Metabolism-dependent hepatotoxicity of amodiaquine in glutathione-depleted mice
We investigated the hepatotoxicity induced by AQ using a glutathione (GSH)-depleted mice model. Although sole administration of either AQ or l -buthionine- S , R -sulfoxinine (BSO), a well-known GSH synthesis inhibitor, produced no significant hepatotoxicity, combined administration of AQ with BSO i...
Gespeichert in:
| Veröffentlicht in: | Archives of toxicology 2009-07, Vol.83 (7), p.701-707 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 707 |
|---|---|
| container_issue | 7 |
| container_start_page | 701 |
| container_title | Archives of toxicology |
| container_volume | 83 |
| creator | Shimizu, Shinji Atsumi, Ryo Itokawa, Kenichi Iwasaki, Masaru Aoki, Takanori Ono, Chiho Izumi, Takashi Sudo, Kenichi Okazaki, Osamu |
| description | We investigated the hepatotoxicity induced by AQ using a glutathione (GSH)-depleted mice model. Although sole administration of either AQ or
l
-buthionine-
S
,
R
-sulfoxinine (BSO), a well-known GSH synthesis inhibitor, produced no significant hepatotoxicity, combined administration of AQ with BSO induced hepatotoxicity characterized by centrilobular necrosis of the hepatocytes and an elevation of plasma alanine aminotransferase activity. Pretreatment of aminobenzotriazole, a nonspecific inhibitor for P450s, completely suppressed the above hepatotoxicity caused by AQ co-treatment with BSO. Administration of radiolabeled AQ in combination with BSO exhibited significantly higher covalent binding to mice liver proteins than that observed after sole dosing of radiolabeled AQ. The results obtained in this GSH-depleted animal model suggest that the reactive metabolite of AQ formed by hepatic P450 binds to liver proteins, and then finally leads to hepatotoxicity. These observations may help to understand the risk factors and the mechanism for idiosyncratic hepatotoxicity of AQ in humans. |
| doi_str_mv | 10.1007/s00204-009-0436-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_21341277</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>21341277</sourcerecordid><originalsourceid>FETCH-LOGICAL-c430t-6684ad0004b728d0b316008ae6609a97e9c68b666c642568945068c0778a49613</originalsourceid><addsrcrecordid>eNp1kMtqHDEQRUVwiMeTfIA3pjHEOyWlx-ixDCaxAw7eJGuhVtfYMt3SuKWG-O-jYYYYAlnVos69VRxCzhl8YgD6cwHgICmApSCFovYNWTEpOAUtzAlZgZBAN1qxU3JWyhMA48aKd-SUWaktl7Ai9z-w-j6PsUx0wB2mAVPtHnHna675dwyxvnR52_kpD9E_LzFhF1P3MC7V18eYE-5jI1YcuikGfE_ebv1Y8MNxrsmvb19_Xt_Su_ub79df7miQAipVykg_AIDsNTcD9IIpAONRKbDearRBmV4pFZTkG2Ws3IAyAbQ2XlrFxJpcHXp3c35esFQ3xRJwHH3CvBTHmZCMa93Ay3_Ap7zMqf3mOLdNFFeiQewAhTmXMuPW7eY4-fnFMXB71e6g2jXVbq_a2Za5OBYv_YTDa-LotgEfj4AvwY_b2acQy1-OM821bGVrwg9caav0gPPrh_-__geBxJRY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>229073263</pqid></control><display><type>article</type><title>Metabolism-dependent hepatotoxicity of amodiaquine in glutathione-depleted mice</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Shimizu, Shinji ; Atsumi, Ryo ; Itokawa, Kenichi ; Iwasaki, Masaru ; Aoki, Takanori ; Ono, Chiho ; Izumi, Takashi ; Sudo, Kenichi ; Okazaki, Osamu</creator><creatorcontrib>Shimizu, Shinji ; Atsumi, Ryo ; Itokawa, Kenichi ; Iwasaki, Masaru ; Aoki, Takanori ; Ono, Chiho ; Izumi, Takashi ; Sudo, Kenichi ; Okazaki, Osamu</creatorcontrib><description>We investigated the hepatotoxicity induced by AQ using a glutathione (GSH)-depleted mice model. Although sole administration of either AQ or
l
-buthionine-
S
,
R
