Anesthetic Preconditioning Improves Adenosine Triphosphate Synthesis and Reduces Reactive Oxygen Species Formation in Mitochondria after Ischemia by a Redox Dependent Mechanism

2003 ◽  
Vol 98 (5) ◽  
pp. 1155-1163 ◽  
Author(s):  
Enis Novalija ◽  
Leo G. Kevin ◽  
Janis T. Eells ◽  
Michele M. Henry ◽  
David F. Stowe
Keyword(s):  
Reactive Oxygen Species ◽  
Cardiac Function ◽  
Adenosine Triphosphate ◽  
Reactive Oxygen ◽  
Atp Synthesis ◽  
Ros Generation ◽  
Oxygen Species ◽  
Protective Effects ◽  
Anesthetic Preconditioning ◽  
Species Formation

Background Mitochondrial changes that characterize the heart after anesthetic preconditioning (APC) or the mechanisms by which mitochondrial triggering factors lead to protection are unknown. This study hypothesized that generation of reactive oxygen species (ROS) during APC is required to initiate the mitochondrial protective effects, and that APC leads to improved mitochondrial electron transport chain function and cardiac function during reperfusion. Methods Isolated guinea pig hearts were subject to 30 min ischemia and 120 min reperfusion. Prior to ischemia hearts were either untreated (I/R), or treated with sevoflurane (APC), in the presence or absence of the ROS scavenger tiron (TIR), or the superoxide dismutase mimetic MnTBAP (TBAP). Intracellular ROS were measured by spectrofluorometry using the fluorescent probe dihydroethidium (DHE). In another series of experiments, using the same protocol, hearts were reperfused for only 5 min and removed for measurement of adenosine triphosphate (ATP) synthesis by luciferin-luciferase luminometry and ROS generation by dichlorohydro-fluorescein (DCF) fluorescence in isolated mitochondria. Results The APC improved cardiac function and reduced infarction. Tiron or MnTBAP abrogated the protection afforded by APC. Mitochondrial ATP synthesis was decreased by 70 +/- 3% after IR alone, by only 7 +/- 3% after APC, by 69 +/- 2% after APC+TIR, and by 71 +/- 3% after APC + TBAP. Mitochondrial ROS formation (DCF) increased by 48 +/- 3% after IR alone, by 0 +/- 2% after APC, by 43 +/- 4% after APC + TIR, and by 46 +/- 3% after APC + TBAP. ROS generation (DHE) was increased in I/R group at 5 and 120 min reperfusion. This was attenuated by APC but this protective effect was abrogated in APC + TIR and APC + TBAP groups. Conclusions The results indicate that ROS are central both in triggering and mediating APC, and that the mitochondrion is the target for these changes.

scholarly journals Reactive oxygen species formation during tetanic contractions in single isolated Xenopus myofibers

2011 ◽  
Vol 111 (3) ◽  
pp. 898-904 ◽  
Author(s):  
Li Zuo ◽  
Leonardo Nogueira ◽  
Michael C. Hogan
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Real Time ◽  
Contractile Activity ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Fatigue Development ◽  
Species Formation ◽  
Significant Difference

Contracting skeletal muscle produces reactive oxygen species (ROS) that have been shown to affect muscle function and adaptation. However, real-time measurement of ROS in contracting myofibers has proven to be difficult. We used amphibian ( Xenopus laevis) muscle to test the hypothesis that ROS are formed during contractile activity in isolated single skeletal muscle fibers and that this contraction-induced ROS formation affects fatigue development. Single myofibers were loaded with 5 μM dihydrofluorescein-DA (Hfluor-DA), a fluorescent probe that reacts with ROS and results in the formation of fluorescein (Fluor) to precisely monitor ROS generation within single myofibers in real time using confocal miscroscopy. Three identical periods of maximal tetanic contractions (1 contraction/3 s for 2 min, separated by 60 min of rest) were conducted by each myofiber ( n = 6) at 20°C. Ebselen (an antioxidant) was present in the perfusate (10 μM) during the second contractile period. Force was reduced by ∼30% during each of the three contraction periods, with no significant difference in fatigue development among the three periods. The Fluor signal, indicative of ROS generation, increased significantly above baseline in both the first (42 ± 14%) and third periods (39 ± 10%), with no significant difference in the increase in fluorescence between the first and third periods. There was no increase of Fluor in the presence of ebselen during the second contractile period. These results demonstrated that, in isolated intact Xenopus myofibers, 1) ROS can be measured in real time during tetanic contractions, 2) contractile activity induced a significant increase above resting levels of ROS production, and 3) ebselen treatment reduced ROS generation to baseline levels but had no effect on myofiber contractility and fatigue development.

scholarly journals Treatment of Rats With Hypolipidemic Compound Pirinixic Acid Protects Their Hearts Against Ischemic Injury: Are Mitochondrial KATP Channels and Reactive Oxygen Species Involved?

