Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses
The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppr...
Gespeichert in:
Veröffentlicht in: | Anti-cancer drugs 2016-01, Vol.27 (1), p.17-23 |
---|---|
Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 23 |
---|---|
container_issue | 1 |
container_start_page | 17 |
container_title | Anti-cancer drugs |
container_volume | 27 |
creator | Nagai, Katsuhito Fukuno, Shuhei Oda, Ayano Konishi, Hiroki |
description | The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment. Elevations in the serum activity levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase by DOX were also dose-dependently attenuated by a concurrent treatment with taurine. Superoxide dismutase activity and reduced glutathione content in the liver were decreased following the administration of DOX, whereas these changes were suppressed when 10 mg/kg taurine was given in combination with DOX. Taurine attenuated the increased expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the formation of cleaved caspase-3 protein in the group given DOX with taurine was lower than that in the group treated with DOX alone. Our results suggest that taurine can protect against DOX-induced acute hepatic damage, the underlying mechanism of which is attributable to the suppression of oxidative stress and apoptotic responses. |
doi_str_mv | 10.1097/CAD.0000000000000299 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1762369759</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1762369759</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4559-ccc5efbd8a3ba34cf27f315de7284db774551f73d93a8392bc87579a81466a433</originalsourceid><addsrcrecordid>eNp9kc1O3DAUha2qqAy0b1AhL7vJEMdOHC9H0x-QRoIFrCPHvm5cMnHqnzI8Am-N6QBCLPDG1rnfOZZ9EPpKyiUpBT9dr74vy9erEuIDWhDGaVFzRj6iRSlqUTDB6SE6CuFPZrJOP6HDqmFVUxOxQPeX3kVQ0f4DDMbkU8DO4CiTtxNgN2Htds6n3io7FXbSSYHGUqUIeIBZRhfdLs_iHY6Dd-n3gEOaZw8h2GzOUXms5f_8EB9lLKccMLs5W63CWZrdFCB8RgdGjgG-PO3H6Prnj6v1WbG5-HW-Xm0Kxer8HKVUDabXraS9pEyZihtKag28apnuOc8UMZxqQWVLRdWrltdcyJawppGM0mP0bZ87e_c3QYjd1gYF4ygncCl0hDcVbQSvRUbZHlXeheDBdLO3W-nvOlJ2jyV0uYTubQnZdvJ0Q-q3oF9Mz7-egXYP3Loxgg83Y7oF3w0gxzi8n_0Az-qXXw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1762369759</pqid></control><display><type>article</type><title>Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Nagai, Katsuhito ; Fukuno, Shuhei ; Oda, Ayano ; Konishi, Hiroki</creator><creatorcontrib>Nagai, Katsuhito ; Fukuno, Shuhei ; Oda, Ayano ; Konishi, Hiroki</creatorcontrib><description>The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment. Elevations in the serum activity levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase by DOX were also dose-dependently attenuated by a concurrent treatment with taurine. Superoxide dismutase activity and reduced glutathione content in the liver were decreased following the administration of DOX, whereas these changes were suppressed when 10 mg/kg taurine was given in combination with DOX. Taurine attenuated the increased expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the formation of cleaved caspase-3 protein in the group given DOX with taurine was lower than that in the group treated with DOX alone. Our results suggest that taurine can protect against DOX-induced acute hepatic damage, the underlying mechanism of which is attributable to the suppression of oxidative stress and apoptotic responses.</description><identifier>ISSN: 0959-4973</identifier><identifier>EISSN: 1473-5741</identifier><identifier>DOI: 10.1097/CAD.0000000000000299</identifier><identifier>PMID: 26426519</identifier><language>eng</language><publisher>England: Copyright Wolters Kluwer Health, Inc. All rights reserved</publisher><subject>Alanine Transaminase - metabolism ; Animals ; Antibiotics, Antineoplastic - toxicity ; Apoptosis - drug effects ; Aspartate Aminotransferases - metabolism ; Chemical and Drug Induced Liver Injury - metabolism ; Chemical and Drug Induced Liver Injury - pathology ; Chemical and Drug Induced Liver Injury - prevention & control ; Doxorubicin - toxicity ; Glutathione - metabolism ; L-Lactate Dehydrogenase - metabolism ; Male ; Mice ; Oxidative Stress - drug effects ; Superoxide Dismutase - metabolism ; Taurine - therapeutic use</subject><ispartof>Anti-cancer drugs, 2016-01, Vol.27 (1), p.17-23</ispartof><rights>Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4559-ccc5efbd8a3ba34cf27f315de7284db774551f73d93a8392bc87579a81466a433</citedby><cites>FETCH-LOGICAL-c4559-ccc5efbd8a3ba34cf27f315de7284db774551f73d93a8392bc87579a81466a433</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/26426519$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nagai, Katsuhito</creatorcontrib><creatorcontrib>Fukuno, Shuhei</creatorcontrib><creatorcontrib>Oda, Ayano</creatorcontrib><creatorcontrib>Konishi, Hiroki</creatorcontrib><title>Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses</title><title>Anti-cancer drugs</title><addtitle>Anticancer Drugs</addtitle><description>The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment. Elevations in the serum activity levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase by DOX were also dose-dependently attenuated by a concurrent treatment with taurine. Superoxide dismutase activity and reduced glutathione content in the liver were decreased following the administration of DOX, whereas these changes were suppressed when 10 mg/kg taurine was given in combination with DOX. Taurine attenuated the increased expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the formation of cleaved caspase-3 protein in the group given DOX with taurine was lower than that in the group treated with DOX alone. Our results suggest that taurine can protect against DOX-induced acute hepatic damage, the underlying mechanism of which is attributable to the suppression of oxidative stress and apoptotic responses.