title: Phenacetin O-deethylation is a useful tool for evaluation of hepatic functional reserve in rats with CCl(4)-induced chronic liver injury.
abstract: BACKGROUND
  Mortality of liver resection is as high as 3.1% to 25% in patients with chronic liver disease. Evaluation of hepatic functional reserve is critical for the prediction of risk of postoperation death. Phenacetin O-deethylation is a marker reaction of cytochrome P4501A2 (CYP1A2) activity. In this study, our aim is to investigate whether phenacetin O-deethylation is a useful tool for the evaluation of hepatic functional reserve in rats with chronic liver injury.
  
  
  METHODS
  Rat model for chronic liver injury was established by subcutaneous administration of 50% CCl(4), 1 mL/kg twice per week for 12 wk. Hepatic CYP1A2 activity, content, and mRNA expression were determined (n = 10). Effects of 15%, 30%, and 45% hepatectomy on phenacetin O-deethylation were evaluated in the rats (n = 5 in each group). Additionally, the correlation of risk of death after 70% hepatectomy with phenacetin O-deethylation was studied in 27 rats with chronic liver injury.
  
  
  RESULTS
  Compared with normal controls, CYP1A2 activity, content, and mRNA expression decreased 33%, 60%, and 50% in the rats with chronic liver injury (P < 0.05), respectively. Following the increasing of liver-resected size, CYP1A2 activity decreased proportionally (r(s) = -0.877, P < 0.05). Six of 27 rats with chronic liver injury died within 7 d after 70% hepatectomy. Phenacetin metabolism was impaired more severely in 6 rats that died than in 21 living rats (P < 0.05).
  
  
  CONCLUSIONS
  Phenacetin O-deethylation is a useful tool for the evaluation of hepatic functional reserve in the rats with CCl(4)-induced chronic liver injury.
authors.affiliation: Department of Anesthesiology, Renji Hospital Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Qu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Meihua
authors.initials: M
authors.lastname: Cai
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Mi
authors.initials: M
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000503:physiopathology* / Q000601:surgery; D002908:Chronic Disease; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D004195:Disease Models, Animal; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D010615:Phenacetin / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; D019388:Cytochrome P-450 CYP1A2; D010615:Phenacetin