The effects of α-lipoic acid on oxidative stress and inflammation in orbital fibroblasts from Graves' orbitopathy

Abstract

Alpha-lipoic acid (ALA) (1,2-dithiolane-3-pentanoic acid) is well known as a powerful antioxidant, helping to protect against oxidative stress and inflammatory damage. Considering the pathophysiological mechanisms of Graves’ orbitopathy (GO), I investigated the effects of ALA in primary cultured orbital fibroblasts from GO, targeting intracellular reactive oxygen species (ROS) generation, inflammation, hyaluronan production, and fat deposition. In results, ALA strongly attenuated ROS production through heme oxygenase-1 (HO-1), and potentiated HO-1 expression with H2O2 stimulation in GO orbital fibroblasts. Also, TNFα-induced intercellular adhesion molecule-1 (ICAM-1), interleukin (IL) -6, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) and CCL5 mRNA expression were inhibited by ALA treatment through suppression of nuclear factor kappa B (NFkB). Treatment of ALA inhibited intracellular accumulation of lipid droplets, and resulted in a dose-dependent decrease in expression of PPARγ, C/EBPα and β, and HO-1 proteins. Taken together, ALA is a promising agent for GO regarding its inhibitory effects on oxidative stress and inflammation, reading to prevention for accumulation of extracellular matrix and adipose tissue expansion.