ANTICONVULSANT TOXICITY INVITRO - POSSIBLE ROLE OF ARENE OXIDES

  • 1 January 1981
    • journal article
    • research article
    • Vol. 217  (2) , 386-389
Abstract
Human lymphocytes incubated with a mouse hepatic microsomal drug metabolizing system were used to study the cytotoxicity of 4 anticonvulsants. In vitro toxicity assessed by trypan blue dye exclusion was significantly greater for compounds with relatively high clinical toxicity (mephenytoin and phenacemide) than those with only rare cytotoxic complications (phenytoin and phenobarbital). No toxicity occurred in the absence of microsomes and toxicity was enhanced by inhibitors of epoxide hydrolase. The cytotoxicity of the drugs may result from arene oxide metabolites in vivo, the covalent binding of such metabolites to cell macromolecules could lead to cell death and, by acting as haptens, to secondary hypersensitivity reactions. The method may be used to assess the potential of a drug for toxicity, the mechanism of cell damage and individual differences in cell defenses within the human population.