TY - JOUR
T1 - Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease
T2 - Hepatic manifestation in wilson disease as a consequence of augmented oxidative stress
AU - Nagasaka, Hironori
AU - Inoue, Ikuo
AU - Inui, Ayano
AU - Komatsu, Haruki
AU - Sogo, Tsuyoshi
AU - Murayama, Kei
AU - Murakami, Tomoko
AU - Yorifuji, Tohru
AU - Asayama, Kotaro
AU - Katayama, Shigeo
AU - Uemoto, Shinji
AU - Kobayashi, Kunihiko
AU - Takayanagi, Masaki
AU - Fujisawa, Tomoo
AU - Tsukahara, Hirokazu
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/10
Y1 - 2006/10
N2 - 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.
AB - 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.
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U2 - 10.1203/01.pdr.0000238341.12229.d3
DO - 10.1203/01.pdr.0000238341.12229.d3
M3 - Article
C2 - 16940238
AN - SCOPUS:33748893007
VL - 60
SP - 472
EP - 477
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 4
ER -