Modulation of drug metabolizing enzymes in guinea pig liver by high intakes of ascorbic acid

Groups of young male adult guinea pigs were fed a diet devoid in supplemental ascorbic acid (AA) or the same diet supplemented with 0.1 or 2.5% AA for four weeks. The animals were then euthanized and Phase I and Phase II drug metabolizing components in the liver were determined Phase I components are those related to the metabolism of xenobiotics and include microsomal cytochrome P-450 and mired function oxygenase activities. Phase II components are those related to conjugation and detoxification reactions of xenobiotics and their metabolites and include glutathione-S-transferases (GST), glutathione (GSH), UDP-glucuronyl transferase (UDP-GT) and DT-diaphorase (quinone reductase, QR), Tissue levels of AA increased progressively with increase in AA intake. The Phase I components increased in response to increased intake of AA from 0 to 0.1%, but were unaffected by further increase in AA intake to 2.5%. However, the Phase II components increased with increased intake of AA except for GST: In vitro metabolism of aflatoxin B-1 (AFB(1)) using liver microsomes showed tendency towards increased production of aflatoxin M-1 (AFM(1)) with increase in AA intake. The production of aflatoxin P-1 (AAP(1)) was not affected by AA intake. AFB(1)-DNA production was increased when AA intake was increased to 0.1%. It was however lowered with further increase in AA intake to 2.5%.