0000000000480777

AUTHOR

Jørn A. Holme

showing 3 related works from this author

Metabolism of nilutamide in rat lung.

2005

Nilutamide is a non-steroidal anti-androgen drug proposed in the treatment of metastatic prostatic carcinoma. Its therapeutic effects are overshadowed by the occurrence of adverse reactions, mediated by mechanisms that remain elusive. To elucidate possible mechanisms for nilutamide toxicity, we investigated the metabolism of nilutamide in rat lung homogenates, in subcellular fractions and in freshly isolated cells. In whole lung homogenates, the nitro group of nilutamide was reduced to the amine and hydroxylamine moieties. These conversions occurred exclusively in the absence of dioxygen, were increased by the addition of FMN, FAD, or NADPH. Reductive metabolism of nilutamide to the amine a…

MaleIn Vitro TechniquesImidazolidinesBiochemistryCofactorMass SpectrometryRats Sprague-Dawleychemistry.chemical_compoundHydroxylamineCytosolMacrophages AlveolarmedicineAnimalsEnzyme InhibitorsLungChromatography High Pressure LiquidPharmacologychemistry.chemical_classificationbiologyAndrogen AntagonistsEpithelial CellsMetabolismRatsNitric oxide synthaseCytosolKineticsEnzymeBiochemistrychemistryNilutamidebiology.proteinOxidation-ReductionDrug metabolismmedicine.drugChromatography LiquidBiochemical pharmacology
researchProduct

Mechanisms involved in lipid accumulation and apoptosis induced by 1-nitropyrene in Hepa1c1c7 cells

2011

International audience; 1-Nitropyrene (1-NP) is a nitro-polycyclic aromatic hydrocarbon (nitro-PAH) present in diesel exhaust and bound to particular matter in urban air. We show that 1-NP and the referent PAH benzo(a)pyrene (BP) induce apoptosis and a lipid accumulation dependent on cytochrome P450 1A1-metabolites in mouse hepatoma cells, whereas 1-amino-pyrene had no effect. The caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (Z-VAD-fmk), inhibits 1-NP-induced apoptosis, but failed to alter 1-NP-triggered lipid accumulation determined by Nile red staining. We further show that cholesterol and fatty acid contents are modified after nitro-PAH exposure and that 1…

endoplasmic-reticulum stressMESH: PyrenesHepatoma cellsliver-cellsactivated protein-kinaseApoptosisAMP-Activated Protein KinasesToxicologyMESH: Liver Neoplasms ExperimentalMicechemistry.chemical_compoundMESH: CholesterolLiver Neoplasms ExperimentalMESH: AnimalsMESH: AMP-Activated Protein KinasesStearoyl-CoA desaturase 1CaspaseMESH: Lipid Metabolismchemistry.chemical_classificationhuman macrophages0303 health sciencesPyrenesbiology8-tetrachlorodibenzo-p-dioxin tcdd030302 biochemistry & molecular biologyGeneral Medicineinhibition[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM]CholesterolBiochemistry[SDV.TOX]Life Sciences [q-bio]/ToxicologyCaspaseslipids (amino acids peptides and proteins)stearoyl-coaStearoyl-CoA DesaturaseMESH: Cell Line Tumor[SDV.BC]Life Sciences [q-bio]/Cellular Biology03 medical and health sciencesMESH: Benzo(a)pyreneCell Line Tumor1-NitropyreneBenzo(a)pyreneAnimalsFatty acidsProtein kinase AMESH: Mice030304 developmental biologyaromatic-hydrocarbonsMESH: CaspasesCholesterolMESH: Apoptosisc-srcFatty acidAMPKCytochrome P450Lipid MetabolismMolecular biologychemistryApoptosisMESH: Stearoyl-CoA Desaturasebiology.proteinStearoyl-CoA desaturase-1desaturaseToxicology Letters
researchProduct

Distribution of nitroreductive activity toward nilutamide in rat.

2004

Abstract Nilutamide is a pneumotoxic and hepatotoxic nitroaromatic (R-NO 2 ) antiandrogen used in the treatment of prostate carcinoma in man. Previously, we established that in the rat lung, the drug is metabolized into the corresponding hydroxylamine (R-NHOH) and amine (R-NH 2 ) derivatives. These results evidenced a cytosolic oxygen-sensitive (type II) nitroreductase activity in lung. In the present studies, we extended the characterization of nilutamide metabolism in liver, brain, kidney, heart, blood, intestine (small, cecum, and large, and their respective luminal contents) of male Sprague–Dawley rats. Subcellular fractions for all tissues (except blood) examined (postmitochondrial, cy…

MaleBiologyToxicologyImidazolidinesKidneyRats Sprague-DawleyNitroreductaseCecumCytosolmedicineAnimalsIntestinal MucosaCells CulturedChromatography High Pressure LiquidPharmacologyKidneyBrainAndrogen AntagonistsMetabolismNitroreductasesSmall intestineRatsCytosolmedicine.anatomical_structureBiochemistryLiverNilutamideMicrosomemedicine.drugToxicology and applied pharmacology
researchProduct