Feasibility of the Ussing chamber technique for the determination of in vitro jejunal permeability of passively absorbed compounds in different animal species.
Abstract: The aim of this study was to assess the feasibility of the Ussing chamber technique for the determination of the jejunal permeability of passively absorbed, high permeability model compounds (acetaminophen and ketoprofen) in different animal species. Additionally, electrophysiological measurements and histological examination of pre- and post-incubation tissue specimens were performed. Apparent permeability coefficients of turkey and dog jejunum were low and highly variable due to tissue fragility caused by differences in thickness of the remaining intestinal layers after stripping and resulting in severe damage. Pig and horse jejunum were markedly more suitable for permeability determinations and mild signs of deterioration were noticed after 120 min of incubation. Transepithelial electrical resistance and potential difference did not correlate well with the observed tissue damage. From these data, the Ussing chamber technique appears to allow for permeability measurements within a species, but seems unsuitable for interspecies permeability comparison. However, further validation of the method with low permeability compounds and actively transported compounds is needed.
© 2010 Blackwell Publishing Ltd.
Publication Date: 2011-04-16 PubMed ID: 21492193DOI: 10.1111/j.1365-2885.2010.01218.xGoogle Scholar: Lookup
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- Journal Article
Summary
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The research focused on testing the effectiveness of the Ussing chamber technique to measure the permeability of certain drugs (acetaminophen and ketoprofen) through the small intestine (jejunum) in different animal species. Results showed that this technique is more suited for studies within a single species, not between different species, due to variances in tissue fragility and thickness.
Study Overview
- The research aimed to determine the viability of using the Ussing chamber method to investigate the permeability of the small intestine (specifically the jejunum) in varying animal species.
- The examined model compounds for this study were passively absorbed, high permeability drugs, namely acetaminophen and ketoprofen.
- Additional aspects of the study included electrophysiological measurements and histological examination of tissue samples before and after the test.
Key Findings
- Returns indicated that permeability coefficients were low and inconsistent in both turkey and dog jejunum due to the fragility of the tissue.
- The fragility of the tissues was possibly due to the varying thickness of remaining intestinal layers post-stripping, which in turn caused significant damage.
- In contrast, the small intestines of pigs and horses were considerably more suitable for these permeability determinations, with only mild signs of deterioration observed after an incubation period of two hours (120 minutes).
Electrophysiological Measurements
- There was a lack of correlation between transepithelial electrical resistance and potential difference with the observed tissue damage.
Conclusions
- From the collected data, it appears that the Ussing chamber technique is suitable for permeability measurements within a single species.
- However, the method seems to have limitations when comparing permeability between different animal species.
- The researchers concluded that further verification of the process is necessary, particularly with low permeability compounds and compounds that are actively transported.
Cite This Article
APA
Neirinckx E, Vervaet C, Michiels J, De Smet S, Van den Broeck W, Remon JP, De Backer P, Croubels S.
(2011).
Feasibility of the Ussing chamber technique for the determination of in vitro jejunal permeability of passively absorbed compounds in different animal species.
J Vet Pharmacol Ther, 34(3), 290-297.
https://doi.org/10.1111/j.1365-2885.2010.01218.x Publication
Researcher Affiliations
- Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Eva.Neirinckx@UGent.be
MeSH Terms
- Acetaminophen / pharmacokinetics
- Analgesics, Non-Narcotic / pharmacokinetics
- Animals
- Chromatography, High Pressure Liquid / veterinary
- Diffusion Chambers, Culture / instrumentation
- Diffusion Chambers, Culture / methods
- Diffusion Chambers, Culture / veterinary
- Dogs
- Electric Impedance
- Feasibility Studies
- Female
- Horses
- In Vitro Techniques
- Intestinal Absorption
- Intestinal Mucosa / anatomy & histology
- Intestinal Mucosa / metabolism
- Intestinal Mucosa / physiology
- Jejunum / anatomy & histology
- Jejunum / metabolism
- Jejunum / physiology
- Ketoprofen / pharmacokinetics
- Male
- Membrane Potentials
- Permeability
- Swine
- Turkeys
Citations
This article has been cited 12 times.- Houriet J, Arnold YE, Pellissier L, Kalia YN, Wolfender JL. Using Porcine Jejunum Ex Vivo to Study Absorption and Biotransformation of Natural Products in Plant Extracts: Pueraria lobata as a Case Study.. Metabolites 2021 Aug 14;11(8).
- Gao Y, Meng L, Liu H, Wang J, Zheng N. The Compromised Intestinal Barrier Induced by Mycotoxins.. Toxins (Basel) 2020 Sep 28;12(10).
- Arnold YE, Kalia YN. Using Ex Vivo Porcine Jejunum to Identify Membrane Transporter Substrates: A Screening Tool for Early-Stage Drug Development.. Biomedicines 2020 Sep 10;8(9).
- Park S, Lee JW, Cowieson AJ, Pappenberger G, Woyengo TA. Soybean meal allergenic protein degradation and gut health of piglets fed protease-supplemented diets.. J Anim Sci 2020 Oct 1;98(10).
- Degroote J, Vergauwen H, Wang W, Van Ginneken C, De Smet S, Michiels J. Changes of the glutathione redox system during the weaning transition in piglets, in relation to small intestinal morphology and barrier function.. J Anim Sci Biotechnol 2020;11:45.
- Degroote J, Vergauwen H, Van Noten N, Wang W, De Smet S, Van Ginneken C, Michiels J. The Effect of Dietary Quercetin on the Glutathione Redox System and Small Intestinal Functionality of Weaned Piglets.. Antioxidants (Basel) 2019 Aug 16;8(8).
- Stewart AS, Pratt-Phillips S, Gonzalez LM. Alterations in Intestinal Permeability: The Role of the "Leaky Gut" in Health and Disease.. J Equine Vet Sci 2017 May;52:10-22.
- Arnold YE, Thorens J, Bernard S, Kalia YN. Drug Transport across Porcine Intestine Using an Ussing Chamber System: Regional Differences and the Effect of P-Glycoprotein and CYP3A4 Activity on Drug Absorption.. Pharmaceutics 2019 Mar 21;11(3).
- Papich MG, Martinez MN. Applying Biopharmaceutical Classification System (BCS) Criteria to Predict Oral Absorption of Drugs in Dogs: Challenges and Pitfalls.. AAPS J 2015 Jul;17(4):948-64.
- Antonissen G, Van Immerseel F, Pasmans F, Ducatelle R, Haesebrouck F, Timbermont L, Verlinden M, Janssens GP, Eeckhaut V, Eeckhout M, De Saeger S, Hessenberger S, Martel A, Croubels S. The mycotoxin deoxynivalenol predisposes for the development of Clostridium perfringens-induced necrotic enteritis in broiler chickens.. PLoS One 2014;9(9):e108775.
- Suenderhauf C, Tuffin G, Lorentsen H, Grimm HP, Flament C, Parrott N. Pharmacokinetics of paracetamol in Göttingen minipigs: in vivo studies and modeling to elucidate physiological determinants of absorption.. Pharm Res 2014 Oct;31(10):2696-707.
- Ruhnke I, DeBiasio JV, Suchodolski JS, Newman S, Musch MW, Steiner JM. Evaluation of endoscopically obtained duodenal biopsy samples from cats and dogs in an adapter-modified Ussing chamber.. J Vet Sci 2014;15(2):297-307.
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