The induction of benzpyrene hydroxylase in the isolated perfused rat liver

Juchau, Mont R.; Cram, Richard L.; Plaa, Gàbriel L.; Fouts, James R.

doi:10.1016/0006-2952(65)90220-0

Cited by 57 publications

(7 citation statements)

References 8 publications

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“…Other methode. Nitrogen or protein content of the microsomal suspensions was determined by a micro-Kjeldahl procedure (Juchau, Cram, Plaa & Fouts, 1965) or by the technique of Lowry, Rosebrough, Farr & Randall (1951). Data were analysed statistically by Student's t test (Snedecor, 1956).…”

Section: Methodsmentioning

confidence: 99%

The submicrosomal distribution of hepatic uridine diphosphate glucuronyltransferases in the rabbit

Gram

Hansen

Fouts

1968

Biochemical Journal

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1. Rabbit liver microsomes were subfractionated into rough- and smooth-surfaced types, and glucuronyltransferase activity in each microsomal subfraction was determined with p-nitrophenol, o-aminophenol and phenolphthalein as substrates. The glucuronyltransferase activity measured with p-nitrophenol and o-aminophenol as substrates was localized predominantly in rough-surfaced microsomes. Glucuronyltransferase measured with phenolphthalein as substrate was equally present in rough- and smooth-surfaced microsomes. 2. Phenobarbital pretreatment of rabbits did not stimulate any of the glucuronyltransferase activities measured in either rough- or smooth-surfaced microsomes. 3. Preincubation of rabbit liver microsomes for 30-60min. at 37 degrees under oxygen did not cause any loss of glucuronyltransferase activity. Such preincubation caused either no change or increased enzyme activity in both submicrosomal fractions. The relative distribution of transferase activity in rough- and smooth-surfaced microsomes was not affected by preincubation.

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Section: Methodsmentioning

confidence: 99%

The submicrosomal distribution of hepatic uridine diphosphate glucuronyltransferases in the rabbit

Gram

Hansen

Fouts

1968

Biochemical Journal

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“…The homogenate was centrifuged at 9000 g for 20 min and the 9000 g supernatant fraction was used in a study of zoxazolamine and ethylmorphine (May & Baker) metabolism. Zoxazolamine ring oxidation was determined by the method of Juchau (8) and ethylmorphine N-demethylation was assessed (9) with the Nash reaction by estimating the amount of methacin) intoxication was due to an induction of the drug metabolizing enzymes of the liver, an already known property for few of these steroids (12,13). This is further confnmed by a quantitative correlation of these effects (Equations 1-5).…”

Section: Materials Andmethodsmentioning

confidence: 99%

Effect of the position of the cyano-group of cyanopregnenolones on their drug metabolic inducing activity

Kourounakis

Rekka

Demopoulos

et al. 1991

European Journal of Drug Metabolism and Pharmacokinetics

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The effect of the position of the cyano-group of several cyanopregnenolones on the body's resistance to drugs and on drug metabolism was investigated. Female rats were pretreated with 2 alpha-, 6-, 16 alpha-, 17 alpha-cyano- or 16 alpha-cyanomethyl-pregnenolone or with pregnenolone, and the (in vivo) resistance to zoxazolamine, digitoxin and indomethacin, as well as the in vitro drug metabolism (post mitochondrial fraction) of zoxazolamine and ethylmorphine were determined. It was found that the 16-derivative was the most active in this respect, the 2- and 17-cyanopregnenolones were less active but significantly potent compared to controls, while the 6-cyano, the 16-cyanomethyl derivatives and pregnenolone were essentially inactive. These differences were explained in terms of an effective or poor fit of the steroids to their receptor. The poor performance of pregnenolone-16 alpha-acetonitrile was attributed to electronic effects. A hypothesis of some structural features of the receptor site for its interaction with the cyanopregnenolone inducers was presented.

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“…The homogenate was centrifuged at 9000g for 20 min and the 9000g supernatant fraction was used in a study on zoxazolamine and ethylmorphine metabolism. Zoxazolamine ring oxidation was determined by the method of Juchau (10) and ethylmorphine N -demethylation was assessed (II) with the Nash reaction by estimating the amount of formaldehyde formed (12). The incubation medium for the assays contained: 0.02 M Tris-HCI buffer (pH 7.4) 5 mM MgCI 2 , 5 mM glucose-6-phosphate, 0.4 mM NADP, 1.2 11M Zoxazolamine or 3 11M ethylmorphine and postmitochondrial supernatant corresponding to 0.220 and 0.083g liver for zoxazolamine and ethylmorphine respectively; the total incubation volume was 3 m!.…”

Section: Methodsmentioning

confidence: 99%

Effect of benzopyrone derivatives on drug activity and metabolism

Kourounakis

Rekka

1986

European Journal of Drug Metabolism and Pharmacokinetics

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In female rats, zoxazolamine paralysis time and mortality caused by indomethacin were significantly reduced by pretreatment with khellin, 7,8-benzoflavone or rutin. Pretreatment with khellin and 7,8-benzoflavone increased the in vitro zoxazolamine and ethylmorphine metabolism. These results were compared with those obtained by equimolar doses of phenobarbital, pregnenolone-16 alpha-carbonitrile and spironolactone in experiments performed simultaneously. It was concluded: Khellin, 7,8-benzoflavone and rutin increased the body's resistance to drugs via induction of the drug metabolizing enzymes of the liver, this action has about the same magnitude with that of phenobarbital and pregnenolone-16 alpha-carbonitrile. For the benzopyrone derivatives, some common structural features have been indicated as probable structural requirements for drug metabolizing enzyme inductive activity in this group of compounds.

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The induction of benzpyrene hydroxylase in the isolated perfused rat liver

Cited by 57 publications

References 8 publications

The submicrosomal distribution of hepatic uridine diphosphate glucuronyltransferases in the rabbit

The submicrosomal distribution of hepatic uridine diphosphate glucuronyltransferases in the rabbit

Effect of the position of the cyano-group of cyanopregnenolones on their drug metabolic inducing activity

Effect of benzopyrone derivatives on drug activity and metabolism

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