Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice
Identifieur interne : 000505 ( Istex/Corpus ); précédent : 000504; suivant : 000506Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice
Auteurs : Ako Koreeda ; Kosei Yonemitsu ; Hiroe Kohmatsu ; Sohtaro Mimasaka ; Yuki Ohtsu ; Toru Oshima ; Kunio Fujiwara ; Shigeyuki TsunenariSource :
- Archives of Toxicology [ 0340-5761 ] ; 2007-07-01.
English descriptors
Abstract
Abstract: Chloroquine (CQ) distribution in tissues of acutely poisoned mice was demonstrated by immunohistochemistry using anti-CQ polyclonal antibodies (PAC). PAC recognized 4-amino-7-chloro-quinoline structure and sufficiently reacted with CQ and CQ’s metabolite bisdesethyl-chloroquine. In the brain, CQ and its metabolites (CQs) localized in the region of the choroids plexus, indicating an important role in the blood–cerebrospinal barrier system. In the heart, most regions showed diffused positive staining, and relatively strong reaction was observed in Purkinje cells, indicating an important role in acute CQ toxicity. In the lungs, CQs were observed in the bronchial epithelium, type II pneumocytes, and on the surface of alveolar walls. It was suggested that CQs were excreted to the alveolar wall with surfactant phospholipids, which are produced by type II pneumocytes. In the liver, CQs were concentrated in the centrolobular area rather than in the periportal area, in agreement with CQ’s metabolic pathway. In the kidneys, tubular cells were strongly stained compared to glomerular capsules, and the distal part of renal tubules was better stained than the proximal tubules. These findings suggested that CQs were predominantly excreted or reabsorbed through the distal tubules and the collecting duct. Distribution of CQs in tissues presented here were mostly consistent with the physico-chemical properties of CQ and its metabolites. However, the elucidation of CQs’ localization in Purkinje cells remains open. Further experimental studies at the level of microorganella will be needed to clarify the present result.
Url:
DOI: 10.1007/s00204-007-0185-6
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ISTEX:EE52F37270A267B0901F773B0775159B62EB97E2Le document en format XML
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Kumamoto, Japan</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: ako@kumamoto-u.ac.jp</mods:affiliation></affiliation></author><author><name sortKey="Yonemitsu, Kosei" sort="Yonemitsu, Kosei" uniqKey="Yonemitsu K" first="Kosei" last="Yonemitsu">Kosei Yonemitsu</name><affiliation><mods:affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kohmatsu, Hiroe" sort="Kohmatsu, Hiroe" uniqKey="Kohmatsu H" first="Hiroe" last="Kohmatsu">Hiroe Kohmatsu</name><affiliation><mods:affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mimasaka, Sohtaro" sort="Mimasaka, Sohtaro" uniqKey="Mimasaka S" first="Sohtaro" last="Mimasaka">Sohtaro Mimasaka</name><affiliation><mods:affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</mods:affiliation></affiliation></author><author><name sortKey="Ohtsu, Yuki" sort="Ohtsu, Yuki" uniqKey="Ohtsu Y" first="Yuki" last="Ohtsu">Yuki Ohtsu</name><affiliation><mods:affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</mods:affiliation></affiliation></author><author><name sortKey="Oshima, Toru" sort="Oshima, Toru" uniqKey="Oshima T" first="Toru" last="Oshima">Toru Oshima</name><affiliation><mods:affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</mods:affiliation></affiliation></author><author><name sortKey="Fujiwara, Kunio" sort="Fujiwara, Kunio" uniqKey="Fujiwara K" first="Kunio" last="Fujiwara">Kunio Fujiwara</name><affiliation><mods:affiliation>Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, 4-22-1 Ikeda, 860-0082, Kumamoto, Japan</mods:affiliation></affiliation></author><author><name sortKey="Tsunenari, Shigeyuki" sort="Tsunenari, Shigeyuki" uniqKey="Tsunenari S" first="Shigeyuki" last="Tsunenari">Shigeyuki Tsunenari</name><affiliation><mods:affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Archives of Toxicology</title><title level="j" type="abbrev">Arch Toxicol</title><idno type="ISSN">0340-5761</idno><idno type="eISSN">1432-0738</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2007-07-01">2007-07-01</date><biblScope unit="volume">81</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="471">471</biblScope><biblScope unit="page" to="478">478</biblScope></imprint><idno type="ISSN">0340-5761</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0340-5761</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acute toxicity</term><term>Chloroquine</term><term>Immunohistochemistry</term><term>Mice</term><term>Tissue distribution</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Chloroquine (CQ) distribution in tissues of acutely poisoned mice was demonstrated by