Children's toxicology from bench to bed - Liver Injury (3): Oxidative stress and anti-oxidant systems in liver of patients with Wilson disease

Hironori Nagasaka, Masaki Takayanagi, Hirokazu Tsukahara

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The role of oxidative stress in the pathogenesis of liver disease in Wilson disease (WD), a genetic disorder characterized by excess hepatic deposition of copper, which generates free radicals, remains unclear. This study investigates oxidative stress on the liver and hepatic anti-oxidant responses in WD using liver specimens from affected patients showing mild liver damage (group I, n = 3), moderate or greater liver damage (group II, n = 5) and fulminant hepatic failure (group III, n = 5), and from asymptomatic carriers (n = 2). Decreased ratios of reduced glutathione (GSH) to oxidized glutathione (GSSG) and increased thiobarbituric acid reactive substance (TBARS), a lipid peroxidation product, were found in every affected patient, especially in groups II and III patients. Activities and protein expressions of Mn-dependent superoxide dismutase (Mn-SOD), CuZn-SOD, and catalase were decreased in all patients, especially in group III patients. Glutathione peroxidase activity was decreased only in group III patients. Asymptomatic carriers without any clinical manifestations showed normal TBARS level and GSH/GSSG ratio with increases in both GSH and GSSG levels. Their CuZn-SOD, Mn-SOD and catalase activities were increased. These results suggest that excessive copper-derived oxidants contribute to development and progression of liver disease in WD.

Original languageEnglish
Pages (from-to)SP229-SP236
JournalJournal of Toxicological Sciences
Volume34
Issue number2 SPEC. ISS.
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • Copper
  • Liver
  • Oxidative stress
  • Wilson disease

ASJC Scopus subject areas

  • Toxicology

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