Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice
Identifieur interne : 001B41 ( Main/Exploration ); précédent : 001B40; suivant : 001B42Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice
Auteurs : Ako Koreeda [Japon] ; Kosei Yonemitsu [Japon] ; Hiroe Kohmatsu [Japon] ; Sohtaro Mimasaka [Japon] ; Yuki Ohtsu [Japon] ; Toru Oshima [Japon] ; Kunio Fujiwara [Japon] ; Shigeyuki Tsunenari [Japon]Source :
- Archives of Toxicology [ 0340-5761 ] ; 2007-07-01.
Descripteurs français
- KwdFr :
- Animaux, Anticorps, Antipaludiques (immunologie), Antipaludiques (intoxication), Antipaludiques (pharmacocinétique), Biotransformation, Chloroquine (analogues et dérivés), Chloroquine (immunologie), Chloroquine (intoxication), Chloroquine (pharmacocinétique), Encéphale (métabolisme), Foie (métabolisme), Immunohistochimie, Myocarde (métabolisme), Mâle, Poumon (métabolisme), Rein (métabolisme), Répartition dans les tissus, Souris, Spécificité des anticorps.
- MESH :
- analogues et dérivés : Chloroquine.
- immunologie : Antipaludiques, Chloroquine.
- intoxication : Antipaludiques, Chloroquine.
- métabolisme : Encéphale, Foie, Myocarde, Poumon, Rein.
- pharmacocinétique : Antipaludiques, Chloroquine.
- Animaux, Anticorps, Biotransformation, Immunohistochimie, Mâle, Répartition dans les tissus, Souris, Spécificité des anticorps.
English descriptors
- KwdEn :
- Acute toxicity, Animals, Antibodies, Antibody Specificity, Antimalarials (immunology), Antimalarials (pharmacokinetics), Antimalarials (poisoning), Biotransformation, Brain (metabolism), Chloroquine, Chloroquine (analogs & derivatives), Chloroquine (immunology), Chloroquine (pharmacokinetics), Chloroquine (poisoning), Immunohistochemistry, Kidney (metabolism), Liver (metabolism), Lung (metabolism), Male, Mice, Myocardium (metabolism), Tissue Distribution, Tissue distribution.
- MESH :
- chemical , analogs & derivatives : Chloroquine.
- chemical , immunology : Antimalarials, Chloroquine.
- chemical , pharmacokinetics : Antimalarials, Chloroquine.
- chemical , poisoning : Antimalarials, Chloroquine.
- chemical : Antibodies.
- metabolism : Brain, Kidney, Liver, Lung, Myocardium.
- Animals, Antibody Specificity, Biotransformation, Immunohistochemistry, Male, Mice, Tissue Distribution.
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
Affiliations:
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(pharmacokinetics)</term><term>Chloroquine (poisoning)</term><term>Immunohistochemistry</term><term>Kidney (metabolism)</term><term>Liver (metabolism)</term><term>Lung (metabolism)</term><term>Male</term><term>Mice</term><term>Myocardium (metabolism)</term><term>Tissue Distribution</term><term>Tissue distribution</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps</term><term>Antipaludiques (immunologie)</term><term>Antipaludiques (intoxication)</term><term>Antipaludiques (pharmacocinétique)</term><term>Biotransformation</term><term>Chloroquine (analogues et dérivés)</term><term>Chloroquine (immunologie)</term><term>Chloroquine (intoxication)</term><term>Chloroquine (pharmacocinétique)</term><term>Encéphale (métabolisme)</term><term>Foie (métabolisme)</term><term>Immunohistochimie</term><term>Myocarde (métabolisme)</term><term>Mâle</term><term>Poumon (métabolisme)</term><term>Rein (métabolisme)</term><term>Répartition dans les tissus</term><term>Souris</term><term>Spécificité des anticorps</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Chloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antimalarials</term><term>Chloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antimalarials</term><term>Chloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="poisoning" xml:lang="en"><term>Antimalarials</term><term>Chloroquine</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Antibodies</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antipaludiques</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="intoxication" 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tissus</term><term>Souris</term><term>Spécificité des anticorps</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><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Koreeda, Ako" sort="Koreeda, Ako" uniqKey="Koreeda A" first="Ako" last="Koreeda">Ako Koreeda</name></noRegion><name sortKey="Fujiwara, Kunio" sort="Fujiwara, Kunio" uniqKey="Fujiwara K" first="Kunio" last="Fujiwara">Kunio Fujiwara</name><name sortKey="Kohmatsu, Hiroe" sort="Kohmatsu, Hiroe" uniqKey="Kohmatsu H" first="Hiroe" last="Kohmatsu">Hiroe Kohmatsu</name><name sortKey="Koreeda, Ako" sort="Koreeda, Ako" uniqKey="Koreeda A" first="Ako" last="Koreeda">Ako Koreeda</name><name sortKey="Mimasaka, Sohtaro" sort="Mimasaka, Sohtaro" uniqKey="Mimasaka S" first="Sohtaro" last="Mimasaka">Sohtaro Mimasaka</name><name sortKey="Ohtsu, Yuki" sort="Ohtsu, Yuki" uniqKey="Ohtsu Y" first="Yuki" last="Ohtsu">Yuki Ohtsu</name><name sortKey="Oshima, Toru" sort="Oshima, Toru" uniqKey="Oshima T" first="Toru" last="Oshima">Toru Oshima</name><name sortKey="Tsunenari, Shigeyuki" sort="Tsunenari, Shigeyuki" uniqKey="Tsunenari S" first="Shigeyuki" last="Tsunenari">Shigeyuki Tsunenari</name><name sortKey="Yonemitsu, Kosei" sort="Yonemitsu, Kosei" uniqKey="Yonemitsu K" first="Kosei" last="Yonemitsu">Kosei Yonemitsu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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