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Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury

In this study, the potential hepatotoxicity of 1,3-dichloro-2-propanol and its hepatotoxic mechanisms in rats was investigated. The test chemical was administered orally to male rats at 0, 27.5, 55, and 110 mg/kg body weight. 1,3-Dichloro-2-propanol administration caused acute hepatotoxicity, as evi...

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Autores principales: Lee, In-Chul, Lee, Sang-Min, Ko, Je-Won, Park, Sung-Hyeuk, Shin, In-Sik, Moon, Changjong, Kim, Sung-Ho, Kim, Jong-Choon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Association for Laboratory Animal Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816994/
https://www.ncbi.nlm.nih.gov/pubmed/27051440
http://dx.doi.org/10.5625/lar.2016.32.1.24
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author Lee, In-Chul
Lee, Sang-Min
Ko, Je-Won
Park, Sung-Hyeuk
Shin, In-Sik
Moon, Changjong
Kim, Sung-Ho
Kim, Jong-Choon
author_facet Lee, In-Chul
Lee, Sang-Min
Ko, Je-Won
Park, Sung-Hyeuk
Shin, In-Sik
Moon, Changjong
Kim, Sung-Ho
Kim, Jong-Choon
author_sort Lee, In-Chul
collection PubMed
description In this study, the potential hepatotoxicity of 1,3-dichloro-2-propanol and its hepatotoxic mechanisms in rats was investigated. The test chemical was administered orally to male rats at 0, 27.5, 55, and 110 mg/kg body weight. 1,3-Dichloro-2-propanol administration caused acute hepatotoxicity, as evidenced by an increase in serum aminotransferases, total cholesterol, and total bilirubin levels and a decrease in serum glucose concentration in a dose-dependent manner with corresponding histopathological changes in the hepatic tissues. The significant increase in malondialdehyde content and the significant decrease in glutathione content and antioxidant enzyme activities indicated that 1,3-dichloro-2-propanol-induced hepatic damage was mediated through oxidative stress, which caused a dose-dependent increase of hepatocellular apoptotic changes in the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and immunohistochemical analysis for caspase-3. The phosphorylation of mitogen-activated protein kinases caused by 1,3-dichloro-2-propanol possibly involved in hepatocellular apoptotic changes in rat liver. Furthermore, 1,3-dichloro-2-propanol induced an inflammatory response through activation of nuclear factor-kappa B signaling that coincided with the induction of pro-inflammatory mediators or cytokines in a dose-dependent manner. Taken together, these results demonstrate that hepatotoxicity may be related to oxidative stress-mediated activation of mitogen-activated protein kinases and nuclear factor-kappa B-mediated inflammatory response.
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spelling pubmed-48169942016-04-05 Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury Lee, In-Chul Lee, Sang-Min Ko, Je-Won Park, Sung-Hyeuk Shin, In-Sik Moon, Changjong Kim, Sung-Ho Kim, Jong-Choon Lab Anim Res Original Article In this study, the potential hepatotoxicity of 1,3-dichloro-2-propanol and its hepatotoxic mechanisms in rats was investigated. The test chemical was administered orally to male rats at 0, 27.5, 55, and 110 mg/kg body weight. 1,3-Dichloro-2-propanol administration caused acute hepatotoxicity, as evidenced by an increase in serum aminotransferases, total cholesterol, and total bilirubin levels and a decrease in serum glucose concentration in a dose-dependent manner with corresponding histopathological changes in the hepatic tissues. The significant increase in malondialdehyde content and the significant decrease in glutathione content and antioxidant enzyme activities indicated that 1,3-dichloro-2-propanol-induced hepatic damage was mediated through oxidative stress, which caused a dose-dependent increase of hepatocellular apoptotic changes in the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and immunohistochemical analysis for caspase-3. The phosphorylation of mitogen-activated protein kinases caused by 1,3-dichloro-2-propanol possibly involved in hepatocellular apoptotic changes in rat liver. Furthermore, 1,3-dichloro-2-propanol induced an inflammatory response through activation of nuclear factor-kappa B signaling that coincided with the induction of pro-inflammatory mediators or cytokines in a dose-dependent manner. Taken together, these results demonstrate that hepatotoxicity may be related to oxidative stress-mediated activation of mitogen-activated protein kinases and nuclear factor-kappa B-mediated inflammatory response. Korean Association for Laboratory Animal Science 2016-03 2016-03-24 /pmc/articles/PMC4816994/ /pubmed/27051440 http://dx.doi.org/10.5625/lar.2016.32.1.24 Text en Copyright © 2016 Korean Association for Laboratory Animal Science http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lee, In-Chul
Lee, Sang-Min
Ko, Je-Won
Park, Sung-Hyeuk
Shin, In-Sik
Moon, Changjong
Kim, Sung-Ho
Kim, Jong-Choon
Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury
title Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury
title_full Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury
title_fullStr Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury
title_full_unstemmed Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury
title_short Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury
title_sort role of mitogen-activated protein kinases and nuclear factor-kappa b in 1,3-dichloro-2-propanol-induced hepatic injury
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816994/
https://www.ncbi.nlm.nih.gov/pubmed/27051440
http://dx.doi.org/10.5625/lar.2016.32.1.24
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