-sulfoxinine (BSO), a well-known GSH synthesis inhibitor, produced no significant hepatotoxicity, combined administration of AQ with BSO induced hepatotoxicity characterized by centrilobular necrosis of the hepatocytes and an elevation of plasma alanine aminotransferase activity. Pretreatment of aminobenzotriazole, a nonspecific inhibitor for P450s, completely suppressed the above hepatotoxicity caused by AQ co-treatment with BSO. Administration of radiolabeled AQ in combination with BSO exhibited significantly higher covalent binding to mice liver proteins than that observed after sole dosing of radiolabeled AQ. The results obtained in this GSH-depleted animal model suggest that the reactive metabolite of AQ formed by hepatic P450 binds to liver proteins, and then finally leads to hepatotoxicity. These observations may help to understand the risk factors and the mechanism for idiosyncratic hepatotoxicity of AQ in humans.</description><identifier>ISSN: 0340-5761</identifier><identifier>EISSN: 1432-0738</identifier><identifier>DOI: 10.1007/s00204-009-0436-9</identifier><identifier>PMID: 19479240</identifier><identifier>CODEN: ARTODN</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Alanine Transaminase - blood ; Amodiaquine - pharmacology ; Animals ; Antimalarials - pharmacology ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Buthionine Sulfoximine - pharmacology ; Chemical and Drug Induced Liver Injury - etiology ; Chemical and Drug Induced Liver Injury - metabolism ; Disease Models, Animal ; Drug Interactions ; Environmental Health ; Enzyme Inhibitors - pharmacology ; Glutathione - antagonists & inhibitors ; Glutathione - deficiency ; Lethal Dose 50 ; Liver ; Liver Diseases - pathology ; Male ; Medical sciences ; Metabolism ; Mice ; Mice, Inbred BALB C ; Models, Biological ; Occupational Medicine/Industrial Medicine ; Organ Toxicity and Mechanisms ; Pharmacology ; Pharmacology/Toxicology ; Prescription drugs ; Risk factors ; Toxicity ; Toxicology</subject><ispartof>Archives of toxicology, 2009-07, Vol.83 (7), p.701-707</ispartof><rights>Springer-Verlag 2009</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-6684ad0004b728d0b316008ae6609a97e9c68b666c642568945068c0778a49613</citedby><cites>FETCH-LOGICAL-c430t-6684ad0004b728d0b316008ae6609a97e9c68b666c642568945068c0778a49613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00204-009-0436-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00204-009-0436-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21727404$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19479240$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimizu, Shinji</creatorcontrib><creatorcontrib>Atsumi, Ryo</creatorcontrib><creatorcontrib>Itokawa, Kenichi</creatorcontrib><creatorcontrib>Iwasaki, Masaru</creatorcontrib><creatorcontrib>Aoki, Takanori</creatorcontrib><creatorcontrib>Ono, Chiho</creatorcontrib><creatorcontrib>Izumi, Takashi</creatorcontrib><creatorcontrib>Sudo, Kenichi</creatorcontrib><creatorcontrib>Okazaki, Osamu</creatorcontrib><title>Metabolism-dependent hepatotoxicity of amodiaquine in glutathione-depleted mice</title><title>Archives of toxicology</title><addtitle>Arch Toxicol</addtitle><addtitle>Arch Toxicol</addtitle><description>We investigated the hepatotoxicity induced by AQ using a glutathione (GSH)-depleted mice model. Although sole administration of either AQ or
l
-buthionine-
S
,
R
-sulfoxinine (BSO), a well-known GSH synthesis inhibitor, produced no significant hepatotoxicity, combined administration of AQ with BSO induced hepatotoxicity characterized by centrilobular necrosis of the hepatocytes and an elevation of plasma alanine aminotransferase activity. Pretreatment of aminobenzotriazole, a nonspecific inhibitor for P450s, completely suppressed the above hepatotoxicity caused by AQ co-treatment with BSO. Administration of radiolabeled AQ in combination with BSO exhibited significantly higher covalent binding to mice liver proteins than that observed after sole dosing of radiolabeled AQ. The results obtained in this GSH-depleted animal model suggest that the reactive metabolite of AQ formed by hepatic P450 binds to liver proteins, and then finally leads to hepatotoxicity. These observations may help to understand the risk factors and the mechanism for idiosyncratic hepatotoxicity of AQ in humans.