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Ann N Y Acad Sci. 2020 Mar 24. doi: 10.1111/nyas.14338. [Epub ahead of print]

Grading animal distress and side effects of therapies.

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Rudolf-Zenker Institute of Experimental Surgery, University Medical Center, Rostock, Germany.
Institute for Laboratory Animal Science, Hannover Medical School, Hanover, Germany.
Unit of Physiology, Pathophysiology and Experimental Endocrinology, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.


In order to combine high-quality research with minimal harm to animals, a prospective severity assessment for animal experiments is legally required in many countries. In addition, an assessment of the evidence-based severity level might allow realistic harm-benefit analysis and the appraisal of refinement methods. However, only a few examples describe the distress of animals by simple, cost-efficient, and noninvasive methods. We, therefore, evaluated the severity of an orthotopic mouse model for pancreatic cancer using C57BL/6J mice when pursuing two different chemotherapies. We assessed fecal corticosterone metabolites, body weight, distress score, and burrowing, as well as nesting activity. Moreover, we established a multifactorial model using multivariate logistic regression to describe animal distress. This multifactorial analysis revealed that metformin + galloflavin treatment caused higher distress than metformin + α-cyano-4-hydroxycinnamate therapy. Similar results were obtained by using the best cutoff calculated by Youden's J index when using only single parameters, such as burrowing activity or fecal corticosterone metabolite concentration. Thus, the present study revealed that single readout parameters, as well as multivariate analysis, can help to assess the severity of animal experiments and detect side effects of therapies.


chemotherapy; distress analysis; pancreatic cancer; severity assessment


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