A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract

Intestinal interactions with nutrients, xenobiotics and endogenous hormones can influence the expression of clinically relevant membrane transporters. These changes in the gastrointestinal (GI) physiology can in turn affect the absorption of numerous drug substrates. Several studies have examined th...

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Autores principales:	Yang Mai, Francesca K. H. Gavins, Liu Dou, Jing Liu, Farhan Taherali, Manal E. Alkahtani, Sudaxshina Murdan, Abdul W. Basit, Mine Orlu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	food effect sex differences hormones efflux pumps preclinical drug development oral delivery Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/2d4b3a316dbd4ec8bb83d4f3f3d1c4d8
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spelling	oai:doaj.org-article:2d4b3a316dbd4ec8bb83d4f3f3d1c4d82021-11-25T18:40:42ZA Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract10.3390/pharmaceutics131117891999-4923https://doaj.org/article/2d4b3a316dbd4ec8bb83d4f3f3d1c4d82021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1789https://doaj.org/toc/1999-4923Intestinal interactions with nutrients, xenobiotics and endogenous hormones can influence the expression of clinically relevant membrane transporters. These changes in the gastrointestinal (GI) physiology can in turn affect the absorption of numerous drug substrates. Several studies have examined the effect of food on intestinal transporters in male and female humans and animal models. However, to our knowledge no studies have investigated the influence of a non-nutritive fibre meal on intestinal efflux transporters and key sex and GI hormones. Here, we show that a fibre meal increased the acute expression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug-resistance-associated protein-2 (MRP2) in small intestinal segments in both male and female Wistar rats. Enzyme-linked immunosorbent assays were used for the protein quantification of efflux transporters and hormonal plasma concentration. In male rats, the fibre meal caused the plasma concentration of the GI hormone cholecystokinin (CCK) to increase by 75% and the sex hormone testosterone to decrease by 50%, whereas, in contrast, the housing food meal caused a decrease in CCK by 32% and testosterone saw an increase of 31%. No significant changes in the hormonal concentrations, however, were seen in female rats. A deeper understanding of the modulation of efflux transporters by sex, food intake and time can improve our understanding of inter- and intra-variability in the pharmacokinetics of drug substrates.Yang MaiFrancesca K. H. GavinsLiu DouJing LiuFarhan TaheraliManal E. AlkahtaniSudaxshina MurdanAbdul W. BasitMine OrluMDPI AGarticlefood effectsex differenceshormonesefflux pumpspreclinical drug developmentoral deliveryPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1789, p 1789 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	food effect sex differences hormones efflux pumps preclinical drug development oral delivery Pharmacy and materia medica RS1-441
spellingShingle	food effect sex differences hormones efflux pumps preclinical drug development oral delivery Pharmacy and materia medica RS1-441 Yang Mai Francesca K. H. Gavins Liu Dou Jing Liu Farhan Taherali Manal E. Alkahtani Sudaxshina Murdan Abdul W. Basit Mine Orlu A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract
description	Intestinal interactions with nutrients, xenobiotics and endogenous hormones can influence the expression of clinically relevant membrane transporters. These changes in the gastrointestinal (GI) physiology can in turn affect the absorption of numerous drug substrates. Several studies have examined the effect of food on intestinal transporters in male and female humans and animal models. However, to our knowledge no studies have investigated the influence of a non-nutritive fibre meal on intestinal efflux transporters and key sex and GI hormones. Here, we show that a fibre meal increased the acute expression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug-resistance-associated protein-2 (MRP2) in small intestinal segments in both male and female Wistar rats. Enzyme-linked immunosorbent assays were used for the protein quantification of efflux transporters and hormonal plasma concentration. In male rats, the fibre meal caused the plasma concentration of the GI hormone cholecystokinin (CCK) to increase by 75% and the sex hormone testosterone to decrease by 50%, whereas, in contrast, the housing food meal caused a decrease in CCK by 32% and testosterone saw an increase of 31%. No significant changes in the hormonal concentrations, however, were seen in female rats. A deeper understanding of the modulation of efflux transporters by sex, food intake and time can improve our understanding of inter- and intra-variability in the pharmacokinetics of drug substrates.
format	article
author	Yang Mai Francesca K. H. Gavins Liu Dou Jing Liu Farhan Taherali Manal E. Alkahtani Sudaxshina Murdan Abdul W. Basit Mine Orlu
author_facet	Yang Mai Francesca K. H. Gavins Liu Dou Jing Liu Farhan Taherali Manal E. Alkahtani Sudaxshina Murdan Abdul W. Basit Mine Orlu
author_sort	Yang Mai
title	A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract
title_short	A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract
title_full	A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract
title_fullStr	A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract
title_full_unstemmed	A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract
title_sort	non-nutritive feeding intervention alters the expression of efflux transporters in the gastrointestinal tract
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2d4b3a316dbd4ec8bb83d4f3f3d1c4d8
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A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract

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