Chitooligosaccharides Derivatives Protect ARPE-19 Cells against Acrolein-Induced Oxidative Injury

Mar Drugs. 2023 Feb 22;21(3):137. doi: 10.3390/md21030137.

Abstract

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. The progression of AMD is closely related to oxidative stress in the retinal pigment epithelium (RPE). Here, a series of chitosan oligosaccharides (COSs) and N-acetylated derivatives (NACOSs) were prepared, and their protective effects on an acrolein-induced oxidative stress model of ARPE-19 were explored using the MTT assay. The results showed that COSs and NACOs alleviated APRE-19 cell damage induced by acrolein in a concentration-dependent manner. Among these, chitopentaose (COS-5) and its N-acetylated derivative (N-5) showed the best protective activity. Pretreatment with COS-5 or N-5 could reduce intracellular and mitochondrial reactive oxygen species (ROS) production induced by acrolein, increase mitochondrial membrane potential, GSH level, and the enzymatic activity of SOD and GSH-Px. Further study indicated that N-5 increased the level of nuclear Nrf2 and the expression of downstream antioxidant enzymes. This study revealed that COSs and NACOSs reduced the degeneration and apoptosis of retinal pigment epithelial cells by enhancing antioxidant capacity, suggesting that they have the potential to be developed into novel protective agents for AMD treatment and prevention.

Keywords: ARPE-19; N-acetylated chitosan oligosaccharide; Nrf2; chitosan oligosaccharide; oxidative stress.

MeSH terms

  • Acrolein / toxicity
  • Aged
  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Cell Survival
  • Humans
  • Macular Degeneration* / chemically induced
  • Macular Degeneration* / drug therapy
  • Macular Degeneration* / prevention & control
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Acrolein
  • oligochitosan
  • Reactive Oxygen Species