Captopril ameliorates myocardial and hematological toxicities induced by adriamycin.
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.
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
O
O
al-Shabanah
M
M
Mansour
H
H
el-Kashef
A
A
al-Bekairi
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D001772:Blood Cell Count / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood; D004317:Doxorubicin / Q000633:toxicity*; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006454:Hemoglobins / Q000032:analysis*; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051381:Rats
D000903:Antibiotics, Antineoplastic; D006454:Hemoglobins; D007527:Isoenzymes; D004317:Doxorubicin; D002216:Captopril; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase