Oxidative/nitrative stress in the pathogenesis of systemic sclerosis: are antioxidants beneficial?

Paul R.J. Ames, Tommaso Bucci, Mira Merashli, Marta Amaral, Alessia Arcaro, Fabrizio Gentile, Jaffar Nourooz-Zadeh, Jose DelgadoAlves

Research output: Contribution to journalReview article

Abstract

Systemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from the clinical side by progressive vasculopathy and fibrosis of the skin and different organs and from the biochemical side by fibroblast deregulation with excessive production of collagen and increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an overproduction of reactive oxygen species that through an autocrine loop maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are implicated in the origin and perpetuation of several clinical manifestations of SSc having vascular damage in common; attempts to dampen oxidative and nitrative stress through different agents with antioxidant properties have not translated into a sustained clinical benefit. Objective of this narrative review is to describe the origin and clinical implications of oxidative and nitrative stress in SSc, with particular focus on the central role of NOX4 and its interactions, to re-evaluate the antioxidant approaches so far used to limit disease progression, to appraise the complexity of antioxidant treatment and to touch on novel pathways elements of which may represent specific treatment targets in the not so distant future.

Original languageEnglish
Pages (from-to)1063-1082
Number of pages20
JournalFree Radical Research
Volume52
Issue number10
DOIs
Publication statusPublished - 3 Oct 2018

Keywords

  • Antioxidant
  • Nfr2
  • NOX
  • oxidative stress
  • systemic sclerosis

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