Animal models of chemically induced intestinal inflammation: Predictivity and ethical issues

Dothel, Giovanni; Vasina, Valentina; Barbara, Giovanni; Ponti, Fabrizio De

doi:10.1016/j.pharmthera.2013.04.005

Cited by 46 publications

(40 citation statements)

References 126 publications

(146 reference statements)

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“…Although animal models have their limitations and do not reproduce all the pathogenic and clinical features of human IBD, each animal model provided an invaluable tool to study complex physiological and biochemical disease aspects that are difficult to address in humans (Elson et al 1995;Dothel et al 2013;Grisham 1993). The Winnie mice used in our study develop inflammation in the colon with multiple similarities to human ulcerative colitis, including goblet cell pathology, depleted mucus layer, and distal gradient of colitis as well as a characteristic immune profile Heazlewood et al 2008;Lourenssen et al 2005;McGuckin et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Alterations in the distal colon innervation in Winnie mouse model of spontaneous chronic colitis

et al. 2015

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The gastrointestinal tract is innervated by extrinsic sympathetic, parasympathetic and sensory nerve fibers as well as by intrinsic fibers from the neurons in myenteric and submucosal ganglia embedded into the gastrointestinal wall. Morphological and functional studies of intestinal innervation in animal models are important for understanding the pathophysiology of inflammatory bowel disease (IBD). The recently established Winnie mouse model of spontaneous chronic colitis caused by a point mutation in the Muc2 mucin gene develops inflammation due to a primary epithelial defect. Winnie mice display symptoms of diarrhea, ulcerations and rectal bleeding similar to those in IBD. In this study, we investigated myenteric neurons, noradrenergic, cholinergic and sensory nerve fibers in the distal colon of Winnie (Win/Win) mice compared to C57/BL6 and heterozygote littermates (Win/Wt) using histological and immunohistochemical methods. All Win/Win mice used in this study had inflammation with signs of mucosal damage, goblet cell loss, thickening of muscle and mucosal layers, and increased CD45-immunoreactivity in the distal colon. The density of sensory, cholinergic and noradrenergic fibers innervating the myenteric plexus, muscle and mucosa significantly decreased in the distal colon of Win/Win mice compared to C57/BL6 and Win/Wt mice, while the total number of myenteric neurons as well as subpopulations of cholinergic and nitrergic neurons remained unchanged. In conclusion, changes in the colon morphology and innervation found in Winnie mice have multiple similarities with changes observed in patients with ulcerative colitis.

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Section: Discussionmentioning

confidence: 99%

Alterations in the distal colon innervation in Winnie mouse model of spontaneous chronic colitis

et al. 2015

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“…The recent debate about ethical issues of animal use in preclinical research has pointed out some key points to ameliorate the prediction capability of these studies, such as the application of clinical procedures into preclinical studies (Dothel, Vasina, Barbara, & De Ponti, 2013). Radiological analysis complies with this principle and, according to the concept of minimization of animal use, may represent a valid tool for future studies.…”

Section: Discussionmentioning

confidence: 99%

Radiological analysis of gastrointestinal dysmotility in a model of central nervous dopaminergic degeneration: Comparative study with conventional in vivo techniques in the rat

Vegezzi

Harraq

Levandis

et al. 2014

Journal of Pharmacological and Toxicological Methods

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“…Experimental colitis could be induced by many techniques include chemically induced colitis, bacterial-induced colitis, and genetically induced colitis. Transgenic (Tg) and gene knockout (KO) strains have been developed as genetically-induced models [240,241]. The most common chemical-induced models are dextran sodium sulfate (DSS) model [242][243][244][245], oxazolone model, TNBS model [246][247][248][249], and acetic acid model [250,251].…”

Section: Biopharmaceutical Aspectsmentioning

confidence: 99%

Colon Drug Delivery Systems for the Treatment of Inflammatory Bowel Disease.

Qelliny

Aly

Khaled

2019

Journal of advanced Biomedical and Pharmaceutical Sciences

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Inflammatory bowel disease (IBD) is one of the most common chronic diseases that affect the entire gastrointestinal tract (GIT) especially the colon. Its symptoms extend from mild diarrhea, abdominal pain, and bloody diarrhea to severe conditions which affect the quality of life. Many treatments have been developed to treat and cure IBD and to improve patient's quality of life. The big challenge faces the newly developed treatments is the site of action as the colon presents at the distal end of the GIT and have a complex biological environment. Many technologies have been investigated to target the colon, load higher amounts of active ingredients, and decrease unwanted side effects resulted from upper GIT absorption. This review briefly discusses the IBD, treatment lines, physiological considerations, and all methods of colon targeting technologies starting from the traditional methods which based on pH, time, and microbial content of the colon. Also, we discussed in detail all new techniques based on Micro and Nanotechnology which improve the effectiveness of used therapeutics.

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Animal models of chemically induced intestinal inflammation: Predictivity and ethical issues

Cited by 46 publications

References 126 publications

Alterations in the distal colon innervation in Winnie mouse model of spontaneous chronic colitis

Alterations in the distal colon innervation in Winnie mouse model of spontaneous chronic colitis

Radiological analysis of gastrointestinal dysmotility in a model of central nervous dopaminergic degeneration: Comparative study with conventional in vivo techniques in the rat

Colon Drug Delivery Systems for the Treatment of Inflammatory Bowel Disease.

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