LOW-DOSE DIETHYLDITHIOCARBAMATE ATTENUATES THE HEPATOTOXICITY OF 1,3-DICHLORO-2-PROPANOL AND SELECTIVELY INHIBITS CYP2E1 ACTIVITY IN THE RAT

The effect of low doses of diethyldithiocarbamate (DEDC) on hepatic cy tochrome P450-dependent enzyme activity and 1,3-dichloro-2-propanol (D CP) hepatotoxicity in the rat have been investigated. DEDC at a dose o f 5 mg/kg selectively inhibited enzyme markers for CYP2E1 activity, an d provided substantial protection against DCP hepatotoxicity. At a hig her dose (25 mg/kg), DEDC also inhibited an enzyme marker for CYP1A2 a ctivity and provided complete protection against DCP hepatotoxicity. I t is concluded: (a) that DEDC at a dose of 5 mg/kg is a selective CYP2 E1 inhibitor in the rat in vivo; and (b) that DCP hepatotoxicity is me diated principally by CYP2E1, with a possible contribution from CYP1A2 .