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Open Access Effects of Azithromycin on Behavior, Pathologic Signs, and Changes in Cytokines, Chemokines, and Neutrophil Migration in C57BL/6 Mice Exposed to Dextran Sulfate Sodium

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Here we characterized the murine dextran sulfate sodium (DSS) model of acute colitis. Specifically, we evaluated azithromycin and metronidazole treatment regimens to assess their effects on animal wellbeing, pathologic changes, barrier function, cytokine and chemokine profiles, and neutrophil migration in colon tissue. Azithromycin treatment significantly reduced the severity of colitis, as assessed through body weight change, water consumption, macroscopic lesions, and animal behaviors (activity level, climbing, and grooming), but did not alter food consumption or feeding behavior. Mucosal barrier function (evaluated by using FITC-labeled dextran) was decreased after DSS exposure; azithromycin did not significantly alter barrier function in mice with colitis, whereas metronidazole exacerbated the colitis-related deficit in barrier function. In addition, metronidazole appeared to exacerbate disease as assessed through water consumption and animal behaviors (overall activity, climbing, grooming, and drinking) but had no effect on weight loss, macroscopic lesions, or eating behavior. Pathologic changes were typical for DSS treatment. Antibiotic treatment resulted in reduced levels of proinflammatory cytokines and chemokines and decreased neutrophil adhesion and emigration in DSS-exposed mice. The results highlight the importance of clinical and behavioral assessments in addition to laboratory evaluation as tools to evaluate animal welfare and therapeutic efficacy in disease models. Data from this study suggest that azithromycin may convey some benefits in the mouse DSS colitis model through modulation of the immune response, including neutrophil migration into tissues, whereas metronidazole may exacerbate colitis.

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Document Type: Miscellaneous

Affiliations: 1: Animal Health Unit, Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada 2: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada 3: Department of Biology, University of British Columbia, Okanagan, Kelowna, British Columbia, Canada 4: Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada 5: Animal Health Unit, University of Calgary, Calgary, Alberta, Canada 6: Department of Microbiology, Immunology, and Infectious Diseases, Department of Physiology and Pharmacology, Mouse Phenomics Resource Laboratory, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada 7: Animal Health Unit, Department of Biological Sciences, University of Calgary, Calgary, Alberta, Department of Biology, University of British Columbia, Okanagan, Kelowna, British Columbia, Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Alberta, Canada;, Email: [email protected]

Publication date: February 1, 2019

This article was made available online on December 13, 2018 as a Fast Track article with title: "Effects of Azithromycin on Behavior, Pathologic Signs, and Changes in Cytokines, Chemokines, and Neutrophil Migration in C57BL/6 Mice Exposed to Dextran Sulfate Sodium".

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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