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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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 |
collection | DOAJ |
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. |
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issn | 1999-4923 |
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spelling | doaj.art-2d4b3a316dbd4ec8bb83d4f3f3d1c4d82023-11-23T00:57:39ZengMDPI AGPharmaceutics1999-49232021-10-011311178910.3390/pharmaceutics13111789A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal TractYang Mai0Francesca K. H. Gavins1Liu Dou2Jing Liu3Farhan Taherali4Manal E. Alkahtani5Sudaxshina Murdan6Abdul W. Basit7Mine Orlu8School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, ChinaUCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UKSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, ChinaUCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UKUCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UKUCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UKUCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UKUCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UKIntestinal 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.https://www.mdpi.com/1999-4923/13/11/1789food effectsex differenceshormonesefflux pumpspreclinical drug developmentoral delivery |
spellingShingle | 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 Pharmaceutics food effect sex differences hormones efflux pumps preclinical drug development oral delivery |
title | 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_short | 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 |
topic | food effect sex differences hormones efflux pumps preclinical drug development oral delivery |
url | https://www.mdpi.com/1999-4923/13/11/1789 |
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