RESUMO
Microbial transformation of two anabolic steroids, ethylestrenol (1) and nandrolone (2), were carried out. Ethylestrenol (1), when incubated with Rhizopus stolonifer (TSY 0471), yielded two oxidative metabolites named 17alpha-ethyl-3beta,17beta-dihydroxy-19-norndrost-4-ene (3) and 17alpha-ethyl-17beta-hydroxy-19-norandrost-4-en-3-one (4), while incubation of compound 2 with the same fungus yielded two oxidative metabolites, 19-norandrost-4-en-3,17-dione (5) and 6alpha,17beta-dihydroxy-19-norandrost-1,4-dien-3-one (6).
Assuntos
Anabolizantes/metabolismo , Androstenóis/isolamento & purificação , Etilestrenol/metabolismo , Nandrolona/metabolismo , Androstenóis/química , Biotransformação , Mesterolona/metabolismo , Estrutura Molecular , Oxirredução , Rhizopus/metabolismoRESUMO
Current veterinary residue analysis mainly focuses on the monitoring of residues of the administered parent compound. However, it is possible that larger amounts of metabolites are excreted and that they can have a prolonged excretion period. In order to unravel specific metabolic steps and to identify possible biological markers, two in vitro liver models were used, i.e. monolayer cultures of isolated hepatocytes and liver microsomes, both prepared from liver tissue of cattle. Chostebol, boldenone, norethandrolone (NE) and ethylestrenol (EES) were used as model substrates. Results show that the metabolic profiles derived from in vitro experiments are predictive for the in vivo metabolic pathways of the steroids evaluated in this study. By means of this strategy, it is possible to identify 17 alpha-ethyl-5 beta-estrane-3 alpha,17 beta-diol (EED) as a common biological marker for NE and EES. By in vivo experiments it was shown that EED is particularly important for the detection of the abuse of NE or EES because of its high excretion levels and its prolonged presence as compared with the parent compounds or any other metabolite.
Assuntos
Anabolizantes/metabolismo , Bovinos/metabolismo , Resíduos de Drogas/análise , Fígado/metabolismo , Anabolizantes/análise , Animais , Biomarcadores/análise , Células Cultivadas , Estradiol/análogos & derivados , Estradiol/análise , Etilestrenol/metabolismo , Fígado/química , Microssomos Hepáticos/metabolismo , Modelos Biológicos , Noretandrolona/metabolismo , Valor Preditivo dos Testes , Testosterona/análogos & derivados , Testosterona/metabolismoRESUMO
1. The absorption, distribution, metabolism and excretion of [3H]ethylestrenol were studied in the rat. 2. Approximately one third of an intragastric dose was absorbed; 17% of the dose was excreted in urine and 83% in faeces within 10 days. 3. The dose is distributed throughout the rat, and kidney and liver were found to contain respectively 2.5-3 and 5-7 times the average specific activity of all other tissues. 4. Unchanged ethylestrenol was the only component detected in urine. Ethylestrenol was also found in faeces, along with two different dihydroxylated dihydro derivatives and one trihydroxylated dihydro derivative.
Assuntos
Etilestrenol/metabolismo , Absorção , Animais , Etilestrenol/urina , Fezes/análise , Rim/metabolismo , Cinética , Fígado/metabolismo , Masculino , Ratos , Distribuição TecidualRESUMO
1. Ethylestrenol incubated with a post-mitochondrial supernatant fraction of rat liver plus co-factors gives norethandrolone as the major metabolite. 2. A second (minor) metabolite was tentatively identified as 17 alpha-ethyl-5 epsilon-estrane-3 epsilon,17 beta-diol. 3. A pathway is suggested for the metabolism of ethylestrenol in the rat.