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The effects of the continuous administration of N,N-dimethyl-4-phenylazoaniline (DAB) on the activities and the inducibilities of some drug-metabolizing enzymes in rat liver.
Metadata
Journalchemico-biological interactions3.723Date
1975-Nov
Publication Type
Journal Article
Volume
1975-Nov / 11 : 313-28
Author
Autrup H , Thurlow BJ , Warwick GP
DoiPMIDMESH
Animals
Carbon Monoxide
Cerebroside-Sulfatase
Cytochrome P-450 Enzyme System
Glucuronidase
Liver
Lysosomes
Male
Methylcholanthrene
Microsomes, Liver
NADPH-Ferrihemoprotein Reductase
Nitrate Reductases
Oxidoreductases
Oxidoreductases, N-Demethylating
Phenobarbital
Rats
p-Dimethylaminoazobenzene
Abstract
(1) The effect of feeding a relatively low-protein diet containing 0.06% DAB for 29 weeks on the activity of DAB-azoreductase, nitroreductase (p-nitrobenzoic acid), N-oxidase (N,N-dimethylaniline), N-demethylase (DAB), cytochrome P-450, NADPH-cytochrome c reductase, beta-glucuronidase and arylsulphatase A were studied. Rapid decreases occurred in the activities of the first six enzymes, reaching minimal values at between 4 and 8 weeks. Activities then increased in all cases to control or nearly control levels. This rate of increase was least for cytochrome P-450. At 4 weeks azoreductase activity with the chemotherapeutic agent CB10-252 (I) as substrate was significantly higher than in control rats. Early increases occurred in the activities of beta-glucuronidase and arylsulphatase A and the activity of the latter never dropped below the control level. (2) An investigation was made of the differential effects of dye feeding on some of the enzyme activities in the two major liver lobes and differences were found. (3) The effect of phenobarbital (PB) pretreatment on the DAB-fed rats was studied at 4-week intervals. The activities of DAB-azoreductase and of nitroreductase increased throughout the whole period, while the activities of the lysosomal enzymes were decreased. (4) After feeding DAB for 4 weeks the effect of PB and 3-methylcholanthrene (MC) on the activities of DAB-azoreductase, CB10-252-azoreductase and components of the azoreductases-cytochrome P-450, NADPH-cytochrome c reductase, the CO-CB10-252-azoreductase was not induced by PB or MC, and CO did not inhibit its reduction. Its reduction depended only slightly on NADH. CO caused a greater relative decrease in the activity of DAB-azoreductase in dye-fed animals and also in animals following PB and MC pretreatment, implying a greater role of cytochrome P-450 in dye-fed animals.
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3.7
Chem Biol Interactchemico-biological interactions
Metadata
LocationIreland
FromELSEVIER IRELAND LTD

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