Edaravone Protected from D-Galactose-Induced Cell Senescence via Reduction of DNA Damage and Downregulation of p53, p21 and p16 Genes in PC12 Cells.

Abstract

Cellular senescence (CS) as an irreversible cell cycle arrest occurs in different tissues and organs. Among the others, CS is one of the most common risk factors for neurodegenerative diseases. The current study aimed to highlight the protective effects of Edaravone (EDN) as a free radical scavenger on D-galactose-induced cell senescence in PC12 cells. CS was induced following 48 h exposure to D-galactose (DG), and the protective effects of EDN at various concentrations (0.1, 1 and 10 µM) were studied. Cell proliferation, oxidative stress biomarkers such as total antioxidant capacity and lipid peroxidation rate, total protein level and protein carbonylation rate, pro-inflammatory cytokines (TNF-α) release, apoptotic cell death biomarkers including caspase 3/7 activities and the expression of p53, p21 and p16 as related genes to CS were analyzed. Experimentally induced CS resulted in a significant (p < 0.05) decrease in cell proliferation, elevation of lipid peroxidation and protein carbonylation rates, increase of TNF-α release, elevation of the number of apoptotic cells and DNA damage, along with 3.4 to 13-fold upregulation of CS-related gene expression. The most practical and effective concentration of EDN to protect PC12 cells from DG-induced injuries was found to be 1 µM. These findings in PC12 cells suggest that EDN with its antioxidant and anti-inflammatory properties could be an effective anti-aging compound to protect cells from various types of DNA-damaging factors.