Therapeutic effect of resveratrol on oxidative stress in Graves’ ophthalmopathy orbital fibroblasts

Abstract

Graves’ ophthalmopathy (GO) is a chronic inflammatory autoimmune disease that causes physical pain and considerable distress. However, it is difficult to manage patients with GO because multiple causative factors complicate its pathogenesis. Glucocorticoids, the most commonly used treatment for GO, have limited utility and many side effects. Recently, it has been suggested that oxidative stress contributes to the development and progression of GO. Therefore, we investigated the therapeutic effect of resveratrol, a potent antioxidant, on oxidative stress levels in GO orbital fibroblasts in vitro. Orbital fibroblasts were cultured from orbital connective tissues obtained from GO patients, and the production of reactive oxygen species (ROS) was induced with 2% cigarette smoke extract or 10 μM hydrogen peroxide. Treatment with 30 or 50 μM resveratrol resulted in reduced ROS production, and lower levels of oxidative stress-induced heme oxygenase-1. We also differentiated orbital fibroblasts into adipocytes and found that resveratrol suppressed adipogenesis, reducing the number of adipocytes and suppressing the accumulation of lipid droplets. Treatment with 50 μM resveratrol also decreased ROS levels during adipogenesis. The extracellular signal-regulated kinase and c-Jun NH(2)-terminal kinase signaling pathways seemed to be associated with these results. This study supports the potential use of resveratrol in GO treatment.