Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice.
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.
Koreeda
Ako
A
Department of Forensic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. ako@kumamoto-u.ac.jp
Yonemitsu
Kosei
K
Kohmatsu
Hiroe
H
Mimasaka
Sohtaro
S
Ohtsu
Yuki
Y
Oshima
Toru
T
Fujiwara
Kunio
K
Tsunenari
Shigeyuki
S
D000818:Animals; D000906:Antibodies; D000918:Antibody Specificity; D000962:Antimalarials / Q000276:immunology / Q000493:pharmacokinetics* / Q000506:poisoning*; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D002738:Chloroquine / Q000031:analogs & derivatives / Q000276:immunology / Q000493:pharmacokinetics* / Q000506:poisoning*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D014018:Tissue Distribution
D000906:Antibodies; D000962:Antimalarials; D002738:Chloroquine; C033490:N,N-dideethylchloroquine