Cardioprotective effect of metformin against doxorubicin cardiotoxicity in ratsMustafa Argun1, Kazım Üzüm1, Mehmet Fatih Sönmez2, Abdullah Özyurt1, Derya Karabulut2, Zeynep Soyersarıca3, Kübra Tuğçe Çilenk2, Sunay Unalmış2, Özge Pamukcu1, Ali Baykan1, Figen Narin4, Ferhan Elmalı5, Nazmi Narin1
1Departments Of Pediatric Cardiology, Faculty Of Medicine, Erciyes University; Kayseri- Turkey
2Histology And Embryology, Faculty Of Medicine, Erciyes University; Kayseri- Turkey
3Hakan Çetinsaya Experimental And Clinical Research Center, Faculty Of Medicine, Erciyes University; Kayseri- Turkey
4Medical Biochemistry, Faculty Of Medicine, Erciyes University; Kayseri- Turkey
5Department Of Biostatistics And Medical Informatics, Faculty Of Medicine, Erciyes University; Kayseri- Turkey
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.Keywords: doxorubicin, cardiotoxicity, metformin, antioxidant, echocardiography
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. (Anatol J Cardiol 2016; 16: 234-41)
Mustafa Argun, Kazım Üzüm, Mehmet Fatih Sönmez, Abdullah Özyurt, Derya Karabulut, Zeynep Soyersarıca, Kübra Tuğçe Çilenk, Sunay Unalmış, Özge Pamukcu, Ali Baykan, Figen Narin, Ferhan Elmalı, Nazmi Narin. Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats. Anatol J Cardiol. 2016; 16(4): 234-241
Corresponding Author: Mustafa Argun, Türkiye