Effect of miconazole and clotrimazole on K+ release and inhibition of ergosterol biosynthesis in Trichophyton mentagrophytes and related ultrastructural observations.
Measurement of K+ ions in extracellular fluids was used to provide evidence of direct membrane damage induced by miconazole and clotrimazole in Trichophyton mentagrophytes mycelium. K+ release from mycelium treated with high concentrations of drug was extensive, although leakage occurred more rapidly and to a greater extent with miconazole than with clotrimazole. Cells treated with fungicidal concentrations of drug were completely necrotic. The effect of miconazole was concentration dependent. A reduction in ergosterol levels was evident after 5 h treatment with miconazole. Further reduction in ergosterol concentration was demonstrated after 24 h with fungistatic concentrations of drug and was a concentration dependent effect. Fungistatic concentrations of miconazole also induced ultrastructural changes in mycelium, which were apparent within 5 h of treatment and became more pronounced after 24 h. Clotrimazole also reduced ergosterol levels and affected ultrastructure of mycelium. The plasma membrane in particular was affected by both these drugs.
Scott
E M
EM
Gorman
S P
SP
Millership
J S
JS
Wright
L R
LR
D002463:Cell Membrane Permeability / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology*; D004875:Ergosterol / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D008825:Miconazole / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D014249:Trichophyton / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D007093:Imidazoles; D008825:Miconazole; D003022:Clotrimazole; D011188:Potassium; D004875:Ergosterol