Kahweol ameliorates cisplatin-induced acute kidney injury through pleiotropic effects in mice

Jung Yeon Kim, Jungmin Jo, Jaechan Leem, Kwan Kyu Park

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.

Original languageEnglish
Article number572
Pages (from-to)1-14
Number of pages14
JournalBiomedicines
Volume8
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • Acute kidney injury
  • Apoptosis
  • Cisplatin
  • Coffee
  • Inflammation
  • Kahweol
  • Necroptosis
  • Oxidative stress

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