Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats

Acta Cir Bras. 2023 Aug 4:38:e382523. doi: 10.1590/acb382523. eCollection 2023.

Abstract

Purpose: To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model.

Methods: Rats were intraperitoneally injected with puerarin (50 or 100 mg/kg) per day for one week before renal I/R. The level of renal collagen deposition and interstitial fibrosis were observed by hematoxylin and eosin and Sirius Red staining, and the expression of α-smooth muscle actin (α-SMA) was examined by immunohistochemical staining. The ferroptosis related factors and TLR4/Nox4-pathway-associated proteins were detected by Western blotting.

Results: Puerarin was observed to alleviate renal collagen deposition, interstitial fibrosis and the α-SMA expression induced by I/R. Superoxide dismutase (SOD) activities and glutathione (GSH) level were decreased in I/R and hypoxia/reoxygenation (H/R), whereas malondialdehyde (MDA) and Fe2+ level increased. However, puerarin reversed SOD, MDA, GSH and Fe2+ level changes induced by I/R and H/R. Besides, Western blot indicated that puerarin inhibited the expression of ferroptosis related factors in a dose-dependent manner, which further demonstrated that puerarin had the effect to attenuate ferroptosis. Moreover, the increased expression of TLR/Nox4-pathway-associated proteins were observed in I/R and H/R group, but puerarin alleviated the elevated TLR/Nox4 expression.

Conclusions: Our results suggested that puerarin inhibited oxidative stress and ferroptosis induced by I/R and, thus, delayed the progression of renal fibrosis, providing a new target for the treatment of renal fibrosis.

MeSH terms

  • Animals
  • Ferroptosis*
  • Fibrosis
  • Ischemia
  • Kidney Diseases*
  • NADPH Oxidase 4 / metabolism
  • Oxidative Stress
  • Rats
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / prevention & control
  • Superoxide Dismutase / metabolism
  • Toll-Like Receptor 4 / metabolism

Substances

  • puerarin
  • Toll-Like Receptor 4
  • Superoxide Dismutase
  • Nox4 protein, rat
  • NADPH Oxidase 4