title: Oxidative-stress-related changes in the livers of bile-duct-ligated rats.
abstract: The role of reactive oxygen species in liver fibrogenesis is not yet clarified. The aim of this study was to investigate oxidative-stress-related changes in cirrhotic rats. Cirrhosis was induced by bile duct ligation in Sprague-Dawley rats. Plasma malondialdehyde (MDA), hepatic 8-hydroxy-2'-deoxyguanosine (8-OHdG), hepatic mitochondrial respiratory functions and gene transcripts were measured at 2 and 4 weeks after surgery in bile-duct-ligated (BDL) and sham-operated-operated rats. The results showed progressive increases in the levels of plasma MDA, hepatic 8-OHdG and procollagen I and III mRNA expression, and progressive impairment of hepatic mitochondrial respiratory function in BDL rats at 2 and 4 weeks after ligation compared with sham-operated rats. Moreover, at 4 weeks after ligation, BDL rats exhibited reduced plasma glutathione and vitamin E levels, impaired hepatic mitochondrial electron transport enzyme activities and oxidative phosphorylation function. In addition, hepatic mRNA expression of transforming growth factor-beta1 was increased. Hepatomegaly, abnormal plasma alanine transaminase and aspartate transaminase levels, and portal hypertension were noted in BDL rats. Our results suggest that bile duct ligation in the rat induces mitochondrial dysfunction and biochemical and molecular changes related to oxidative stress in the liver.
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. huangyt@ym.edu.tw
authors.forename: Yi-Tsau
authors.initials: YT
authors.lastname: Huang
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Hsu
authors.forename: Chi-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Chien-Tzu
authors.initials: CT
authors.lastname: Liu
authors.forename: Yau-Huei
authors.initials: YH
authors.lastname: Wei
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001652:Bile Ducts / Q000473:pathology*; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004195:Disease Models, Animal; D004579:Electron Transport; D005978:Glutathione / Q000097:blood; D008026:Ligation; D008099:Liver / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008928:Mitochondria / Q000378:metabolism; D008930:Mitochondria, Liver / Q000473:pathology; D018384:Oxidative Stress; D010101:Oxygen Consumption; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011347:Procollagen / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1; D014810:Vitamin E / Q000097:blood
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D011347:Procollagen; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014810:Vitamin E; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione