title: Early stage of biliary atresia is associated with significant changes in 8-hydroxydeoxyguanosine and mitochondrial copy number.
abstract: OBJECTIVE
  Oxidative stress is known to be involved in the pathogenesis of biliary atresia (BA), but the mechanism has yet to be elucidated. We studied 8-hydroxydeoxyguanosine (8-OHdG) and mitochondrial copy number as potential markers for oxidative stress in BA.
  
  
  METHODS
  Hepatic immunoreactive 8-OHdG expression was investigated during the early stage of BA when the patients received Kasai portoenterostomy (KP), during the late stage when the patients received liver transplantation (LT), in patients with choledochal cyst as disease control, and in patients with histologically normal liver as normal control. Apoptosis of liver cells was examined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end-labeling stain. The mitochondrial DNA copy number was measured by real-time polymerase chain reaction.
  
  
  RESULTS
  The number of hepatocytes positive for immunoreactive 8-OHdG was significantly increased in KP (65% +/- 18%) compared with LT (30% +/- 32%; P = 0.029) and choledochal cyst (25% +/- 20%; P = 0.037). The 8-OHdG labeling index was significantly correlated with the grade of chronic hepatitis activity (Spearman r = 0.495; P = 0.037). The hepatocyte terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end-labeling index in KP (15% +/- 4%) was significantly higher than that in LT (5% +/- 2%; P = 0.018) and in choledochal cyst (3% +/- 2%; P = 0.010). Mitochondrial copy number was significantly less in KP than in LT (7.33 +/- 0.75 vs 8.91 +/- 1.32; P = 0.045) and in normal control (7.33 +/- 0.75 vs 9.20 +/- 1.20; P = 0.021).
  
  
  CONCLUSIONS
  The early stage of BA is associated with stronger inflammatory reaction, augmented oxidative DNA, and mitochondrial DNA damage as manifested by higher immunoreactive 8-OHdG and apoptotic activities and by a decrease in mitochondrial copy number.
authors.affiliation: Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.
authors.forename: Mao-Meng
authors.initials: MM
authors.lastname: Tiao
authors.forename: Tsu-Kung
authors.initials: TK
authors.lastname: Lin
authors.forename: Fang-Ying
authors.initials: FY
authors.lastname: Kuo
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Yung-Ying
authors.initials: YY
authors.lastname: Du
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001656:Biliary Atresia / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000032:analysis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine