaluated statistically.. Baseline and post-reperfusion levels of glutathione peroxidase (GPx), super oxide dismutase (SOD), malonyldialdehyde (MDA), and nitric oxide (NO) changed significantly. While MDA levels increased in the control group, it decreased in the other study groups. The increase in GPx and SOD levels were significant in all groups except the control group. Levels of NO were found to have decreased in the control group, whereas it had increased in the other groups.. Antioxidant medication may help lowering limb ischemia reperfusion injury. All mentioned medications in our study are shown to be able to have an effective role for preventing ischemia reperfusion injury to some extent through their antioxidant properties.

Topics: Acetylcysteine; Animals; Antioxidants; beta-Glucans; Coenzymes; Cytoprotection; Female; Glutathione Peroxidase; Hindlimb; Malondialdehyde; Muscle, Skeletal; Nitric Oxide; Rabbits; Reperfusion Injury; Superoxide Dismutase; Ubiquinone

Ischemia-reperfusion (I/R) is a condition leading to serious complications due to death of cardiac myocytes. We used the cardiomyocyte-like cell line H9c2 to study the mechanism underlying cell damage. Exposure of the cells to simulated I/R lead to their apoptosis. Over-expression of Bcl-2 and Bcl-x(L) protected the cells from apoptosis while over-expression of Bax sensitized them to programmed cell death induction. Mitochondria-targeted coenzyme Q (mitoQ) and superoxide dismutase both inhibited accumulation of reactive oxygen species (ROS) and apoptosis induction. Notably, mtDNA-deficient cells responded to I/R by decreased ROS generation and apoptosis. Using both in situ and in vivo approaches, it was found that apoptosis occurred during reperfusion following ischemia, and recovery was enhanced when hearts from mice were supplemented with mitoQ. In conclusion, I/R results in apoptosis in cultured cardiac myocytes and heart tissue largely via generation of mitochondria-derived superoxide, with ensuing apoptosis during the reperfusion phase.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Caspase 3; Cell Line; DNA, Mitochondrial; Mice; Mice, Inbred C57BL; Mitochondria; Myocytes, Cardiac; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Superoxide Dismutase; Ubiquinone

The role of oxygen free radical generation during reversible focal cerebral ischemia and its relationship to nitric oxide mediated mechanisms were examined. In this study, a left frontal cortex microdialysis probe was placed into the previously defined ischemic penumbra region and perfused with a salicylate/CSF solution in the presence or absence of the nitric oxide synthase (NOS) inhibitor L-NAME. Rats were then subjected to transient left hemisphere focal cerebral ischemia. Dialysate was collected at baseline and during the ischemic/reperfusion phase, and the hydroxylation products of salicylate were measured by HPLC with electrochemical detection. A significant elevation of free radical adduct formation was observed in the penumbra region during ischemia/reperfusion. This elevation was significantly attenuated by L-NAME during the reperfusion phase. Elevation of free radical adduct formation within the penumbra region during cerebral ischemia/reperfusion may be mediated in part by NOS-dependent mechanisms.

Topics: Animals; Enzyme Inhibitors; Free Radicals; Ischemic Attack, Transient; Neocortex; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ubiquinone

Expression of immediate early genes has been reported during reperfusion after ischemia in rat livers due to oxygen radical formation. This study investigates in perfused pig livers the effect of the antioxidant idebenone and of cold ischemia time on the gene expression of c-fos and c-jun.. Livers were perfused for 210 min after 0.5 h or 20 h ischemic storage (4 degrees C). One group of pigs was fed idebenone (280 mg/day/7days) prior to organ harvesting. C-fos and c-jun mRNA were determined by RT-PCR at 3, 30, 60, 120 180, 210 min during reperfusion.. Lipid peroxidation increased in liver tissue form 0.54 +/- 0.21 to 1. 09 +/- 0.54 nmol MDA/mg protein during reperfusion after 20 h compared to 0.5 h cold storage. This was antagonized by idebenone (0. 68 +/- 0.20 nmol/MDA/mg protein). C-fos and c-jun were strongly induced in livers stored for 20 h, which was attenuated by idebenone (p < 0.05).. These findings suggest that cold ischemia time and oxygen radicals are critical for immediate early gene expression and that application of an effective antioxidant can attenuate this early stress reaction of the pig liver.

