The contribution of human small intestine to chlorpyrifos biotransformation

Claudia Leoni, Maria Balduzzi, Franca Maria Buratti, Emanuela Testai

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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. © 2012 Elsevier Ireland Ltd.
Original languageEnglish
Pages (from-to)42 - 48
Number of pages7
JournalToxicology Letters
Volume215
Issue number1
DOIs
Publication statusPublished - 23 Nov 2012
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this