کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5863019 1133789 2012 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Screening of the inhibitory effect of xenobiotics on alcohol metabolism using S9 rat liver fractions
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Screening of the inhibitory effect of xenobiotics on alcohol metabolism using S9 rat liver fractions
چکیده انگلیسی

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 × 10−3 mM, followed by cimetidine (IC50 of 122.9 × 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.

► Method to evaluate inhibition of liver ADH activity by xenobiotics. ► Useful method to screen for drugs that may inhibit ethanol metabolism. ► Tramadol showed higher inhibitory effect than cimetidine, a known ADH inhibitor. ► Alprazolam and flunitrazepam reduced liver ADH activity but to a smaller extent.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 26, Issue 7, October 2012, Pages 1177-1180
نویسندگان
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