title: Excised segments of rat small intestine in Ussing chamber studies: A comparison of native and stripped tissue viability and permeability to drugs.
abstract: Excised rat intestinal tissue mounted in an Ussing chamber can be used for intestinal permeability assessments in drug development. The outer layer of the intestine, the serosa and part of the muscle layer, is traditionally removed since it is considered a barrier to the diffusion of nutrients and oxygen as well as to that of pharmaceutical substances. However, the procedure for removing the serosal-muscle layer, i.e. stripping, is a technically challenging process in the pre-experimental preparation of the tissue which may result in tissue damage and reduced viability of the segment. In this study, the viability of stripped and native (non-stripped) rat small intestine tissue segments mounted in Ussing chambers was monitored and the apparent permeability of the tissue to a set of test compounds across both tissue preparations was determined. Electrical measurements, in particular the potential difference (PD) across the intestinal membrane, were used to evaluate the viability. In this study, there were no differences in initial PD (health status of the tissue) or PD over time (viability throughout the experiment) between native and stripped rat jejunum segments. Overall, there were also no significant differences in permeability between stripped and native rat intestinal tissue for the compounds in this study. Based on these results, we propose that stripping can be excluded from the preparation procedures for rat jejunal tissue for permeability studies when using the Ussing chamber technique.
authors.affiliation: Department of Pharmacy, Uppsala University, Uppsala 75233, Sweden. Electronic address: erik.sjogren@farmaci.uu.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Sjögren
authors.affiliation: Department of Pharmacy, Uppsala University, Uppsala 75233, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Eriksson
authors.affiliation: DSM, Safety and ADME Translational Sciences, AstraZeneca Innovative Medicines and Early Development, Mölndal 43183, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Vedin
authors.affiliation: DSM, Safety and ADME Translational Sciences, AstraZeneca Innovative Medicines and Early Development, Mölndal 43183, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Breitholtz
authors.affiliation: DSM, Safety and ADME Translational Sciences, AstraZeneca Innovative Medicines and Early Development, Mölndal 43183, Sweden.
authors.forename: Constanze
authors.initials: C
authors.lastname: Hilgendorf
mesh_terms: D000818:Animals; D015194:Diffusion Chambers, Culture; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014022:Tissue Survival
chemical_list: D004364:Pharmaceutical Preparations
keywords: Drug permeability; Rat jejunum; Serosal-muscle layer; Ussing chamber