Ameliorative Effect of Carvedilol and N-acetylcysteine on Doxorubicin- induced Cardiotoxicity in Rats, Possible Role of SIRT 1.

[摘要] Doxorubicin (DOX) is one of the most potent antitumor agents, but its use is limited by developmentof cardiotoxicity involving cardiomyocyte apoptosis and myocardial fibrosis. This study was aimed to evaluatethe cardio- protective effects of carvedilol and N-acetylcysteine alone and in combination on doxorubicin- st induced cardiotoxicity in rats. Male albino rats were classified into 7 equal groups; 1 group which is normalnd rd control group, 2 and 3 group involve normal rats receive carvedilol (10 mg/kg/day) and N-acetylcysteine(200 mg/kg/day) respectively. Cardiotoxicity was induced by I.P injection of 6 equal doses of doxorubicin (2.5mg/kg) within two weeks. Cardio-toxic rats were divided into 4 groups; DOX untreated group, carvediloltreated group, N-acetylcysteine treated group and (carvedilol + N-acetylcysteine) treated group. The drugswere given for 14 day concomitantly with I.P doxorubicin administration. The current work revealed thattreatment with either carvedilol or/and N-acetylcysteine resulted in a significant improvement of doxorubicin- induced cardiotoxicity; evident by a significant reduction of heart rate, ST segment elevation, serum creatininephosphokinase (CPK-MB), troponin-I activity, serum interluken-6 (IL-6),cardiacmalondialdehyde (MDA) ,significant elevation of reduced glutathione (GSH) and serum SIRT 1 gene expression . Both drugs showedsignificant improvement of electrophysiological and biochemical parameters which were confirmed withhistopathological examination with more significant effect of combination therapy over the effect of each drugalone.

[学科分类] 工程和技术（综合）

[关键词] Doxorubicin;Cardiotoxicity;Carvedilol;N-Acetylcysteine;SIRT 1.