Clotrimazole, an antifungal drug possessing diverse actions, increases membrane permeation of cadmium in rat thymocytes.
In previous study, clotrimazole, an antifungal drug, exerted potent cytotoxic action on rat thymocytes in presence of metal divalent cations such as Cd(2+) and Pb(2+). To reveal one of toxicological characteristics of clotrimazole, we examined the effect of clotrimazole on intracellular concentration of metal divalent cations by flow cytometer with fluo-3, a fluorescent. Simultaneous application of clotrimazole and CdCl(2) significantly decreased the cell viability although their concentrations were not cytotoxic, respectively. Clotrimazole alone increased the intensity of fluo-3 fluorescence, suggesting an increased concentration of intracellular Ca(2+). The intensity of fluo-3 fluorescence augmented by the combination of clotrimazole and CdCl(2) was much higher than that by respective agents. Removal of external Ca(2+) further increased the intensity of fluorescence augmented by the combination. Furthermore, the application of MnCl(2) did not attenuate the intensity in the presence of CdCl(2). Therefore, it is suggested that the augmentation of fluo-3 fluorescence in the simultaneous presence of clotrimazole and CdCl(2) is Cd(2+)-dependent. Clotrimazole may increase membrane permeation of Cd(2+).
Oyama
Tomohiro M
TM
Laboratory of Cell Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.
Oyama
Toshihisa B
TB
Oyama
Keisuke
K
Sakanashi
Yoko
Y
Morimoto
Midori
M
Matsui
Hiroko
H
Oyama
Yasuo
Y
D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D002104:Cadmium / Q000378:metabolism*; D000001:Calcimycin; D002462:Cell Membrane / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D002712:Chlorides; D003022:Clotrimazole / Q000633:toxicity*; D008297:Male; D017895:Manganese Compounds; D051381:Rats; D017208:Rats, Wistar; D013950:Thymus Gland / Q000166:cytology*
D000935:Antifungal Agents; D002712:Chlorides; D017895:Manganese Compounds; D002104:Cadmium; D000001:Calcimycin; D003022:Clotrimazole; C025340:manganese chloride