Mansour M A, El-Kashef H A, Al-Shabanah O A
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Pharmacol Res. 1999 Mar;39(3):233-7. doi: 10.1006/phrs.1998.0432.
Biochemical evaluations of the effects of the sulfhydryl-containing angiotensin-converting enzyme inhibitor (captopril) on the nephrotoxicity induced by doxorubicin in normal rats were carried out. A single dose of doxorubicin (15 mg kg-1) which caused nephrotoxicity was manifested biochemically by the elevation of serum urea after 24 and 48 h of administration. Also a severe decrease in total proteins and albumin after 4, 24 and 48 h was observed. Moreover, a decrease of non-protein sulfhydryl (-SH) concentrations in the kidney tissues after 24 h and an increase in the lipid peroxidation was observed after 4 h administration of doxorubicin. Captopril (60 mg kg-1 i.p.) injection did not induce any change in the biochemical parameters measured, however, captopril administered 1 h before doxorubicin ameliorated the biochemical toxicity induced by doxorubicin. This was evidenced by a significant reduction in serum urea and the lipid peroxidation after 4 and 24 h and a significant reduction in creatinine after 48 h. Also, the captopril amelioration was evidenced by an increase in total proteins and albumin after 4 and 24 h of doxorubicin administration. Captopril did not change non-protein sulfhydryl (-SH) concentrations or protein content in the kidney tissues. These results suggest that captopril may be beneficial as a protective agent against nephrotoxicity induced by doxorubicin.
对含巯基的血管紧张素转换酶抑制剂（卡托普利）对正常大鼠阿霉素诱导的肾毒性作用进行了生化评估。单剂量阿霉素（15 mg kg-1）导致肾毒性，给药24小时和48小时后血清尿素升高在生化上表现出来。此外，在4小时、24小时和48小时后观察到总蛋白和白蛋白严重下降。而且，阿霉素给药24小时后肾组织中非蛋白巯基（-SH）浓度下降，给药4小时后脂质过氧化增加。腹腔注射卡托普利（60 mg kg-1）未引起所测生化参数的任何变化，然而，在阿霉素给药前1小时给予卡托普利可改善阿霉素诱导的生化毒性。这在给药4小时和24小时后血清尿素和脂质过氧化显著降低以及给药48小时后肌酐显著降低中得到证明。此外，在阿霉素给药4小时和24小时后总蛋白和白蛋白增加也证明了卡托普利的改善作用。卡托普利未改变肾组织中的非蛋白巯基（-SH）浓度或蛋白质含量。这些结果表明，卡托普利作为预防阿霉素诱导的肾毒性的保护剂可能有益。
