Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis

Biology

Jungmin Jo¹  Jaechan Leem²  Jung-Yeon Kim²  Misun Choe³  Jae-Hyung Park⁴  JongWoo Kim⁴ 

[1] Department of Hematology-Oncology, Inje University Seoul Paik Hospital, Seoul 04551, Korea;Department of Immunology, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea;Department of Pathology, School of Medicine, Keimyung University, Daegu 42472, Korea;Department of Physiology, School of Medicine, Keimyung University, Daegu 42601, Korea;

关键词: melatonin;    cisplatin;    acute kidney injury;    apoptosis;    necroptosis;   

DOI  :  10.3390/biology8030064

来源: DOAJ

【 摘 要 】

Melatonin is well known to modulate the sleep−wake cycle. Accumulating evidence suggests that melatonin also has favorable effects such as anti-oxidant and anti-inflammatory properties in numerous disease models. It has been reported that melatonin has therapeutic effects against cisplatin-induced acute kidney injury (AKI). However, mechanisms underlying the therapeutic action of melatonin on the renal side-effects of cisplatin therapy remain poorly understood. In this study, we showed that melatonin treatment significantly ameliorates cisplatin-induced acute renal failure and histopathological alterations. Increased expression of tubular injury markers was largely reduced by melatonin. Melatonin treatment inhibited caspase-3 activation and apoptotic cell death. Moreover, protein levels of key components of the molecular machinery for necroptosis were decreased by melatonin. Melatonin also attenuated nuclear factor-κB activation and suppressed expression of pro-inflammatory cytokines. Consistent with in vivo findings, melatonin dose-dependently decreased apoptosis and necroptosis in cisplatin-treated mouse renal tubular epithelial cells. Collectively, our findings suggest that melatonin ameliorates cisplatin-induced acute renal failure and structural damages through dual suppression of apoptosis and necroptosis. These results reveal a novel mechanism underlying the therapeutic effect of melatonin against cisplatin-induced AKI and strengthen the idea that melatonin might be a promising therapeutic agent for the renal side-effects of cisplatin therapy.

【 授权许可】

Unknown