Biochemical and histological changes in the small intestine of mice with dextran sulfate sodium colitis

Abstract

The dextran sulfate sodium (DSS) model of colitis has been commonly utilized in mice to assess novel treatments for ulcerative colitis. Recent studies have indicated that morphological and biochemical changes extend to the small intestine (SI). This study aimed to characterize histological and biochemical changes in the SI during DSS colitis in wild-type (WT) and DPIV knock-out (DPIV(-/-) ) mice treated with saline or the DPIV inhibitors, Ile-Pyrr-(2-CN)*TFA or Ile-Thia. Groups (n = 10) of DPIV(-/-) and WT mice were orally gavaged twice daily with saline, Ile-Pyrr-(2-CN)*TFA or Ile-Thia. Mice consumed 2% DSS in drinking water for 6 days to induce colitis. Small intestinal tissue was assessed for histological changes, sucrase, and DPIV activity and neutrophil infiltration. Jejunal villus length was increased in all groups after 6 days DSS consumption (P < 0.05). Jejunal DPIV activity was significantly lower by 35% in WT mice receiving Ile-Pyrr-(2-CN)*TFA compared to saline controls. Jejunal MPO activity was significantly increased in the WT + saline and DPIV(-/-) + saline groups following DSS consumption, compared to WT and DPIV(-/-) controls at day 0. Increased sucrase activity was apparent at day 0 in DPIV(-/-) compared to WT mice (P < 0.05). We conclude that DSS-induced damage is not restricted to the colon, but also extends to the small intestine. Furthermore, reduced or absent DPIV activity resulted in functional adaptations to brush border enzyme activity. DPIV inhibitors are now a recognized therapy for type-II diabetes. The work presented here highlights the need to delineate any long-term effects of DPIV inhibitors on SI function, to further validate their safety and tolerability.

Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse

“…It is generally accepted that DSS-induced colitis causes inflammation and mucus hypersecretion in the small intestine [20], so we used this model of induced colitis to observe nanoparticle distribution in the inflamed small intestine after oral administration. Inflammation was evident by the lack of organized alignment of cell nuclei and general damage to the small intestine villi compared to healthy mice.…”

“…To induce TNBS-colitis, mice were anesthetized with isoflurane and dosed rectally with 0.125 mg/g of 2,4,6-trinitrobenzenesulfonic acid (TNBS, also known as picrylsulfonic acid, Sigma-Aldrich) in 50% ethanol as previously described [19]. To induce DSS-colitis, mice were given 4% w/v dextran sulfate sodium (DSS, Sigma-Aldrich) in their drinking water for four days, as previously described [20]. Only mice that lost at least 5% of their body weight, a common measure of disease induction, were used [19].…”

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

“…Furthermore, CD26-mediated co-stimulation of CD4 1 T cells induced greater lymphocyte-activation gene 3 (LAG3) expression than CD28-mediated co-stimulation [92]. Whether or not the other DASH proteins contribute to the overall DPP4-like activity in Th2 cells such DPP8 still needs to be investigated [2,7,13,51,88,94,95]. In addition, DPP4/CD26 is expressed highly on the CD45RO 1 CD29 1 memory T helper subset CD26 bright CD4 1 , which responds to recall antigens, induces B cell immunoglobulin (Ig)G synthesis and activates cytotoxic T cells [7,8,13,51,94,96].…”

Glutamine Supplementation Attenuates Expressions of Adhesion Molecules and Chemokine Receptors on T Cells in a Murine Model of Acute Colitis

“…DSS-induced colitis is characterized by extensive crypt and epithelial cell damage with ulceration, tissue edema, and infiltration of immune cells predominantly in the distal colon that mimics the histological features of UC [22]. Recent studies indicated that DSS-induced morphological and biochemical damage also extends to the small intestines [23]. Susceptibilities to DSS-induced colitis differ in various inbred mouse strains [24].…”