Synergic cytotoxic action induced by simultaneous application of zinc and clotrimazole in rat thymocytes.
In our previous study, the application of clotrimazole, an antifungal drug, with CdCl(2) or PbCl(2) significantly increased cell lethality of rat thymocytes, even though their individual concentrations were ineffective in affecting the viability. This observation prompted us to study the case for the combination of clotrimazole and ZnCl(2) because the use of zinc as a nutritional supplement has become common. Their combination induced very potent cytotoxic action on rat thymocytes with "bell-shape" dose-response relation. An acceleration of apoptotic process by the combination was suggested for the mechanism. The present result may provide a new insight into toxicological characteristics of clotrimazole.
Oyama
Yasuo
Y
Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan. oyama@ias.tokushima-u.ac.jp
Matsui
Hiroko
H
Morimoto
Midori
M
Sakanashi
Yoko
Y
Nishimura
Yumiko
Y
Ishida
Shiro
S
Okano
Yoshiro
Y
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000935:Antifungal Agents / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D003022:Clotrimazole / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007202:Indicators and Reagents; D008297:Male; D008856:Microscopy, Fluorescence; D010718:Phosphatidylserines / Q000378:metabolism; D011419:Propidium; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000187:drug effects*; D015032:Zinc / Q000633:toxicity*
D017304:Annexin A5; D000935:Antifungal Agents; D007202:Indicators and Reagents; D010718:Phosphatidylserines; D011419:Propidium; D003022:Clotrimazole; D015032:Zinc