Action of low doses of Aspirin in Inflammation and Oxidative Stress induced by aβ1-42 on Astrocytes in primary culture

Int J Med Sci. 2020 Mar 13;17(6):834-843. doi: 10.7150/ijms.40959. eCollection 2020.

Abstract

Aspirin has been used as anti-inflammatory and anti-aggregate for decades but the precise mechanism(s) of action after the presence of the toxic peptide Aβ1-42 in cultured astrocytes remains poorly resolved. Here we use low-doses of aspirin (10-7 M) in astrocytes in primary culture in presence or absence of Aβ1-42 toxic peptide. We noted an increase of cell viability and proliferation with or without Aβ1-42 peptide presence in aspirin treated cells. In addition, a decrease in apoptosis, determined by Caspase 3 activity and the expression of Cyt c and Smac/Diablo, were detected. Also, aspirin diminished necrosis process (LDH levels), pro-inflammatory mediators (IL-β and TNF-α) and NF-ᴋB protein expression, increasing anti-inflammatory PPAR-γ protein expression, preventing Aβ1-42 toxic effects. Aspirin inhibited COX-2 and iNOS without changes in COX-1 expression, increasing anti-oxidant protein (Cu/Zn-SOD and Mn-SOD) expression in presence or absence of Aβ1-42. Taken together, our results show that aspirin, at low doses increases cell viability by decreasing inflammation and oxidative stress, preventing the deleterious effects of the Aβ1-42 peptide on astrocytes in primary culture. The use of low doses of aspirin may be more suitable for Alzheimer's disease.

Keywords: Alzheimer's disease; Amyloid-β; aspirin; inflammation; oxidative stress.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Aspirin / pharmacology*
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Interleukin-1beta / drug effects
  • NF-kappa B / genetics
  • Oxidative Stress / drug effects*
  • Oxidative Stress / genetics
  • Peptide Fragments / toxicity
  • Primary Cell Culture
  • Rats
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Amyloid beta-Peptides
  • Interleukin-1beta
  • NF-kappa B
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • amyloid beta-protein (1-42)
  • Aspirin