title: Cardioprotective effect of polydatin against ischemia/reperfusion injury: roles of protein kinase C and mito K(ATP) activation.
abstract: Polydatin preconditioning (PPC) has been reported to be protective against brain and intestine ischemia/reperfusion injury (I/R injury), but whether polydatin exerts cardioprotective effect against myocardial ischemia/reperfusion and the underlying mechanisms remain unclear. Previous studies have demonstrated that oxidative stress plays an important role in the process of I/R. Elevation of oxidative agents and decline in anti-oxidant substance would promote I/R. Meanwhile, the activation of PKC signaling seems to mediate the cardioprotective effects of many drugs by alleviating Ca(2+) influx. In the present study, we reported for the first time that intravenous administration of polydatin before I/R significantly limited the infarct size, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) leakage from the damaged myocardium after I/R. The activity of SOD and the content of MDA remarkably changed in the presence of polydatin as well. However, the cardiac function-preserving and myocardial enzymes leakage-limiting effects of polydatin vanished in the presence of PKC inhibitors and mito K(ATP) channel blockers. But there was not a significant change in the activity of SOD and MDA content. We therefore conclude that PPC exerts cardioprotective effect by the activation of PKC-K(ATP)-dependent signaling and the direct anti-oxidative stress mechanisms.
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, Shaanxi, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Miao
authors.forename: Siwang
authors.initials: S
authors.lastname: Wang
authors.forename: Shan
authors.initials: S
authors.lastname: Miao
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Xie
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045468:Fallopia japonica / Q000737:chemistry; D005960:Glucosides / Q000493:pharmacokinetics / Q000494:pharmacology*; D007275:Injections, Intravenous; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013267:Stilbenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D005960:Glucosides; D054086:KATP Channels; D013267:Stilbenes; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D011493:Protein Kinase C; D003402:Creatine Kinase; C058229:polydatin