Abstract
The cynomolgus monkey (Macaca fascicularis) is a well-known non-human primate species commonly used in non-clinical research. It is important to know basal clinical pathology parameters in order to have a reference for evaluating any potential treatment-induced effects, maintaining health status among animals and, if needed, evaluating correct substantiative therapies. In this study, data from 238 untreated cynomolgus monkeys (119 males and 119 females of juvenile age, 2.5 to 3.5 years) kept under laboratory conditions were used to build up a reference database of clinical pathology parameters. Twenty-two hematology markers, 24 clinical chemistry markers and two blood coagulation parameters were analyzed. Gender-related differences were evaluated using statistical analyses. To assess the possible effects of stress induced by housing or handling involved in treatment procedures, 78 animals (35 males and 35 females out of 238 juvenile monkeys and four adult males and four adult females) were used to evaluate cortisol, corticosterone and behavioral assessment over time. Data were analyzed using a non-parametric statistical test and machine learning approaches. Reference clinical pathology data obtained from untreated animals may be extremely useful for investigators employing cynomolgus monkeys as a test system for non-clinical safety studies.
Highlights
Non-human Primates (NHP) are the closest phylogenic relatives to man which makes them a suitable and sometimes indispensable model in many fields of biomedical research [1,2,3,4]
The study was aimed at establishing an internal database of physiological and biological parameters of baseline cynomolgus monkey (Macaca fascicularis), a well-known non-human primate species commonly used in non-clinical research
We focused our analysis on two cohorts of Macaca fascicularis in order to to identify parameters indicating experimental conditions that can cause stress in animals
Summary
Non-human Primates (NHP) are the closest phylogenic relatives to man which makes them a suitable and sometimes indispensable model in many fields of biomedical research [1,2,3,4]. The use of animals in biomedical research is limited to pre-screening tests, initial drug development phases, or when there is the supplementary aim of giving indications of the species to use in PLOS ONE | DOI:10.1371/journal.pone.0157003. Issues may be raised regarding their management and the ethics of their use, over and above the intrinsic issues of testing on other animal species [13,14,15]. Baseline biological databases are important to evaluate the health status of animals prior to their use for scientific purposes and to manage diagnosis as well as to improve therapies and experimental techniques [7, 8]
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