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 Cd2+ and Pb2+. 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 CdCl2 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 Ca2+. The intensity of fluo-3 fluorescence augmented by the combination of clotrimazole and CdCl2 was much higher than that by respective agents. Removal of external Ca2+ further increased the intensity of fluorescence augmented by the combination. Furthermore, the application of MnCl2 did not attenuate the intensity in the presence of CdCl2. Therefore, it is suggested that the augmentation of fluo-3 fluorescence in the simultaneous presence of clotrimazole and CdCl2 is Cd2+-dependent. Clotrimazole may increase membrane permeation of Cd2+.