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Intracellular balance of oxidative stress and cytoprotective molecules in damaged interlobular bile ducts in autoimmune hepatitis and primary biliary cirrhosis: In situ detection of 8‐hydroxydeoxyguanosine and glutathione‐S‐transferase‐pi
Author(s) -
Kadokawa Yoshiko,
Ohba Kazuo,
Omagari Katsuhisa,
Akazawa Shiho,
Hayashida Kenji,
Ohnita Ken,
Takeshima Fuminao,
Mizuta Yohei,
Kohno Shigeru
Publication year - 2007
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2007.00093.x
Subject(s) - primary biliary cirrhosis , oxidative stress , glutathione , bile duct , autoimmune hepatitis , intracellular , liver injury , medicine , pathology , biliary cirrhosis , pathogenesis , biology , hepatitis , autoimmune disease , biochemistry , enzyme , disease
Aim: Bile duct injury has been thought to be absent in autoimmune hepatitis (AIH), but recent studies have indicated that AIH patients do have bile duct injury. In this study, the intracellular balance of oxidative stress and cytoprotection in biliary epithelial cells was investigated to clarify the pathogenesis of bile duct injury in AIH. Methods: The intracellular status of oxidative DNA damage caused by oxidative stress and glutathione, an endogenous cytoprotective molecule, were examined in patients with AIH, primary biliary cirrhosis (PBC), and normal controls by immunostaining of 8‐hydroxydeoxyguanosine (8‐OHdG) and glutathione‐S‐transferase‐pi. Results: Immunohistochemically, 8‐OHdG expression was detected as abundantly in the damaged bile ducts of AIH patients as in PBC patients. Moreover, in AIH, 8‐OHdG expression was detected in damaged bile ducts more than in undamaged bile ducts. Glutathione‐S‐transferase‐pi expression was relatively preserved in the damaged bile ducts of AIH patients compared to PBC patients, reflecting preservation of intracellular glutathione. Conclusions: In AIH, oxidative stress and DNA damage may be involved in the pathogenesis of bile duct injury in a manner similar to that found in PBC. However, relatively preserved intracellular glutathione may play a key role in preventing progressive bile duct loss following bile duct injury in AIH.