A review on the cardioprotective mechanisms of metformin against doxorubicin

Abstract

Doxorubicin (DOX) is an antineoplastic agent obtained from Streptomyces peucetius. It is utilized in treating different kinds of cancers, such as leukemia, lymphoma, and lung, and breast cancers. The main side effect of DOX is cardiotoxicity. Metformin (MET) is an antihyperglycemic drug used for type 2 diabetes treatment. It is proposed that MET has a protective effect against DOX cardiotoxicity. Our review demonstrated that MET has several possible mechanisms of action, which can prevent or at least reduce DOX cardiotoxicity including a decrease of free radical generation and oxidative stress, 5′ adenosine monophosphate-activated protein kinase activation, and ferritin heavy chain expression in cardiomyocytes cells. The combination of MET and DOX has been shown to enhance the anticancer activity of DOX by a number of authors. The literature reviewed in the present report supports the hypothesis that MET can reduce the cardiotoxicity that often occurs with DOX treatment.