Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/8522
Título: Screening of the inhibitory effect of xenobiotics on alcohol metabolism using S9 rat liver fractions
Autor: Dias, Catarina
Testa, Bernard
Soveral, Graça
Dias, Mário
Constantino, Luís
Palavras-chave: Ethanol metabolism
Alcohol dehydrogenase
Alprazolam
Cimetidine
Flunitrazepam
Tramadol
Data: 2012
Citação: Dias, C., et al. Screening of the inhibitory effect of xenobiotics on alcohol metabolism using S9 rat liver fractions. Toxicol. in Vitro (2012), http://dx.doi.org/10.1016/j.tiv.2012.06.011
Resumo: The purpose of this work was to develop and optimize a simple and suitable method to detect the potential inhibitory effect of drugs and medicines on alcohol dehydrogenase (ADH) activity in order to evaluate the possible interactions between medicines and alcohol metabolism. Commonly used medicines that are often involved in court litigations related with driving under the influence of alcohol were selected. Alprazolam, flunitrazepam and tramadol were tested as drugs with no known effect on ADH activity. Cimetidine, reported previously as having inhibitory effect on ADH, and 4-methylpyrazole (4-MP), a well known ADH inhibitor, were tested as positive controls. Apart from 4-MP, tramadol was identified as having the higher inhibitory effect with an IC50 of 44.7 x 10-3 mM, followed by cimetidine (IC50 of 122.9 x 10-3 mM). Alprazolam and flunitrazepam also reduced liver ADH activity but to a smaller extent (inhibition of 11.8 ± 5.0% for alprazolam 1.0 mM and 34.5 ± 7.1% for flunitrazepam 0.04 mM). Apart from cimetidine, this is the first report describing the inhibitory effect of these drugs on ethanol metabolism. The results also show the suitability of the method to screen for inhibitory effect of drugs on ethanol metabolism helping to identify drugs for which further study is justified.
Peer review: yes
URI: http://dx.doi.org/10.1016/j.tiv.2012.06.011
http://hdl.handle.net/10451/8522
ISSN: 0887-2333
Versão do Editor: http://www.sciencedirect.com/science/article/pii/S0887233312001610
Aparece nas colecções:FF - Artigos em Revistas Internacionais
iMed.ULisboa - Artigos em Revistas Internacionais

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