Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury

Jungmin Jo, Jung Yeon Kim, Jaechan Leem

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4 Scopus citations

Abstract

Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers, but its application is often limited due to complications such as acute kidney injury (AKI). Orexins are hypothalamic neuropeptides that modulate the sleep-wake cycle, neuroendocrine function, and the autonomic nervous system. Emerging evidence suggests that orexin A (OXA) has anti-inflammatory and neuroprotective effects in animal models of neuroinflammatory diseases of the central nervous system. However, the effect of OXA on kidney diseases has not been examined. Here, we investigated whether OXA has a protective effect in a murine model of cisplatin-induced AKI. Intraperitoneal administration of OXA ameliorated renal dysfunction, and histological abnormalities in mice injected with cisplatin. OXA inhibited cisplatin-induced oxidative stress through the modulation of prooxidant and antioxidant enzymes. This peptide reduced apoptotic cell death by inhibiting the p53-mediated pathway in mice injected with cisplatin. OXA also alleviated cisplatin-induced cytokine production and macrophage infiltration into injured kidneys. Taken together, these results showed that OXA ameliorates cisplatin-induced AKI via antioxidant, anti-apoptotic, and anti-inflammatory actions. This peptide could be a potential therapeutic agent for cisplatin-induced AKI.

Original languageEnglish
Article number7196
JournalJournal of Clinical Medicine
Volume11
Issue number23
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning (MSIP) (NRF-2017R1C1B5076410 and NRF-2017R1E1A2A02023467).

Publisher Copyright:
© 2022 by the authors.

Keywords

  • acute kidney injury
  • apoptosis
  • cisplatin
  • inflammation
  • orexin A
  • oxidative stress

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