immunohistochemistry using anti-CQ polyclonal antibodies (PAC). PAC recognized 4-amino-7-chloro-quinoline structure and sufficiently reacted with CQ and CQ’s metabolite bisdesethyl-chloroquine. In the brain, CQ and its metabolites (CQs) localized in the region of the choroids plexus, indicating an important role in the blood–cerebrospinal barrier system. In the heart, most regions showed diffused positive staining, and relatively strong reaction was observed in Purkinje cells, indicating an important role in acute CQ toxicity. In the lungs, CQs were observed in the bronchial epithelium, type II pneumocytes, and on the surface of alveolar walls. It was suggested that CQs were excreted to the alveolar wall with surfactant phospholipids, which are produced by type II pneumocytes. In the liver, CQs were concentrated in the centrolobular area rather than in the periportal area, in agreement with CQ’s metabolic pathway. In the kidneys, tubular cells were strongly stained compared to glomerular capsules, and the distal part of renal tubules was better stained than the proximal tubules. These findings suggested that CQs were predominantly excreted or reabsorbed through the distal tubules and the collecting duct. Distribution of CQs in tissues presented here were mostly consistent with the physico-chemical properties of CQ and its metabolites. However, the elucidation of CQs’ localization in Purkinje cells remains open. Further experimental studies at the level of microorganella will be needed to clarify the present result.</div></front></TEI><istex><corpusName>springer-journals</corpusName><author><json:item><name>Ako Koreeda</name><affiliations><json:string>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</json:string><json:string>E-mail: ako@kumamoto-u.ac.jp</json:string></affiliations></json:item><json:item><name>Kosei Yonemitsu</name><affiliations><json:string>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</json:string></affiliations></json:item><json:item><name>Hiroe Kohmatsu</name><affiliations><json:string>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</json:string></affiliations></json:item><json:item><name>Sohtaro Mimasaka</name><affiliations><json:string>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</json:string></affiliations></json:item><json:item><name>Yuki Ohtsu</name><affiliations><json:string>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</json:string></affiliations></json:item><json:item><name>Toru Oshima</name><affiliations><json:string>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</json:string></affiliations></json:item><json:item><name>Kunio Fujiwara</name><affiliations><json:string>Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, 4-22-1 Ikeda, 860-0082, Kumamoto, Japan</json:string></affiliations></json:item><json:item><name>Shigeyuki Tsunenari</name><affiliations><json:string>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Chloroquine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Immunohistochemistry</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Tissue distribution</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Acute toxicity</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Mice</value></json:item></subject><articleId><json:string>185</json:string><json:string>s00204-007-0185-6</json:string></articleId><arkIstex>ark:/67375/VQC-367Q68WG-K</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>OriginalPaper</json:string></originalGenre><abstract>Abstract: Chloroquine (CQ) distribution in tissues of acutely poisoned mice was demonstrated by immunohistochemistry using anti-CQ polyclonal antibodies (PAC). PAC recognized 4-amino-7-chloro-quinoline structure and sufficiently reacted with CQ and CQ’s metabolite bisdesethyl-chloroquine. In the brain, CQ and its metabolites (CQs) localized in the region of the choroids plexus, indicating an important role in the blood–cerebrospinal barrier system. In the heart, most regions showed diffused positive staining, and relatively strong reaction was observed in Purkinje cells, indicating an important role in acute CQ toxicity. In the lungs, CQs were observed in the bronchial epithelium, type II pneumocytes, and on the surface of alveolar walls. It was suggested that CQs were excreted to the alveolar wall with surfactant phospholipids, which are produced by type II pneumocytes. In the liver, CQs were concentrated in the centrolobular area rather than in the periportal area, in agreement with CQ’s metabolic pathway. In the kidneys, tubular cells were strongly stained compared to glomerular capsules, and the distal part of renal tubules was better stained than the proximal tubules. These findings suggested that CQs were predominantly excreted or reabsorbed through the distal tubules and the collecting duct. Distribution of CQs in tissues presented here were mostly consistent with the physico-chemical properties of CQ and its metabolites. However, the elucidation of CQs’ localization in Purkinje cells remains open. Further experimental studies at the level of microorganella will be needed to clarify the present result.