Triacetyloleandomycin as inducer of cytochrome P-450 LM3c from rabbit liver microsomes

Bonfils, Claude; Dalet-Beluche, Isabelle; Maurel, Patrick

doi:10.1016/0006-2952(85)90524-6

Cited by 27 publications

(12 citation statements)

References 11 publications

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“…This conclusion follows from the following observations: (1) Rifampicin, a specific inducer of P450IIIA and of erythromycin demethylase in human liver microsomes (Combalbert et al, 1989), strongly induced cortisol 61-hydroxylase. (2) In liver microsomes from both organ donors and rifampicin-treated patients, cortisol 6,B-hydroxylase activity correlated with P450IIIA level, determined immunologically with two different antibodies, as well as with erythromycin demethylase, a P450IIIA-dependent activity (Watkins et al, 1985;Bonfils et al, 1985); in contrast cortisol 6,B-hydroxylase did not correlate with either ethoxyresorufin deethylase, a P4501A dependent activity (Guengerich et al, 1982b), or P450IA or P450IlC specific content. (3) Antibodies directed against P450IIIA selectively inhibited cortisol 61-hydroxylase.…”

Section: Discussionmentioning

confidence: 92%

“…This activity could not be measured in microsomes from needle liver biopsy of patients before rifampicin treatment, because the amount of material was insufficient. The data reported in Table 3 indicate that cortisol 613-hydroxylase activity in liver microsomes increased from 15 ± 6 in organ (Daujat et al, 1987), human P450 MP '(IIC) (Shimada et al, 1986), human P450 NF (IIIA) or rabbit P450 3c (IIIA3) (Bonfils et al, 1985;Daujat et al, 1987). Results are presented in Figure 2 and in Human liver microsomes from kidney transplantation donors were incubated for 20 min at room temperature in the presence of increasing amounts of preimmune IgG or of anti P450 antibodies.…”

Section: Resultsmentioning

confidence: 99%

“…Monoclonal (anti P450 NF) or polyclonal antibodies (anti P450 NF and MP) were produced in mice or in New Zealand white rabbits as described by Le Provost et al (1981) and Beaune et al (1985). Rabbit P450 3c (P450-IIIA6), the orthologous form of human P450 NF, and rabbit P450 LM4 (P450IA2) and the corresponding antibodies were prepared and purified as described by Bonfils et al (1985) Haugen and Coon (1976) and Daujat et al (1987). When necessary, immunoglobulins were further purified by ammonium sulphate precipitation and chromatography on DEAE cellulose (Le Provost et al, 1981).…”

Section: Cytochromes P450 and Antibodiesmentioning

confidence: 99%

“…The reaction was initiated at 370 C by addition of 1 mm NADPH. Erythromycin and benzphetamine demethylases were evaluated as described by Kremers et al (1981) and Bonfils et al (1985); the substrate concentration was 1 mM. Ethoxyresorufin deethylation was determined spectrofluorometrically according to the method of Burke & Mayer (1974), resorufin being used as a standard.…”

Section: Other Monooxygenase Assaysmentioning

confidence: 99%

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The increase in urinary excretion of 6 beta‐hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction.

Ged

Rouillon

Pichard

et al. 1989

Brit J Clinical Pharma

312

156

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1. Urinary excretion of 6 beta‐hydroxycortisol, hepatic microsomal cortisol 6 beta‐hydroxylase and the specific content of several forms of cytochrome P450 were measured in 8 to 14 patients before and after treatment with rifampicin (600 mg orally per day for 4 days). 2. Rifampicin treatment produced an average five fold increase in daily excretion of urinary 6 beta‐hydroxycortisol. 3. Cortisol 6 beta‐ hydroxylase activity increased from 15 +/‐ 6 pmol min‐1 mg‐1 in organ donors (considered as 'control subjects') to 87 +/‐ 31 pmol min‐1 mg‐1 in rifampicin treated patients. 4. Among three forms of human P450 (P450IA, IIC and IIIA), (1), (2), measured by Western blots, only P450IIIA was significantly induced by the antibiotic. 5. Only antibodies against P450IIIA selectively inhibited cortisol 6 beta‐ hydroxylase in human liver microsomes. 6. Cortisol 6 beta‐hydroxylase was correlated with P450IIIA specific content. 7. The urinary level of 6 beta‐hydroxycortisol correlated with liver microsomal cortisol 6 beta‐ hydroxylase and P450IIIA specific content. 8. We conclude that P450IIIA is predominantly responsible for cortisol 6 beta‐hydroxylase activity in human liver microsomes and that urinary 6 beta‐hydroxycortisol is a marker of the induction of this cytochrome P450.

