Cargando…

Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice

An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration...

Descripción completa

Detalles Bibliográficos
Autores principales: Jiang, Wen-Ping, Huang, Shyh-Shyun, Matsuda, Yoshikazu, Saito, Hiroshi, Uramaru, Naoto, Ho, Hui-Ya, Wu, Jin-Bin, Huang, Guan-Jhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154347/
https://www.ncbi.nlm.nih.gov/pubmed/28524081
http://dx.doi.org/10.3390/molecules22050830
_version_ 1783357679724396544
author Jiang, Wen-Ping
Huang, Shyh-Shyun
Matsuda, Yoshikazu
Saito, Hiroshi
Uramaru, Naoto
Ho, Hui-Ya
Wu, Jin-Bin
Huang, Guan-Jhong
author_facet Jiang, Wen-Ping
Huang, Shyh-Shyun
Matsuda, Yoshikazu
Saito, Hiroshi
Uramaru, Naoto
Ho, Hui-Ya
Wu, Jin-Bin
Huang, Guan-Jhong
author_sort Jiang, Wen-Ping
collection PubMed
description An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, TA attenuated the APAP-induced production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6. Furthermore, the Western blot analysis showed that TA blocked the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation in APAP-injured liver tissues. TA also retained the superoxidase dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the liver. These results suggest that the hepatoprotective effects of TA may be related to its anti-inflammatory effect by decreasing thiobarbituric acid reactive substances (TBARS), iNOS, COX-2, TNF-α, IL-1β, and IL-6, and inhibiting NF-κB and MAPK activation. Antioxidative properties were also observed, as shown by heme oxygenase-1 (HO-1) induction in the liver, and decreases in lipid peroxides and ROS. Therefore, TA may be a potential therapeutic candidate for the prevention of APAP-induced liver injury by inhibiting oxidative stress and inflammation.
format Online
Article
Text
id pubmed-6154347
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-61543472018-11-13 Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice Jiang, Wen-Ping Huang, Shyh-Shyun Matsuda, Yoshikazu Saito, Hiroshi Uramaru, Naoto Ho, Hui-Ya Wu, Jin-Bin Huang, Guan-Jhong Molecules Article An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, TA attenuated the APAP-induced production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6. Furthermore, the Western blot analysis showed that TA blocked the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation in APAP-injured liver tissues. TA also retained the superoxidase dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the liver. These results suggest that the hepatoprotective effects of TA may be related to its anti-inflammatory effect by decreasing thiobarbituric acid reactive substances (TBARS), iNOS, COX-2, TNF-α, IL-1β, and IL-6, and inhibiting NF-κB and MAPK activation. Antioxidative properties were also observed, as shown by heme oxygenase-1 (HO-1) induction in the liver, and decreases in lipid peroxides and ROS. Therefore, TA may be a potential therapeutic candidate for the prevention of APAP-induced liver injury by inhibiting oxidative stress and inflammation. MDPI 2017-05-18 /pmc/articles/PMC6154347/ /pubmed/28524081 http://dx.doi.org/10.3390/molecules22050830 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jiang, Wen-Ping
Huang, Shyh-Shyun
Matsuda, Yoshikazu
Saito, Hiroshi
Uramaru, Naoto
Ho, Hui-Ya
Wu, Jin-Bin
Huang, Guan-Jhong
Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice
title Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice
title_full Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice
title_fullStr Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice
title_full_unstemmed Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice
title_short Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice
title_sort protective effects of tormentic acid, a major component of suspension cultures of eriobotrya japonica cells, on acetaminophen-induced hepatotoxicity in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154347/
https://www.ncbi.nlm.nih.gov/pubmed/28524081
http://dx.doi.org/10.3390/molecules22050830
work_keys_str_mv AT jiangwenping protectiveeffectsoftormenticacidamajorcomponentofsuspensionculturesoferiobotryajaponicacellsonacetaminopheninducedhepatotoxicityinmice
AT huangshyhshyun protectiveeffectsoftormenticacidamajorcomponentofsuspensionculturesoferiobotryajaponicacellsonacetaminopheninducedhepatotoxicityinmice
AT matsudayoshikazu protectiveeffectsoftormenticacidamajorcomponentofsuspensionculturesoferiobotryajaponicacellsonacetaminopheninducedhepatotoxicityinmice
AT saitohiroshi protectiveeffectsoftormenticacidamajorcomponentofsuspensionculturesoferiobotryajaponicacellsonacetaminopheninducedhepatotoxicityinmice
AT uramarunaoto protectiveeffectsoftormenticacidamajorcomponentofsuspensionculturesoferiobotryajaponicacellsonacetaminopheninducedhepatotoxicityinmice
AT hohuiya protectiveeffectsoftormenticacidamajorcomponentofsuspensionculturesoferiobotryajaponicacellsonacetaminopheninducedhepatotoxicityinmice
AT wujinbin protectiveeffectsoftormenticacidamajorcomponentofsuspensionculturesoferiobotryajaponicacellsonacetaminopheninducedhepatotoxicityinmice
AT huangguanjhong protectiveeffectsoftormenticacidamajorcomponentofsuspensionculturesoferiobotryajaponicacellsonacetaminopheninducedhepatotoxicityinmice