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Article

Sex Differences in Intestinal P-Glycoprotein Expression in Wistar versus Sprague Dawley Rats

1
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29–39 Brunswick Square, London WC1N 1AX, UK
2
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou 510275, China
*
Authors to whom correspondence should be addressed.
These authors equally contributed to this work.
Academic Editor: Avi Domb
Pharmaceutics 2022, 14(5), 1030; https://doi.org/10.3390/pharmaceutics14051030
Received: 5 April 2022 / Revised: 4 May 2022 / Accepted: 6 May 2022 / Published: 10 May 2022
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. View Full-Text
Keywords: animal models; sex differences; rodents; pharmacokinetics and pharmacodynamics; oral bioavailability; protein quantification; P-glycoprotein; MDR1; ABCB1; efflux transporters animal models; sex differences; rodents; pharmacokinetics and pharmacodynamics; oral bioavailability; protein quantification; P-glycoprotein; MDR1; ABCB1; efflux transporters
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MDPI and ACS Style

Madla, C.M.; Qin, Y.; Gavins, F.K.H.; Liu, J.; Dou, L.; Orlu, M.; Murdan, S.; Mai, Y.; Basit, A.W. Sex Differences in Intestinal P-Glycoprotein Expression in Wistar versus Sprague Dawley Rats. Pharmaceutics 2022, 14, 1030. https://doi.org/10.3390/pharmaceutics14051030

AMA Style

Madla CM, Qin Y, Gavins FKH, Liu J, Dou L, Orlu M, Murdan S, Mai Y, Basit AW. Sex Differences in Intestinal P-Glycoprotein Expression in Wistar versus Sprague Dawley Rats. Pharmaceutics. 2022; 14(5):1030. https://doi.org/10.3390/pharmaceutics14051030

Chicago/Turabian Style

Madla, Christine M., Yujia Qin, Francesca K.H. Gavins, Jing Liu, Liu Dou, Mine Orlu, Sudaxshina Murdan, Yang Mai, and Abdul W. Basit. 2022. "Sex Differences in Intestinal P-Glycoprotein Expression in Wistar versus Sprague Dawley Rats" Pharmaceutics 14, no. 5: 1030. https://doi.org/10.3390/pharmaceutics14051030

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