Metabolism of nilutamide in rat lung.

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…

Distribution of nitroreductive activity toward nilutamide in rat.

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…

094 Transition épithélio-mésenchymateuse (TEM) lors de la fibrose pleurale induite par Transforming Growth Factor (TGF)-1

017 Fibrose pleurale progressive induite par le transfert du gène de Transforming Growth Factor (TGF)-β1 à la plèvre

Introduction De nombreux agents ou toxines (medicaments, radiation, amiante, maladies infectieuses) sont responsables de fibrose pleurale, pathologie invalidante entrainant un syndrome restrictif parfois severe. Les mecanismes conduisant a cette fibrose pleurale ont ete jusqu’ici peu explores. TGF-β est un facteur cle de l’initiation et de la progression de la fibrose dans de nombreux organes. Le transfert transitoire du gene de TGF-β1 actif (AdTGF-β1) aux poumons de rat, a l’aide d’adenovirus induit une fibrose pulmonaire severe et progressive ( J Clin Invest 1997; 100: 768-76). Nous avons developpe un modele de fibrose pleurale par transfert du gene de TGF-β1 au mesothelium pleural afin d…