Topics: Animals; Antioxidants; Benzoquinones; Cold Temperature; Disease Models, Animal; Female; Gene Expression Regulation; Genes, fos; Genes, jun; Humans; In Vitro Techniques; Lipid Peroxidation; Liver; Liver Transplantation; Male; Molecular Structure; Perfusion; Rats; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Ubiquinone

In this study, we examined the effect of the neuroprotective agent 2, 3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone (CV-2619) on reperfusion injury in cultured rat astrocytes after exposure to hydrogen peroxide (H(2)O(2))-containing medium. CV-2619 (10 nM to 10 microM) significantly attenuated the reperfusion-induced decrease in cell viability. The compound showed an anti-apoptotic effect in this astrocyte injury model. Antioxidants such as ascorbic acid, alpha-tocopherol and reduced glutathione also inhibited H(2)O(2) exposure-induced cytotoxicity. CV-2619 did not affect the levels of reactive oxygen species, but it increased nerve growth factor (NGF) production. The effect of CV-2619 on H(2)O(2) exposure-induced cytotoxicity was blocked by cycloheximide and anti-NGF antibody. The protective effect of CV-2619 was antagonized by the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase inhibitor 2'-amino-3'-methoxyflavone and the phosphatidylinositol-3 kinase inhibitor wortmannin. These findings suggest that the effect of CV-2619 is mediated at least partly by NGF production in astrocytes and that ERK and phosphatidylinositol-3 kinases play a role in the downstream mechanism.

Topics: Animals; Antioxidants; Astrocytes; Benzoquinones; Cells, Cultured; Nerve Growth Factor; Neuroprotective Agents; Rats; Rats, Wistar; Reperfusion Injury; Ubiquinone

The distribution patterns of amyloid precursor protein (APP) fragments were studied immunocytochemically in the rat brain before, after 10 min ischemia and following treatment by idebenone. Six months after brain ischemia intense staining for APP appeared in extra- and intracellular space. These findings indicate that APP is involved in the degeneration process of brain neuronal and glial cells following ischemia-reperfusion injury and anti-oxidative therapy did not prevent and/or stop this phenomenon.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Amyloidosis; Animals; Antioxidants; Benzoquinones; Cell Death; Drug Evaluation, Preclinical; Extracellular Space; Female; Free Radicals; Heart Arrest; Hypoxia-Ischemia, Brain; Intracellular Fluid; Neuroglia; Neurons; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Risk Factors; Ubiquinone

We examined the effect of coenzyme Q10 (Co Q10) on superoxide radical (O2-) production in a model of rat reperfusion injury. The chemiluminescence method using a derivative of luciferin was used to quantify O2- production by erythrocytes in the reperfused limb after a period of ischaemia. A total of 20 limbs from Lewis rats were preserved at 4 degrees C in Euro-Collins solution for 72 hours, and were grafted orthotopically to syngeneic rats by a microsurgical technique. In the treated group (n = 10), Co Q10 (10 mg/kg) was injected intraperitoneally into the recipients one hour before reperfusion. In the control group (n = 10), the same dose of solvent was given. To measure the extent of oxidative stress, heparinised blood from the treated and control recipients was collected before, and at 15, 30, and 60 minutes after reperfusion for the measurement of chemiluminescence. O2- production in the Co Q10-treated group was significantly lower than in the control group (p < 0.05). Although these findings suggest that Co Q10 scavenged O2- that was produced in the replanted limbs as a result of ischaemia-reperfusion injury, we should consider other possible mechanisms by which this agent may protect against ischaemia-induced reperfusion injury.

