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

Year 2019, Volume: 5 Issue: 4, 649 - 657, 04.07.2019

Serdar Savaş Gül , Hatice Aygün

https://doi.org/10.18621/eurj.410029

Cited By: 12

Abstract

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 plus melatonin (DOX+MEL,
n = 7), doxorubicin
plus
vitamin D (DOX+Vit D, n = 7), and doxorubicin plus 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), ^99mTechnetium 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 ^99mTechnetium 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 ^99mTechnetium pyrophosphate
uptake (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

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