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Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources
Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081583/ https://www.ncbi.nlm.nih.gov/pubmed/32257904 http://dx.doi.org/10.1186/s42826-019-0017-x |
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author | Jeong, Tae Bin Kim, Joung-Hee Kim, Sou Hyun Lee, Seunghyun Son, Seung Won Lim, Yong Cho, Joon-Yong Hwang, Dae Youn Kim, Kil Soo Kwak, Jae-Hwan Jung, Young-Suk |
author_facet | Jeong, Tae Bin Kim, Joung-Hee Kim, Sou Hyun Lee, Seunghyun Son, Seung Won Lim, Yong Cho, Joon-Yong Hwang, Dae Youn Kim, Kil Soo Kwak, Jae-Hwan Jung, Young-Suk |
author_sort | Jeong, Tae Bin |
collection | PubMed |
description | Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochrome P450–mediated oxidation. However, APAP overdose results in production of excess reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by cytochromes P450; NAPQI overwhelms the level of glutathione (GSH), which could otherwise detoxify it. NAPQI binds covalently to proteins, leading to cell death. A number of studies aimed at the prevention and treatment of APAP-induced toxicity are underway. Rats are more resistant than mice to APAP hepatotoxicity, and thus mouse models are mainly used. In the present study, we compared the toxic responses induced by APAP overdose in the liver of ICR mice obtained from three different sources and evaluated the usability of the Korl:ICR stock established by the National Institute of Food and Drug Safety Evaluation in Korea. Administration of APAP (300 mg/kg) by intraperitoneal injection into male ICR mice enhanced CYP2E1 protein expression and depleted hepatic GSH level 2 h after treatment accompanied with significantly increased level of hepatic malondialdehyde, a product of lipid peroxidation. Regardless of the source of the mice, hepatotoxicity, as evidenced by activity of serum alanine aminotransferase, increased from 8 h and peaked at 24 h after APAP treatment. In summary, hepatotoxicity was induced after the onset of oxidative stress by overdose of APAP, and the response was the same over time among mice of different origins. |
format | Online Article Text |
id | pubmed-7081583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-70815832020-04-01 Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources Jeong, Tae Bin Kim, Joung-Hee Kim, Sou Hyun Lee, Seunghyun Son, Seung Won Lim, Yong Cho, Joon-Yong Hwang, Dae Youn Kim, Kil Soo Kwak, Jae-Hwan Jung, Young-Suk Lab Anim Res Research Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochrome P450–mediated oxidation. However, APAP overdose results in production of excess reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by cytochromes P450; NAPQI overwhelms the level of glutathione (GSH), which could otherwise detoxify it. NAPQI binds covalently to proteins, leading to cell death. A number of studies aimed at the prevention and treatment of APAP-induced toxicity are underway. Rats are more resistant than mice to APAP hepatotoxicity, and thus mouse models are mainly used. In the present study, we compared the toxic responses induced by APAP overdose in the liver of ICR mice obtained from three different sources and evaluated the usability of the Korl:ICR stock established by the National Institute of Food and Drug Safety Evaluation in Korea. Administration of APAP (300 mg/kg) by intraperitoneal injection into male ICR mice enhanced CYP2E1 protein expression and depleted hepatic GSH level 2 h after treatment accompanied with significantly increased level of hepatic malondialdehyde, a product of lipid peroxidation. Regardless of the source of the mice, hepatotoxicity, as evidenced by activity of serum alanine aminotransferase, increased from 8 h and peaked at 24 h after APAP treatment. In summary, hepatotoxicity was induced after the onset of oxidative stress by overdose of APAP, and the response was the same over time among mice of different origins. BioMed Central 2019-09-03 /pmc/articles/PMC7081583/ /pubmed/32257904 http://dx.doi.org/10.1186/s42826-019-0017-x Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Jeong, Tae Bin Kim, Joung-Hee Kim, Sou Hyun Lee, Seunghyun Son, Seung Won Lim, Yong Cho, Joon-Yong Hwang, Dae Youn Kim, Kil Soo Kwak, Jae-Hwan Jung, Young-Suk Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources |
title | Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources |
title_full | Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources |
title_fullStr | Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources |
title_full_unstemmed | Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources |
title_short | Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources |
title_sort | comparison of toxic responses to acetaminophen challenge in icr mice originating from different sources |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081583/ https://www.ncbi.nlm.nih.gov/pubmed/32257904 http://dx.doi.org/10.1186/s42826-019-0017-x |
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