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Publication Detail

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

Authors: MacDonald, J R; Gandolfi, A J; Sipes, I G

Published In Toxicology, (1986 May)

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 appearance 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.

PubMed ID: 3705080 Exiting the NIEHS site

MeSH Terms: Administration, Oral; Alanine Transaminase/blood; Animals; Calcium/metabolism; Carbon Tetrachloride/toxicity*; Cystamine/administration & dosage; Cystamine/therapeutic use*; DNA/biosynthesis; Hypothermia/chemically induced; Injections, Intraperitoneal; Liver/drug effects; Liver/pathology*; Male; Necrosis; Rats; Rats, Inbred Strains; Thymidine/metabolism; Tritium

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