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Alpha-lipoic acid exerts a liver-protective effect in acute liver injury rats
Abstract Background Recent evidence indicates that alpha-lipoic acid (α-LA) has a variety of liver-protective effects through the suppression of inflammatory mediators including tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS). However, there are few reports that α-LA markedl...
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Published in: | The Journal of surgical research 2015-02, Vol.193 (2), p.675-683 |
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creator | Tanaka, Yoshito, MD Kaibori, Masaki, MD, PhD Miki, Hirokazu, MD Nakatake, Richi, MD Tokuhara, Katsuji, MD, PhD Nishizawa, Mikio, MD, PhD Okumura, Tadayoshi, PhD Kwon, A-Hon, MD, PhD |
description | Abstract Background Recent evidence indicates that alpha-lipoic acid (α-LA) has a variety of liver-protective effects through the suppression of inflammatory mediators including tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS). However, there are few reports that α-LA markedly enhanced the survival rate in animal models of liver injury with more than 90% death. The aim of this study was to investigate the beneficial effects of α-LA in a rat model of acute liver injury and to clarify the mechanisms of α-LA action. Methods Rats were treated with d -galactosamine and lipopolysaccharide (GalN and LPS) to induce acute liver injury. α-LA (100 mg/kg) was administered intraperitoneally 1 h before GalN and LPS injection. Inflammatory mediators including TNF-α and iNOS were analyzed. Results A single injection of α-LA improved the survival rate by more than 80%. α-LA prevented serum transaminase increases, histopathologic changes, and apoptosis in the liver. In the serum, α-LA decreased TNF-α production and increased interleukin (IL)-10 production. In the liver, α-LA reduced TNF-α and IL-6 messenger RNA (mRNA) but enhanced IL-10 mRNA. α-LA decreased the expression of iNOS mRNA and its antisense transcript, leading to the reduction of iNOS protein expression and resulting in the inhibition of nitric oxide production. An electrophoretic mobility shift assay revealed that α-LA reduced the activation of nuclear factor-kappa B induced by GalN and LPS. Conclusions α-LA inhibited the induction of inflammatory mediators, such as TNF-α and iNOS, in part through the inhibition of nuclear factor-kappa B activation and enhanced the induction of IL-10. α-LA may have therapeutic potential for use in the prevention of acute liver injury. |
doi_str_mv | 10.1016/j.jss.2014.08.057 |
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However, there are few reports that α-LA markedly enhanced the survival rate in animal models of liver injury with more than 90% death. The aim of this study was to investigate the beneficial effects of α-LA in a rat model of acute liver injury and to clarify the mechanisms of α-LA action. Methods Rats were treated with d -galactosamine and lipopolysaccharide (GalN and LPS) to induce acute liver injury. α-LA (100 mg/kg) was administered intraperitoneally 1 h before GalN and LPS injection. Inflammatory mediators including TNF-α and iNOS were analyzed. Results A single injection of α-LA improved the survival rate by more than 80%. α-LA prevented serum transaminase increases, histopathologic changes, and apoptosis in the liver. In the serum, α-LA decreased TNF-α production and increased interleukin (IL)-10 production. In the liver, α-LA reduced TNF-α and IL-6 messenger RNA (mRNA) but enhanced IL-10 mRNA. α-LA decreased the expression of iNOS mRNA and its antisense transcript, leading to the reduction of iNOS protein expression and resulting in the inhibition of nitric oxide production. An electrophoretic mobility shift assay revealed that α-LA reduced the activation of nuclear factor-kappa B induced by GalN and LPS. Conclusions α-LA inhibited the induction of inflammatory mediators, such as TNF-α and iNOS, in part through the inhibition of nuclear factor-kappa B activation and enhanced the induction of IL-10. α-LA may have therapeutic potential for use in the prevention of acute liver injury.