</abstract><qualityIndicators><score>8.023</score><pdfWordCount>3191</pdfWordCount><pdfCharCount>20310</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>8</pdfPageCount><pdfPageSize>595 x 791 pts</pdfPageSize><refBibsNative>false</refBibsNative><abstractWordCount>236</abstractWordCount><abstractCharCount>1636</abstractCharCount><keywordCount>5</keywordCount></qualityIndicators><title>Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice</title><genre><json:string>research-article</json:string></genre><host><title>Archives of 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type="first">Ako</forename><surname>Koreeda</surname></persName><email>ako@kumamoto-u.ac.jp</email><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Kosei</forename><surname>Yonemitsu</surname></persName><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Hiroe</forename><surname>Kohmatsu</surname></persName><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Sohtaro</forename><surname>Mimasaka</surname></persName><affiliation>Department of Forensic Medicine, Graduate 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PAC recognized 4-amino-7-chloro-quinoline structure and sufficiently reacted with CQ and CQ’s metabolite bisdesethyl-chloroquine. In the brain, CQ and its metabolites (CQs) localized in the region of the choroids plexus, indicating an important role in the blood–cerebrospinal barrier system. In the heart, most regions showed diffused positive staining, and relatively strong reaction was observed in Purkinje cells, indicating an important role in acute CQ toxicity. In the lungs, CQs were observed in the bronchial epithelium, type II pneumocytes, and on the surface of alveolar walls. It was suggested that CQs were excreted to the alveolar wall with surfactant phospholipids, which are produced by type II pneumocytes. In the liver, CQs were concentrated in the centrolobular area rather than in the periportal area, in agreement with CQ’s metabolic pathway. In the kidneys, tubular cells were strongly stained compared to glomerular capsules, and the distal part of renal tubules was better stained than the proximal tubules. These findings suggested that CQs were predominantly excreted or reabsorbed through the distal tubules and the collecting duct. Distribution of CQs in tissues presented here were mostly consistent with the physico-chemical properties of CQ and its metabolites. However, the elucidation of CQs’ localization in Purkinje cells remains open. Further experimental studies at the level of microorganella will be needed to clarify the present result.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Chloroquine</term></item><item><term>Immunohistochemistry</term></item><item><term>Tissue distribution</term></item><item><term>Acute toxicity</term></item><item><term>Mice</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Biomedicine</head><item><term>Allergology</term></item><item><term>Cancer Research</term></item><item><term>Pharmacology/Toxicology</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006-11-22">Created</change><change 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NumberingStyle="Unnumbered"><JournalID>204</JournalID><JournalPrintISSN>0340-5761</JournalPrintISSN><JournalElectronicISSN>1432-0738</JournalElectronicISSN><JournalTitle>Archives of Toxicology</JournalTitle><JournalAbbreviatedTitle>Arch Toxicol</JournalAbbreviatedTitle><JournalSubjectGroup><JournalSubject Type="Primary">Biomedicine</JournalSubject><JournalSubject Type="Secondary">Allergology</JournalSubject><JournalSubject Type="Secondary">Cancer Research </JournalSubject><JournalSubject Type="Secondary">Pharmacology/Toxicology </JournalSubject></JournalSubjectGroup></JournalInfo><Volume OutputMedium="All"><VolumeInfo TocLevels="0" VolumeType="Regular"><VolumeIDStart>81</VolumeIDStart><VolumeIDEnd>81</VolumeIDEnd><VolumeIssueCount>12</VolumeIssueCount></VolumeInfo><Issue IssueType="Regular" OutputMedium="All"><IssueInfo TocLevels="0"><IssueIDStart>7</IssueIDStart><IssueIDEnd>7</IssueIDEnd><IssueArticleCount>8</IssueArticleCount><IssueHistory><OnlineDate><Year>2007</Year><Month>6</Month><Day>26</Day></OnlineDate><PrintDate><Year>2007</Year><Month>6</Month><Day>26</Day></PrintDate><CoverDate><Year>2007</Year><Month>7</Month></CoverDate></IssueHistory><IssueCopyright><CopyrightHolderName>Springer-Verlag</CopyrightHolderName><CopyrightYear>2007</CopyrightYear></IssueCopyright></IssueInfo><Article ID="s00204-007-0185-6" OutputMedium="All"><ArticleInfo