Cocaine toxicity in cultured rat hepatocytes

Toxicol Lett. 1990 Feb;50(2-3):283-8. doi: 10.1016/0378-4274(90)90021-d.


Cocaine hydrochloride was added to primary cultures of hepatocytes isolated from naive and phenobarbital-induced (80 mg/kg i.p. for 3 d) Sprague-Dawley rats. Cocaine was cytotoxic, as measured by lactate dehydrogenase release, to cells from naive rats in concentrations of 1 mM or greater. Phenobarbital induction greatly increased the cytotoxic potency of cocaine in vitro, with nearly complete loss of cell viability at cocaine concentrations in culture as low as 0.01 mM. The addition of 10 microM SK&F-525-A to the cultures blocked cocaine cytotoxicity in cells from both naive and phenobarbital-induced rats. These results suggest that the metabolic pathways leading to cocaine hepatotoxicity identified in the mouse also exist in the rat hepatocyte.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cocaine / antagonists & inhibitors
  • Cocaine / toxicity*
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Enzyme Induction
  • L-Lactate Dehydrogenase / metabolism
  • Liver / drug effects*
  • Liver / enzymology
  • Male
  • Phenobarbital / pharmacology
  • Proadifen / pharmacology
  • Rats
  • Rats, Inbred Strains


  • Cytochrome P-450 Enzyme System
  • Proadifen
  • L-Lactate Dehydrogenase
  • Cocaine
  • Phenobarbital