Covalent binding of 14c-1,1,2-trichloroethane to hepatic proteins following acetone pretreatment

J. R. Macdonald, A. J. Gandolfi, I. G. Sipes

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

We have recently reported that pretreatment of rats with acetone potentiates both the hepatic glutathione (GSH) depletion and subsequent hepatotoxicity caused by 1,1,2-trichloroethane (TCEA). To determine if acetone treatment enhances the bioactivation of TCEA, the covalent binding of 14C-TCEA to tissue proteins was assessed both in vivo and in vitro. Male, Sprague-Dawley rats were treated with acetone (0.5 ml/kg; po), fasted 16 hr prior to dosing with 14C-TCEA (1.2 mmole/kg; ip), and killed 4 hr later. Overnight fasting, alone resulted in a six fold increase in covalent binding of 14C-TCEA to hepatic proteins compared to non-fasted rats. Acetone pretreatment, however, did not cause an increase in binding of 14C-TCEA 4 hr after dosing compared to fasted controls, although it did produce a 30% further decrease in hepatic GSH. When microsomes from acetone treated rats were incubated with 14C-TCEA, covalent binding to protein was significantly increased (35% over using, microsomes from fasted control rats. The covalent binding of 14C-TCEA to microsomal protein was inhibited 80% by the addition of GSH (1 mM). The data suggest that potentiation of TCEA hepatotoxicity by acetone may result in part, from alterations of TCEA bioactivation and hepatic GSH concentrations.

Original languageEnglish (US)
Pages (from-to)233-247
Number of pages15
JournalDrug and Chemical Toxicology
Volume5
Issue number3
DOIs
StatePublished - Jan 1 1982

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis
  • Chemical Health and Safety

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