ArticleType="OriginalPaper" ContainsESM="No" Language="En" NumberingStyle="Unnumbered" TocLevels="0"><ArticleID>185</ArticleID><ArticleDOI>10.1007/s00204-007-0185-6</ArticleDOI><ArticleSequenceNumber>2</ArticleSequenceNumber><ArticleTitle Language="En">Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice</ArticleTitle><ArticleCategory>Toxicokinetics and Metabolism</ArticleCategory><ArticleFirstPage>471</ArticleFirstPage><ArticleLastPage>478</ArticleLastPage><ArticleHistory><RegistrationDate><Year>2007</Year><Month>1</Month><Day>19</Day></RegistrationDate><Received><Year>2006</Year><Month>11</Month><Day>22</Day></Received><Accepted><Year>2007</Year><Month>1</Month><Day>18</Day></Accepted><OnlineDate><Year>2007</Year><Month>2</Month><Day>16</Day></OnlineDate></ArticleHistory><ArticleCopyright><CopyrightHolderName>Springer-Verlag</CopyrightHolderName><CopyrightYear>2007</CopyrightYear></ArticleCopyright><ArticleGrants Type="Regular"><MetadataGrant Grant="OpenAccess"></MetadataGrant><AbstractGrant Grant="OpenAccess"></AbstractGrant><BodyPDFGrant Grant="Restricted"></BodyPDFGrant><BodyHTMLGrant Grant="Restricted"></BodyHTMLGrant><BibliographyGrant Grant="Restricted"></BibliographyGrant><ESMGrant Grant="Restricted"></ESMGrant></ArticleGrants></ArticleInfo><ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1" CorrespondingAffiliationID="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Ako</GivenName><FamilyName>Koreeda</FamilyName></AuthorName><Contact><Phone>+81-96-3735123</Phone><Fax>+81-96-3735123</Fax><Email>ako@kumamoto-u.ac.jp</Email></Contact></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Kosei</GivenName><FamilyName>Yonemitsu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Hiroe</GivenName><FamilyName>Kohmatsu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Sohtaro</GivenName><FamilyName>Mimasaka</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Yuki</GivenName><FamilyName>Ohtsu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Toru</GivenName><FamilyName>Oshima</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Kunio</GivenName><FamilyName>Fujiwara</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Shigeyuki</GivenName><FamilyName>Tsunenari</FamilyName></AuthorName></Author><Affiliation ID="Aff1"><OrgDivision>Department of Forensic Medicine, Graduate School of Medical Sciences</OrgDivision><OrgName>Kumamoto University</OrgName><OrgAddress><Street>1-1-1 Honjo</Street><City>Kumamoto</City><Postcode>860-8556</Postcode><Country Code="JP">Japan</Country></OrgAddress></Affiliation><Affiliation ID="Aff2"><OrgDivision>Department of Applied Life Science, Faculty of Biotechnology and Life Science</OrgDivision><OrgName>Sojo University</OrgName><OrgAddress><Street>4-22-1 Ikeda</Street><City>Kumamoto</City><Postcode>860-0082</Postcode><Country Code="JP">Japan</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En"><Heading>Abstract</Heading><Para>Chloroquine (CQ) distribution in tissues of acutely poisoned mice was demonstrated by immunohistochemistry using anti-CQ polyclonal antibodies (PAC). PAC recognized 4-amino-7-chloro-quinoline structure and sufficiently reacted with CQ and CQ’s metabolite bisdesethyl-chloroquine. In the brain, CQ and its metabolites (CQs) localized in the region of the choroids plexus, indicating an important role in the blood–cerebrospinal barrier system. In the heart, most regions showed diffused positive staining, and relatively strong reaction was observed in Purkinje cells, indicating an important role in acute CQ toxicity. In the lungs, CQs were observed in the bronchial epithelium, type II pneumocytes, and on the surface of alveolar walls. It was suggested that CQs were excreted to the alveolar wall with surfactant phospholipids, which are produced by type II pneumocytes. In the liver, CQs were concentrated in the centrolobular area rather than in the periportal area, in agreement with CQ’s metabolic pathway. In the kidneys, tubular cells were strongly stained compared to glomerular capsules, and the distal part of renal tubules was better stained than the proximal tubules. These findings suggested that CQs were predominantly excreted or reabsorbed through the distal tubules and the collecting duct. Distribution of CQs in tissues presented here were mostly consistent with the physico-chemical properties of CQ and its metabolites. However, the elucidation of CQs’ localization in Purkinje cells remains open. Further experimental studies at the level of microorganella will be needed to clarify the present result.