Stress In Heart Mitochondria Research Articles

Calcitriol Reduces Adverse Effects of Diclofenac on Mitochondrial Function in Isolated Rat Heart Mitochondria.

The safety of diclofenac (DIC) use in clinical practice has been questioned because of adverse cardiovascular effects. Previous studies have indicated that DIC cause mitochondrial dysfunction and oxidative stress in heart mitochondria. The aim of this study was to investigate the protective effect of calcitriol against the mitochondrial toxicity potency of diclofenac in heart rat mitochondria. For this purpose, rat heart mitochondria were isolated with mechanical lysis and differential centrifugation. Then isolated mitochondria were pretreated with 3 different concentrations of calcitriol (2.5, 5 and 10 µM) for 5 min at 37°C, after which DIC (10 µg/ml) was added to promote deleterious effects on mitochondria. During 1 hour of incubation, using by flow cytometry and biochemical evaluations, the parameters of mitochondrial toxicity were evaluated. Our results showed that DIC (10 µg/ml) caused a significant decrease in succinate dehydrogenase (SDH) activity, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling, and a significant increase in reactive oxygen species (ROS) formation, lipid peroxidation (LP) and oxidative stress. Also, our results revealed that co-administration of calcitriol (5 and 10 µM) with diclofenac markedly ameliorates the mitochondrial toxicity effects in rat hart mitochondria. In this study, we showed that DIC impairs mitochondrial function and induces mitochondrial toxicity in rat heart isolated mitochondria, which were ameliorated by calcitriol. These findings suggest that calcitriol may be a preventive/therapeutic strategy for cardiotoxicity complications caused by DIC.

Induction of Oxidative Stress in Heart Mitochondria under Focal Cerebral Ischemia-Reperfusion and Protective Effect of Ecdysterone

Based on the fact that the acute phase of ischemic stroke is accompanied by the development of cerebrocardial syndrome, oxidative stress in the rat heart mitochondria and possible mechanisms of cardioprotective action of ecdysterone were examined using the model of focal cerebral ischemia-reperfusion. When focal cerebral ischemia-reperfusion, the rate of reactive oxygen species generation, namely superoxide (. O2− ) and hydroxyl radical (. OH), pools of stable hydrogen peroxide (H2O2) increases, and products of lipid peroxidation (diene conjugates and malonic dialdehyde) are accumulated due to the activation of xanthine oxidase (uric acid as a marker), lipoxygenase (leukotriene C4 as marker), and cyclooxygenase (thromboxane B2 as a marker) ways of·O2- generating. In animals treated with ecdysterone for 18 days, the rate of reactive oxygen species generation decreases, pools of lipid peroxidation products are reduced, the ways of·O2-generating are inhibited, mortality of animals decreases. The results obtained confirm the development of oxidative stress in the rat heart mitochondria, strong antiradical properties of ecdysterone, cardioprotective effect of the latter under focal cerebral ischemia-reperfusion.

Індукція нітрозативного стресу в мітохондріях серця щурів за експериментальної ішемії–реперфузії головного мозку та його корекція екдистероном

On the model of focal ischemia-reperfusion of the brain investigated the induction of nitrosative stress in mitochondria of rats hearts and possible mechanisms of protective action of ecdysterone. It is shown that focal ischemia-reperfusion of the brain induced in myocardial mitochondria the activation of constitutive and inducible de novo synthesis of NO by oxidation of L-arginine and not oxidative synthesis of NO through the recovery of oxidized stable metabolites of NO. Strong evidence of induction of nitrosative stress in heart mitochondria by focal ischemia-reperfusion of the brain, was a significant increase in mitochondrial pool of nitrate- and nitrite-anions and pools of nitrosothiols, that is proof of the formation and decay of peroxynitrite--a key marker of nitrosative stress. Also was observed increase in heart mitochondria by focal ischemia-reperfusion of the brain, content key regulator of de novo synthesis of NO-hydrogen sulfide and activity of inducible arginase II and, as a result, the pool of carbamide, which is also a regulator of the synthesis of NO. Previous introduction for animals herbal extract Serratsula coronata, enriched ecdysterone, reduces induction nitrosative stress in mitochondria of rats hearts under conditions of focal ischemia-reperfusion of the brain.

Індукція оксидативного стресу в мітохондріях серця за фокальної ішемії−реперфузії головного мозку та протекторна дія екдистерону

Based on the fact that the acute phase of ischemic stroke is accompanied by the development of heart damage, manifestations of which are oxidative stress, morphological changes in the myocardium, in the model of brain focal ischemia-reperfusion, we investigated the oxidative stress in rat heart mitochondria and possible mechanisms of cardioprotective effect of ecdysterone. Under the conditions of brain focal ischemia-reperfusion, there is an increase rate of the generation of reactive oxygen species: superoxide (*O2-) and hydroxyl radicals (*OH), pools of stable hydrogen peroxide (H2O2), accumulate products of lipid peroxidation (diene conjugates and malonic dialdehyde), as a result of activation xanthine oxidase (marker uric acid), lipooxygenase (marker leukotriene C4) and cyclooxygenase (marker tromboksane B2) ways of *O2-(generating). In animals that received ecdysterone for 18 days, under conditions of brain focal ischemia-reperfusion, the rate of reactive oxygen species generation and the pools of lipid peroxidation products were decreased, and the survival of animals was increased. The obtained results support the development of oxidative stress in heart mitochondria of rats, powerful antiradical properties ofecdysterone, its cardioprotective effect, in conditions of brain focal ischemia-reperfusion.

