Validation of murine dextran sulfate sodium-induced colitis using four therapeutic agents for human inflammatory bowel disease

Melgar, Silvia; Karlsson, Lisa; Rehnström, Erika; Karlsson, Agneta; Utkovic, Helena; Jansson, Liselotte; Michaëlsson, Erik

doi:10.1016/j.intimp.2008.01.036

Cited by 176 publications

(132 citation statements)

References 37 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…The use of DSS to induce ulcerative colitis in mice has been widely documented (29) and the model is considered clinically and histologically reminiscent of human UC (19,29). The possibility that the DSS effects observed in intestinal conditional Flvcr1a-null mice are due to an enhanced permeability of their mucosa to this toxic compound is unlikely.…”

Section: Flvcr1a Depletion Impairs Mice Survival To Ulcerative Colitismentioning

confidence: 99%

“…The remaining animals were administered tap water for nine additional days and sacrified at day 17. Colon-rectum sections were stained with H&E. Damage scores on colon-rectum slides were assigned in a blinded fashion, on an scale of 0 to 6, as reported previously (19), where 0 = no signs of damage; 1 = few inflammatory cells, no signs of epithelial degeneration; 2 = mild inflammation, few signs of epithelial degeneration; 3 = moderate inflammation, few epithelial ulcerations; 4 = moderate to severe inflammation, ulcerations in more than 25% of the tissue section; 5 = moderate to severe inflammation, large ulcerations of more than 50% of the tissue section; 6 = severe inflammation and ulcerations of more than 75% of the tissue section.…”

Section: Induction Of Colitismentioning

confidence: 99%

See 1 more Smart Citation

Crucial Role of FLVCR1a in the Maintenance of Intestinal Heme Homeostasis

Fiorito

Forni²,

Silengo

et al. 2015

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Section: Flvcr1a Depletion Impairs Mice Survival To Ulcerative Colitismentioning

confidence: 99%

Section: Induction Of Colitismentioning

confidence: 99%

Crucial Role of FLVCR1a in the Maintenance of Intestinal Heme Homeostasis

Fiorito

Forni²,

Silengo

et al. 2015

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

“…In preclinical models of IBD, this can be challenging as the number of clinically validated therapies is relatively low and the number of models that respond to these therapies is also low. Although they are not typically used in the clinic due to safety issues, high-dose immunosuppressants can be used in most inflammation-mediated models as a positive control (Hoshino et al 1992;Melgar et al 2008;Hirano and Kudo 2009;McNamee et al 2010McNamee et al , 2013. In Table 1, we summarize the standard controls used in various animal models and their respective effects on disease.…”

Section: Treatment Controlsmentioning

confidence: 99%

Murine Models of Inflammatory Bowel Disease (IBD)

DeVoss¹,

Diehl²

2013

Toxicol Pathol

View full text Add to dashboard Cite

Animal models of human disease are a critical tool in both basic research and drug development. The results of preclinical efficacy studies often inform progression of therapeutic candidates through the drug development pipeline; however, the extent to which results in inflammatory bowel disease (IBD) models predict human drug response is an ongoing concern. This review discusses how murine models are currently being used in IBD research. We focus on the considerations and caveats for commonly used models in preclinical efficacy studies and discuss the value of models that utilize specific pathogenic pathways of interest rather than model all aspects of human disease.

show abstract

“…Consquently, a drug maybe effective in one, but ineffective in other model of intestinal inflammation depending on its mechanism of action (Park et al 2004). Moreover, although DSS-induced colitis is one of the most widely used IBD models, due to the convenient induction, defined onset of intestinal inflammation, and its relevance for the translation of animal data to human IBD (Melgar et al 2008), even the clinically widely used, effective drugs, such as olsalazine, budesonide or methotrexate have had variable positive effects in this model, depending on several factors (concentration of DSS and 19 duration of exposure, route of drug administration, genetic background of animals, etc.) (see e.g.…”

Section: Discussionmentioning

confidence: 99%

Analysing the effect of I1 imidazoline receptor ligands on DSS-induced acute colitis in mice

et al. 2016

View full text Add to dashboard Cite

Imidazoline receptors (IRs) have been recognized as promising targets in the treatment of numerous diseases, and moxonidine and rilmenidine, agonists of I1-IRs are widely used as antihypertensive agents. Some evidence suggests that IR ligands may induce anti-inflammatory effects acting on I1-IRs or other molecular targets, which could be beneficial in patients with inflammatory bowel disease (IBD). On the other hand, several IR ligands may stimulate also alpha2-adrenoceptors, which was earlier shown to inhibit, but in more recent studies to rather aggravate colitis. Hence, this study aimed to analyse for the first time the effect of various I1-IR ligands on intestinal inflammation. Colitis was induced in C57BL/6 mice by adding dextran sulfate sodium (DSS) to the drinking water for 7 days. Mice were treated daily with different IR ligands; moxonidine and rilmenidine (I1-IR agonists), AGN 192403 (highly selective I1-IR ligand, putative antagonist), efaroxan (I1-IR antagonist), as well as with the endogenous IR agonists agmatine and harmane. It was found that moxonidine and rilmenidine at clinically relevant doses, similarly to the other IR ligands, do not have a significant impact on the macroscopic and histological signs of DSS-evoked inflammation. Likewise, colonic myeloperoxidase and serum interleukin-6 levels remained unchanged in response to these agents. Thus, our study demonstrates that imidazoline ligands do not influence significantly the severity of DSS-colitis in mice and suggest that they probably neither affect the course of IBD in humans. However, the translational value of these findings needs to be verified with other experimental colitis models and human studies.

show abstract

Validation of murine dextran sulfate sodium-induced colitis using four therapeutic agents for human inflammatory bowel disease

Cited by 176 publications

References 37 publications

Crucial Role of FLVCR1a in the Maintenance of Intestinal Heme Homeostasis

Crucial Role of FLVCR1a in the Maintenance of Intestinal Heme Homeostasis

Murine Models of Inflammatory Bowel Disease (IBD)

Analysing the effect of I1 imidazoline receptor ligands on DSS-induced acute colitis in mice

Contact Info

Product

Resources

About