Afonso-Pereira, F;
Dou, L;
Trenfield, SJ;
Madla, CM;
Murdan, S;
Sousa, J;
Veiga, F;
(2018)
Sex differences in the gastrointestinal tract of rats and the implications for oral drug delivery.
European Journal of Pharmaceutical Sciences
, 115
pp. 339-344.
10.1016/j.ejps.2018.01.043.
Preview |
Text
Basit_Sex differences in the GI tract of adult rats - Revised manuscript.pdf - Accepted Version Download (414kB) | Preview |
Preview |
Text
Basit Sex differences in the GI tract of adult rats - FIGURES.pdf - Accepted Version Download (543kB) | Preview |
Abstract
Pre-clinical research often uses rodents as animal models to guide the selection of appropriate oral drug and dose selection in humans. However, traditionally, such research fails to consider the gastrointestinal differences between the sexes of rats and the impact on oral drug delivery. This study aimed to identify and characterise the potential sex-related differences in the gastrointestinal environment of sacrificed male and female Wistar rats. Their gastrointestinal tracts were excised and segmented into the stomach, duodenum, jejunum, ileum, caecum and colon. The respective contents and tissue sections were collected and analysed for pH, buffer capacity, surface tension, osmolality and relative P-glycoprotein (P-gp) expression. The pH in the stomach of females was found to be lower than in males. Female rats also exhibited a higher buffer capacity in the caecum and colon when compared with their male counterparts. Males were found to have a higher osmolality than females in the duodenum, ileum and colon. Significant sex differences (p < 0.05) in surface tension were observed in the ileum, where females exhibited a higher surface tension. Interestingly, female rats displayed significantly higher relative P-gp expression levels (p < 0.05) when compared with male rats in the duodenum (1.24 ± 0.85 vs. 0.36 ± 0.26), jejunum (1.45 ± 0.88 vs. 0.38 ± 0.26) and ileum (0.92 ± 0.43 vs. 0.40 ± 0.18) but not in the colon (0.5 ± 0.32 vs. 0.33 ± 0.16) segments. The work reported has demonstrated the stark physiological differences between male and female rats at a physiological level, indicating how the 'sex of the gut' could influence oral drug delivery. These findings, therefore, are of critical importance in pre-clinical research and drug development.
| Type: | Article |
|---|---|
| Title: | Sex differences in the gastrointestinal tract of rats and the implications for oral drug delivery |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejps.2018.01.043 |
| Publisher version: | https://doi.org/10.1016/j.ejps.2018.01.043 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Gastrointestinal, Oral drug delivery, P-glycoprotein, Pre-clinical development, Rat models, Sex differences |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences 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 UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10044057 |
Archive Staff Only
 |
View Item |
