Pravastatin for thioacetamide-induced hepatic failure and encephalopathy

Hui Chun Huang, Ching Chih Chang, Sun Sang Wang, Cho Yu Chan, Fa Yauh Lee*, Chiao Lin Chuang, I. Fan Hsin, Tzu Hua Teng, Han Chieh Lin, Shou Dong Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 (350mg/kg per day, i.p. for 3days) was administered to induce acute liver failure. Control rats received saline. Rats received distilled water or pravastatin (20mg/kg per day, p.o.) from 2days before to 3days 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 14days 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.

Original languageEnglish
Pages (from-to)139-145
Number of pages7
JournalEuropean Journal of Clinical Investigation
Volume42
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • 3-hydroxy-methyl-3-glutamylcoenzyme A reductase inhibitors
  • Bile duct ligation
  • Hepatic encephalopathy
  • Thioacetamide

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