کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8544619 | 1561552 | 2018 | 25 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Simultaneous determination of intestinal permeability and potential drug interactions of complex mixtures using Caco-2â¯cells and high-resolution mass spectrometry: Studies with Rauwolfia serpentina extract
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Caco-2â¯cells are a commonly used model for estimating the intestinal bioavailability of single chemical entity pharmaceuticals. Caco-2â¯cells, when induced with calcitriol, also express other biological functions such as phase I (CYP) and phase II (glucuronosyltransferases) drug metabolizing enzymes which are relevant to drug-supplement interactions. Intestinal bioavailability is an important factor in the overall safety assessment of products consumed orally. Foods, including herbal dietary supplements, are complex substances with multiple chemical components. Because of potential interactions between components of complex mixtures, more reliable safety assessments can be obtained by studying the commercial products “as consumed” rather than by testing individual chemical components one at a time. The present study evaluated the apparent intestinal permeability (Papp) of a model herbal extract, Rauwolfia serpentina, using both whole plant extracts and the individual purified Rauwolfia alkaloids. All test compounds, endpoint substrates, and their metabolites were quantified using liquid chromatography and high-resolution mass spectrometry. The Papp values for individual Rauwolfia alkaloids were comparable whether measured individually or as components of the complete extract. Both Rauwolfia extract and all individual Rauwolfia alkaloids except yohimbine inhibited CYP3A4 activity (midazolam 1â²-hydroxylation). Both Rauwolfia extract and all individual Rauwolfia alkaloids except corynanthine and reserpic acid significantly increased glucuronosyltransferase activity (glucuronidation of 4-methylumbelliferone). The positive control, ketoconazole, significantly inhibited both CYP3A4 and glucuronosyltransferase activities. These findings suggest that the Caco-2 assay is capable of simultaneously identifying both bioavailability and potentially hazardous intestinal drug-supplement interactions in complex mixtures.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 290, 25 June 2018, Pages 37-43
Journal: Chemico-Biological Interactions - Volume 290, 25 June 2018, Pages 37-43
نویسندگان
Thomas J. Flynn, Sanah N. Vohra,