</description><subject>Alanine Transaminase - blood</subject><subject>Amodiaquine - pharmacology</subject><subject>Animals</subject><subject>Antimalarials - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Buthionine Sulfoximine - pharmacology</subject><subject>Chemical and Drug Induced Liver Injury - etiology</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Disease Models, Animal</subject><subject>Drug Interactions</subject><subject>Environmental Health</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Glutathione - antagonists & inhibitors</subject><subject>Glutathione - deficiency</subject><subject>Lethal Dose 50</subject><subject>Liver</subject><subject>Liver Diseases - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Models, Biological</subject><subject>Occupational Medicine/Industrial Medicine</subject><subject>Organ Toxicity and Mechanisms</subject><subject>Pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Prescription drugs</subject><subject>Risk factors</subject><subject>Toxicity</subject><subject>Toxicology</subject><issn>0340-5761</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kMtqHDEQRUVwiMeTfIA3pjHEOyWlx-ixDCaxAw7eJGuhVtfYMt3SuKWG-O-jYYYYAlnVos69VRxCzhl8YgD6cwHgICmApSCFovYNWTEpOAUtzAlZgZBAN1qxU3JWyhMA48aKd-SUWaktl7Ai9z-w-j6PsUx0wB2mAVPtHnHna675dwyxvnR52_kpD9E_LzFhF1P3MC7V18eYE-5jI1YcuikGfE_ebv1Y8MNxrsmvb19_Xt_Su_ub79df7miQAipVykg_AIDsNTcD9IIpAONRKbDearRBmV4pFZTkG2Ws3IAyAbQ2XlrFxJpcHXp3c35esFQ3xRJwHH3CvBTHmZCMa93Ay3_Ap7zMqf3mOLdNFFeiQewAhTmXMuPW7eY4-fnFMXB71e6g2jXVbq_a2Za5OBYv_YTDa-LotgEfj4AvwY_b2acQy1-OM821bGVrwg9caav0gPPrh_-__geBxJRY</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Shimizu, Shinji</creator><creator>Atsumi, Ryo</creator><creator>Itokawa, Kenichi</creator><creator>Iwasaki, Masaru</creator><creator>Aoki, Takanori</creator><creator>Ono, Chiho</creator><creator>Izumi, Takashi</creator><creator>Sudo, Kenichi</creator><creator>Okazaki, Osamu</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><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>3V.</scope><scope>7T2</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope></search><sort><creationdate>20090701</creationdate><title>Metabolism-dependent hepatotoxicity of amodiaquine in glutathione-depleted mice</title><author>Shimizu, Shinji ; Atsumi, Ryo ; Itokawa, Kenichi ; Iwasaki, Masaru ; Aoki, Takanori ; Ono, Chiho ; Izumi, Takashi ; Sudo, Kenichi ; Okazaki, Osamu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-6684ad0004b728d0b316008ae6609a97e9c68b666c642568945068c0778a49613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alanine Transaminase - blood</topic><topic>Amodiaquine - pharmacology</topic><topic>Animals</topic><topic>Antimalarials - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Buthionine Sulfoximine - pharmacology</topic><topic>Chemical and Drug Induced Liver Injury - etiology</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Disease Models, Animal</topic><topic>Drug Interactions</topic><topic>Environmental Health</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Glutathione - antagonists & inhibitors</topic><topic>Glutathione - deficiency</topic><topic>Lethal Dose 50</topic><topic>Liver</topic><topic>Liver Diseases - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Models, Biological</topic><topic>Occupational Medicine/Industrial Medicine</topic><topic>Organ Toxicity and Mechanisms</topic><topic>Pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Prescription drugs</topic><topic>Risk factors</topic><topic>Toxicity</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shimizu, Shinji</creatorcontrib><creatorcontrib>Atsumi, Ryo</creatorcontrib><creatorcontrib>Itokawa, Kenichi</creatorcontrib><creatorcontrib>Iwasaki, Masaru</creatorcontrib><creatorcontrib>Aoki, Takanori</creatorcontrib><creatorcontrib>Ono, Chiho</creatorcontrib><creatorcontrib>Izumi, Takashi</creatorcontrib><creatorcontrib>Sudo, Kenichi</creatorcontrib><creatorcontrib>Okazaki, Osamu</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Research