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Tetrahydrocurcumin Attenuates Polymyxin B Sulfate-Induced HK-2 Cells Apoptosis by Inhibiting Endoplasmic Reticulum

Junjie Chen1,2, Weibin Fan2,3, Jing Fan2,3

  • 1Department of Intensive Care Medicine, Changxing People's Hospital; Changxing Branch, Second Affiliated Hospital of Zhejiang University School of Medicine, Huzhou, China.

Environmental Toxicology
|July 18, 2024
PubMed

Insights

Tetrahydrocurcumin (THC) protects kidney cells from polymyxin B (PMB) damage by reducing endoplasmic reticulum stress. This finding highlights THC as a potential therapy to mitigate PMB-induced nephrotoxicity.

Area of Science:

  • Nephrology
  • Pharmacology
  • Cell Biology

Background:

  • Polymyxin B (PMB) is a critical antibiotic, but its clinical use is limited by significant nephrotoxicity.
  • Reducing PMB-induced kidney damage is a major clinical challenge.
  • Tetrahydrocurcumin (THC) shows promise for mitigating drug-induced toxicities, but its mechanism against PMB nephrotoxicity is unclear.

Purpose of the Study:

  • To investigate the protective effects of Tetrahydrocurcumin (THC) against polymyxin B (PMB)-induced nephrotoxicity.
  • To elucidate the underlying molecular mechanisms by which THC mitigates PMB-induced kidney cell injury.

Main Methods:

  • In vitro assessment of THC's efficacy in a model of PMB-induced kidney cell injury (HK-2 cells).
  • Cell counting kit-8 and flow cytometry assays to evaluate cell viability and apoptosis.
  • Analysis of the endoplasmic reticulum (ER) stress pathway, specifically the PERK/eIF2α/ATF4/CHOP axis.
  • Pharmacological inhibition of ER stress using PERK inhibitor GSK2606414.

Main Results:

  • THC significantly protected HK-2 cells against PMB-induced apoptosis.
  • THC suppressed PMB-induced endoplasmic reticulum (ER) stress.
  • THC's protective effect was mediated through the inhibition of the PERK/eIF2α/ATF4/CHOP pathway.
  • Inhibition of ER stress with GSK2606414 also reduced PMB-induced apoptosis.

Conclusions:

  • Tetrahydrocurcumin (THC) effectively alleviates polymyxin B (PMB)-induced nephrotoxicity in vitro.
  • THC mitigates PMB-induced kidney injury by inhibiting ER stress via the PERK/eIF2α/ATF4/CHOP pathway.
  • THC represents a promising therapeutic strategy to reduce PMB-associated nephrotoxicity and improve clinical outcomes.
Keywords:
HK‐2 cellsPERK/eIF2α/ATF4/CHOPapoptosisendoplasmic reticulum stresspolymyxin Btetrahydrocurcumin

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