Topics: Animals; Antioxidants; Coenzymes; Cytoprotection; Hindlimb; Luminescent Measurements; Male; Oxidative Stress; Rats; Rats, Inbred Lew; Reperfusion Injury; Superoxides; Ubiquinone

In a surgical model of liver ischemia lipid peroxidation occurs, as shown by increase of lipid peroxidation end products, endogenous CoQ9 is oxidized and mitochondrial respiration is lowered; however, pre-treatment of the rats by i.p. injection of CoQ10 for 14 days normalizes the above parameters, presumably by way of the observed high extent of reduction of the incorporated quinone; moreover, liver homogenates of the CoQ10-treated rats are more resistant than those of non-treated rats to oxidative stress induced by an azido free radical initiator. This preliminary study suggests that CoQ10 pre-treatment can be of beneficial effect against oxidative damage during liver surgery transplantation.

Topics: Amidines; Animals; Antioxidants; Ischemia; Lipid Peroxidation; Liver; Oxidants; Rats; Reperfusion; Reperfusion Injury; Ubiquinone; Vitamin A; Vitamin E

Ischemia and subsequent reperfusion induce lipid peroxidation in the cerebrum of the fetal rat. The present study evaluated the antioxidant activity of endogenous coenzyme Q in protecting against the lipid peroxidation induced in the fetal rat brain by ischemia/reperfusion.. We used wistar rats at day 19 of pregnancy. Fetal ischemia was induced by bilateral occlusion of the utero-ovarian artery for 20 minutes. For reperfusion, the occlusion was released and the circulation was restored for 30 minutes. Control rats underwent sham operation. We determined the levels of thiobarbituric acid-reactive substances, the concentrations of coenzyme Q9, coenzyme Q10, and the mitochondrial respiratory control index in fetal brains.. Occlusion for 20 minutes significantly reduced the respiratory control index (p < 0.01), but did not alter the levels of thiobarbituric acid-reactive substances, coenzyme Q9 or coenzyme Q10. Subsequent reperfusion, however, significantly increased the level of thiobarbituric acid-reactive substances (from 6.53+/-1.54 to 11.46+/-3.31 nM/mg of protein, p < 0.01) and significantly decreased the level of coenzyme Q9 (from 291.73+/-108.94 to 162.44+/-56.83 pM/mg of protein, p < 0.05) and that of coenzyme Q10 (from 153.10+/-75.24 to 79.84+/-30.40 pM/mg of protein, p < 0.05). The respiratory control index was still significantly lower following reperfusion than in controls (p < 0.01). Significant negative correlations were observed between the level of thiobarbituric acid-reactive substances and the concentrations of either coenzyme Q9 (r = -0.68, p < 0.001) or coenzyme Q10 (r = -0.70, p < 0.001).. Endogenous coenzyme Q may protect the fetal rat brain against the lipid peroxidation induced by ischemia/reperfusion.

Topics: Animals; Brain Ischemia; Disease Models, Animal; Female; Fetal Hypoxia; Lipid Peroxidation; Mitochondria; Oxygen Consumption; Pregnancy; Rats; Rats, Wistar; Reperfusion Injury; Thiobarbituric Acid Reactive Substances; Ubiquinone

Hepatic ischemia was induced by clamping the hepatic artery, portal vein, and bile duct. After 15 min of ischemia, the hepatic glutathione (GSH) content rapidly decreased. On the other hand, after the start of reperfusion, the hepatic GSH levels promptly increased and reached a peak at about 1 h, and thereafter decreased to a minimum level by 2 h. Under such conditions, we examined the changes in the methionine adenosyltransferase (MAT) activity in the liver. Though the time course of MAT activity was somewhat delayed compared with that of the hepatic GSH levels, both patterns were substantially similar during ischemia-reperfusion. In contrast to the changes in the MAT activity during ischemia-reperfusion, the levels of MAT protein were unchanged during these periods. When endogenous antioxidant coenzyme Q(10) (CoQ(10)) was administered to rats prior to ischemia, both the reduction in the MAT activity and hepatic GSH levels induced by ischemia-reperfusion were protected. Our findings suggest that CoQ(10) may posttranslationally regulate the MAT activity via the changes in the GSH level in the liver.