</description><subject>Alanine Transaminase - metabolism</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - toxicity</subject><subject>Apoptosis - drug effects</subject><subject>Aspartate Aminotransferases - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - pathology</subject><subject>Chemical and Drug Induced Liver Injury - prevention & control</subject><subject>Doxorubicin - toxicity</subject><subject>Glutathione - metabolism</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Oxidative Stress - drug effects</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Taurine - therapeutic use</subject><issn>0959-4973</issn><issn>1473-5741</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1O3DAUha2qqAy0b1AhL7vJEMdOHC9H0x-QRoIFrCPHvm5cMnHqnzI8Am-N6QBCLPDG1rnfOZZ9EPpKyiUpBT9dr74vy9erEuIDWhDGaVFzRj6iRSlqUTDB6SE6CuFPZrJOP6HDqmFVUxOxQPeX3kVQ0f4DDMbkU8DO4CiTtxNgN2Htds6n3io7FXbSSYHGUqUIeIBZRhfdLs_iHY6Dd-n3gEOaZw8h2GzOUXms5f_8EB9lLKccMLs5W63CWZrdFCB8RgdGjgG-PO3H6Prnj6v1WbG5-HW-Xm0Kxer8HKVUDabXraS9pEyZihtKag28apnuOc8UMZxqQWVLRdWrltdcyJawppGM0mP0bZ87e_c3QYjd1gYF4ygncCl0hDcVbQSvRUbZHlXeheDBdLO3W-nvOlJ2jyV0uYTubQnZdvJ0Q-q3oF9Mz7-egXYP3Loxgg83Y7oF3w0gxzi8n_0Az-qXXw</recordid><startdate>201601</startdate><enddate>201601</enddate><creator>Nagai, Katsuhito</creator><creator>Fukuno, Shuhei</creator><creator>Oda, Ayano</creator><creator>Konishi, Hiroki</creator><general>Copyright Wolters Kluwer Health, Inc. All rights reserved</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>7TO</scope><scope>H94</scope></search><sort><creationdate>201601</creationdate><title>Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses</title><author>Nagai, Katsuhito ; Fukuno, Shuhei ; Oda, Ayano ; Konishi, Hiroki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4559-ccc5efbd8a3ba34cf27f315de7284db774551f73d93a8392bc87579a81466a433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alanine Transaminase - metabolism</topic><topic>Animals</topic><topic>Antibiotics, Antineoplastic - toxicity</topic><topic>Apoptosis - drug effects</topic><topic>Aspartate Aminotransferases - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Chemical and Drug Induced Liver Injury - prevention & control</topic><topic>Doxorubicin - toxicity</topic><topic>Glutathione - metabolism</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Oxidative Stress - drug effects</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Taurine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nagai, Katsuhito</creatorcontrib><creatorcontrib>Fukuno, Shuhei</creatorcontrib><creatorcontrib>Oda, Ayano</creatorcontrib><creatorcontrib>Konishi, Hiroki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Anti-cancer drugs</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagai, Katsuhito</au><au>Fukuno, Shuhei</au><au>Oda, Ayano</au><au>Konishi, Hiroki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses</atitle><jtitle>Anti-cancer drugs</jtitle><addtitle>Anticancer Drugs</addtitle><date>2016-01</date><risdate>2016</risdate><volume>27</volume><issue>1</issue><spage>17</spage><epage>23</epage><pages>17-23</pages><issn>0959-4973</issn><eissn>1473-5741</eissn><abstract>The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment. Elevations in the serum activity levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase by DOX were also dose-dependently attenuated by a concurrent treatment with taurine. Superoxide dismutase activity and reduced glutathione content in the liver were decreased following the administration of DOX, whereas these changes were suppressed when 10 mg/kg taurine was given in combination with DOX. Taurine attenuated the increased expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the formation of cleaved caspase-3 protein in the group given DOX with taurine was lower than that in the group treated with DOX alone. Our results suggest that taurine can protect against DOX-induced acute hepatic damage, the underlying mechanism of which is attributable to the suppression of oxidative stress and apoptotic responses.</abstract><cop>England</cop><pub>Copyright Wolters Kluwer Health, Inc. All rights reserved</pub><pmid>26426519</pmid><doi>10.1097/CAD.0000000000000299</doi><tpages>7</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0959-4973 |
ispartof | Anti-cancer drugs, 2016-01, Vol.27 (1), p.17-23 |
issn | 0959-4973 1473-5741 |
language | eng |
recordid | cdi_proquest_miscellaneous_1762369759 |
source | MEDLINE; Journals@Ovid Complete |
subjects | Alanine Transaminase - metabolism Animals Antibiotics, Antineoplastic - toxicity Apoptosis - drug effects Aspartate Aminotransferases - metabolism Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury - pathology Chemical and Drug Induced Liver Injury - prevention & control Doxorubicin - toxicity Glutathione - metabolism L-Lactate Dehydrogenase - metabolism Male Mice Oxidative Stress - drug effects Superoxide Dismutase - metabolism Taurine - therapeutic use |
title | Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T17%3A56%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Protective%20effects%20of%20taurine%20on%20doxorubicin-induced%20acute%20hepatotoxicity%20through%20suppression%20of%20oxidative%20stress%20and%20apoptotic%20responses&rft.jtitle=Anti-cancer%20drugs&rft.au=Nagai,%20Katsuhito&rft.date=2016-01&rft.volume=27&rft.issue=1&rft.spage=17&rft.epage=23&rft.pages=17-23&rft.issn=0959-4973&rft.eissn=1473-5741&rft_id=info:doi/10.1097/CAD.0000000000000299&rft_dat=%3Cproquest_cross%3E1762369759%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1762369759&rft_id=info:pmid/26426519&rfr_iscdi=true |