</Para></Abstract><KeywordGroup Language="En"><Heading>Keywords</Heading><Keyword>Chloroquine</Keyword><Keyword>Immunohistochemistry</Keyword><Keyword>Tissue distribution</Keyword><Keyword>Acute toxicity</Keyword><Keyword>Mice</Keyword></KeywordGroup></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Ako</namePart><namePart type="family">Koreeda</namePart><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation><affiliation>E-mail: ako@kumamoto-u.ac.jp</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kosei</namePart><namePart type="family">Yonemitsu</namePart><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hiroe</namePart><namePart type="family">Kohmatsu</namePart><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sohtaro</namePart><namePart type="family">Mimasaka</namePart><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yuki</namePart><namePart type="family">Ohtsu</namePart><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Toru</namePart><namePart type="family">Oshima</namePart><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kunio</namePart><namePart type="family">Fujiwara</namePart><affiliation>Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, 4-22-1 Ikeda, 860-0082, Kumamoto, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Shigeyuki</namePart><namePart type="family">Tsunenari</namePart><affiliation>Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Springer-Verlag</publisher><place><placeTerm type="text">Berlin/Heidelberg</placeTerm></place><dateCreated encoding="w3cdtf">2006-11-22</dateCreated><dateIssued encoding="w3cdtf">2007-07-01</dateIssued><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: Chloroquine (CQ) distribution in tissues of acutely poisoned mice was demonstrated by immunohistochemistry using anti-CQ polyclonal antibodies (PAC). PAC recognized 4-amino-7-chloro-quinoline structure and sufficiently reacted with CQ and CQ’s metabolite bisdesethyl-chloroquine. In the brain, CQ and its metabolites (CQs) localized in the region of the choroids plexus, indicating an important role in the blood–cerebrospinal barrier system. In the heart, most regions showed diffused positive staining, and relatively strong reaction was observed in Purkinje cells, indicating an important role in acute CQ toxicity. In the lungs, CQs were observed in the bronchial epithelium, type II pneumocytes, and on the surface of alveolar walls. It was suggested that CQs were excreted to the alveolar wall with surfactant phospholipids, which are produced by type II pneumocytes. In the liver, CQs were concentrated in the centrolobular area rather than in the periportal area, in agreement with CQ’s metabolic pathway. In the kidneys, tubular cells were strongly stained compared to glomerular capsules, and the distal part of renal tubules was better stained than the proximal tubules. These findings suggested that CQs were predominantly excreted or reabsorbed through the distal tubules and the collecting duct. Distribution of CQs in tissues presented here were mostly consistent with the physico-chemical properties of CQ and its metabolites. However, the elucidation of CQs’ localization in Purkinje cells remains open. Further experimental studies at the level of microorganella will be needed to clarify the present result.</abstract><note>Toxicokinetics and Metabolism</note><subject lang="en"><genre>Keywords</genre><topic>Chloroquine</topic><topic>Immunohistochemistry</topic><topic>Tissue distribution</topic><topic>Acute toxicity</topic><topic>Mice</topic></subject><relatedItem type="host"><titleInfo><title>Archives of Toxicology</title></titleInfo><titleInfo type="abbreviated"><title>Arch Toxicol</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>Springer</publisher><dateIssued encoding="w3cdtf">2007-06-26</dateIssued><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><subject><genre>Biomedicine</genre><topic>Allergology</topic><topic>Cancer Research</topic><topic>Pharmacology/Toxicology</topic></subject><identifier type="ISSN">0340-5761</identifier><identifier type="eISSN">1432-0738</identifier><identifier type="JournalID">204</identifier><identifier type="IssueArticleCount">8</identifier><identifier type="VolumeIssueCount">12</identifier><part><date>2007</date><detail type="volume"><number>81</number><caption>vol.</caption></detail><detail type="issue"><number>7</number><caption>no.</caption></detail><extent unit="pages"><start>471</start><end>478</end></extent></part><recordInfo><recordOrigin>Springer-Verlag, 2007</recordOrigin></recordInfo></relatedItem><identifier type="istex">EE52F37270A267B0901F773B0775159B62EB97E2</identifier><identifier type="ark">ark:/67375/VQC-367Q68WG-K</identifier><identifier type="DOI">10.1007/s00204-007-0185-6</identifier><identifier type="ArticleID">185</identifier><identifier type="ArticleID">s00204-007-0185-6</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer-Verlag, 2007</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource><recordOrigin>Springer-Verlag, 2007</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-367Q68WG-K/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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