Topics: Animals; Antioxidants; Coenzymes; Cytoprotection; Glutathione; Liver; Male; Methionine Adenosyltransferase; Rats; Rats, Wistar; Reperfusion Injury; Time Factors; Ubiquinone

We examined whether pentoxifylline (PTX) and coenzyme Q10 (Q) pretreatment affect ischemia-reperfusion damage in the rat liver.. Twenty minutes of reflow following 30 min of ischemia was performed. Before the experiment, rats were treated PTX 50 mg/kg, IP or PTX 50 mg/kg IP + Q10 mg/kg, intragastric, or untreated. Rats were divided into four groups: control (C), ischemia-reperfusion (IR), PTX-treated (P), and Q+PTX-treated (QP) groups. Hepatic glutathione (GSH) and malondialdehyde (MDA) levels and catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reductase (GSSGR) activities were measured.. In IR group GSH levels decreased (p<0.01), conversely MDA levels increased (p<0.01). PTX pretreatment did not affect GSH and MDA values, but Q+PTX pretreatment improved of those (p<0.01). It was shown that catalase and GSH-Px activities increased during ischemia-reperfusion (p<0.01, both of), but PTX pretreatment did not significantly ameliorate those activities. GSSGR activity was higher in IR group than in basal levels (p<0.01). The decrease GSSGR activity that was observed in P group was not significant compared to IR group. During ischemia/reperfusion also SOD activity increased as compared with controls (p<0.05). In PTX-treated group, SOD activity was significantly higher than control and ischemia/reperfusion groups (p<0.01, both of). Q+PTX treatment ameliorated those enzyme activities to the control values.. Short-term hepatic ischemia-reperfusion diminished GSH, increased MDA levels and induced some antioxidant enzyme activities. Q+PTX pretreatment was useful in hepatic ischemia-reperfusion injury, but treatment of PTX alone did not cause beneficial effect in the present study.

Topics: Animals; Catalase; Coenzymes; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Hematologic Agents; Ischemia; Liver; Male; Malondialdehyde; Pentoxifylline; Rats; Rats, Wistar; Reperfusion Injury; Superoxide Dismutase; Ubiquinone

Despite the large body of evidence for a major role of neutrophils and oxidant stress, the exact pathogenesis of the early ischemia/reperfusion injury after cold preservation of the liver is not well understood. The potential benefit of an antioxidant on metabolic liver function during reperfusion has been demonstrated in several studies.. We describe a cold storage/reperfusion damage model with isolated perfused pig livers, where the effects of neutrophils and idebenone, a recently developed benzoquinone antioxidant were studied. The integrity of sinusoidal endothelial cells (SEC) was estimated by hyaluronic acid concentration in perfusate and the expression of endothelial constitutive nitric oxide synthase (ecNOS) after reperfusion and compared to lipid peroxidation and antioxidant content.. Hyaluronic acid displayed the highest levels and ecNOS mRNA was most depressed in livers reperfused with neutrophils after 20 h cold storage; this was accompanied by an increase in lipid peroxidation (TBARS) and a breakdown of endogenous lipophilic antioxidants (alpha-tocopherol and coenzyme Q-10). These effects were attenuated, when neutrophils were excluded from reperfusion and almost completely abolished by the addition of 200 mumol/L idebenone.. These data suggest that a leukocyte-mediated damage based on reactive oxygen species markedly contributes to the reperfusion injury of SEC after cold preservation of the liver. Therefore, the presence of effective antioxidants in the early reperfusion phase may be beneficial for liver graft integrity.

