ABSTRACT
We have studied the influence of dietary ω-3 polyunsaturated fatty acids (ω-3 PUFA) on the functioning of subsarcolemmal and interfibrillar mitochondrial fractions of rat myocardium, changes in expression of cytochrome P450 (CYP2E1) and the activity of enzymes of prooxidant-antioxidant system after isoproterenol-induced myocardial injury. It has been found that in vivo administration of ω-3 PUFA (Epadol 0.1 ml/100 gr of weight for 4 weeks) significantly reduced the swelling of subsarcolemmal and interfibrillar mitochondrial fractions by 65.52% 54.84% respectively, pointing for a decrease of damage of the mitochondrial function evoked by in vivo administration of isoproterenol. In vivo administration of ω-3 PUFAs prevents a decrease in the activity of antioxidant enzymes catalase and superoxide dismutase (2.65 and 7.1- fold, respectively) after isoproterenol-induced myocardial injury. We suggest that the development of oxidative stress after isoproterenol-induced myocardial injury can be caused by a significant increase in the expression of cytochrome P450 2E1 (73.3%), and administration of ω-3 PUFAs prevents such changes.
Subject(s)
Cardiomyopathies/diet therapy , Cardiotonic Agents/pharmacology , Cytochrome P-450 CYP2E1 Inhibitors/pharmacology , Cytochrome P-450 CYP2E1/genetics , Fatty Acids, Omega-3/pharmacology , Mitochondria, Heart/drug effects , Administration, Oral , Animals , Cardiomyopathies/chemically induced , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Catalase/genetics , Catalase/metabolism , Cytochrome P-450 CYP2E1/metabolism , Gene Expression Regulation , Isoproterenol/administration & dosage , Isoproterenol/antagonists & inhibitors , Male , Mitochondria, Heart/metabolism , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Oxidative Stress , Rats , Rats, Wistar , Sarcolemma/drug effects , Sarcolemma/metabolism , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolismABSTRACT
We have studied the functional parameters of mitochondria from hearts after isopreterenol-induced injury (two subcutaneous injections of isopreterenol at the dose 60 mg/kg/day). We investigated the influence of dietary omega-3 polyunsaturated fatty acids (omega-3 PUFAs) administered to rats (Epadol, 0.1 mg/100 gr of weight for 4 weeks) on these parameters. Isoproterenol-induced heart injury leads to a decreased parameters of respiration of isolated mitochondria in the presence of succinate. Administration of omega-3 PUFAs significantly restored the respiration rate of mitochondria: the state 3 respiration was increased by 70.12%, the state 4 by 39.87% and the respiratory control ratio by 45.19% compared to the corresponding parameters of experimental group. Also, it was shown the ability of omega-3 PUFAs to decrease mitochondria swelling (by 60%) in nominally free calcium solution. The results of the study indicate that omega-3 PUFAs improve the altered functions of the heart mitochondria evoked by isoproterenol-induced injury.
