al-Shabanah O, Mansour M, el-Kashef H, al-Bekairi A
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Biochem Mol Biol Int. 1998 Jun;45(2):419-27. doi: 10.1080/15216549800202802.
Adriamycin has a wide spectrum of antitumor activity with dose related cardiotoxicity as a major side effect. The objective of this study was to investigate the influence of captopril, a sulphydryl containing angiotensin converting enzyme inhibitor, on the cardio- and hematotoxicity of adriamycin in normal rats. A single dose of adriamycin (15 mg/kg) caused myocardial toxicity after 24 h manifested biochemically by elevation of serum enzymes:- Aspartate transaminase (AST, EC: 2.6.1.1), lactate dehydrogenase (LDH, EC: 1.1.1.27), creatine phosphokinase (CPK, EC: 2.7.3.2) and the cardiac iso-enzymes of LDH and CPK. The hematotoxicity was characterized by severe leukopenia and anemia that appeared after 72 h of adriamycin administration. Captopril (60 mg/kg i.p.) 1 h before adriamycin injection ameliorated the biochemical toxicity induced by adriamycin. This was evidenced by a significant reduction in serum enzymes, after 24 and 48 h and a significant reduction of serum cardiac iso-enzymes after 48 h. Also restoration of the white blood cell counts as well as hemoglobin concentration occurred after 72 h of captopril administration. These results suggest that captopril may be benificial as a protective agent against cardio- and hematotoxicity induced by adriamycin.
阿霉素具有广泛的抗肿瘤活性，其主要副作用是与剂量相关的心脏毒性。本研究的目的是探讨含巯基的血管紧张素转换酶抑制剂卡托普利对正常大鼠阿霉素心脏毒性和血液毒性的影响。单剂量阿霉素（15 mg/kg）给药24小时后可导致心肌毒性，表现为血清酶升高：天冬氨酸转氨酶（AST，EC：2.6.1.1）、乳酸脱氢酶（LDH，EC：1.1.1.27）、肌酸磷酸激酶（CPK，EC：2.7.3.2）以及LDH和CPK的心脏同工酶。血液毒性的特征是在阿霉素给药72小时后出现严重的白细胞减少和贫血。在注射阿霉素前1小时腹腔注射卡托普利（60 mg/kg）可改善阿霉素诱导的生化毒性。这在给药24小时和48小时后血清酶显著降低以及48小时后血清心脏同工酶显著降低中得到证明。在卡托普利给药72小时后，白细胞计数和血红蛋白浓度也恢复正常。这些结果表明，卡托普利作为一种预防阿霉素诱导的心脏毒性和血液毒性的保护剂可能是有益的。