2013 ◽  
pp. 577-584 ◽  
Author(s):  
M. NEMČEKOVÁ ◽  
S. ČARNICKÁ ◽  
M. FERKO ◽  
M. MURÁRIKOVÁ ◽  
V. LEDVÉNYIOVÁ ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Rat Heart ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Katp Channels ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Protective Effects ◽  
Mitochondrial Katp Channels

Hypolipidemic compound pirinixic acid (WY-14643, WY) is known to exert pleiotropic (other than primary) effects, such as activation of peroxisome proliferator-activated receptors (PPAR-α), transcription factors regulating different cardiac functions. Their role in ischemia-reperfusion (I/R) injury and cardioprotection is less clear, although protective effects of PPAR agonists have been documented. This study was designed to explore the effects of WY on the I/R injury in the rat heart and potential mechanisms involved, including mitochondrial KATP channels (mitoKATP) opening and production of reactive oxygen species (ROS). Langendorff-perfused hearts of rats intragastrally treated with WY (3 mg/kg/day) for 5 days and of control animals were subjected to 30-min global ischemia and 2-h reperfusion with or without 15-min perfusion with mitoKATP blocker 5-hydroxydecanoate (5-HD) prior to I/R. Evaluation of the infarct size (IS, TTC staining) served as the main end-point of protection. Lipid peroxidation (a marker of ROS production) was determined by measurement of myocardial concentration of conjugated dienes (CD), whereas protein expression of endothelial NO synthase was analysed by Western blotting. A 2-fold increase in the cardiac protein levels of eNOS after treatment with WY was accompanied by lower post-I/R levels of CD compared with those in the hearts of untreated controls, although WY itself enhanced ROS generation prior to ischemia. IS was reduced by 47 % in the hearts of WY-treated rats (P<0.05), and this effect was reversed by 5-HD. Results suggest that PPAR-α activation may confer protection against lethal I/R injury in the rat heart that involves up-regulation of eNOS, mitoKATP opening and reduced oxidative stress during I/R.

Attenuation of Mitochondrial Respiration by Sevoflurane in Isolated Cardiac Mitochondria Is Mediated in Part by Reactive Oxygen Species

2004 ◽  
Vol 100 (3) ◽  
pp. 498-505 ◽  
Author(s):  
Matthias L. Riess ◽  
Janis T. Eells ◽  
Leo G. Kevin ◽  
Amadou K. S. Camara ◽  
Michele M. Henry ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Electron Transport ◽  
Complex I ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cardiac Mitochondria ◽  
Reactive Oxygen Species Formation ◽  
Complex Ii ◽  
Anesthetic Preconditioning ◽  
Species Formation

Background Anesthetic preconditioning protects against cardiac ischemia/reperfusion injury. Increases in reduced nicotinamide adenine dinucleotide and reactive oxygen species during sevoflurane exposure suggest attenuated mitochondrial electron transport as a trigger of anesthetic preconditioning. The authors investigated the effects of sevoflurane on respiration in isolated cardiac mitochondria. Methods Mitochondria were isolated from fresh guinea pig hearts, and mitochondrial oxygen consumption was measured in the presence of complex I (pyruvate) or complex II (succinate) substrates. The mitochondria were exposed to 0, 0.13, 0.39, 1.3, or 3.9 mM sevoflurane. State 3 respiration was determined after adenosine diphosphate addition. The reactive oxygen species scavengers manganese(III) tetrakis (4-benzoic acid) porphyrin chloride and N-tert-Butyl-a-(2-sulfophenyl)nitrone sodium (10 microM each), or the K(ATP) channel blockers glibenclamide (2 microM) or 5-hydroxydecanoate (300 microM), were given alone or before 1.3 mM sevoflurane. Results Sevoflurane attenuated respiration for both complex I and complex II substrates, depending on the dose. Glibenclamide and 5-hydroxydecanoate had no effect on this attenuation. Both scavengers, however, abolished the sevoflurane-induced attenuation for complex I substrates, but not for complex II substrates. Conclusion The findings suggest that sevoflurane-induced attenuation of complex I is mediated by reactive oxygen species, whereas attenuation of other respiratory complexes is mediated by a different mechanism. The opening of mitochondrial K(ATP) channels by sevoflurane does not seem to be involved in this effect. Thus, reactive oxygen species formation may not only result from attenuated electron transport by sevoflurane, but it may also contribute to complex I attenuation, possibly leading to a positive feedback and amplification of sevoflurane-induced reactive oxygen species formation in triggering anesthetic preconditioning.