Topics: Animals; Antioxidants; Benzoquinones; Cold Temperature; Depression, Chemical; Endothelium; Leukocytes; Liver; Oxidative Stress; Reperfusion Injury; Swine; Ubiquinone

The purpose of the present study was to elucidate the effect of hepatic reflow following ischemia on the remnant liver after hepatectomy with occluded hepatic blood inflow in dogs with obstructive jaundice. When 40% hepatectomy was performed with 10-min occlusion of hepatic blood inflow in dogs with obstructive jaundice, the lipid peroxide content in the remnant liver increased significantly, together with a reduction in superoxide dismutase (SOD)-like activity. The levels of endotoxin and beta-N-acetyl hexosaminase (NAH) in peripheral blood also increased. The phagocytic index increased transiently after 30 min, followed by a marked decrease after 3h. Histologically, degeneration and necrosis of the hepatic parenchymal cells were demonstrated, and survival rate at 7 days was only 23.1%. With the administration of coenzyme Q10 (CoQ10) or styrene-co-maleic acid SOD (SM-SOD), these phenomena were significantly inhibited, and the survival rate improved. After hepatectomy, Kupffer cells in the remnant liver were activated by increased endotoxin levels in the portal vein, inducing the production of free radicals, which, in turn, damaged the Kupffer cells by reducing endotoxin clearance. Finally, the impaired functional reserve in the remnant liver provoked liver failure. The administration of CoQ10 or SM-SOD prevented the occurrence of these phenomena triggered by the free radicals generated by Kupffer cells, stimulated by endotoxin in the portal vein.

Topics: Animals; beta-N-Acetylhexosaminidases; Cholestasis; Coenzymes; Dogs; Endotoxins; Female; Free Radicals; Hepatectomy; Kupffer Cells; Lipid Peroxides; Liver; Male; Phagocytosis; Polystyrenes; Reperfusion Injury; Superoxide Dismutase; Survival Rate; Ubiquinone

Cardiac ischemia reperfusion (I/R) injury causes coronary vascular dysfunction. Coenzyme Q10 (CoQ), which preserves cardiac mechanical function after I/R, recently has been recognized as a free radical scavenger. We hypothesized that CoQ protects coronary vascular reactivity after I/R via an antioxidant mechanism.. Rats were pretreated with either CoQ (20 mg/kg intramuscular and 10 mg/kg intraperitoneal [CoQ group]) or a vehicle (Control) before the experiment. Isolated perfused rat hearts were subjected to 25 minutes of global normothermic ischemia and 40 minutes of reperfusion. The reperfusion-induced oxidative burst was directly assessed by lucigenin enhanced chemiluminescence. Coronary flow was measured at equilibration and after reperfusion with or without bradykinin, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator. The effect of intracoronary infusion of hydrogen peroxide (H2O2 0.1 mumol/gm body weight given over 5 minutes), simulating the free radical burst after I/R, also was evaluated.. I/R decreased the bradykinin-induced change in coronary flow (-5% +/- 4% versus 26% +/- 3% at equilibration; p < 0.05) and the SNP-induced change (+20% +/- 6% versus +56% +/- 5% at equilibration; p < 0.05). The coronary vasculature after H2O2 infusion revealed a similar loss in vasodilatory responsiveness (+4% +/- 4% in response to bradykinin, +35% +/- 8% in response to SNP; p < 0.05 versus equilibration). Pretreatment with CoQ improved BK-induced vasorelaxation after I/R (+12% +/- 2%; p < 0.05 versus control I/R) or H2O2 infusion (18% +/- 4%; p < 0.05 versus control I/R) but failed to improve SNP-induced vasorelaxation. The CoQ pretreatment decreased the I/R-induced maximal free radical burst (9.3 +/- 0.8 x 10(3) cpm versus 11.5 +/- 1.1 x 10(3) cpm; p < 0.05) during the early period of reperfusion.. Endothelium-dependent vasorelaxation is more sensitive than endothelium-independent relaxation to I/R injury. Via a direct antioxidant effect, CoQ preserved endothelium-dependent vasorelaxation by improving tolerance to I/R injury.

