Phenacetin O-Deethylation is a Useful Tool for Evaluation of Hepatic Functional Reserve in Rats with CCl₄-Induced Chronic Liver Injury

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• 作者：Zhe Liu ; M.S.^&lowast ; ; Zengqiang Qu ; M.D.^&dagger ; ; Xiaodong Li ; M.S.^&Dagger ; ; Meihua Cai ; M.S.^&lowast ; ; Ping He ; M.D.^&lowast ; ; Mi Zhou ; M.D.^&lowast ; ; Jie Xiao ; M.D.^&lowast ; ; Xiangrui Wang ; M.D.^&lowast ; ; ^{xiangruiwang@gmail.com}
• 关键词：cytochrome P4501A2 ; hepatic functional reserve ; carbon tetrachloride ; phenacetin ; hepatectomy
• 刊名：Journal of Surgical Research
• 出版年：2012
• 期刊代码：299_00224804
• 类别：med
• 出版时间：15 June, 2012
• 卷：175
• 期：2
• 页码：e61-e66
• 文件大小：312 K

摘要

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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.

Materials and Methods

Rat model for chronic liver injury was established by subcutaneous administration of 50%CCl₄, 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 = 鈭?.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 CCl₄-induced chronic liver injury.