Cardioprotective effect of vitamin D and melatonin on doxorubicin-induced cardiotoxicity in rat model: an electrocardiographic, scintigraphic and biochemical study

Authors : Serdar Savaş GÜL, Hatice AYGÜN

Pages : 649-657

Doi:10.18621/eurj.410029

View : 17 | Download : 10

Publication Date : 2019-07-04

Article Type : Research Paper

Abstract :Objectives: Doxorubicin insert ignore into journalissuearticles values( DOX); is an antineoplastic drug that is widely used in chemotherapy but its cardiotoxicity is the most important side effect that limits the clinical use of this drug . We investigated DOX treatment and the effects of vitamin D and melatonin on heart by electrocardiography, scintigraphic and biochemical methods. Methods: In this study, forty-nine adult male Wistar albino rats insert ignore into journalissuearticles values(220 ± 15 g); were randomly divided into seven groups insert ignore into journalissuearticles values(n  =  7 each); , namely control insert ignore into journalissuearticles values(CON, n = 7);, doxorubicin insert ignore into journalissuearticles values(DOX, n = 7);, melatonin insert ignore into journalissuearticles values(MEL, n = 7);, vitamin D insert ignore into journalissuearticles values(Vit D, n = 7);, doxorubicin p lus melatonin insert ignore into journalissuearticles values(DOX+MEL, n = 7);, doxorubicin plus vitamin D insert ignore into journalissuearticles values(DOX+Vit D, n = 7);, and doxorubicin p lus melatonin and vitamin D insert ignore into journalissuearticles values(DOX+MEL+Vit D, n = 7); groups. Cardiotoxicity was induced by intraperitoneal injection insert ignore into journalissuearticles values(i.p.); of DOX insert ignore into journalissuearticles values(18 mg/kg, i.p.); on the 15 th , 16 th and 17 th days . Rats receiving vitamin D and melatonin treatment in the DOX-induced cardiotoxicity group received vitamin D insert ignore into journalissuearticles values(60,000 IU/kg, i.p.); were administered in a single dose and melatonin insert ignore into journalissuearticles values(40 mg/kg/day, i.p.); for 17 days and were injected with insert ignore into journalissuearticles values(18 mg/kg, i.p.); on doxorubicin 15 th , 16 th , and 17 th days. On the 18 th day electrocardiography insert ignore into journalissuearticles values(ECG);, 99m Technetium pyrophosphate scintigraphy and biochemical parameters were assessed. Results: DOX caused changes in the ECG pattern, a significant decrease in heartbeat insert ignore into journalissuearticles values( p < 0.01);, P wave insert ignore into journalissuearticles values( p < 0.001); and QRS complex durations insert ignore into journalissuearticles values( p < 0.001);, R wave amplitude insert ignore into journalissuearticles values( p < 0.001);; elevation in ST-segment insert ignore into journalissuearticles values( p < 0.001); and decrease in QT interval insert ignore into journalissuearticles values( p < 0,001);,  and R-R interval durations insert ignore into journalissuearticles values( p < 0.001);; increase in the serum levels of cardiac injury markers insert ignore into journalissuearticles values(CK, BUN, cardiac troponin T);, insert ignore into journalissuearticles values( p < 0.01); , and increased 99m Technetium pyrophosphate uptake insert ignore into journalissuearticles values( p < 0.001); as compared to the CON group. MEL , Vit D and MEL+Vit D administration showed a same protective effect against DOX-induced altered ECG pattern. Pre-treatment with MEL , Vit D and MEL+Vit D significantly protected the heart from the toxic effect of DOX, by decreasing the levels of of cardiac injury markers insert ignore into journalissuearticles values(CK, BUN, cardiac troponin T); insert ignore into journalissuearticles values( p < 0.001); and decreased the elevated level of 99m Technetium pyrophosphate uptake insert ignore into journalissuearticles values( p < 0.001);. Conclusion: Vitamin D and melatonin treatment prevented all the parameters of DOX -induced cardiotoxicity in rats. 
Keywords : doxorubicin induced cardiotoxicty, vitamin D, melatonin, 99mTechnetium pyrophosphate