ENHANCEMENT OF REDUCTIVE METABOLISM OF PARA-NITROBENZOATE AND NITRAZEPAM IN ISOLATED PERFUSED RAT-LIVER BY ETHANOL

  • 1 January 1979
    • journal article
    • research article
    • Vol. 7  (3) , 176-180
Abstract
Reductive metabolism of p-nitrobenzoate (2 mM) was studied in the isolated perfused rat liver, after acute ethanol dosing, with use of a Hb-free perfusion medium. Formation of reduced metabolites under control conditions (0.3 .mu.mol/g liver per h) was enhanced 5-fold (1.4 .mu.mol/g per h) in the presence of ethanol (38 mM), thus reaching hepatic reductase activities occurring under anaerobic conditions (1.4 .mu.mol/g per h). Ethanol failed to increase hepatic nitro reduction when alcohol dehydrogenase was inhibited by pyrazole. Addition of acetaldehyde led to a marked stimulation of nitroreductase activity. CO did not influence the ethanol-mediated enhancement of nitroreductase activity but almost abolished the enhancement caused by anoxia. Reductive azo cleavage of salazosulfamide was not enhanced by ethanol. When nitrazepam was used as the substrate (1 mM) for the isolated perfused rat liver, addition of ethanol (38 mM) led to an enhanced content of 7-amino derivative in the liver and in the perfusate, whereas the formation of 7-acetylamino derivative remained unchanged. The distribution of nitrazepam in liver and perfusate was not altered by ethanol.