Renoprotective effect of N-acetylcystein and vitamin E in bisphenol A-induced rat nephrotoxicity; Modulators of Nrf2/ NF-κB and ROS signaling pathway

Acta Biomed. 2022 Dec 16;93(6):e2022301. doi: 10.23750/abm.v93i6.13732.

Abstract

Background and aim of the work: Bisphenol A (BPA) is a chemical product that is widely used as a plastic precursor. It acts directly on the kidney mitochondria, causing renal dysfunction. N-acetylcysteine is effective in protecting the kidneys from chemical-induced damage. Vitamin E is an antioxidant that protects cells from the damaging effects of free radicals. The aim of this study is to further evaluate and compare NAC and vitamin E to oppose the nephrotoxicity caused by BPA.

Research design and methods: Forty-two adult male rats were divided into 7 groups: control, BPA, NAC, vitamin E, BPA plus NAC, BPA plus vitamin E, and combined BPA, NAC and vitamin E. BPA, NAC, vitamin E were given orally at doses of 50 mg/kg, 200 mg/kg, and 1000 mg/kg respectively, for 5 weeks.

Results: NAC and vitamin E groups showed improved kidney function tests and alleviated BPA-induced oxidative stress; increased GSH and decreased MDA, NO and iNOS levels. NAC and vitamin E significantly attenuated inflammation; decreased NF-κB and increased IL-4, and Nrf2, in addition there was alleviation of renal histopathology. To some extent, vitamin E administration showed significant improvement. Moreover, combined NAC and vitamin E treatment showed more significance than either NAC or vitamin E separate groups.

Conclusions: This study determined the substantial protective effects of NAC and/or vitamin E in BPA-induced nephrotoxicity through modulation of Nrf2 with subsequent improvement of oxidative stress and inflammation. The alleviation was more significant in combined NAC and vitamin E treatment mainly through their synergistic effect on Nrf2.

MeSH terms

  • Animals
  • Inflammation / drug therapy
  • Male
  • NF-E2-Related Factor 2* / metabolism
  • NF-E2-Related Factor 2* / pharmacology
  • NF-E2-Related Factor 2* / therapeutic use
  • NF-kappa B* / metabolism
  • NF-kappa B* / pharmacology
  • NF-kappa B* / therapeutic use
  • Oxidative Stress
  • Rats
  • Reactive Oxygen Species / adverse effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Vitamin E / adverse effects

Substances

  • bisphenol A
  • NF-kappa B
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Vitamin E