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

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).

Exogenous follistatin administration ameliorates cisplatin-induced acute kidney injury through anti-inflammation and anti-apoptosis effects.

OBJECTIVES: This study was aimed to explore the effects of follistatin on cisplatin-induced renal dysfunction, histopathological changes, apoptosis, inflammation and oxidative damage in rats. BACKGROUND: Follistatin plays an important role in the developmental and regeneration processes of kidney by blocking the actions of activin, which is a member of transforming growth factor-ß superfamily. METHODS: Twenty seven rats were separated into 4 equal groups: Control, Cp (cisplatin, 6 mg/kg, intrapertoneally (ip)), F1 (cisplatin + 1 µg/day follistatin ip for 4 consecutive days) and F4 (cisplatin + 4 µg/day follistatin ip single dose) groups. Renal health was monitored by blood urea nitrogen, serum creatinine and histological analysis. Apoptosis, inflammation and oxidative stress was investigated in kidney tissue. Activin A levels in serum and kidney were evaluated as well. RESULTS: Follistatin administration showed a considerable nephroprotective effect against cisplatin-induced nephrotoxicity by preventing renal functional and structural abnormalities, apoptosis and inflammation. The activin A levels in both serum and kidney were also suppressed by follistatin administration. CONCLUSION: Exogenous follistatin ameliorates acute kidney injury, by blocking activin A. The renoprotective effect of follistatin against cisplatin-induced nephrotoxicity appears to be associated with its anti-inflammatory, antiapoptotic and direct nephroprotective actions (Tab. 1, Fig. 7, Ref. 23).