Antioxidant Therapy in Graves' Orbitopathy.

Giulia Lanzolla,Michele Marinò,Claudio Marcocci

doi:10.3389/fendo.2020.608733

Giulia Lanzolla, Michele Marinò + Show 1 more

Open Access

https://doi.org/10.3389/fendo.2020.608733

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Abstract

The balance of the cell redox state is a key point for the maintenance of cellular homeostasis. Increased reactive oxygen species (ROS) generation leads to oxidative damage of tissues, which is involved in the development of several diseases, including autoimmune diseases. Graves’ Orbitopathy (GO) is a disfiguring autoimmune-related condition associated with Graves’ Disease (GD). Patients with active, moderate-to-severe GO, are generally treated with high doses intravenous glucocorticoids (ivGCs) and/or orbital radiotherapy. On the contrary, up to recently, local ointments were the treatment most frequently offered to patients with mild GO, because the risks related to ivGCs does not justify the relatively poor benefits expected in mild GO. However, a medical treatment for these patients is heavily wanted, considering that GO can progress into more severe forms and also patients with mild GO complain with an impairment in their quality of life. Thus, based on the role of oxidative stress in the pathogenesis of GO, a therapy with antioxidant agents has been proposed and a number of studies have been performed, both in vitro and in vivo, which is reviewed here.

Highlights

Graves’ Orbitopathy (GO) is an autoimmune, disfiguring disease observed in ~25%–30% of patients with Graves’ Disease (GD)
A role of oxidative stress in GO is supported by a number of basic studies suggesting that reactive oxygen species (ROS) promote the proliferation of orbital fibroblasts (OFs) and the release of GAGs, the synthesis and secretion of cytokines, and the expression of other factors involved in the pathogenesis of GO, namely heat shock protein 72 (HSP-72), HLA-DR and ICAM1 [14]
A study performed in primary cultures of OFs from GO patients and control subjects demonstrated that quercetin exerts an inhibitory effect on fibroblasts proliferation and hyaluronic acid (HA) release, with no difference between GO and control fibroblasts [16]

Summary

INTRODUCTION

Graves’ Orbitopathy (GO) is an autoimmune, disfiguring disease observed in ~25%–30% of patients with Graves’ Disease (GD). A role of oxidative stress in GO is supported by a number of basic studies suggesting that ROS promote the proliferation of OFs and the release of GAGs, the synthesis and secretion of cytokines, and the expression of other factors involved in the pathogenesis of GO, namely heat shock protein 72 (HSP-72), HLA-DR and ICAM1 [14] In this context, a number of studies, performed both in vitro and in vivo, investigated the effects of antioxidant agents in GO, including selenium, pentoxifylline, quercetin, enalapril, vitamin C, N-acetyl-L-cysteine and melatonin [14,15,16,17,18, 24, 25]. A study performed in primary cultures of OFs from GO patients and control subjects demonstrated that quercetin exerts an inhibitory effect on fibroblasts proliferation and HA release, with no difference between GO and control fibroblasts [16]

Results

Findings

CONCLUSIONS