Amelioration of carbon tetrachloride-induced hepatic necrosis by post-toxicant treatment with cystamine

John R. Macdonald, A. Jay Gandolfi, I. Glenn Sipes

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

A quantitative animal model was developed to study amelioration of carbon tetrachloride-induced hepatic injury by post-toxicant administration of cystamine. Amelioration of CCl4-induced injury by post-toxicant cystamine treatment was compared to prevention of injury by cystamine pretreatment and possible mechanisms of the post-toxicant cytoprotective effect were investigated. Pretreatment of rats with cystamine dihydrochloride (300 mg/kg, p.o.) 30 min prior to CCl4 (0.25 ml/kg, i.p.) prevented CCl4-induced hepatic necrosis, plasma enzyme elevations, and hepatic calcium accumulation. When administered up to 12 h after CCl4, a single oral dose of cystamine inhibited necrosis in a dose-dependent manner, but did not reduce CCl4-induced plasma enzyme elevation or hepatic calcium accumulation. Cystamine post-treatment, therefore, does not appear to inhibit toxicant-induced influx of extracellular calcium into toxicant-damaged cells. This also suggests that the influx of extracellular calcium does not necessarily constitute an irreversible event leading to cell death. The mild hypothermia induced by post-toxicant treatment with cystamine did not delay the apperance of the lesion. Evidence for a slightly earlier regeneration of hepatic tissue was noted when cystamine was administered 12 h after CCl4. However, this effect was observed too long after exposure to the toxicant to account for the protection from necrosis observed 24 h after CCl4.

Original languageEnglish (US)
Pages (from-to)135-148
Number of pages14
JournalToxicology
Volume39
Issue number2
DOIs
StatePublished - May 1986

Keywords

  • Cystamine
  • Cytoprotection
  • Hepatic
  • Necrosis
  • Tetrachloride

ASJC Scopus subject areas

  • Toxicology

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