How to protect doxorubicin-induced cardiomyopathy in male albino rats?
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.
Shaker
Olfat
O
Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt. olfatshaker@yahoo.com
Sourour
Doaa A
DA
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004317:Doxorubicin / Q000633:toxicity*; D004359:Drug Therapy, Combination; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019382:Human Growth Hormone / Q000494:pharmacology*; D017706:Lisinopril / Q000494:pharmacology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019382:Human Growth Hormone; D004317:Doxorubicin; D017706:Lisinopril; D052247:Nitric Oxide Synthase Type II; D020778:Matrix Metalloproteinase 2