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

Abstract

Aim: The present study aimed to determine the protective effect of melatonin and agomelatine on DOX-induced cardiotoxicity in rats by electrocardiographic, scintigraphic and biochemical methods.

Materials and methods: Forty-nine male Wistar rats were randomly separated into seven groups; control (CON), doxorubicin (DOX), melatonin (MEL), agomelatine (AGO), melatonin+doxorubicin (MEL+DOX), agomelatine+doxorubicin (AGO+DOX) and melatonin+ agomelatine+ doxorubicin (MEL+AGO+DOX) groups. Cardiotoxicity was induced by intraperitoneal (i.p.) injection of DOX (18 mg/kg daily for three days). Rats receiving MEL and AGO treatment in the DOX-induced cardiotoxicity group received MEL and AGO (40 mg/kg/day, i.p., for seven days). They were injected with doxorubicin (18 mg/kg, i.p.) on days 5, 6, and 7. The rats were given MEL and AGO as substance control (40 mg/kg/day, i.p., for 7 days). On day 8 of the experiment, animals were evaluated by means of electrocardiography (ECG) and 99mtechnetium pyrophosphate (99mTc PYP) scintigraphy and their biochemical parameters [blood urea nitrogen (BUN), creatine kinase (CK), cardiac troponin T (cTnT)] were examined.

Results: DOX-induced acute cardiotoxicity in rats is characterized by conduction abnormalities in the ECG pattern (including decreased P wave and QRS complex duration, increased QT and RR intervals, and ST-segment elevation), increased serum BUN, CK, and cTnT parameters and increased 99mTc PYP uptake (p < 0.001). Pretreatment with MEL, AGO, or MEL+AGO effectively alleviated DOX-induced ECG abnormalities close to normal (p < 0.001). Moreover, serum biochemical evidence and 99mTc PYP uptake values demonstrated that pretreatment with MEL, AGO, or MEL+AGO has the same protective effect against the abnormalities produced in the heart by DOX (p < 0.001).

Conclusions: MEL and AGO have a potential protective effect on DOX-induced cardiotoxicity. At the same time, this study suggests that 99mTc PYP is a non-invasive method suitable for early determination of DOX-induced cardiotoxicity (Tab. 3, Fig. 5, Ref. 41).

Keywords: agomelatine; cardiotoxicity; doxorubicin; melatonin; rat 99mTc pyrophosphate..