Nrf2/ARE is the potential pathway to protect Sprague-Dawley rats against oxidative stress induced by quinocetone

Regul Toxicol Pharmacol. 2013 Aug;66(3):279-85. doi: 10.1016/j.yrtph.2013.04.005. Epub 2013 Apr 26.

Abstract

3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) is a newly used veterinary drug which has been proven to promote feed efficiency and growth of animals; however, its potential toxicity can't be ignored. Therefore, the present study was aimed to investigate the nephrotoxicity of QCT and the oxidative stress induced by it. Sprague-Dawley rats (SD rats) were randomly divided into four groups with doses of 2400, 800, 50 and 0mg/kg/day with administration of QCT for 4 weeks. Results proved that QCT could induce nephrotoxicity and this phenomenon had dose dependent manner. Simultaneously, this phenomenon was accompanied by intracellular reactive oxygen species (ROS) accumulation, enhanced lipid peroxidation and inhibited antioxidant system, i.e. glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GSH). Additionally, the higher expression of Nrf2 in QCT treated groups illustrated that QCT-induced oxidative stress would be partly mitigated by the induction of phase II detoxifying enzymes via increasing Nrf2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidant Response Elements / drug effects*
  • Antioxidant Response Elements / genetics
  • Antioxidants / metabolism
  • Biomarkers / blood
  • Catalase / blood
  • DNA Damage*
  • Dose-Response Relationship, Drug
  • Glutathione / blood
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control
  • Kidney Function Tests
  • Male
  • Malondialdehyde / blood
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / genetics
  • Quinoxalines / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Superoxide Dismutase / blood

Substances

  • Antioxidants
  • Biomarkers
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Quinoxalines
  • Reactive Oxygen Species
  • quinocetone
  • Malondialdehyde
  • Catalase
  • Superoxide Dismutase
  • Glutathione