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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Renal transporter OAT1 and PPAR-α pathway co-contribute to icaritin-induced nephrotoxicity

Dalong Wang1,2, Jing Liu1, Xiaodong Chen1,2

  • 1College of Pharmacy, Dalian Medical University, Dalian, China.

Phytotherapy Research : PTR
|November 4, 2022
PubMed

Insights

Icaritin causes kidney damage by inducing cell death and lipid metabolism disorders. This study reveals icaritin accumulates in renal cells, potentially via OAT1 uptake, leading to ferroptosis.

Area of Science:

  • Nephrology
  • Toxicology
  • Molecular Biology

Background:

  • Icaritin is a compound with potential therapeutic applications.
  • Understanding its potential side effects, particularly nephrotoxicity, is crucial for its safe use.

Purpose of the Study:

  • To investigate the nephrotoxicity of icaritin.
  • To elucidate the underlying mechanisms of icaritin-induced kidney damage.

Main Methods:

  • In vitro studies using HK-2 cells and hOAT1-HEK293 cells.
  • In vivo experiments in mice.
  • Proteomics technology to analyze signaling pathways.
  • Biochemical assays to measure cell damage, apoptosis, and lipid metabolism markers.

Main Results:

  • Icaritin induced cytotoxicity, apoptosis, and tubular damage in renal cells and mice.
  • Icaritin uptake was higher in OAT1-expressing cells, suggesting renal accumulation.
  • Proteomic analysis revealed alterations in the PPAR signaling pathway, indicating lipid metabolism dysfunction.
  • Icaritin promoted ferroptosis by increasing iron and lipid peroxidation and decreasing GPX4 activity.

Conclusions:

  • Icaritin exhibits significant nephrotoxicity through multiple mechanisms.
  • Lipid metabolism disorder and ferroptosis are key pathways involved in icaritin-induced kidney injury.
  • OAT1 may play a role in the renal accumulation of icaritin.
Keywords:
FerroptosisIcaritinOAT1PPAR-αnephrotoxicity

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