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Multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture

A ketamine/xylazine (K/X) mixture is widely used before and during experiments in rodents. However, the impact of short-term use of K/X mixture and its influences on data interpretation have rarely been discussed. In this study, we administered one shot of a K/X mixture and examined acute hepatic re...

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Autores principales: Chen, Fang-Hsin, Yu, Ching-Fang, Yang, Chung-Lin, Lin, Yu-Chun, Lin, Gigin, Wang, Chun-Chieh, Yu, Huang-Ping, Fang, Jui, Chang, Ning-Fang, Hong, Ji-Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046666/
https://www.ncbi.nlm.nih.gov/pubmed/32108154
http://dx.doi.org/10.1038/s41598-020-60347-1
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author Chen, Fang-Hsin
Yu, Ching-Fang
Yang, Chung-Lin
Lin, Yu-Chun
Lin, Gigin
Wang, Chun-Chieh
Yu, Huang-Ping
Fang, Jui
Chang, Ning-Fang
Hong, Ji-Hong
author_facet Chen, Fang-Hsin
Yu, Ching-Fang
Yang, Chung-Lin
Lin, Yu-Chun
Lin, Gigin
Wang, Chun-Chieh
Yu, Huang-Ping
Fang, Jui
Chang, Ning-Fang
Hong, Ji-Hong
author_sort Chen, Fang-Hsin
collection PubMed
description A ketamine/xylazine (K/X) mixture is widely used before and during experiments in rodents. However, the impact of short-term use of K/X mixture and its influences on data interpretation have rarely been discussed. In this study, we administered one shot of a K/X mixture and examined acute hepatic responses using biochemical analysis, histopathological examination, and non-invasive imaging to determine the delay required prior to further assessment of the liver to avoid confounding effects triggered by anaesthesia. After the K/X injection, aspartate aminotransferase (AST) in serum was significantly elevated from 3 to 48 h. Obstructed sinusoidal circulation lasting for 24 or 36 h was revealed by DCE-MRI and drug distribution analysis, respectively. Metabolic alterations were detected at 3 h by NMR analysis and FDG-PET. Moreover, ultrasonography showed that lipid droplet accumulation increased from 1 to 16 h and declined thereafter. Taken together, our findings show that the K/X mixture induces acute hepatotoxicity and metabolic disturbance, and these disturbances cause hemodynamical disorders in the liver. The required time interval for recovery from K/X impact was dependent on the chosen assay. It took at least 16 h for metabolic recovery and 36 h for recovery of sinusoidal circulation. However, the liver was not fully recovered from the injury within 48 h.
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spelling pubmed-70466662020-03-04 Multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture Chen, Fang-Hsin Yu, Ching-Fang Yang, Chung-Lin Lin, Yu-Chun Lin, Gigin Wang, Chun-Chieh Yu, Huang-Ping Fang, Jui Chang, Ning-Fang Hong, Ji-Hong Sci Rep Article A ketamine/xylazine (K/X) mixture is widely used before and during experiments in rodents. However, the impact of short-term use of K/X mixture and its influences on data interpretation have rarely been discussed. In this study, we administered one shot of a K/X mixture and examined acute hepatic responses using biochemical analysis, histopathological examination, and non-invasive imaging to determine the delay required prior to further assessment of the liver to avoid confounding effects triggered by anaesthesia. After the K/X injection, aspartate aminotransferase (AST) in serum was significantly elevated from 3 to 48 h. Obstructed sinusoidal circulation lasting for 24 or 36 h was revealed by DCE-MRI and drug distribution analysis, respectively. Metabolic alterations were detected at 3 h by NMR analysis and FDG-PET. Moreover, ultrasonography showed that lipid droplet accumulation increased from 1 to 16 h and declined thereafter. Taken together, our findings show that the K/X mixture induces acute hepatotoxicity and metabolic disturbance, and these disturbances cause hemodynamical disorders in the liver. The required time interval for recovery from K/X impact was dependent on the chosen assay. It took at least 16 h for metabolic recovery and 36 h for recovery of sinusoidal circulation. However, the liver was not fully recovered from the injury within 48 h. Nature Publishing Group UK 2020-02-27 /pmc/articles/PMC7046666/ /pubmed/32108154 http://dx.doi.org/10.1038/s41598-020-60347-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Fang-Hsin
Yu, Ching-Fang
Yang, Chung-Lin
Lin, Yu-Chun
Lin, Gigin
Wang, Chun-Chieh
Yu, Huang-Ping
Fang, Jui
Chang, Ning-Fang
Hong, Ji-Hong
Multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture
title Multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture
title_full Multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture
title_fullStr Multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture
title_full_unstemmed Multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture
title_short Multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture
title_sort multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046666/
https://www.ncbi.nlm.nih.gov/pubmed/32108154
http://dx.doi.org/10.1038/s41598-020-60347-1
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