The Role of Oxidative Stress and Bioenergetic Dysfunction in Sulfite Oxidase Deficiency: Insights from Animal Models

Neurotox Res. 2019 Feb;35(2):484-494. doi: 10.1007/s12640-018-9986-z. Epub 2018 Dec 5.


Sulfite oxidase (SO) deficiency is an autosomal recessive inherited neurometabolic disease caused by deficient activity of SO. It is biochemically characterized by tissue accumulation and high urinary excretion of sulfite, thiosulfate, and S-sulfocysteine. Severe neurological symptoms, including neonatal seizures, encephalopathy, and psychomotor retardation, are commonly observed in the affected patients, but the pathogenesis of the neurologic dysfunction is still poorly understood. In this minireview, we will briefly summarize the knowledge obtained from in vivo and in vitro findings from animal studies indicating that oxidative stress and mitochondrial dysfunction are involved in the pathophysiology of the brain damage in this disease. Recent reports have shown that sulfite induces free radical generation, impairs brain antioxidant defenses, and disturbs mitochondrial energy metabolism and biogenesis. Moreover, it has been evidenced that free radical scavengers and the pan-PPAR agonist bezafibrate are able to prevent most deleterious effects elicited by sulfite on the brain. These promising data offer new perspectives for potential therapeutic strategies for this condition, which may include the early use of appropriate antioxidants and PPAR agonists in addition to the available treatment.

Keywords: Brain; Mitochondrial function; Redox homeostasis; Sulfite; Sulfite oxidase deficiency.

Publication types

  • Review

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / drug therapy
  • Amino Acid Metabolism, Inborn Errors / metabolism*
  • Animals
  • Disease Models, Animal*
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology*
  • Free Radical Scavengers / metabolism*
  • Free Radical Scavengers / pharmacology
  • Free Radical Scavengers / therapeutic use
  • Humans
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Sulfite Oxidase / deficiency*
  • Sulfite Oxidase / metabolism


  • Free Radical Scavengers
  • Sulfite Oxidase

Supplementary concepts

  • Sulfite oxidase deficiency