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Antimicrob Agents Chemother. 1977 April; 11(4): 675-678
Copyright © 1977 American Society for Microbiology. All Rights Reserved.

Measurement of Polyene Antibiotic-Mediated Erythrocyte Damage by Release of Hemoglobin and Radioactive Chromium

Waksman Institute of Microbiology, Rutgers University, New Brunswick, New Jersey 08903

ABSTRACT

Polyene antifungal antibiotics produce various degrees of membrane damage in sheep erythrocytes in vitro. Mediocidin, filipin, amphotericin B, and candicidin were found to result in greater damage than nystatin, pimaricin, and amphotericin B methyl ester. The degree of sensitivity of the cells varied by 100-fold for mediocidin verus amphotericin B methyl ester as measured by curves of hemoglobin release versus drug concentration. In erythrocytes prelabeled with radioactive chromium, release of the isotope through polyene-damaged cell membranes was found to occur at lower drug concentrations than measurable hemoglobin release, and the percentage of isotope released at the highest drug dose was consistently greater than the percentage of hemoglobin released. Thus, the isotope assay is a more sensitive indicator of polyene-induced membrane damage in the test system. These significant differences in release of molecules through polyene-induced membrane lesions indicate the complex nature of the binding and further interactions of this class of drugs with the plasma membrane.

¹ Present address: Biological Sciences Research Center of the Child Development Institute, Division of Health Affairs, University of North Carolina, Chapel Hill, NC 27514.