FIG 9.

Hypothetical model showing intracellular events in conferring amphotericin B resistance. The model diagram illustrates that AmB inside the cells after auto-oxidation generates free radicals, which changes the mitochondrial membrane potential. Due to depolarization of the mitochondrial membrane, there is a release of Cyt c into the cytosol. The released cytochrome c is oxidized and moves toward apoptosis by means of caspase-like activity in the case of the sensitive strain but by means of the upregulation of ascorbate peroxidase in the case of the resistant strain, which is scavenged by the ascorbate-glutathione cascade, as is the by-product. ASC, ascorbate; DHA, dehydroascorbate; GSH, reduced glutathione; GSSG, oxidized glutathione. Ascorbate and glutathione also reduced the cytochrome c and bypassed the pathway of apoptosis.