Melatonin attenuates cisplatin-induced acute kidney injury through dual suppression of apoptosis and necroptosis

Jong Woo Kim, Jungmin Jo, Jung Yeon Kim, Misun Choe, Jaechan Leem, Jae Hyung Park

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish
Article number64
JournalBiology
Volume8
Issue number3
DOIs
StatePublished - Sep 2019

Keywords

  • Acute kidney injury
  • Apoptosis
  • Cisplatin
  • Melatonin
  • Necroptosis

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