scholarly journals Sirtuin 3 Alleviates Diabetic Cardiomyopathy by Regulating TIGAR and Cardiomyocyte Metabolism

2021 ◽  
Author(s):  
Lanfang Li ◽  
Heng Zeng ◽  
Xiaochen He ◽  
Jian‐Xiong Chen
Keyword(s):  
Reactive Oxygen Species ◽  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Sirtuin 3 ◽  
Reactive Oxygen Species Formation ◽  
Species Formation

Background Impairment of glycolytic metabolism is suggested to contribute to diabetic cardiomyopathy. In this study, we explored the roles of SIRT3 (Sirtuin 3) on cardiomyocyte glucose metabolism and cardiac function. Methods and Results Exposure of H9c2 cardiomyocyte cell lines to high glucose (HG) (30 mmol/L) resulted in a gradual decrease in SIRT3 and 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase isoform 3 (PFKFB3) expression together with increases in p53 acetylation and TP53‐induced glycolysis and apoptosis regulator (TIGAR) expression. Glycolysis was significantly reduced in the cardiomyocyte exposed to HG. Transfection with adenovirus‐SIRT3 significantly increased PFKFB3 expression and reduced HG‐induced p53 acetylation and TIGAR expression. Overexpression of SIRT3 rescued impaired glycolysis and attenuated HG–induced reactive oxygen species formation and apoptosis. Knockdown of TIGAR in cardiomyocytes by using siRNA significantly increased PFKFB3 expression and glycolysis under hyperglycemic conditions. This was accompanied by a significant suppression of HG–induced reactive oxygen species formation and apoptosis. In vivo, overexpression of SIRT3 by an intravenous jugular vein injection of adenovirus‐SIRT3 resulted in a significant reduction of p53 acetylation and TIGAR expression together with upregulation of PFKFB3 expression in the heart of diabetic db/db mice at day 14. Overexpression of SIRT3 further reduced reactive oxygen species formation and blunted microvascular rarefaction in the diabetic db/db mouse hearts. Overexpression of SIRT3 significantly blunted cardiac fibrosis and hypertrophy and improved cardiac function at day 14. Conclusions Our study demonstrated that SIRT3 attenuated diabetic cardiomyopathy via regulating p53 acetylation and TIGAR expression. Therefore, SIRT3 may be a novel target for abnormal energy metabolism in diabetes mellitus.

scholarly journals The Role of Oxidative Stress in Metals Toxicity; Mitochondrial Dysfunction as a Key Player

2014 ◽  
Vol 3 (1) ◽  
pp. 2-13
Author(s):  
Akram Ranjbar ◽  
Hassan Ghasemi ◽  
Farshad Rostampour‎
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Energy Production ◽  
Reactive Oxygen ◽  
Atp Synthesis ◽  
Ros Generation ◽  
Oxygen Species ◽  
Cellular Oxygen ◽  
A Site

Metals can cause oxidative stress by increasing the formation of reactive oxygen species (ROS), which make antioxidants incapable of defiance against growing amounts of free radicals. Metal toxicity is related to their oxidative state and reactivity with other compounds. However, several reports about metals have been published in the recent years. Mitochondria, as a site of cellular oxygen consumption and energy production, can be a target for metals toxicity. Dysfunction of Mitochondrial oxidative phosphorylation led to the production of some metals toxicities metals through alteration in the activities of I, II, III, IV and V complexes and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy production. In the present review study, the researchers have criticized reviews and some evidence about the oxidative stress as a mechanism of toxicity of metals. The metals disrupt cellular and antioxidant defense, reactive oxygen species (ROS) generation, and promote oxidative damage. The oxidative injuries induced by metals can be restored by use of antioxidants such as chelators, vitamin E and C, herbal medicine, and through increasing the antioxidants level. However, to elucidate many aspect of mechanism toxicity of metals, further studies are yet to be carried out.

Protective effects of Brazilian native fruits against reactive oxygen species

Planta Medica ◽  
2014 ◽  
Vol 80 (10) ◽  
Author(s):  
J Infante ◽  
A Massarioli ◽  
PL Rosalen ◽  
S Alencar
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Protective Effects
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