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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| Veröffentlicht in: | Experimental Animals 2024, Vol.73(1), pp.73-82 |
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| creator | Fujisawa, Nozomi Matsushita, Tomochika Matsuo, Saori Hiranuma, Mayumi Azabu, Hiroko Saito, Ryota Komatsu, Shun-Ichiro Kato, Atsuhiko Toyota, Naoto Taketo, Junko Suzuki, Hiromi |
| description | 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. |
| doi_str_mv | 10.1538/expanim.23-0017 |
| format | Article |
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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.</description><identifier>ISSN: 1341-1357</identifier><identifier>EISSN: 1881-7122</identifier><identifier>DOI: 10.1538/expanim.23-0017</identifier><identifier>PMID: 37648485</identifier><language>eng</language><publisher>Japan: Japanese Association for Laboratory Animal Science</publisher><subject>Adipocytes ; Animal species ; Animals ; Aspartate aminotransferase ; Atrophy ; Body Weight ; Bone marrow ; Bones ; cynomolgus monkeys ; Dietary restrictions ; Eating ; EKG ; Electrocardiography ; Erythrocytes ; Erythropoiesis ; Food ; Food availability ; Food consumption ; Food intake ; food restriction ; Granuloma ; Granulomas ; Haematology ; Hematology ; Histopathology ; Inflammation ; Macaca fascicularis ; Male ; Malnutrition ; Monkeys ; Original ; Parameters ; Reticulocytes ; Toxicity testing ; toxicity tests ; toxicological parameters ; Triglycerides ; Urinalysis</subject><ispartof>Experimental Animals, 2024, Vol.73(1), pp.73-82</ispartof><rights>2024 Japanese Association for Laboratory Animal Science</rights><rights>2024. This work is published under https://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Japanese Association for Laboratory Animal Science 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c590t-fc541c76e3bfd0593677ed1544575ad2b5f8d2f4357f8d69a7d82fc53e3ffd6c3</citedby><cites>FETCH-LOGICAL-c590t-fc541c76e3bfd0593677ed1544575ad2b5f8d2f4357f8d69a7d82fc53e3ffd6c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877149/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877149/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,1877,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37648485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujisawa, Nozomi</creatorcontrib><creatorcontrib>Matsushita, Tomochika</creatorcontrib><creatorcontrib>Matsuo, Saori</creatorcontrib><creatorcontrib>Hiranuma, Mayumi</creatorcontrib><creatorcontrib>Azabu, Hiroko</creatorcontrib><creatorcontrib>Saito, Ryota</creatorcontrib><creatorcontrib>Komatsu, Shun-Ichiro</creatorcontrib><creatorcontrib>Kato, Atsuhiko</creatorcontrib><creatorcontrib>Toyota, Naoto</creatorcontrib><creatorcontrib>Taketo, Junko</creatorcontrib><creatorcontrib>Suzuki, Hiromi</creatorcontrib><title>Effects of two weeks of food restriction on toxicological parameters in cynomolgus monkeys</title><title>Experimental Animals</title><addtitle>Exp Anim</addtitle><description>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.</description><subject>Adipocytes</subject><subject>Animal species</subject><subject>Animals</subject><subject>Aspartate aminotransferase</subject><subject>Atrophy</subject><subject>Body Weight</subject><subject>Bone marrow</subject><subject>Bones</subject><subject>cynomolgus monkeys</subject><subject>Dietary restrictions</subject><subject>Eating</subject><subject>EKG</subject><subject>Electrocardiography</subject><subject>Erythrocytes</subject><subject>Erythropoiesis</subject><subject>Food</subject><subject>Food availability</subject><subject>Food consumption</subject><subject>Food intake</subject><subject>food restriction</subject><subject>Granuloma</subject><subject>Granulomas</subject><subject>Haematology</subject><subject>Hematology</subject><subject>Histopathology</subject><subject>Inflammation</subject><subject>Macaca fascicularis</subject><subject>Male</subject><subject>Malnutrition</subject><subject>Monkeys</subject><subject>Original</subject><subject>Parameters</subject><subject>Reticulocytes</subject><subject>Toxicity testing</subject><subject>toxicity tests</subject><subject>toxicological