Effects of administration of subtoxic doses of acetaminophen on liver and blood levels of insulin-like growth factor-1 in rats

Toxicol Ind Health. 2016 Jan;32(1):39-46. doi: 10.1177/0748233713498439. Epub 2013 Aug 1.

Abstract

Acetaminophen (APAP) is widely used in the treatment of pain. Toxic doses of APAP cause acute liver failure, but therapeutic doses are believed to be safe. The purpose of this study is to investigate the effects of administration of subtoxic doses of APAP on liver and blood levels of insulin-like growth factor-1 (IGF-1) in rats. Low dose (100 mg/kg) and high dose (250 mg/kg) of APAP were intraperitoneally injected into Wistar albino rats. Following administration of therapeutic doses of APAP, there were no significant changes in serum transaminases and liver glutathione levels. Both doses of APAP induced a decrease in liver and blood levels of IGF-1 when compared with the controls. There was no significant difference in liver IGF-1 levels between the high-dose and low-dose APAP groups; however, there was a significant difference in blood IGF-1 levels between both the groups. The histological examination showed that low dose of APAP induced mild degree of structural change, while high dose of APAP induced severe structural damage. In conclusion, these results suggest that blood IGF-1 levels may have a value in predicting hepatic damage resulting from therapeutic doses of APAP.

Keywords: APAP; IGF-1; apoptosis; glutathione; liver damage.

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / pharmacology*
  • Animals
  • Antioxidants / pharmacology
  • Chemical and Drug Induced Liver Injury / pathology
  • Dose-Response Relationship, Drug
  • Glutathione / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • insulin-like growth factor-1, rat
  • Acetaminophen
  • Insulin-Like Growth Factor I
  • Glutathione