期刊
LIFE SCIENCES
卷 67, 期 2, 页码 101-112出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0024-3205(00)00607-X
关键词
melatonin; isolated rat heart; reperfusion injury; DHBA; salicylate method; TBARS; hydroxyl radical
During postischemic reperfusion, free radicals are produced and have deleterious effects in isolated rat hearts. We investigated whether melatonin (MEL) reduces the production of hydroxyl radical (. OH) in the effluent and aids in recovery of left ventricular (LV) function. Hearts were subjected to 30 min of ischemia followed by 30 min of reperfusion. Salicylic acid (SAL) was used as the probe for . OH, and its derivatives 2,5- and 2,3-dihydroxybenzoic acid (DHBA) were quantified using HPLC. In addition, thiobarbituric acid reactive substances (TBARS) in the myocardium was measured. Plateaus in the measurement of 2,5- and 2,3-DHBA were seen from 3 to 8 min after reperfusion in each group. The group that received 100 mu M MEL + SAL had significantly reduced amounts of 2,5- and 2,3-DHBA by multiple folds, compared to the SAL group. TEARS was significantly decreased in the 100 mu M MEL group (1.20 +/- 0.36 vs 1.85 +/- 0.10 mu mol/g of drug-free group, p<0.001). More importantly, the 100 mu M MEL group significantly recovered in LV function (LV developed pressure, +dp/dt, and -dp/dt; 63.0%, 60.3%, and 59.4% in the 100 mu M MEL group; 30.2%, 29.7%, and 31.5% in the drug-free group, respectively; p<0.05). Duration of ventricular tachycardia or ventricular fibrillation significantly decreased in the 100 mu M MEL group (100 mu M MEL, 159 +/- 67 sec; drug-free, 1244 +/- 233 sec; p<0.05). As a result of scavenging . OH and reducing the extent of lipid peroxidation, MEL is an effective agent for protection against postischemic reperfusion injury. (C) 2000 Elsevier Science Inc. All rights reserved.
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