How to protect doxorubicin-induced cardiomyopathy in male albino rats?J Cardiovasc Pharmacol 2010; 55(3):262-8JC
The present study was designed to compare the cardioprotective effects of the combination of lisinopril with growth hormone over lisinopril alone in doxorubicin (Dox)-induced cardiomyopathy in rats. Forty male Wister albino rats were divided into 4 groups: group 1, control group; group 2, received Dox; group 3, received lisinopril + Dox; and group 4, received lisinopril + Dox + growth hormone. Dox (cumulative dose) was administered to rats in 6 equal intraperitoneal injections over a period of 2 weeks. Histopathological changes and plasma aspartate aminotransferase, lactate dehydrogenase, and creatine kinase and plasma levels of matrix metalloproteinase (MMP)-2, tissue inhibitor matrix metalloproteinase (TIMP)-1, and cardiac inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression were determined 9 weeks after the first dose of Dox. Dox produced cardiac structural injury and significant elevation in plasma levels of cardiac enzymes, MMP-2, and cardiac iNOS mRNA expression together with significant reduction in plasma TIMP-1 level. Lisinopril significantly decreases plasma MMP-2 level and cardiac iNOS mRNA expression by 13% and 15%, respectively, in group 3 compared with 36% and 47%, respectively, in group 4 as compared with group 2. In addition, compared with Dox group, lisinopril significantly increases plasma TIMP-1 level by 23% compared with 49% in group 4. We can conclude that the combination of lisinopril and growth hormone produced better cardioprotective effect against Dox-induced cardiomyopathy. This effect may be attributed on their antiremodeling actions by regulating plasma MMP-2/TIMP-1 levels and to the reduction of cardiac iNOS mRNA expression.