Dietary fatty acids and oxidative stress in the heart mitochondria

Our study compared the effects of different oils on oxidative stress in rat heart mitochondria, as well as on plasma parameters used as risk factors for cardiovascular disease. The rats were fed for 16 weeks with coconut, olive, or fish oil diet (saturated, monounsaturated, or polyunsaturated fatty acids, respectively). The cardiac mitochondria from rats fed with coconut oil showed the lowest concentration of oxidized proteins and peroxidized lipids. The fish oil diet leads to the highest oxidative stress in cardiac mitochondria, an effect that could be partly prevented by the antioxidant probucol. Total and LDL cholesterols decreased in plasma of rats fed fish oil, compared to olive and coconut oils fed rats. A diet enriched in saturated fatty acids offers strong advantages for the protection against oxidative stress in heart mitochondria.

Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice

The existence of an inducible mitochondrial nitric oxide synthase has been recently related to the nitrosative/oxidative damage and mitochondrial dysfunction that occurs during endotoxemia. Melatonin inhibits both inducible nitric oxide synthase and inducible mitochondrial nitric oxide synthase activities, a finding related to the antiseptic properties of the indoleamine. Hence, we examined the changes in inducible nitric oxide synthase/inducible mitochondrial nitric oxide synthase expression and activity, bioenergetics and oxidative stress in heart mitochondria following cecal ligation and puncture-induced sepsis in wild-type (iNOS(+/+)) and inducible nitric oxide synthase-deficient (iNOS(-/-)) mice. We also evaluated whether melatonin reduces the expression of inducible nitric oxide synthase/inducible mitochondrial nitric oxide synthase, and whether this inhibition improves mitochondrial function in this experimental paradigm. The results show that cecal ligation and puncture induced an increase of inducible mitochondrial nitric oxide synthase in iNOS(+/+) mice that was accompanied by oxidative stress, respiratory chain impairment, and reduced ATP production, although the ATPase activity remained unchanged. Real-time PCR analysis showed that induction of inducible nitric oxide synthase during sepsis was related to the increase of inducible mitochondrial nitric oxide synthase activity, as both inducible nitric oxide synthase and inducible mitochondrial nitric oxide synthase were absent in iNOS(-/-) mice. The induction of inducible mitochondrial nitric oxide synthase was associated with mitochondrial dysfunction, because heart mitochondria from iNOS(-/-) mice were unaffected during sepsis. Melatonin treatment blunted sepsis-induced inducible nitric oxide synthase/inducible mitochondrial nitric oxide synthase isoforms, prevented the impairment of mitochondrial homeostasis under sepsis, and restored ATP production. These properties of melatonin should be considered in clinical sepsis.

Copper deficiency: A potential model for determining the role of mitochondria in cardiac aging

Heart mitochondria experience age-related declines in cytochrome c oxidase (CCO) activity and increases in the generation of reactive oxygen species (ROS) that may contribute to loss of cardiac function and the development of disease that occur with advancing age. In a manner similar to aging, copper deficiency also suppresses heart CCO activity and has cardiovascular consequences related to increased peroxidation. Food restriction is often used as a tool to study oxidative mechanisms of aging and the present study examines the potential of copper deficiency to model the role of mitochondria in cardiac aging by determining if the effect of food restriction on CCO activity and oxidative stress in heart mitochondria parallels its effect on cardiac mitochondria during aging. Overall, copper deficiency severely inhibited CCO activity and increased both Mn superoxide dismutase (MnSOD) and glutathione peroxidase (GPX) in isolated heart mitochondria. However, a 20% reduction in food intake by copper-deficient rats increased CCO activity by 65% and decreased MnSOD activity by 25% but had no effect in rats fed adequate copper. Copper deficiency also reduced the carbonyl content of 80-100 kDa mitochondrial proteins, but the reduction in carbonyl content was unaffected by food restriction. Food restriction did, however, completely prevent the enlargement of cardiac mitochondria in copper-deficient rats. Together, these findings indicate that copper deficiency induces mitochondrial antioxidant enzyme activity and hypertrophy in cardiac tissue in response to reduced CCO activity and that food restriction may counteract these changes by reducing oxidative stress. Because the action of food restriction on CCO activity and mitochondrially generated oxidative stress are similar in copper deficiency and aging, copper deficiency may serve as a short-term model for studying the potential roles of mitochondria in cardiac aging.

Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria

Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria

Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria.

Rat heart mitochondria became permeabilized to sucrose when incubated with 100 nmol of Ca2+/mg of protein in the presence of Pi. Ca2+ chelation with EGTA restored impermeability to sucrose, which became entrapped in the matrix space. t-Butylhydroperoxide markedly promoted permeabilization in the presence of Ca2+ but not in its absence, and Ca2+-plus-t-butylhydroperoxide-induced permeabilization was reversed by EGTA. The data suggest that Ca2+ and oxidative stress synergistically promote the reversible opening of an inner membrane pore.

A reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria

A reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria