Research Article: Fluid supplementation accelerates epithelial repair during chemical colitis

Date Published: April 19, 2019

Publisher: Public Library of Science

Author(s): Juan F. Burgueño, Jessica K. Lang, Ana M. Santander, Irina Fernández, Ester Fernández, Julia Zaias, Maria T. Abreu, David L. Boone.

http://doi.org/10.1371/journal.pone.0215387

Abstract

The dextran sulfate sodium (DSS) model of colitis is a common animal model of inflammatory bowel disease that causes pain and distress. In this study, we aimed to determine whether fluid supplementation can be used as a welfare-based intervention to minimize animal suffering. C57Bl/6 females undergoing acute colitis by administration of 3% DSS in drinking water were supplemented with 1 mL intraperitoneal injections of NaCl and compared to non-supplemented control mice. Mouse behavior and locomotive activity were assessed on days 5–6 after DSS initiation by means of tail suspension, novel object recognition and open field activity tests. Mice were euthanized after either the acute (day 7) or the recovery phase (day 12) of colitis and inflammation, epithelial proliferation, and differentiation were assessed by means of histology, immunohistochemistry, quantitative PCR, and western blot. We found that fluid-supplemented mice had reduced signs of colitis with no alterations in behavior or locomotive activity. Furthermore, we observed an accelerated epithelial repair response after fluid hydration during the acute phase of colitis, characterized by increased crypt proliferation, activation of ERK1/2, and modulation of TGF-β1 expression. Consistent with these findings, fluid-supplemented mice had increased numbers of goblet cells, upregulated expression of differentiation markers for absorptive enterocytes, and reduced inflammation during the recovery phase. Our results show that fluid hydration does not reduce stress in DSS-treated mice but alters colitis evolution by reducing clinical signs and accelerating epithelial repair. These results argue against the routine use of fluid supplementation in DSS-treated mice.

Partial Text

Inflammatory bowel disease (IBD) refers to a group of pathologies of increasing incidence worldwide that affects more than 1.3 million patients in the United States [1, 2]. The most common forms of IBD, Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by chronic and relapsing inflammation of the gut. Although therapy has greatly improved, the pathogenesis of IBD is still not fully understood, making research in animal models necessary to generate mechanistic insights of these diseases. There are several animal models of IBD. Although none of them recapitulate all pathogenic and clinical features of IBD, they collectively contribute to strengthening our understanding of the processes driving gut inflammation [3, 4].

Supportive care interventions can be required by institutional committees to manage welfare-threatening conditions in several animal models of disease. In the chemical model of acute colitis induced by DSS, dehydration and weight loss can be addressed by fluid supplementation of mice. In this study, we demonstrate that IP fluid administration during moderate DSS colitis does not affect stress but leads to earlier recovery from epithelial injury. The improvement in epithelial healing is not associated with an appreciable change in inflammation, but with an increased proliferative response of the crypts that flank the ulcers. Subsequently, accelerated regeneration of the epithelium leads to earlier epithelial differentiation and resolution of erosions and ulcers. These findings have very serious practical implications for researchers to consider in experimental design, as well as for the IBD community.

 

Source:

http://doi.org/10.1371/journal.pone.0215387

 

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