parameters</subject><subject>Triglycerides</subject><subject>Urinalysis</subject><issn>1341-1357</issn><issn>1881-7122</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1vGyEQhlHVqknTnnurkHrehM9l91RVkZNUitRLc8kFYXZwcHbBBZzE_744dlethGDQPPMyw4vQZ0rOqeTdBbxsTPDTOeMNIVS9Qae062ijKGNva8wFbSiX6gR9yHlNCFOK9e_RCVet6EQnT9H9wjmwJePocHmO-Bng8fXiYhxwglySt8XHgOsq8cXbOMaVt2bEG5PMBAVSxj5guwtxiuNqm_EUwyPs8kf0zpkxw6fjeYburha_Lm-a25_XPy6_3zZW9qQ0zkpBrWqBL91AZM9bpWCgUgippBnYUrpuYE7UMWrQ9kYNHatFHLhzQ2v5Gfp20N1slxMMFkJJZtSb5CeTdjoar__PBP-gV_FJU9IpRUVfFb4eFVL8va0z63XcplCb1pxIoZjgSlbq4kDZFHNO4OYnKNF7N_TRDc243rtRK77829nM__3-CiwOwDoXs4IZMKl4O8IsqLim--0oPOftg0kaAv8DO-OjeA</recordid><startdate>2024</startdate><enddate>2024</enddate><creator>Fujisawa, Nozomi</creator><creator>Matsushita, Tomochika</creator><creator>Matsuo, Saori</creator><creator>Hiranuma, Mayumi</creator><creator>Azabu, Hiroko</creator><creator>Saito, Ryota</creator><creator>Komatsu, Shun-Ichiro</creator><creator>Kato, Atsuhiko</creator><creator>Toyota, Naoto</creator><creator>Taketo, Junko</creator><creator>Suzuki, Hiromi</creator><general>Japanese Association for Laboratory Animal Science</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>2024</creationdate><title>Effects of two weeks of food restriction on toxicological parameters in cynomolgus monkeys</title><author>Fujisawa, Nozomi ; Matsushita, Tomochika ; Matsuo, Saori ; Hiranuma, Mayumi ; Azabu, Hiroko ; Saito, Ryota ; Komatsu, Shun-Ichiro ; Kato, Atsuhiko ; Toyota, Naoto ; Taketo, Junko ; Suzuki, Hiromi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c590t-fc541c76e3bfd0593677ed1544575ad2b5f8d2f4357f8d69a7d82fc53e3ffd6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adipocytes</topic><topic>Animal species</topic><topic>Animals</topic><topic>Aspartate aminotransferase</topic><topic>Atrophy</topic><topic>Body Weight</topic><topic>Bone marrow</topic><topic>Bones</topic><topic>cynomolgus monkeys</topic><topic>Dietary restrictions</topic><topic>Eating</topic><topic>EKG</topic><topic>Electrocardiography</topic><topic>Erythrocytes</topic><topic>Erythropoiesis</topic><topic>Food</topic><topic>Food availability</topic><topic>Food consumption</topic><topic>Food intake</topic><topic>food restriction</topic><topic>Granuloma</topic><topic>Granulomas</topic><topic>Haematology</topic><topic>Hematology</topic><topic>Histopathology</topic><topic>Inflammation</topic><topic>Macaca fascicularis</topic><topic>Male</topic><topic>Malnutrition</topic><topic>Monkeys</topic><topic>Original</topic><topic>Parameters</topic><topic>Reticulocytes</topic><topic>Toxicity testing</topic><topic>toxicity tests</topic><topic>toxicological parameters</topic><topic>Triglycerides</topic><topic>Urinalysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujisawa, Nozomi</creatorcontrib><creatorcontrib>Matsushita, Tomochika</creatorcontrib><creatorcontrib>Matsuo, Saori</creatorcontrib><creatorcontrib>Hiranuma, Mayumi</creatorcontrib><creatorcontrib>Azabu, Hiroko</creatorcontrib><creatorcontrib>Saito, Ryota</creatorcontrib><creatorcontrib>Komatsu, Shun-Ichiro</creatorcontrib><creatorcontrib>Kato, Atsuhiko</creatorcontrib><creatorcontrib>Toyota, Naoto</creatorcontrib><creatorcontrib>Taketo, Junko</creatorcontrib><creatorcontrib>Suzuki, Hiromi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental Animals</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujisawa, Nozomi</au><au>Matsushita, Tomochika</au><au>Matsuo, Saori</au><au>Hiranuma, Mayumi</au><au>Azabu, Hiroko</au><au>Saito, Ryota</au><au>Komatsu, Shun-Ichiro</au><au>Kato, Atsuhiko</au><au>Toyota, Naoto</au><au>Taketo, Junko</au><au>Suzuki, Hiromi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of two weeks of food restriction on toxicological parameters in cynomolgus monkeys</atitle><jtitle>Experimental Animals</jtitle><addtitle>Exp Anim</addtitle><date>2024</date><risdate>2024</risdate><volume>73</volume><issue>1</issue><spage>73</spage><epage>82</epage><pages>73-82</pages><artnum>23-0017</artnum><issn>1341-1357</issn><eissn>1881-7122</eissn><abstract>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.</abstract><cop>Japan</cop><pub>Japanese Association for Laboratory Animal Science</pub><pmid>37648485</pmid><doi>10.1538/expanim.23-0017</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes Animal species Animals Aspartate aminotransferase Atrophy Body Weight Bone marrow Bones cynomolgus monkeys Dietary restrictions Eating EKG Electrocardiography Erythrocytes Erythropoiesis Food Food availability Food consumption Food intake food restriction Granuloma Granulomas Haematology Hematology Histopathology Inflammation Macaca fascicularis Male Malnutrition Monkeys Original Parameters Reticulocytes Toxicity testing toxicity tests toxicological parameters Triglycerides Urinalysis |
| title | Effects of two weeks of food restriction on toxicological parameters in cynomolgus monkeys |
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