Protective effects of caspase-9 and poly(ADP-ribose) polymerase inhibitors on ischemia-reperfusion-induced myocardial injury.
The present study was designed to investigate the cardio-protective effect of Ac-LEDH-cmk a selective caspase-9 inhibitor and 5-aminoisoquinolinone a selective Poly (ADP-ribose) polymerase inhibitor on ischemia and reperfusion induced apoptotic and necrotic cell death in rats. Isolated rat hearts were exposed to 30 minutes of global ischemia followed by 120 minutes of reperfusion using Langendorff's apparatus. Myocardial injury was assessed in the terms of infarct size, release of lactate dehydrogenase, creatine kinase enzymes and apoptotic index was assessed by DNA smearing on agarose gel electrophoresis. Pretreatments with specific inhibitor of caspase-9, Ac-LEHD-cmk (0.07 muM and 0.105 muM), and inhibitor of PARP, 5-aminoisoquinolinone (5 microM and 7.5 muM), significantly attenuated I/R induced increase in infarct size, release of lactate dehydrogenase and creatine kinase in the coronary effluent, and apoptotic index. Therefore, it may be concluded that inhibition of caspase-9 and PARP prevent ischemia and reperfusion-induced activation of apoptotic cascade and necrosis in rat myocardium.
Sodhi
Rupinder K
RK
ASBASJS College of Pharmacy, Bela (Ropar), Punjab, India.
Singh
Manjeet
M
Singh
Nirmal
N
Jaggi
Amteshwar S
AS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009336:Necrosis; D009842:Oligopeptides / Q000494:pharmacology*; D010477:Perfusion; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
C411425:5-aminoisoquinolinone; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009842:Oligopeptides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases; D003402:Creatine Kinase; C506435:Casp9 protein, rat; D053453:Caspase 9