Myo-Inositol Supplementation Alleviates Cisplatin-Induced Acute Kidney Injury via Inhibition of Ferroptosis

Huiyue Qi, Fei Deng, Yinghuai Wang, Hao Zhang, Yashpal S. Kanwar*, Yingbo Dai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Myo-inositol, a carbocyclic sugar, is believed to be relevant to renal pathobiology since the kidney is the major site for its catabolism. Its role in acute kidney injury (AKI) has not been fully investigated. Ferroptosis, a unique form of regulated cell death, is involved in various types of renal injuries. The relevance of myo-inositol with respect to the process of ferroptosis has not been explored either. Herein, our current exploratory studies revealed that supplementation of myo-inositol attenuates cisplatin-induced injury in cultured Boston University mouse proximal tubular (BUMPT) cells and renal tubules in vivo. Moreover, our studies unraveled that metabolic parameters pertaining to ferroptosis were disrupted in cisplatin-treated proximal tubular cells, which were seemingly remedied by the administration of myo-inositol. Mechanistically, we noted that cisplatin treatment led to the up-regulation of NOX4, a key enzyme relevant to ferroptosis, which was normalized by the administration of myo-inositol. Furthermore, we observed that changes in the NOX4 expression induced by cisplatin or myo-inositol were modulated by carboxy-terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase. Taken together, our investigation suggests that myo-inositol promotes CHIP-mediated ubiquitination of NOX4 to decelerate the process of ferroptosis, leading to the amelioration of cisplatin-induced AKI.

Original languageEnglish (US)
Article number16
JournalCells
Volume12
Issue number1
DOIs
StatePublished - Jan 2023

Keywords

  • acute kidney injury
  • cisplatin
  • ferroptosis
  • myo-inositol

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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