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2014.08.057</identifier><identifier>PMID: 25266599</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acute liver injury ; Animals ; Antioxidants - pharmacology ; Antioxidants - therapeutic use ; Chemical and Drug Induced Liver Injury - prevention & control ; d-galactosamine and lipopolysaccharide ; Drug Evaluation, Preclinical ; Galactosamine ; Inducible nitric oxide synthase ; Interleukin-10 ; Interleukin-10 - metabolism ; Lipopolysaccharides ; Liver - drug effects ; Liver - metabolism ; Male ; NF-kappa B - metabolism ; Nitric Oxide - blood ; Nitric Oxide Synthase Type II - metabolism ; Nuclear factor-κB ; Rats, Sprague-Dawley ; Surgery ; Thioctic Acid - pharmacology ; Thioctic Acid - therapeutic use ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α</subject><ispartof>The Journal of surgical research, 2015-02, Vol.193 (2), p.675-683</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-4c4be40e8ee0597cedd84a2b748f22332efb3eb1e98e72b95addbd8edfb63f823</citedby><cites>FETCH-LOGICAL-c474t-4c4be40e8ee0597cedd84a2b748f22332efb3eb1e98e72b95addbd8edfb63f823</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25266599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tanaka, Yoshito, MD</creatorcontrib><creatorcontrib>Kaibori, Masaki, MD, PhD</creatorcontrib><creatorcontrib>Miki, Hirokazu, MD</creatorcontrib><creatorcontrib>Nakatake, Richi, MD</creatorcontrib><creatorcontrib>Tokuhara, Katsuji, MD, PhD</creatorcontrib><creatorcontrib>Nishizawa, Mikio, MD, PhD</creatorcontrib><creatorcontrib>Okumura, Tadayoshi, PhD</creatorcontrib><creatorcontrib>Kwon, A-Hon, MD, PhD</creatorcontrib><title>Alpha-lipoic acid exerts a liver-protective effect in acute liver injury rats</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Abstract Background Recent evidence indicates that alpha-lipoic acid (α-LA) has a variety of liver-protective effects through the suppression of inflammatory mediators including tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS). However, there are few reports that α-LA markedly enhanced the survival rate in animal models of liver injury with more than 90% death. The aim of this study was to investigate the beneficial effects of α-LA in a rat model of acute liver injury and to clarify the mechanisms of α-LA action. Methods Rats were treated with d -galactosamine and lipopolysaccharide (GalN and LPS) to induce acute liver injury. α-LA (100 mg/kg) was administered intraperitoneally 1 h before GalN and LPS injection. Inflammatory mediators including TNF-α and iNOS were analyzed. Results A single injection of α-LA improved the survival rate by more than 80%. α-LA prevented serum transaminase increases, histopathologic changes, and apoptosis in the liver. In the serum, α-LA decreased TNF-α production and increased interleukin (IL)-10 production. In the liver, α-LA reduced TNF-α and IL-6 messenger RNA (mRNA) but enhanced IL-10 mRNA. α-LA decreased the expression of iNOS mRNA and its antisense transcript, leading to the reduction of iNOS protein expression and resulting in the inhibition of nitric oxide production. An electrophoretic mobility shift assay revealed that α-LA reduced the activation of nuclear factor-kappa B induced by GalN and LPS. Conclusions α-LA inhibited the induction of inflammatory mediators, such as TNF-α and iNOS, in part through the inhibition of nuclear factor-kappa B activation and enhanced the induction of IL-10. α-LA may have therapeutic potential for use in the prevention of acute liver injury.</description><subject>Acute liver injury</subject><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Antioxidants - therapeutic use</subject><subject>Chemical and Drug Induced Liver Injury - prevention & control</subject><subject>d-galactosamine and lipopolysaccharide</subject><subject>Drug Evaluation, Preclinical</subject><subject>Galactosamine</subject><subject>Inducible nitric oxide synthase</subject><subject>Interleukin-10</subject><subject>Interleukin-10 - metabolism</subject><subject>Lipopolysaccharides</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>NF-kappa B - metabolism</subject><subject>Nitric Oxide - blood</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Nuclear factor-κB</subject><subject>Rats, Sprague-Dawley</subject><subject>Surgery</subject><subject>Thioctic Acid - pharmacology</subject><subject>Thioctic Acid - therapeutic use</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor necrosis factor-α</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9kU1P3DAQhq0KVJaPH8AF5cglYfyVOEJCQitakEAc2p4tx54Ih2yy2Ali_329WuDAgZNnpGdeeZ4h5JRCQYGWF13RxVgwoKIAVYCsfpAFhVrmqqz4HlkAMJYLBeKAHMbYQerriv8kB0yyspR1vSAP1_36yeS9X4_eZsZ6l-EbhilmJuv9K4Z8HcYJ7ZTqDNs2VZkfEjhPuANS281hkwUzxWOy35o-4sn7e0T-_br5u7zN7x9_3y2v73MrKjHlwooGBaBCBFlXFp1TwrCmEqpljHOGbcOxoVgrrFhTS-Nc4xS6til5qxg_Iue73PS5lxnjpFc-Wux7M-A4R01LXkkpawkJpTvUhjHGgK1eB78yYaMp6K1F3elkUW8talA6WUwzZ-_xc7NC9znxoS0BlzsA05KvHoOO1uOQFvEhGdJu9N_GX32Ztr0fvDX9M24wduMchmRPUx2ZBv1ne8btFakAUFQw_h-HE5iS</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Tanaka, Yoshito, MD</creator><creator>Kaibori, Masaki, MD, PhD</creator><creator>Miki, Hirokazu, MD</creator><creator>Nakatake, Richi, MD</creator><creator>Tokuhara, Katsuji, MD, PhD</creator><creator>Nishizawa, Mikio, MD, PhD</creator><creator>Okumura, Tadayoshi, PhD</creator><creator>Kwon, A-Hon, MD, PhD</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150201</creationdate><title>Alpha-lipoic acid exerts a liver-protective effect in acute liver injury rats</title><author>Tanaka, Yoshito, MD ; Kaibori, Masaki, MD, PhD ; Miki, Hirokazu, MD ; Nakatake, Richi, MD ; Tokuhara, Katsuji, MD, PhD ; Nishizawa, Mikio, MD, PhD ; Okumura, Tadayoshi, PhD ; Kwon, A-Hon, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-4c4be40e8ee0597cedd84a2b748f22332efb3eb1e98e72b95addbd8edfb63f823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acute liver injury</topic><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Antioxidants - therapeutic use</topic><topic>Chemical and Drug Induced Liver Injury - prevention & control</topic><topic>d-galactosamine and lipopolysaccharide</topic><topic>Drug Evaluation, Preclinical</topic><topic>Galactosamine</topic><topic>Inducible nitric oxide synthase</topic><topic>Interleukin-10</topic><topic>Interleukin-10 - metabolism</topic><topic>Lipopolysaccharides</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>NF-kappa B - metabolism</topic><topic>Nitric Oxide - blood</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Nuclear factor-κB</topic><topic>Rats, Sprague-Dawley</topic><topic>Surgery</topic><topic>Thioctic Acid - pharmacology</topic><topic>Thioctic Acid - therapeutic use</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tanaka, Yoshito, MD</creatorcontrib><creatorcontrib>Kaibori, Masaki, MD, PhD</creatorcontrib><creatorcontrib>Miki, Hirokazu, MD</creatorcontrib><creatorcontrib>Nakatake, Richi, MD</creatorcontrib><creatorcontrib>Tokuhara, Katsuji, MD, PhD</creatorcontrib><creatorcontrib>Nishizawa, Mikio, MD, PhD</creatorcontrib><creatorcontrib>Okumura, Tadayoshi, PhD</creatorcontrib><creatorcontrib>Kwon, A-Hon, MD, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tanaka, Yoshito, MD</au><au>Kaibori, Masaki, MD, PhD</au><au>Miki, Hirokazu, MD</au><au>Nakatake, Richi, MD</au><au>Tokuhara, Katsuji, MD, PhD</au><au>Nishizawa, Mikio, MD, PhD</au><au>Okumura, Tadayoshi, PhD</au><au>Kwon, A-Hon, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alpha-lipoic acid exerts a liver-protective effect in acute liver injury rats</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2015-02-01</date><risdate>2015</risdate><volume>193</volume><issue>2</issue><spage>675</spage><epage>683</epage><pages>675-683</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><abstract>Abstract Background Recent evidence indicates that alpha-lipoic acid (α-LA) has a variety of liver-protective effects through the suppression of inflammatory mediators including tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS). However, there are few reports that α-LA markedly enhanced the survival rate in animal models of liver injury with more than 90% death. The aim of this study was to investigate the beneficial effects of α-LA in a rat model of acute liver injury and to clarify the mechanisms of α-LA action. Methods Rats were treated with d -galactosamine and lipopolysaccharide (GalN and LPS) to induce acute liver injury. α-LA (100 mg/kg) was administered intraperitoneally 1 h before GalN and LPS injection. Inflammatory mediators including TNF-α and iNOS were analyzed. Results A single injection of α-LA improved the survival rate by more than 80%. α-LA prevented serum transaminase increases, histopathologic changes, and apoptosis in the liver. In the serum, α-LA decreased TNF-α production and increased interleukin (IL)-10 production. In the liver, α-LA reduced TNF-α and IL-6 messenger RNA (mRNA) but enhanced IL-10 mRNA. α-LA decreased the expression of iNOS mRNA and its antisense transcript, leading to the reduction of iNOS protein expression and resulting in the inhibition of nitric oxide production. An electrophoretic mobility shift assay revealed that α-LA reduced the activation of nuclear factor-kappa B induced by GalN and LPS. Conclusions α-LA inhibited the induction of inflammatory mediators, such as TNF-α and iNOS, in part through the inhibition of nuclear factor-kappa B activation and enhanced the induction of IL-10. α-LA may have therapeutic potential for use in the prevention of acute liver injury.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25266599</pmid><doi>10.1016/j.jss.2014.08.057</doi><tpages>9</tpages></addata></record> |
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subjects | Acute liver injury Animals Antioxidants - pharmacology Antioxidants - therapeutic use Chemical and Drug Induced Liver Injury - prevention & control d-galactosamine and lipopolysaccharide Drug Evaluation, Preclinical Galactosamine Inducible nitric oxide synthase Interleukin-10 Interleukin-10 - metabolism Lipopolysaccharides Liver - drug effects Liver - metabolism Male NF-kappa B - metabolism Nitric Oxide - blood Nitric Oxide Synthase Type II - metabolism Nuclear factor-κB Rats, Sprague-Dawley Surgery Thioctic Acid - pharmacology Thioctic Acid - therapeutic use Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α |
title | Alpha-lipoic acid exerts a liver-protective effect in acute liver injury rats |
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