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Ultrastructural changes associated with reversal of chloroquine resistance by verapamil in Plasmodium chabaudi

Published online by Cambridge University Press:  06 April 2009

K. Ohsawa ,
K. Tanabe ,
I. Kimata  and
A. Miki
K. Ohsawa
Affiliation:
Department of Medical Zoology, Osaka City University Medical School, Asahi-machi, Abeno-ku, Osaka 545, Japan
K. Tanabe
Affiliation:
Laboratory of Biology, Osaka Institute of Technology, Ohmiya, Asahi-ku, Osaka 535, Japan
I. Kimata
Affiliation:
Department of Medical Zoology, Osaka City University Medical School, Asahi-machi, Abeno-ku, Osaka 545, Japan
A. Miki
Affiliation:
Department of Medical Zoology, Osaka City University Medical School, Asahi-machi, Abeno-ku, Osaka 545, Japan
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Abstract

Reversal of chloroquine (CQ) resistance by verapamil, a Ca2+ antagonist, has been shown in CQ-resistant human and rodent malaria parasites. Here, we report ultrastructural changes associated with this phenomenon in CQ-resistant Plasmodium chabaudi (AS strain) after infected mice were administered CQ and verapamil. At parasitaemias of 5–7%, CQ at 6 mg/kg caused little morphological effect on CQ-resistant parasites. In contrast, co-administration of CQ and verapamil at 50 mg/kg induced swelling of food vacuoles with clumped pigment at 2.5 h. Morphological changes other than food vacuole enlargement occurred at 21 and 45 h: disappearance of endoplasmic reticulum, formation of myelin structures, focal cytoplasmic vacuolization and coarse clumping of electron-dense material in nuclei. These structural changes appeared to be very similar to those observed in CQ-sensitive P. chabaudi in mice injected with CQ alone or CQ plus verapamil. On the other hand, verapamil at 50 mg/kg alone did not induce any effect on both CQ-sensitive and CQ-resistant P. chabaudi. These results suggest that swelling of the food vacuoles is an initial event associated with reversal of CQ-resistance by verapamil.

Keywords

Plasmodium chabaudichloroquinedrug resistanceCa2+ antagonistverapamil
Type
Research Article
Information
Parasitology , Volume 103 , Issue 2 , October 1991 , pp. 185 - 189
Copyright
Copyright © Cambridge University Press 1991

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