Protective effect of low molecular-weight seleno-aminopolysaccharides against H2O2-induecd oxidative stress in intestinal epithelial cells

Int J Biol Macromol. 2018 Jun:112:745-753. doi: 10.1016/j.ijbiomac.2018.01.191. Epub 2018 Feb 1.

Abstract

Organoselemium compounds possess strong antioxidant activity as well as protecting cells from DNA damage, mitochondrial injury, lipid peroxidation, protein denaturation and cell death. Herein, we used an in vitro oxidative model to further investigate the antioxidant effects of a novel organoselemium compound, low molecular-weight seleno-aminopolysaccharides (LSA) in intestinal porcine epithelial cells (IPEC-1), and the molecular mechanisms of these effects. Analysis by MTT assay showed that LSA could significantly increase the viability of IPEC-1 cells compared to cells exposed to H2O2. We found that the levels of different antioxidant enzymes could dramatically increase in LSA pretreatment group compared to H2O2 treatment group. Furthermore, LSA significantly increased the gene expression of antioxidant enzymes and phase 2 detoxifying enzymes in IPEC-1 cells, as measured by qRT-PCR. In addition, LSA up-regulated the expression level of intracellular transcription factor NF-E2-related factor 2 (Nrf2) and inhibited the level of kelch-like ECH-associated protein 1 (Keap1) with western blot analysis. Collectively, the present study suggested that LSA has the protective effect of IPEC-1 cells against H2O2-induecd oxidative stress, and its mechanism may be related to activation of Keap1/Nrf2 signaling pathway in intestinal epithelial cells.

Keywords: Antioxidant activity; Keap1/Nrf2 signaling pathway; Low molecular-weight seleno-aminopolysaccharide.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Death / drug effects
  • Cell Line
  • Cytoprotection / drug effects
  • Enterocytes / drug effects
  • Enterocytes / enzymology
  • Enterocytes / pathology*
  • Gene Expression Regulation / drug effects
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Hydrogen Peroxide / toxicity*
  • Inactivation, Metabolic / drug effects
  • Inactivation, Metabolic / genetics
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Lipid Peroxidation / drug effects
  • Malondialdehyde / metabolism
  • Molecular Weight
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects*
  • Polysaccharides / pharmacology*
  • Protective Agents / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Selenium / pharmacology*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Sus scrofa

Substances

  • Antioxidants
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Polysaccharides
  • Protective Agents
  • RNA, Messenger
  • Malondialdehyde
  • Hydrogen Peroxide
  • L-Lactate Dehydrogenase
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Selenium