Effect of Metformin on inflammatory markers involved in Cardiotoxicity induced by Doxorubicin

Abstract

Doxorubicin is a secondary metabolite of Streptomyces peucetius and is one of the anthracyclines families, greatly effective anticancer drugs that used to treat many pediatric and adult cancers, e.g. solid tumors, lymphomas, leukemia and breast cancer. Doxorubicin has severe toxicities, but the cardiotoxicity being the most important. Metformin has been reported to have cardioprotective effect in addition to reducing basal and postprandial glucose levels, weight loss, and reducing lipid serum levels. Animal model studies of isolated myocardial infarction and heart failure shown that metformin increases the tolerance of myocardial cells to ischemia-reperfusion injury, and reduce the development of heart failure after infarction. Thirty-six male rabbits divided randomly into six groups, each group comprising of six rabbits. 1: Control group received single dose of 2ml saline intraperitoneally. 2: Metformin group received 300mg/kg/day, daily for 14 days orally. 3: Chronic doxorubicin induction group received 4mg/kg, twice a week for two weeks intraperitoneally. 4: Acute doxorubicin induction group received 16mg/kg single dose intraperitoneally. 5: Metformin+chronic doxorubicin induction group received doxorubicin 4mg/kg, twice a week for two weeks intraperitoneally and Metformin 300 mg/kg/day, daily for 14 days orally, starting three days prior to doxorubicin therapy. 6: Metformin + acute doxorubicin induction group received doxorubicin 16 mg/kg single dose intraperitoneally and Metformin 300 mg/kg/day, daily for 14 days orally, starting three days prior to doxorubicin therapy. The result of this study revealed that metformin treatment significantly (p<0.05) decreased the MMP2, TNF-a, iNOS level in addition to improve the histological change of cardiac tissues produced by acute and chronic doxorubicin induction toxicity. This study showed that metformin therapy has a good cardioprotective effect against acute and chronic doxorubicin induction cardiotoxicity.