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Pravastatin for thioacetamide-induced hepatic failure and encephalopathy

Authors

  • Hui-Chun Huang,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital
    2. Faculty of Medicine, National Yang-Ming University School of Medicine
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    • These authors contributed equally to this work.

  • Ching-Chih Chang,

    1. Faculty of Medicine, National Yang-Ming University School of Medicine
    2. Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital
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    • These authors contributed equally to this work.

  • Sun-Sang Wang,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital
    2. Faculty of Medicine, National Yang-Ming University School of Medicine
    3. Department of Medical Affair and Planning, Taipei Veterans General Hospital, Taipei
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  • Cho-Yu Chan,

    1. Faculty of Medicine, National Yang-Ming University School of Medicine
    2. Department of Education, China Medical University Hospital, Taichung, Taiwan
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  • Fa-Yauh Lee,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital
    2. Faculty of Medicine, National Yang-Ming University School of Medicine
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  • Chiao-Lin Chuang,

    1. Faculty of Medicine, National Yang-Ming University School of Medicine
    2. Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital
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  • I-Fan Hsin,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital
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  • Tzu-Hua Teng,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital
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  • Han-Chieh Lin,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital
    2. Faculty of Medicine, National Yang-Ming University School of Medicine
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  • Shou-Dong Lee

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital
    2. Faculty of Medicine, National Yang-Ming University School of Medicine
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Fa-Yauh Lee, M.D., FACG, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No.201, Sec 2, Shih-Pai Road, Taipei, Taiwan 11217. Tel.: 886 2 28757500; fax: 886 2 28739318; e-mail: fylee@vghtpe.gov.tw

Abstract

Eur J Clin Invest 2011

Abstract

Background  Nitric oxide (NO) inhibition aggravates hepatic damage and encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure. Statins enhance NO production but whether they influence the above parameters are unknown.

Material and methods  Male Sprague-Dawley rats were used. In the first series, TAA (350 mg/kg per day, i.p. for 3 days) was administered to induce acute liver failure. Control rats received saline. Rats received distilled water or pravastatin (20 mg/kg per day, p.o.) from 2 days before to 3 days after TAA or saline injection. In the second series, liver cirrhosis was induced by common bile duct ligation (BDL). Sham-operated rats served as controls. Rats received distilled water or pravastatin for 5 or 14 days until the 42nd day after operation. On the last day of treatment, survival, motor activities, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, ammonia and brain histology were evaluated.

Results  Thioacetamide and BDL rats showed higher ALT, AST, bilirubin and ammonia levels and lower motor activity counts compared with their corresponding control groups. In TAA rats, pravastatin elicited higher total and ambulatory motor activity counts and lower AST and total bilirubin levels. Survival was improved, whereas brain H&E staining was not significantly different in TAA rats with or without pravastatin treatment. In BDL groups, rats with or without pravastatin treatment were not different in motor activity counts and liver biochemistry.

Conclusions  Pravastatin ameliorates hepatic encephalopathy and liver biochemistry and improves survival in rats with acute liver failure, but not in those with cirrhosis.

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