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Common Handling Procedures Conducted in Preclinical Safety Studies Result in Minimal Hepatic Gene Expression Changes in Sprague-Dawley Rats

Gene expression profiling is a tool to gain mechanistic understanding of adverse effects in response to compound exposure. However, little is known about how the common handling procedures of experimental animals during a preclinical study alter baseline gene expression. We report gene expression ch...

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Autores principales: He, Yudong D., Karbowski, Christine M., Werner, Jon, Everds, Nancy, Di Palma, Chris, Chen, Yuan, Higgins-Garn, Marnie, Tran, Sandra, Afshari, Cynthia A., Hamadeh, Hisham K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925150/
https://www.ncbi.nlm.nih.gov/pubmed/24551150
http://dx.doi.org/10.1371/journal.pone.0088750
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author He, Yudong D.
Karbowski, Christine M.
Werner, Jon
Everds, Nancy
Di Palma, Chris
Chen, Yuan
Higgins-Garn, Marnie
Tran, Sandra
Afshari, Cynthia A.
Hamadeh, Hisham K.
author_facet He, Yudong D.
Karbowski, Christine M.
Werner, Jon
Everds, Nancy
Di Palma, Chris
Chen, Yuan
Higgins-Garn, Marnie
Tran, Sandra
Afshari, Cynthia A.
Hamadeh, Hisham K.
author_sort He, Yudong D.
collection PubMed
description Gene expression profiling is a tool to gain mechanistic understanding of adverse effects in response to compound exposure. However, little is known about how the common handling procedures of experimental animals during a preclinical study alter baseline gene expression. We report gene expression changes in the livers of female Sprague-Dawley rats following common handling procedures. Baseline gene expression changes identified in this study provide insight on how these changes may affect interpretation of gene expression profiles following compound exposure. Rats were divided into three groups. One group was not subjected to handling procedures and served as controls for both handled groups. Animals in the other two groups were weighed, subjected to restraint in Broome restrainers, and administered water via oral gavage daily for 1 or 4 days with tail vein blood collections at 1, 2, 4, and 8 hours postdose on days 1 and 4. Significantly altered genes were identified in livers of animals following 1 or 4 days of handling when compared to the unhandled animals. Gene changes in animals handled for 4 days were similar to those handled for 1 day, suggesting a lack of habituation. The altered genes were primarily immune function related genes. These findings, along with a correlating increase in corticosterone levels suggest that common handling procedures may cause a minor immune system perturbance.
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spelling pubmed-39251502014-02-18 Common Handling Procedures Conducted in Preclinical Safety Studies Result in Minimal Hepatic Gene Expression Changes in Sprague-Dawley Rats He, Yudong D. Karbowski, Christine M. Werner, Jon Everds, Nancy Di Palma, Chris Chen, Yuan Higgins-Garn, Marnie Tran, Sandra Afshari, Cynthia A. Hamadeh, Hisham K. PLoS One Research Article Gene expression profiling is a tool to gain mechanistic understanding of adverse effects in response to compound exposure. However, little is known about how the common handling procedures of experimental animals during a preclinical study alter baseline gene expression. We report gene expression changes in the livers of female Sprague-Dawley rats following common handling procedures. Baseline gene expression changes identified in this study provide insight on how these changes may affect interpretation of gene expression profiles following compound exposure. Rats were divided into three groups. One group was not subjected to handling procedures and served as controls for both handled groups. Animals in the other two groups were weighed, subjected to restraint in Broome restrainers, and administered water via oral gavage daily for 1 or 4 days with tail vein blood collections at 1, 2, 4, and 8 hours postdose on days 1 and 4. Significantly altered genes were identified in livers of animals following 1 or 4 days of handling when compared to the unhandled animals. Gene changes in animals handled for 4 days were similar to those handled for 1 day, suggesting a lack of habituation. The altered genes were primarily immune function related genes. These findings, along with a correlating increase in corticosterone levels suggest that common handling procedures may cause a minor immune system perturbance. Public Library of Science 2014-02-14 /pmc/articles/PMC3925150/ /pubmed/24551150 http://dx.doi.org/10.1371/journal.pone.0088750 Text en © 2014 Karbowski et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
He, Yudong D.
Karbowski, Christine M.
Werner, Jon
Everds, Nancy
Di Palma, Chris
Chen, Yuan
Higgins-Garn, Marnie
Tran, Sandra
Afshari, Cynthia A.
Hamadeh, Hisham K.
Common Handling Procedures Conducted in Preclinical Safety Studies Result in Minimal Hepatic Gene Expression Changes in Sprague-Dawley Rats
title Common Handling Procedures Conducted in Preclinical Safety Studies Result in Minimal Hepatic Gene Expression Changes in Sprague-Dawley Rats
title_full Common Handling Procedures Conducted in Preclinical Safety Studies Result in Minimal Hepatic Gene Expression Changes in Sprague-Dawley Rats
title_fullStr Common Handling Procedures Conducted in Preclinical Safety Studies Result in Minimal Hepatic Gene Expression Changes in Sprague-Dawley Rats
title_full_unstemmed Common Handling Procedures Conducted in Preclinical Safety Studies Result in Minimal Hepatic Gene Expression Changes in Sprague-Dawley Rats
title_short Common Handling Procedures Conducted in Preclinical Safety Studies Result in Minimal Hepatic Gene Expression Changes in Sprague-Dawley Rats
title_sort common handling procedures conducted in preclinical safety studies result in minimal hepatic gene expression changes in sprague-dawley rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925150/
https://www.ncbi.nlm.nih.gov/pubmed/24551150
http://dx.doi.org/10.1371/journal.pone.0088750
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