Library (Corporate)</collection><collection>Environmental Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><jtitle>Archives of toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shimizu, Shinji</au><au>Atsumi, Ryo</au><au>Itokawa, Kenichi</au><au>Iwasaki, Masaru</au><au>Aoki, Takanori</au><au>Ono, Chiho</au><au>Izumi, Takashi</au><au>Sudo, Kenichi</au><au>Okazaki, Osamu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolism-dependent hepatotoxicity of amodiaquine in glutathione-depleted mice</atitle><jtitle>Archives of toxicology</jtitle><stitle>Arch Toxicol</stitle><addtitle>Arch Toxicol</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>83</volume><issue>7</issue><spage>701</spage><epage>707</epage><pages>701-707</pages><issn>0340-5761</issn><eissn>1432-0738</eissn><coden>ARTODN</coden><abstract>We investigated the hepatotoxicity induced by AQ using a glutathione (GSH)-depleted mice model. Although sole administration of either AQ or
l
-buthionine-
S
,
R
-sulfoxinine (BSO), a well-known GSH synthesis inhibitor, produced no significant hepatotoxicity, combined administration of AQ with BSO induced hepatotoxicity characterized by centrilobular necrosis of the hepatocytes and an elevation of plasma alanine aminotransferase activity. Pretreatment of aminobenzotriazole, a nonspecific inhibitor for P450s, completely suppressed the above hepatotoxicity caused by AQ co-treatment with BSO. Administration of radiolabeled AQ in combination with BSO exhibited significantly higher covalent binding to mice liver proteins than that observed after sole dosing of radiolabeled AQ. The results obtained in this GSH-depleted animal model suggest that the reactive metabolite of AQ formed by hepatic P450 binds to liver proteins, and then finally leads to hepatotoxicity. These observations may help to understand the risk factors and the mechanism for idiosyncratic hepatotoxicity of AQ in humans.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>19479240</pmid><doi>10.1007/s00204-009-0436-9</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-5761 |
| ispartof | Archives of toxicology, 2009-07, Vol.83 (7), p.701-707 |
| issn | 0340-5761 1432-0738 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_21341277 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Alanine Transaminase - blood Amodiaquine - pharmacology Animals Antimalarials - pharmacology Biological and medical sciences Biomedical and Life Sciences Biomedicine Buthionine Sulfoximine - pharmacology Chemical and Drug Induced Liver Injury - etiology Chemical and Drug Induced Liver Injury - metabolism Disease Models, Animal Drug Interactions Environmental Health Enzyme Inhibitors - pharmacology Glutathione - antagonists & inhibitors Glutathione - deficiency Lethal Dose 50 Liver Liver Diseases - pathology Male Medical sciences Metabolism Mice Mice, Inbred BALB C Models, Biological Occupational Medicine/Industrial Medicine Organ Toxicity and Mechanisms Pharmacology Pharmacology/Toxicology Prescription drugs Risk factors Toxicity Toxicology |
| title | Metabolism-dependent hepatotoxicity of amodiaquine in glutathione-depleted mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T03%3A26%3A36IST&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=Metabolism-dependent%20hepatotoxicity%20of%20amodiaquine%20in%20glutathione-depleted%20mice&rft.jtitle=Archives%20of%20toxicology&rft.au=Shimizu,%20Shinji&rft.date=2009-07-01&rft.volume=83&rft.issue=7&rft.spage=701&rft.epage=707&rft.pages=701-707&rft.issn=0340-5761&rft.eissn=1432-0738&rft.coden=ARTODN&rft_id=info:doi/10.1007/s00204-009-0436-9&rft_dat=%3Cproquest_cross%3E21341277%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=229073263&rft_id=info:pmid/19479240&rfr_iscdi=true |