Protective effects of proanthocyanidins against cadmium-induced testicular injury through the modification of Nrf2-Keap1 signal path in rats

Environ Toxicol Pharmacol. 2018 Jan:57:1-8. doi: 10.1016/j.etap.2017.11.002. Epub 2017 Nov 3.

Abstract

The purpose of this study was to evaluate the potential chemoprotective effects of proanthocyanidins (PAs) against cadmium (Cd)-induced oxidative damage of testes via Nrf2-Keap1 signal pathway in rats. Briefly, by using biochemical histological analysis, as well as the real time PCR and western blot approach, oxidative damage in rat testicular tissue was observed after exposure to Cd. In addition, significant down-regulations of mRNA and protein levels of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), γ-glutamyl cysteine synthetase (γ-GCS), glutathione peroxidase (GSH-Px) and quinone oxidoreductase 1 (NQO1), as well as a significant up-regulation of Kelch sample related protein-1 (Keap1) levels in testicular tissue were observed after Cd exposure. Notably, these alterations were reverted back to near normalcy in Cd+PAs group rats. In conclusion, PAs exhibited a significant chemopreventive potential against Cd-induced testicular oxidative damage in rats, possibly through the modification of Nrf2-Keap1 signal path.

Keywords: Cadium; Nrf2-Keap1; Oxidative damage; Proanthocyanidins; Signal path; Testes; Wistar rats.

MeSH terms

  • Animals
  • Cadmium / toxicity*
  • Glutamate-Cysteine Ligase / genetics
  • Glutathione / metabolism
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Hydrogen Peroxide / metabolism
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Male
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Proanthocyanidins / pharmacology*
  • Protective Agents / pharmacology*
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Sperm Count
  • Sperm Motility / drug effects
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology

Substances

  • KEAP1 protein, rat
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Proanthocyanidins
  • Protective Agents
  • RNA, Messenger
  • Cadmium
  • Hydrogen Peroxide
  • Glutathione Peroxidase
  • Heme Oxygenase-1
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, rat
  • Glutamate-Cysteine Ligase
  • Glutathione