title: Beneficial effects of astringinin, a resveratrol analogue, on the ischemia and reperfusion damage in rat heart.
abstract: Oxidative stress plays an important role in the pathogenesis of myocardial ischemia and infarction. Antioxidants might then be beneficial in the prevention of these diseases. Astringinin (3,3',4',5-tetrahydroxystilbene), a resveratrol (3,4',5-trihydroxystilbene) analogue with considerably higher antioxidative activity and free radical scavenging capacity, was introduced to examine its cardioprotective effects in ischemia or ischemia-reperfusion (I/R) rats. In the present study, the left main coronary artery was occluded by the following procedures: (i) 30 min occlusion, (ii) 5 min occlusion followed by 30 min reperfusion, and (iii) 4 h occlusion. Animals were infused with and without astringinin before coronary artery occlusion. Mortality, and the severity of ischemia- and I/R-induced arrhythmias were compared. Pretreatment of astringinin dramatically reduced the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during either ischemia or I/R period. Astringinin at 2.5 x 10(-5) and 2.5 x 10(-4) g/kg completely prevented the mortality of animals during ischemia or I/R. During the same period, astringinin pretreatment also increased nitric oxide (NO) and decreased lactate dehydrogenase (LDH) levels in the carotid blood. In animals subjected to 4 h coronary occlusion, the cardiac infarct size (expressed as a percentage of occluded zone) was reduced from 44.4 + or - 4.1% to 19.1 + or - 2.4% by astringinin (2.5 x 10(-4) g/kg). We conclude that, astringinin is a potent antiarrhythmic agent with cardioprotective activity in ischemic and ischemic-reperfused rat heart. The beneficial effects of astringinin in the ischemic and ischemic-reperfused hearts may be correlated with its antioxidant activity and upregulation of NO production.
authors: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: L M
authors: LM
authors: Hung
authors: J K
authors: JK
authors: Chen
authors: R S
authors: RS
authors: Lee
authors: H C
authors: HC
authors: Liang
authors: M J
authors: MJ
authors: Su
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D017180:Tachycardia, Ventricular / Q000188:drug therapy; D014693:Ventricular Fibrillation / Q000188:drug therapy
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D009566:Nitrates; D009573:Nitrites; D013267:Stilbenes; D009569:Nitric Oxide; C041525:3,3',4,5'-tetrahydroxystilbene; D007770:L-Lactate Dehydrogenase; D000077185:Resveratrol