The hepatotoxicity of chloroform in precision-cut rat liver slices

Shana Azri-Meehan, Heriberto P. Mata, A. Jay Gandolfi, Klaus Brendel

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Chloroform hepatotoxicity was investigated in precision-cut liver slices from male Sprague-Dawley rats pretreated with phenobarbital to predispose animals to CHCl3 intoxication. Liver slices were exposed to 0.2, 0.5 and 1.0 mM chloroform for a total of 9 h in a roller culture system. Intracellular K+ loss was found to be concentration- and time-dependent over the duration of the experiment. Histophathological changes were also evident. Glucose 6-phosphate dehydrogenase and β-glucuronidase were significantly decreased at 3 h relative to controls where a loss of 61% and 36% occurred, respectively. Enzyme levels of alanine aminotransferase and lactate dehydrogenase, both found predominantly in periportal hepatocytes, remained identical to controls over the duration of the experiment. A significant time-dependent depletion of glutathione occurred as early as 3 h following the administration of 0.5 mM chloroform. Mitochondrial viability, measured by the reduction of a specific dye, was significantly lower than controls in treated slices at 6 h following chloroform administration. Precision-cut liver slices appear to be especially useful for the biochemical and histopathological examination of site-specific hepatotoxicants such as CHCl3.

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalToxicology
Volume73
Issue number3
DOIs
StatePublished - 1992

Keywords

  • Centrilobular
  • Chloroform
  • Glutathione
  • Histopathology
  • Periportal
  • Toxicity

ASJC Scopus subject areas

  • Toxicology

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