Grading animal distress and side effects of therapies.
Animals
Antineoplastic Agents
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Corticosterone
/ blood
Disease Models, Animal
Laparotomy
/ adverse effects
Male
Mice
Mice, Inbred C57BL
Pancreatic Neoplasms
/ blood
Psychological Distress
Xenograft Model Antitumor Assays
/ methods
chemotherapy
distress analysis
pancreatic cancer
severity assessment
Journal
Annals of the New York Academy of Sciences
ISSN: 1749-6632
Titre abrégé: Ann N Y Acad Sci
Pays: United States
ID NLM: 7506858
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
15
11
2019
revised:
30
01
2020
accepted:
05
03
2020
pubmed:
25
3
2020
medline:
15
12
2020
entrez:
25
3
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Antineoplastic Agents
0
Corticosterone
W980KJ009P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20-34Informations de copyright
© 2020 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC. on behalf of New York Academy of Sciences.
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