title: Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  The present study provided evidence that metformin has cardioprotective effects against doxorubicin cardiotoxicity.
authors.affiliation: Department of Pediatric Cardiology, Faculty of Medicine, Erciyes University; Kayseri-Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Argun
authors.affiliation: Department of Pediatric Cardiology, Faculty of Medicine, Erciyes University; Kayseri-Turkey.
authors.forename: Kazım
authors.initials: K
authors.lastname: Üzüm
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Erciyes University; Kayseri-Turkey.
authors.forename: Mehmet Fatih
authors.initials: MF
authors.lastname: Sönmez
authors.affiliation: Department of Pediatric Cardiology, Faculty of Medicine, Erciyes University; Kayseri-Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Özyurt
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Erciyes University; Kayseri-Turkey.
authors.forename: Karabulut
authors.initials: K
authors.lastname: Derya
authors.forename: Kübra Tuğçe
authors.initials: KT
authors.lastname: Çilenk
authors.forename: Sunay
authors.initials: S
authors.lastname: Unalmış
authors.forename: Özge
authors.initials: Ö
authors.lastname: Pamukcu
authors.forename: Ali
authors.initials: A
authors.lastname: Baykan
authors.forename: Figen
authors.initials: F
authors.lastname: Narin
authors.forename: Ferhan
authors.initials: F
authors.lastname: Elmalı
authors.forename: Nazmi
authors.initials: N
authors.lastname: Narin
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants; D066126:Cardiotoxicity / Q000517:prevention & control*; D004317:Doxorubicin / Q000633:toxicity*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D009206:Myocardium; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D007004:Hypoglycemic Agents; D004317:Doxorubicin; D008687:Metformin