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Penehyclidine Hydrochloride Improves Rhabdomyolysis-Mediated Acute Kidney Injury by Inhibiting Ferroptosis through

Li Chen1, ShaSha Luo2, HongBao Tan2

  • 1Department of Nephrology, Brain Hospital of Hunan Province (The Second People's Hospital of Hunan Province), Changsha, China.

Nephron
|October 15, 2023
PubMed
Abstract

Insights

Penehyclidine hydrochloride (PHC) effectively treats rhabdomyolysis-induced acute kidney injury (AKI) by inhibiting ferroptosis. This study elucidates PHC

Area of Science:

  • Biochemistry
  • Pharmacology
  • Nephrology

Background:

  • Rhabdomyolysis-induced acute kidney injury (AKI) is a serious clinical condition.
  • Penehyclidine hydrochloride (PHC) has demonstrated potential in treating AKI.
  • The precise mechanisms of PHC in mitigating rhabdomyolysis-induced AKI require detailed investigation.

Purpose of the Study:

  • To investigate the pharmacological effects of Penehyclidine hydrochloride (PHC) on rhabdomyolysis (RM)-induced acute kidney injury (AKI).
  • To elucidate the underlying molecular mechanisms by which PHC exerts its protective effects against RM-induced AKI.

Main Methods:

  • Established rhabdomyolysis-induced AKI models using FeG treatment and glycerol injection.
  • Assessed cell viability, reactive oxygen species (ROS), LDH, Fe2+, MPO, MDA, and GSH levels.
  • Analyzed ferroptosis-related proteins (SLC7A11, GPX4, ACSL4) and the HIF-1α/MT1G interaction via dual-luciferase reporter gene and chromatin immunoprecipitation assays.

Main Results:

  • PHC treatment enhanced cell viability and reduced markers of oxidative stress and ferroptosis (ROS, LDH, Fe2+, MPO, MDA) in FeG-treated HK-2 cells.
  • PHC increased levels of protective molecules (GSH, SLC7A11, GPX4), indicating suppression of ferroptosis.
  • PHC alleviated kidney injury in a rat model, demonstrating its protective role against glycerol-induced AKI by inhibiting ferroptosis.

Conclusions:

  • Penehyclidine hydrochloride (PHC) effectively ameliorates rhabdomyolysis-mediated acute kidney injury (AKI).
  • PHC exerts its protective effects by inhibiting ferroptosis via the HIF-1α/MT1G/SLC7A11/GPX4 signaling pathway.
  • These findings highlight PHC as a promising therapeutic agent for AKI associated with rhabdomyolysis.
Keywords:
FerroptosisHIF-1αMT1GPenehyclidine hydrochlorideRhabdomyolysis-induced acute kidney injury

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