Kinetics of induction of cytosolic benzaldehyde: NADP and propionaldehyde: NAD aldehyde dehydrogenase activities in rat livers from male Wistar rats.
The time courses of induction of liver cytosolic aldehyde dehydrogenases using benzaldehyde and propionaldehyde as substrates and NADP and NAD as co-factors after i.p. and intragastric (i.g.) administration of 2-acetylaminofluorene (2-AAF), 20-methylcholanthrene (20-MC), beta-naphthoflavone (beta-NF) and benzo[alpha]pyrene (B[alpha]P) were investigated in male Wistar rats. 2-AAF did not induce the aldehyde dehydrogenase activities with any substrate:co-factor combination. The other three inducers all induced the oxidation of the aldehydes in a reversible manner. With an i.p. route of administration (one daily dose for four consecutive days) (20-MC) was the most potent inducer giving a 240-fold increase of benzaldehyde: NADP activity on the ninth day. beta-NF elevated the activity 20-fold with peak activity at day 7, while B[alpha]P gave maximal induction on day 5 with a 60-fold increase in activity over the corresponding value for normal liver. The i.g. administration resulted in a weaker but coordinated induction of activity with peak activity on the sixth day for the different inducers. The activity ratio benzaldehyde:NADP/propionaldehyde:NAD, 0.78 in normal rats, was altered in all induced states to a level close to 4. The interpretation of our work supports the hypothesis that the inducers in this respect use the same mechanisms of induction. The differences noted can be explained by variations in the exposure of the liver to the administered dose and/or by differences in receptor affinity. The inducibility of benzaldehyde:NADP aldehyde dehydrogenase in rat liver exceeds by orders of magnitude the ability of the same inducers to increase the amount of the activity of other drug metabolizing enzymes such as glutathione S-transferase, cytochrome P450 and cytochrome b5. The reversible, drug-dependent induction characterized in normal rat liver in this work differs entirely from the persistent constitutive elevation of the same enzymes in preneoplastic liver nodules.
Ritter
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Department of Pathology, Huddinge Hospital, Sweden.
Eriksson
L C
LC
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D001571:Benzoflavones / Q000633:toxicity; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D002273:Carcinogens; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D000444:Aldehyde Dehydrogenase; D005982:Glutathione Transferase