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 mixed 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 B1 (AFB1) using liver microsomes showed tendency towards increased production of aflatoxin M1 (AFM1) with increase in AA intake. The production of aflatoxin P1 (AFP1) was not affected by AA intake. AFB1-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%.
Roomi
M W
MW
Linus Pauling Institute of Science and Medicine, Palo Alto, CA 94306, USA.
Netke
S
S
Tsao
C
C
D000348:Aflatoxins / Q000378:metabolism; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D015331:Cohort Studies; D019587:Dietary Supplements; D004798:Enzymes / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000187:drug effects / Q000378:metabolism
D000348:Aflatoxins; D004798:Enzymes; D016660:NAD(P)H Dehydrogenase (Quinone); D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D005978:Glutathione; D001205:Ascorbic Acid