Effects of two weeks of food restriction on toxicological parameters in cynomolgus monkeys

Animals frequently eat less after a test-article treatment in nonclinical toxicological studies, and it can be difficult to distinguish test article-derived toxicities from secondary changes related to this reduced food intake. Therefore, in this study, we restricted the food intake of cynomolgus mo...

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Bibliographic Details
Published in:Experimental Animals 2024, Vol.73(1), pp.73-82
Main Authors: Fujisawa, Nozomi, Matsushita, Tomochika, Matsuo, Saori, Hiranuma, Mayumi, Azabu, Hiroko, Saito, Ryota, Komatsu, Shun-Ichiro, Kato, Atsuhiko, Toyota, Naoto, Taketo, Junko, Suzuki, Hiromi
Format: Article
Language:English
Subjects:
Adipocytes
Animal species
Aspartate aminotransferase
Atrophy
Body weight
Bone marrow
Bones
cynomolgus monkeys
Dietary restrictions
EKG
Electrocardiography
Erythrocytes
Erythropoiesis
Food
Food availability
Food consumption
Food intake
food restriction
Granuloma
Granulomas
Haematology
Hematology
Histopathology
Inflammation
Malnutrition
Monkeys
Original
Parameters
Reticulocytes
Toxicity testing
toxicity tests
toxicological parameters
Triglycerides
Urinalysis
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Summary:Animals frequently eat less after a test-article treatment in nonclinical toxicological studies, and it can be difficult to distinguish test article-derived toxicities from secondary changes related to this reduced food intake. Therefore, in this study, we restricted the food intake of cynomolgus monkeys (Cambodian, male, n=2 or 3, 48 ± 3 months old) to 25% of the control for two weeks and evaluated the effects on toxicological parameters (general conditions, body weight, electrocardiography, urinalysis, hematology, blood chemistry, bone marrow analysis, pathological examination). After 2 weeks, the monkeys exhibited decreases in bone marrow erythropoiesis (e.g., decreases in reticulocytes and bone marrow erythrocytes), as well as glycogenesis induction (e.g., increase in aspartate aminotransferase (AST)) and malnutrition (e.g., decrease in triglyceride and systemic adipocytes atrophy). Additionally, histopathological analysis revealed granuloma and inflammatory cell infiltration in coronary fat, which had never been found in previous food restriction studies using other animal species. These findings will enable researchers to more accurately evaluate the toxicological risks of test articles that simultaneously induce food intake reduction.
ISSN:1341-1357
1881-7122
DOI:10.1538/expanim.23-0017