Topics: Acridines; Animals; Antioxidants; Bradykinin; Coenzymes; Coronary Circulation; Endothelium, Vascular; Hydrogen Peroxide; Luminescent Measurements; Male; Myocardial Ischemia; Nitroprusside; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ubiquinone; Ventricular Function, Left

Topics: Animals; Antibodies, Monoclonal; Coenzymes; Intercellular Adhesion Molecule-1; Intestine, Small; Lymphocyte Function-Associated Antigen-1; Male; Mesenteric Artery, Superior; Organ Preservation; Rats; Rats, Wistar; Reperfusion Injury; Ubiquinone

Preservation with University of Wisconsin (UW) solution can maintain liver graft function and produces survival rates of recipients higher than that with Euro Collins (EC) solution. To explore the underlying mechanisms, we transplanted rat livers following cold preservation with EC or UW solution for 18 hr, and measured hepatic adenine nucleotide levels, the percentage of water content, lactate levels, and endogenous antioxidant levels (alpha-tocopherol [alpha-Toc], reduced coenzyme Q9 [CoQ9H2], reduced coenzyme Q10, [CoQ1OH2] and reduced glutathione [GSH] during preservation and after transplantation. The adenosine triphosphate levels of the liver grafts preserved with UW solution recovered after reperfusion more rapidly and reached a higher level than those preserved with EC solution. UW solution caused a reduction in hepatic water content during preservation. Conversely, EC solution induced remarkable tissue edema. In addition, UW solution reduced the rate of hepatic lactate production both during preservation and after reperfusion. The concentrations of hepatic GSH, alpha-Toc, CoQ9H2, and CoQ1OH2 immediately after the graftectomy, and after the 18 hr of preservation with both EC and UW solutions, did not differ from those in the normal liver, and decreased only after transplantation. However, UW solution suppressed significantly the reduction in hepatic GSH, alpha-Toc, and CoQ9H2 after reperfusion, compared with EC solution. These results suggest that long-term cold storage induces tissue edema, reflecting a disturbance of the microcirculation during preservation, followed by parenchymal cell damage mediated by free radicals after reperfusion. The protective effects of UW solution could be attributable to the inhibition of free radical production after reperfusion.

Topics: Adenine Nucleotides; Adenosine; Adenosine Triphosphate; Allopurinol; Animals; Antioxidants; Cold Temperature; Glutathione; Insulin; Lactates; Liver; Liver Transplantation; Male; Organ Preservation Solutions; Raffinose; Rats; Rats, Wistar; Reperfusion Injury; Survival Rate; Tissue Preservation; Ubiquinone; Vitamin E; Water

The authors prepared an experimental animal model of ischemia and reperfusion of the limbs to evaluate in vivo the reactive oxygen species involvement and protective role of coenzyme Q10 in reperfusion injury. A group of male rabbits (untreated group) underwent clamping of abdominal aorta for 3 hr and then declamping; at intervals blood sampling was drawn for coenzyme Q10, vitamin E, lactic acid and creatine kinase assays. Another group of male rabbits (treated group) underwent the same ischemia period but before declamping coenzyme Q10 was administered intra aorta. In untreated group, coenzyme Q10 and vitamin E plasma levels decreased while lactic acid and creatine kinase plasma levels increased during reperfusion. These data demonstrate that, after only 3 hr of ischemia, the extremities show a biochemical reperfusion injury, and this involves an increased consumption of antioxidants such as coenzyme Q10 and vitamin E. In the treated group, the increase of creatine kinase plasma levels during reperfusion was not significant, while the decrease in vitamin E was more marked.

