Madla, Christine M;
Qin, Yujia;
Gavins, Francesca KH;
Liu, Jing;
Dou, Liu;
Orlu, Mine;
Murdan, Sudaxshina;
... Basit, Abdul W; + view all
(2022)
Sex Differences in Intestinal P-glycoprotein Expression in Wistar versus Sprague Dawley Rats.
Pharmaceutics
, 14
(5)
, Article 1030. 10.3390/pharmaceutics14051030.
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Abstract
Wistar and Sprague Dawley are the most common strains of rat used in pharmaceutical research and are used interchangeably in pre-clinical drug development. No studies have assessed whether Wistar and Sprague Dawley rats are equivalent in the gastrointestinal factors that influence oral drug absorption, specifically in relation to intestinal transporters. Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) are two reliable methods for quantifying intestinal protein levels with their own distinct advantages and limitations. In this study, P-glycoprotein (P-gp), a key efflux transporter, was quantified using ELISA and LC-MS/MS along the complete intestinal tract of male and female Wistar and Sprague Dawley rats. This work presents that Sprague Dawley rats have innately higher baseline P-gp expression than Wistar rats. Significant sex differences in P-gp expression were identified in the jejunum, ileum and colon between male and female Wistar rats using both techniques, with males exhibiting higher P-gp levels. Sprague Dawley rats showed no sex differences in P-gp expression through ELISA and LC-MS/MS. Both methods demonstrated similar trends for P-gp quantification, but ELISA could offer faster data acquisition. Our findings report significant sex differences between the strains and highlight that Wistar and Sprague Dawley rats are not equivalent in their P-gp expression. As humans exhibit distinct sex differences in intestinal P-gp levels, Wistar rats may therefore be a more suitable pre-clinical animal strain to model oral drug absorption of P-gp substrates in male and female subjects.
| Type: | Article |
|---|---|
| Title: | Sex Differences in Intestinal P-glycoprotein Expression in Wistar versus Sprague Dawley Rats |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/pharmaceutics14051030 |
| Publisher version: | https://doi.org/10.3390/pharmaceutics14051030 |
| Language: | English |
| Additional information: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
| Keywords: | Animal models; sex differences; rodents; pharmacokinetics and pharmacodynamics; oral bioavailability; protein quantification; P-glycoprotein; MDR1; ABCB1; efflux transporters |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10148432 |
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