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

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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 - 1986

Fingerprint

Cystamine
Carbon Tetrachloride
Necrosis
Liver
Calcium
Therapeutics
Wounds and Injuries
Hypothermia
Plasmas
Induced Hypothermia
Cell death
Enzymes
Rats
Regeneration
Animals
Cell Death
Animal Models
Tissue

Keywords

  • Cystamine
  • Cytoprotection
  • Hepatic
  • Necrosis
  • Tetrachloride

ASJC Scopus subject areas

  • Toxicology

Cite this

Amelioration of carbon tetrachloride-induced hepatic necrosis by post-toxicant treatment with cystamine. / Macdonald, John R.; Gandolfi, A Jay; Sipes, I. Glenn.

In: Toxicology, Vol. 39, No. 2, 1986, p. 135-148.

Research output: Contribution to journalArticle

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