کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2599551 1133216 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The contribution of human small intestine to chlorpyrifos biotransformation
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
The contribution of human small intestine to chlorpyrifos biotransformation
چکیده انگلیسی

Despite the oral intake is the major route of exposure to chlorpyrifos for the general population, few data are available on human intestine biotransformation. In this study the contribution of chlorpyrifos (CPF) metabolism in human small intestine was investigated in microsomes from duodenum (HDM) and ileum/jejunum (HS2M) from 11 individual donors. Samples were characterized for testosterone hydroxylated metabolite formation and CYP content quantification by means of Western blotting. The two methods gave consistent results, evidencing the presence of CY3A4 and its-related activity in 10/11 samples, among which one showed also the presence of CYP2C9. Analogously, although with high interindividual variability (about 10 fold), CPF bioactivation to chlorpyrifos-oxon (CPFO) was observed in 10/11 HDM: intrinsic clearance highest value was 0.75 pmol CPFO/(mg protein min μM). Detoxication to 3,5,6-trichloropyrin-2-ol formation was negligible. The comparison between HDM and HS2M indicates that most CPF bioactivation was confined in the duodenum, declining toward the distal ileum. Results suggest that following oral exposure, the small intestine CPF bioactivation, although much lower when compared to the total hepatic metabolism, could play a role in the pre-systemic CPF clearance, with CPFO transported into the lumen by the efflux P-glycoprotein and further metabolized by esterases.


► Human microsomes from duodenum and ileum/jejunum were used.
► The toxic metabolite chlorpyrifos-oxon was the only one formed.
► 10-fold interindividual variability was observed.
► Bioactivation was confined in the duodenum, declining toward the distal ileum.
► Intestinal metabolism could play a role in CPF pre-systemic bioactivation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 215, Issue 1, 23 November 2012, Pages 42–48
نویسندگان
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