Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats

Abstract

Objective:The clinical use of doxorubicin, which is a strong antineoplastic agent, is limited due to its cardiotoxic side effects. Metformin is a drug with antihyperglycemic effects, and it has been shown to have a cardioprotective effect on left ventricular function in experimental animal models of myocardial ischemia. The present study investigated the cardioprotective effect of metformin in rats with doxorubicin cardiotoxicity.Methods:Wistar albino rats were used in the study. Forty male, 10-week-old Wistar albino rats were randomly divided four groups. The control group rats were intraperitoneally administered saline solution twice a week, four doses in total. The doxorubicin group rats received doxorubicin (4 mg/kg, twice a week, cumulative dose: 16 mg/kg) intraperitoneally. The metformin group rats received metformin (250 mg/kg/day, every day for 14 days) via gavage. The doxorubicin + metformin group rats received doxorubicin and metformin at the same dose. Left ventricular functions were evaluated by using M-mode echocardiography one day after the last dose of doxorubicin. Heart tissue samples were histopathologically examined. Cardiomyocyte apoptosis was detected using in situ terminal deoxynucleotide transferase assay (TUNEL). Serum brain natriuretic peptide and C-type natriuretic peptide levels were measured. Catalase, superoxide dismutase, glutathione peroxidase, and tumor necrosis factor alpha levels were analyzed in the heart tissue. The assumptions of equality of variances and normal distribution were checked for all variables (Shapiro-Wilk test and Q-Q graphics). To identify intergroup differences, one-way variant analysis or the Kruskal-Wallis test was used. A p<0.05 value was accepted as statistically significant.Results:Our results showed that doxorubicin treatment caused significant deterioration in left ventricular functions by echocardiography, histological heart tissue damage, and increase in cardiomyocyte apoptosis. Doxorubicin + metformin group showed protection in left ventricular function, elimination of histopathologic change, and reduced of cardiomyocyte apoptosis.Conclusion:The present study provided evidence that metformin has cardioprotective effects against doxorubicin cardiotoxicity.

Bioinformatics identification of potential candidate blood indicators for doxorubicin‑induced heart failure

“…In light of the prominent role of chemotherapy, anthracycline especially doxorubicin remains to be considered the footstone chemotherapy regimen of cancer treatment for a wide range of malignancies, particularly for breast cancer and lymphoma (2,3). Over decades from its discovery, the anti-tumor and cardiotoxic mechanisms of doxorubicin seem to continuously evoke considerable interest in basic science and clinical trial research.…”

Drug-induced toxic Myocarditis: Doxorubicin once again leading to Heart Failure

“…Studies in humans are lacking 7 . Metformin, an oral antidiabetic agent, has proven in vitro benefit 8,9 . Studies in humans are lacking.…”

Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats

“…Many in vivo studies revealing the effects of metformin in alleviating the adverse side effects of doxorubicin have focused on biochemical changes such as reduction in free radical generation and mitochondrial damage (1, 8). The paper by Argun et al (9) entitled “Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats” published in this issue of the Anatolian Journal of Cardiology took a slightly different approach. In this in vivo study, the authors used echocardiography as a direct readout to demonstrate the beneficial effect of metformin.…”

“…For example, recently, Chang et al (10) demonstrated the beneficial effects of angiotensin receptor blockers (ARBs) in preventing doxorubicin-induced cardiotoxicity in rats. Although the clinical application of ARBs for reducing doxorubicin-induced adverse effects is debatable, the use of metformin is so far reached now such that the study by Argun et al (9) should have much more translational value. To date, the majority of the clinical investigations have focused on cancer survival rate in type 2 diabetes patients.…”