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

Objectives: Doxorubicin ( 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 (220 ± 15 g) were randomly divided into seven groups (n  =  7 each) , namely control (CON, n = 7), doxorubicin (DOX, n = 7), melatonin (MEL, n = 7), vitamin D (Vit D, n = 7), doxorubicin p lus melatonin (DOX+MEL, n = 7), doxorubicin plus vitamin D (DOX+Vit D, n = 7), and doxorubicin p lus melatonin and vitamin D (DOX+MEL+Vit D, n = 7) groups. Cardiotoxicity was induced by intraperitoneal injection (i.p.) of DOX (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 (60,000 IU/kg, i.p.) were administered in a single dose and melatonin (40 mg/kg/day, i.p.) for 17 days and were injected with (18 mg/kg, i.p.) on doxorubicin 15 th , 16 th , and 17 th days. On the 18 th day electrocardiography (ECG), 99m Technetium pyrophosphate scintigraphy and biochemical parameters were assessed. Results: DOX caused changes in the ECG pattern, a significant decrease in heartbeat ( p < 0.01), P wave ( p < 0.001) and QRS complex durations ( p < 0.001), R wave amplitude ( p < 0.001); elevation in ST-segment ( p < 0.001) and decrease in QT interval ( p < 0,001),  and R-R interval durations ( p < 0.001); increase in the serum levels of cardiac injury markers (CK, BUN, cardiac troponin T), ( p < 0.01) , and increased 99m Technetium pyrophosphate uptake ( 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 (CK, BUN, cardiac troponin T) ( p < 0.001) and decreased the elevated level of 99m Technetium pyrophosphate uptake ( p < 0.001). Conclusion: Vitamin D and melatonin treatment prevented all the parameters of DOX -induced cardiotoxicity in rats.