Topics: Animals; Aorta, Abdominal; Coenzymes; Constriction; Creatine Kinase; Extremities; Ischemia; Isoenzymes; Lactates; Lactic Acid; Male; Rabbits; Reactive Oxygen Species; Reperfusion Injury; Ubiquinone; Vitamin E

Sixteen dogs, divided randomly into a control group and coenzyme Q10 group (10mg/kg, intraperitoneally before the operation), underwent deep hypothermic circulatory arrest with cardiopulmonary bypass, as is done clinically. At four time points cerebral cortex and cerebrospinal fluid specimens were collected to study free radical formation, energy metabolism, and ultrastructure. During cardiopulmonary bypass cerebral electron spin resonance spectra and malondialdehyde contents were progressively higher than before bypass, especially at the 60 minutes of circulatory arrest and 30 minutes of reperfusion (p1 < 0.01, p2 < 0.05). In the coenzyme Q10 group at the latter two time points, they had increased less than in the control group at same time points (p1 < 0.02, p2 < 0.005). Adenosine triphosphate content in the cortex during bypass decreased gradually from the prebypass level (p1 < 0.02, p2 = p3 < 0.001), while lactate in cerebrospinal fluid increased (p1 < 0.05, p2 = p3 < 0.001). In the coenzyme Q10 group, adenosine triphosphate at the latter two time points was greater than that in the control group (p1 = p2 < 0.05), while the lactate changes were not significantly different from control at each time point (all p > 0.05). Ultrastructure of the cortex was normal before bypass and almost normal during bypass, but it was obviously abnormal at 60 minutes of circulatory arrest and more seriously abnormal at 30 minutes of reperfusion. In the coenzyme Q10 group the abnormality was obviously reduced. The results suggest that oxygen-derived free radicals and abnormal energy metabolism might play critical roles in brain ischemia/reperfusion injury. Coenzyme Q10 could protect the brain by improving cerebral metabolism.

Topics: Adenosine Triphosphate; Animals; Cardiopulmonary Bypass; Cerebral Cortex; Coenzymes; Dogs; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Heart Arrest, Induced; Hypothermia, Induced; Lactates; Male; Malondialdehyde; Reperfusion Injury; Ubiquinone

Topics: Animals; Free Radicals; Glutathione; Ischemia; Liver; Liver Diseases; Mitochondria, Liver; Rats; Reperfusion Injury; Ubiquinone; Vitamin E; Xanthine Dehydrogenase; Xanthine Oxidase

We examined simple cold preservation of rat limbs in Euro-Collins' solution to elucidate the protective effect of coenzyme Q10 (CoQ10) on the ischemia-induced reperfusion injury in an ischemic extremity replant model. A total of 126 Lewis rat limb replants were performed. Limbs were amputated from donor rats and preserved at 4 degrees C in Euro-Collins' solution and were orthotopically grafted to isogeneic rats by microsurgical technique. In the experimental groups (n = 42), coenzyme Q10 (10 mg/kg) was injected intraperitoneally into the recipients about 1 hour before reperfusion. In the control groups (n = 84), the same dose of solvent was given by the same route. We evaluated vascular patency of anastomoses by direct observation or microangiogram and performed histologic examinations 7 days after replantation. In the control groups, the ischemic limit was 96 hours. Ischemic limbs treated with coenzyme Q10 showed a statistically significant (p < 0.05) improvement in vascular patency after 72 and 96 hours of ischemia. Histologically, bone viability with osteoblastic activity was maintained in coenzyme Q10-treated animals of the 72-hour ischemic group. We conclude that the protective effect of coenzyme Q10 on reperfusion injury is suggested in this replant model.

