Oxidative-stress-related changes in the livers of bile-duct-ligated rats.
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.
Huang
Yi-Tsau
YT
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. huangyt@ym.edu.tw
Hsu
Yi-Chao
YC
Chen
Chi-Jen
CJ
Liu
Chien-Tzu
CT
Wei
Yau-Huei
YH
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
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