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Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats   
Yazarlar
Mustafa Argun
Kazim Uzum
Mehmet Fatih Sonmez
Abdullah Ozyurt
Derya Karabulut
Zeynep Soyersarica
Dr. Öğr. Üyesi Kübra Tuğçe KALKAN Dr. Öğr. Üyesi Kübra Tuğçe KALKAN
Kırşehir Ahi Evran Üniversitesi
Sunay Unalmis
Ozge Pamukcu
Ali Baykan
Figen Narin
Ferhan Elmali
Nazmi Narin
Özet
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.
Anahtar Kelimeler
doxorubicin | cardiotoxicity | metformin | antioxidant | echocardiography
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı ANATOLIAN JOURNAL OF CARDIOLOGY
Dergi ISSN 2149-2263
Dergi Grubu Q4
Makale Dili İngilizce
Basım Tarihi 04-2016
Cilt No 16
Sayı 4
Sayfalar 234 / 241
Doi Numarası 10.5152/akd.2015.6185
BM Sürdürülebilir Kalkınma Amaçları
Atıf Sayıları
WoS 57
Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats

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