title: Therapeutic Effect of Resveratrol on Oxidative Stress in Graves' Orbitopathy Orbital Fibroblasts.
abstract: OBJECTIVE
  Multiple causative factors complicate the pathogenesis in Graves' orbitopathy (GO). 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, upon oxidative stress levels in GO orbital fibroblasts in vitro.
  
  
  METHODS
  Orbital fibroblasts were cultured from orbital connective tissues obtained from GO patients. Intracellular reactive oxygen species (ROS) levels and the expression of heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, and thioredoxin (Trx), were measured after resveratrol treatment. Adipogenesis was induced, and ROS levels were examined during adipogenic differentiation. Western blot assay was performed to evaluate the effects of resveratrol on the expression of antioxidants levels and transcriptional regulators.
  
  
  RESULTS
  Treatment with 30 or 50 μM resveratrol reduced ROS production and HO-1 level induced by oxidative stress. Levels of Cu/Zn-SOD, catalase, and Trx were also reduced, while Mn-SOD increased with 50 μM resveratrol treatment. 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. Expression of the transcriptional regulators phosphor-extracellular signal-regulated kinase and phospho-c-Jun NH(2)-terminal kinase significantly increased after treatment with 50 μM resveratrol, and decreased in response to inhibitors of each protein. Phosphonuclear factor kappa-light-chain-enhancer of activated B cells p65 levels also increased after treatment with 50 μM resveratrol.
  
  
  CONCLUSIONS
  Resveratrol reduced ROS levels and inhibited adipogenesis in GO orbital fibroblasts in vitro. This study supports the potential use of resveratrol in GO treatment.
authors.affiliation: Institute of Vision Research Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chang Yeom
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Catholic University College of Medicine, Seoul, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Institute of Vision Research Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Chae
authors.affiliation: Institute of Endocrine research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Byun
authors.affiliation: Institute of Endocrine research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Jig
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Institute of Vision Research Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Yoon
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology*; D050156:Adipogenesis / Q000187:drug effects*; D020533:Angiogenesis Inhibitors; D000975:Antioxidants / Q000627:therapeutic use; D049109:Cell Proliferation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000077185:Resveratrol