Protective effects of combination of quercetin and α-tocopherol on mitochondrial dysfunction and myocardial infarct size in isoproterenol-treated myocardial infarcted rats: biochemical, transmission electron microscopic, and macroscopic enzyme mapping evidences.
Mitochondrial dysfunction plays an important role in the pathology of myocardial infarction. We evaluated the combined protective effects of quercetin and α-tocopherol on mitochondrial damage and myocardial infarct size in isoproterenol-induced myocardia- infarcted rats. Rats were pretreated with quercetin (10 mg/kg) alone, α-tocopherol (10 mg/kg) alone, and combination of quercetin (10 mg/kg) and α-tocopherol (10 mg/kg) orally using an intragastric tube daily for 14 days. After pretreatment, rats were induced myocardial infarction by isoproterenol (100 mg/kg) at an interval of 24 h for 2 days. Isoproterenol treatment caused significant increase in mitochondrial lipid peroxides with significant decrease in mitochondrial antioxidants. Significant decrease in the activities of isocitrate, succinate, malate, and α-ketoglutarate and NADH dehydrogenases and cytochrome-c-oxidase, significant increase in calcium, and significant decrease in adenosine triphosphate were observed in mitochondria of myocardial infarcted rats. Combined pretreatment with quercetin and α-tocopherol normalized all the biochemical parameters and preserved the integrity of heart tissue and restored normal mitochondrial function in myocardial-infarcted rats. Transmission electron microscopic findings on heart mitochondria and macroscopic enzyme mapping assay on the size of myocardial infarct also correlated with these biochemical parameters. The present study showed that combined pretreatment was highly effective than single pretreatment.
Punithavathi
V R
VR
Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar 608 002, India.
Stanely Mainzen Prince
P
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004357:Drug Synergism; D003576:Electron Transport Complex IV / Q000378:metabolism; D007523:Isocitrates / Q000378:metabolism; D007545:Isoproterenol; D007656:Ketoglutaric Acids / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009245:NADH Dehydrogenase / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000378:metabolism; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; D007523:Isocitrates; D007656:Ketoglutaric Acids; D008054:Lipid Peroxides; D008293:Malates; D020011:Protective Agents; D013386:Succinates; D000255:Adenosine Triphosphate; D011794:Quercetin; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D024502:alpha-Tocopherol; D007545:Isoproterenol; D002118:Calcium