title: Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease: hepatic manifestation in Wilson disease as a consequence of augmented oxidative stress.
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 that generates free radicals, remains unclear. This study investigates oxidative stress on the liver and hepatic antioxidant 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 group II and III patients. Activities and protein expressions of Mn-dependent superoxide dismutase (Mn-SOD), CuZn-dependent superoxide dismutase (CuZn-SOD), and catalase were decreased in all patients, especially in group III patients. Glutathione peroxidase (GPx) 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.
authors.affiliation: Division of Metabolism, Chiba Children's Hospital, Chiba 266-0007, Japan. nagasa-hirono@k2.dion.ne.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Nagasaka
authors.forename: Ikuo
authors.initials: I
authors.lastname: Inoue
authors.forename: Ayano
authors.initials: A
authors.lastname: Inui
authors.forename: Haruki
authors.initials: H
authors.lastname: Komatsu
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sogo
authors.forename: Kei
authors.initials: K
authors.lastname: Murayama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Murakami
authors.forename: Tohru
authors.initials: T
authors.lastname: Yorifuji
authors.forename: Kotaro
authors.initials: K
authors.lastname: Asayama
authors.forename: Shigeo
authors.initials: S
authors.lastname: Katayama
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Tomoo
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsukahara
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000032:analysis*; D001774:Blood Chemical Analysis; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D006527:Hepatolenticular Degeneration / Q000175:diagnosis*; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000201:enzymology; D008107:Liver Diseases / Q000175:diagnosis*; D008297:Male; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000032:analysis; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D010088:Oxidoreductases; D005978:Glutathione; D019803:Glutathione Disulfide