Thioacetamide-induced hepatic damage in a rat nutritional model of steatohepatitis

Yona Avni, Haim Shirin, Hussein Aeed, Zipora Matas, Mark Shahmurov, Shlomo Birkenfeld, Rafael Bruck

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Nonalcoholic steatohepatitis is most often attributed to the effects of obesity, hyperlipidemia, diabetes mellitus and drugs. It is still unknown whether livers with steatohepatitis are more vulnerable to toxic damage. Aim: To determine the effect of the hepatotoxicant thioacetamide in a rat nutritional model of hepatic steatohepatitis. Methods: Fatty liver was induced in rats by placing them on a methionine-choline deficient diet for one month. Thioacetamide was administered by 3 consecutive intraperitoneal injections (300 mg/kg) at 24 h intervals. Results: Following treatment with thioacetamide, the elevated serum levels of liver enzymes and blood ammonia, liver necrotic inflammation and the survival rate after 48 h were not different between rats with normal or fatty liver. However, those parameters were significantly worse when fatty liver regressed after return to normal diet for one month (p < 0.01). Western blot analysis of hepatic extracts revealed no difference in cytochrome P4502E1 levels between fatty livers and fatty livers after regression, suggesting that the enhanced hepatotoxicity after regression of fatty liver could not be attributed to increased cytochrome P4502E1. Conclusions: In a nutritional model of steatohepatitis, rats with fatty liver were not more vulnerable than normal rats to liver damage induced by thioacetamide. However, liver damage was significantly more severe in rats with fatty livers after one month regression of steatosis.

Original languageEnglish
Pages (from-to)121-137
Number of pages17
JournalJournal of Medicine
Volume34
Issue number1-6
StatePublished - 2003
Externally publishedYes

Keywords

  • Blood ammonia
  • Cytochrome P4502E1
  • Fatty liver
  • Fulminant hepatic failure
  • Hepatic enzymes
  • Steatohepatitis
  • Thioacetamide

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