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Section: Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Cytochromes P450 and Antibodiesmentioning

confidence: 99%

Section: Other Monooxygenase Assaysmentioning

confidence: 99%

See 2 more Smart Citations

The increase in urinary excretion of 6 beta‐hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction.

Ged

Rouillon

Pichard

et al. 1989

Brit J Clinical Pharma

312

156

View full text Add to dashboard Cite

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“…Erythromycin has been reported to specifically induce the cytochrome P-450 isozyme IIIA2 in rats also termed IIIA4 in rabbits Bonfils et al 1985;Wrighton et al 1985a). Male Wistar rats (200-250 g) were supplied by Iffa-Credo animal services.…”

Section: Cmentioning

confidence: 99%

The Interaction between Cyclosporin A and Erythromycin Studied by Means of an Isolated Perfused Rat Liver Model

Fabre

Richard

Combalbert

et al. 1989

Pharmacology & Toxicology

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The isolated perfused rat liver model was successfully used to study the clinical interaction observed between cyclosporin A (CsA) and erythromycin (ER). Three experimental studies were performed. In a "Control group", isolated rat livers were perfused with 60 micrograms 3H-CsA for 20 min. In an "ER group", isolated rat livers were simultaneously perfused with 60 micrograms 3H-CsA and 6.0 mg ER. In an "ER ind group", rats were treated with ER for 5 days, conditions under which the P450IIIA gene subfamily, principally involved in CsA metabolism, was specifically induced, and isolated rat livers were perfused with 60 micrograms 3H-CsA for 20 min. Biological parameters of the liver model such as biliary flow, oxygen consumption and pH were similar whatever group of animals. Biliary excretion of total radiolabel (sum of CsA and all the metabolites = CsAT) was similar in both the "Control" and "ER" groups but significantly higher in the "ER ind" group with respectively 8.05 +/- 0.81%, 8.45 +/- 1.93% and 14.54 +/- 2.12% of the entire amount of infused drug excreted during 2 hr. Using a high performance liquid chromatography method which specifically resolves unchanged CsA from its metabolites, we demonstrated that, although similar amounts of radiolabelled material were excreted in both the "Control" and "ER" groups, the CsA/metabolite ratio was lower than 1.0 in the "Control group" and higher than 1.0 in the "ER group", suggesting an inhibition of CsA metabolism by ER in the "ER group". These data could explain the increase in CsA blood levels observed in the clinic following administration of high ER doses and the reversing effect when ER administration is stopped.

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Resolution of rabbit liver cytochrome P450 3b and 3c (P450 IIC3 and IIIA4) from microsomal membrane by two‐dimensional gel electrophoresis

Bonfils

Combalbert

1990

Electrophoresis

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Two-dimensional gel electrophoresis was applied to the separation of microsomal proteins and P450 isozymes. The experimental conditions of the first-dimensional isoelectric focusing were optimized. The best results were obtained under the following conditions: (i) a mixture of two detergents (Tergitol NP 10 and CHAPS) in the focusing gel and sample buffer, (ii) a carrier ampholyte gradient between pH 6.5 and 9.0, (iii) sample loading at the anodic end of the gel, and (iv) low protein loading in the sample (below 50 micrograms). Four P450 forms, including P450 3b and 3c, could be resolved under these conditions.

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Triacetyloleandomycin as inducer of cytochrome P-450 LM3c from rabbit liver microsomes

Cited by 27 publications

References 11 publications

The increase in urinary excretion of 6 beta‐hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction.

The increase in urinary excretion of 6 beta‐hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction.

The Interaction between Cyclosporin A and Erythromycin Studied by Means of an Isolated Perfused Rat Liver Model

Resolution of rabbit liver cytochrome P450 3b and 3c (P450 IIC3 and IIIA4) from microsomal membrane by two‐dimensional gel electrophoresis

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