Cocaine hepatotoxicity in cultured liver slices: a species comparison

Suzanne Connors, David R. Rankin, A. Jay Gandolfi, Carlos L. Krumdieck, Lawrence J. Koep, Klaus Brendel

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Studies were carried out in order to find a sensitive in vitro model with which to investigate cocaine-mediated hepatotoxicity. Precision-cut liver slices were prepared from: human, domestic pig, New Zealand white rabbit, Sprague-Dawley (S/D) rat, and two mouse strains (DBA/2Ha and ICR). The rationale for the choice of these species was that information on in vivo effects of cocaine was available in the literature. Slices were cultured for up to 6 h in the presence of 0-5 mM cocaine. Indices of toxicity consisted of K+ retention and Ca2+ uptake. Minimal effects and no clear dose-response relationships were observed. In addition to the studies with non-pretreated animals, liver slices were prepared from DBA/2Ha and ICR mice, both induced by housing on pine shavings, and phenobarbital pretreated Sprague-Dawley rats. The induced ICR mouse and rat were approximately 3 times more sensitive to cocaine-mediated hepatotoxicity. The following order of sensitivity to cocaine-mediated hepatotoxicity was established: induced rat = induced ICR mouse ≫ induced DBA/2Ha mouse = rabbit = uninduced ICR mouse = uninduced DBA/2Ha mouse = uninduced rat > pig = human.

Original languageEnglish (US)
Pages (from-to)171-183
Number of pages13
JournalToxicology
Volume61
Issue number2
DOIs
StatePublished - Apr 17 1990

Keywords

  • Cocaine hepatotoxicity
  • Human liver
  • Liver slices
  • Mouse liver
  • Pig liver
  • Rabbit liver
  • Rat liver
  • Species comparison

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Cocaine hepatotoxicity in cultured liver slices: a species comparison'. Together they form a unique fingerprint.

  • Cite this

    Connors, S., Rankin, D. R., Gandolfi, A. J., Krumdieck, C. L., Koep, L. J., & Brendel, K. (1990). Cocaine hepatotoxicity in cultured liver slices: a species comparison. Toxicology, 61(2), 171-183. https://doi.org/10.1016/0300-483X(90)90018-C