The effects of melatonin and thymoquinone on doxorubicin-induced cardiotoxicity in rats

Abstract

OBJECTIVES: This study aims to investigate the protective effects of thymoquinone and melatonin on the heart against doxorubicin-induced cardiotoxicity in rats. BACKGROUND: Melatonin and thymoquinone may play an important role in cardiotoxicity. METHODS: The subjects were divided into four groups: Control (physiological serum on 5th day), Doxorubicin (DXR), Doxorubicin+Melatonin (DXR+MEL, 10 mg/kg melatonin, intraperitoneally), and Doxorubicin+Thymoquinone (DXR+TQ, 50 mg/kg thymoquinone, orally). On the 5th day of the experiment, all groups were injected with 45 mg/kg DXR into the tail vein. On the 8th day of the experiment, ECG recordings were performed under anaesthesia. RESULTS: Thymoquinone reduced the PR, QRS and QTc intervals, which were increased by DXR, while melatonin only reduced the QTc interval. Melatonin had a protective effect against the histopathological changes induced by DXR, while TQ did not demonstrate such an effect. DXR increased CK-MB, IL-6, MDA, IL-1, IL-18 levels and decreased SOD in the cardiac tissue. MEL reduced the levels of CK-MB, MDA, NO, SOD, IL-1, IL-6, IL-18. Meanwhile, TQ only reduced CK-MB, IL-1 and IL-18. CONCLUSION: Our study showed that DXR induces cardiac injury and that melatonin improves biochemical parameters and offers histological protection; while thymoquinone improves ECG parameters and causes partial recovery of biochemical parameters (Tab. 4, Fig. 2, Ref. 41).

Investigation of the efficacy of tyrosol on doxorubicin-induced acute cardiotoxicity in rats

“…Doxorubicin is an anthracycline group used to a variety cancers, including hematologic cancer, solid tumors, and soft tissue sarcomas, and can commonly cause heart failure and heart damage as a side effect (Pehlivan et al 2020). Doxorubicin causes serious morphological and functional cardiac changes and ultimately irreversible cardiomyopathy and heart failure (Gandhi et al 2013, Kim et al 2017.…”

Potential Roles of Melatonin in Doxorubicin-Induced Cardiotoxicity: From Cellular Mechanisms to Clinical Application

“…Melatonin attenuated the increase in ROS production caused by doxorubicin [ 22 , 30 ]. Doxorubicin also increased nitric oxide (NO) levels in both rat and mouse models, however melatonin cotreatment effectively attenuated the increase in the NO level [ 34 , 35 , 36 ]. A reduced glutathione (GSH) level was also reduced in rats and mice treated with doxorubicin, melatonin therapy attenuating the reduction of GSH level [ 36 , 37 , 38 , 39 , 40 , 41 ].…”

Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis

“…Earlier researh demonstrated that TQ showed significant protective effects against Dox-induced cardiotoxicity in rats (8). More recently, a series of studies suggested that the inhibition of oxidative stress levels may be responsible for TQ action on the protective effects of cardiotoxicity (9,10). However, the potential mechanism of TQ on the protection of Dox-induced cardiotoxicity is still not fully understood.…”