Depression of glutathione content, elevation of CYP2E1-dependent activation, and the principal determinant of the fasting-mediated enhancement of 1,3-dichloro-2-propanol hepatotoxicity in the rat

The influence of fasting (18 hours) on the hepatotoxicity of 1,3-dichloro-2 -propanol (1,3-DCP) and on various hepatic parameters has been assessed in the rat. Fasting produced an enhancement of the hepatotoxicity which was as sociated with alterations in a variety of hepatic parameters when measured relative to protein content, most notably glutathione (GSH) levels (decreas e) and CYP2E1-mediated enzyme activity (increase), two parameters previousl y identified as being important determinants to the toxicity. Fasting also decreased the liver weight normalized to body weight. When this was taken i nto account, total liver CYP2E1-mediated enzyme activity was not significan tly altered whereas the total liver GSH level was markedly reduced followin g fasting, These results imply that the reduction in hepatic GSH is the pri ncipal determinant of the enhanced susceptibility to 1,3-DCP hepatotoxicity following fasting. (C) 1999 Elsevier Science Ltd. All rights reserved.