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.
Highlights
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]
To determine the utility of fluid supplementation in managing the clinical signs of colitis and improving overall condition and welfare, mice receiving IP fluid injection during acute dextran sulfate sodium (DSS)-induced colitis were compared to non-supplemented control mice
The body condition of mice was normal throughout the entire experiment and we did not see any significant increases in total plasma protein in either the fluid-supplemented or non-supplemented mice (S1D Fig), suggesting that moderate colitis does not induce overt dehydration
Summary
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]. When administered at 2–5% concentration in drinking water for 5–7 days, the 40 kDa form of DSS causes inflammation in the mid-distal colon that is characterized by mononuclear infiltration of the mucosa, edema, and crypt destruction with formation of erosions and ulcers [7, 8]. This model is simple, rapid, and can be used in genetically modified mice to interrogate the participation of specific proteins in the onset of inflammation
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