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

Research Paper

Action of low doses of Aspirin in Inflammation and Oxidative Stress induced by aβ_1-42 on Astrocytes in primary culture

Adrian Jorda^1,2*, Martin Aldasoro^1*, Constanza Aldasoro¹, Sol Guerra-Ojeda¹, Antonio Iradi¹, Jose Mª Vila¹, Juan Campos-Campos^1,2, Soraya L. Valles^1✉

1. Department of Physiology, School of Medicine, University of Valencia, Spain.
2. Faculty of Nursing and Podiatry, University of Valencia, Spain.
*These authors contributed equally to this work.

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 Aβ_1-42 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 Aβ_1-42 toxic peptide. We noted an increase of cell viability and proliferation with or without Aβ_1-42 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 Aβ_1-42 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 Aβ_1-42. 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 Aβ_1-42 peptide on astrocytes in primary culture. The use of low doses of aspirin may be more suitable for Alzheimer's disease.

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