Topics: Animals; Antioxidants; Coenzymes; Cold Temperature; Hindlimb; Hypertonic Solutions; Male; Rats; Rats, Inbred Lew; Reperfusion Injury; Time Factors; Tissue Preservation; Ubiquinone

Topics: Adenosine Triphosphate; Animals; Coenzymes; Intestine, Small; Ischemia; Kinetics; Rats; Rats, Inbred Strains; Reperfusion Injury; Time Factors; Ubiquinone

This study was made in a canine isolated gracilis muscle model to measure directly the free radicals, to predict the severity of ischemia and reperfusion injury of the skeletal muscle by measuring its surface pH (mspH), and to determine the effect of Coenzyme Q10 (CoQ10) in reducing the extent of muscle injury. Animals were divided into three groups: group A (control, n = 10), group B (untreated, n = 10), and group C (CoQ10 treated, n = 10). In both groups B and C, 5 hr ischemia followed by 40 min of reperfusion was made. Free radicals were measured directly by electron spin resonance spectrometer (ESR) and mspH was measured using a pH microprobe. Serum creatine phosphokinase (CPK) was estimated before ischemia, 5 and 30 min after reperfusion. The extent of muscle injury was evaluated morphologically by Evan's blue dye exclusion test. ESR intensity in group B was 0.55 +/- 0.19 and decreased to 0.30 +/- 0.04 in group C (P less than 0.01). Rate of recovery of mspH was higher in group C (7.16 +/- 0.06) compared to group B (6.88 +/- 0.11, P less than 0.01) and CPK in group C was less (847 +/- 381 IU/liter) than in group B (1356 +/- 519 IU/liter, P less than 0.05) after 30 min of reperfusion. In group C the morphological muscle injury was less (37.8 +/- 5%) compared to group B (56.7 +/- 3.6%, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Coenzymes; Dogs; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Hydrogen-Ion Concentration; Ischemia; Male; Muscles; Oxygen; Reperfusion Injury; Ubiquinone

Gastric mucosal blood flow and its regulating factors were studied in normal and stressed rats. In addition, vascular regulating factors and the role of CoQ10 anion radical and SOD (superoxide dismutase) level in gastric mucosa were also investigated as well as the influence of 5-HT (5-hydroxytryptamine) on gastric mucosal blood flow. Gastric mucosal blood flow was measured by the hydrogen gas clearance method. The vascular pattern of the stomach was investigated by the infusion method with two-colored silicon rubber. CoQ10 anion radical and SOD levels in gastric tissue were assayed by electron spin resonance (ESR) and radioimmunoassay. The gastric mucosal blood flow decreased significantly early after the induction of stress. Impairment of gastric mucosal blood flow was highly correlated with 5-HT and CoQ10 anion radical and SOD levels. Reduction in gastric mucosal blood flow was consequently due to opening of arteriovenular shunt and hyperpermeability of true capillaries influenced by 5-HT. These results demonstrate that ischemia and reperfusion after reduction of the gastric mucosal blood flow resulted in the sequence of events that led to formation of acute gastric mucosal lesions.

Topics: Animals; Arteriovenous Anastomosis; Burns; Gastric Mucosa; Male; Rats; Rats, Inbred Strains; Reperfusion Injury; Serotonin; Stress, Physiological; Superoxide Dismutase; Ubiquinone

Topics: Allopurinol; Animals; Aspartate Aminotransferases; Coenzymes; Dose-Response Relationship, Drug; Free Radicals; Glutathione; Liver; Necrosis; Oxygen; Rats; Rats, Inbred Lew; Reperfusion Injury; Superoxide Dismutase; Temperature; Ubiquinone

Topics: Adenosine Triphosphate; Animals; Glutathione; Ischemia; Kidney; Lipid Peroxides; Liver; Liver Diseases; Male; Mice; Mice, Inbred ICR; Rats; Rats, Inbred Strains; Reperfusion Injury; Shock, Septic; Ubiquinone; Vitamin E

Topics: Animals; Coenzymes; Free Radicals; Lipid Peroxides; Liver Transplantation; Rats; Reperfusion Injury; Shock, Septic; Superoxide Dismutase; Ubiquinone