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

Hironori Nagasaka, Ikuo Inoue, Ayano Inui, Haruki Komatsu, Tsuyoshi Sogo, Kei Murayama, Tomoko Murakami, Tohru Yorifuji, Kotaro Asayama, Shigeo Katayama, Shinji Uemoto, Kunihiko Kobayashi, Masaki Takayanagi, Tomoo Fujisawa, Hirokazu Tsukahara

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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.

Original languageEnglish
Pages (from-to)472-477
Number of pages6
JournalPediatric Research
Volume60
Issue number4
DOIs
Publication statusPublished - Oct 2006

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Nagasaka, H., Inoue, I., Inui, A., Komatsu, H., Sogo, T., Murayama, K., Murakami, T., Yorifuji, T., Asayama, K., Katayama, S., Uemoto, S., Kobayashi, K., Takayanagi, M., Fujisawa, T., & Tsukahara, H. (2006). 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. Pediatric Research, 60(4), 472-477. https://doi.org/10.1203/01.pdr.0000238341.12229.d3