Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1977 Apr;11(4):675–678. doi: 10.1128/aac.11.4.675

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

E B Siegel 1,1
PMCID: PMC352048  PMID: 856027

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.

Full text

PDF
676

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bonner D. P., Mechlinski W., Schaffner C. P. Polyene macrolide derivatives. 3. Biological properties of polyene macrolide ester salts. J Antibiot (Tokyo) 1972 Apr;25(4):261–262. [PubMed] [Google Scholar]
  2. Brier A. M., Wohlenberg C., Rosenthal J., Mage M., Notkins A. L. Inhibition or enhancement of immunological injury of virus-infected cells. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3073–3077. doi: 10.1073/pnas.68.12.3073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Harada M., Pearson G., Pettigrew H., Redmon L., Orr T. Enhancement of normal lymphocyte cytotoxicity by sera with high antibody titers against H-2 or virus-associated antigens. Cancer Res. 1973 Nov;33(11):2886–2893. [PubMed] [Google Scholar]
  4. KINSKY S. C., AVRUCH J., PERMUTT M., ROGERS H. B. The lytic effect of polyene antifungal antibiotics on mammalian erythrocytes. Biochem Biophys Res Commun. 1962 Dec 19;9:503–507. doi: 10.1016/0006-291x(62)90116-x. [DOI] [PubMed] [Google Scholar]
  5. KINSKY S. C. COMPARATIVE RESPONSES OF MAMMALIAN ERYTHROCYTES AND MICROBIAL PROTOPLASTS TO POLYENE ANTIBIOTICS AND VITAMIN A. Arch Biochem Biophys. 1963 Aug;102:180–188. doi: 10.1016/0003-9861(63)90169-3. [DOI] [PubMed] [Google Scholar]
  6. Keim G. R., Jr, Poutsiaka J. W., Kirpan J., Keysser C. H. Amphotericin B methyl ester hydrochloride and amphotericin B: comparative acute toxicity. Science. 1973 Feb 9;179(4073):584–585. doi: 10.1126/science.179.4073.584. [DOI] [PubMed] [Google Scholar]
  7. Kjellén L., Ankerst J. Cytotoxicity of adenovirus-antibody aggregates: sensitivity to different cell strains, and inhibition by hexon antiserum and by complement. J Virol. 1973 Jul;12(1):25–32. doi: 10.1128/jvi.12.1.25-32.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Pancake S. J., Mora P. T. Comparison of SV40 induced antigens on the surface of cultivated cells by a cytolytic microassay. Virology. 1974 May;59(1):323–327. doi: 10.1016/0042-6822(74)90230-x. [DOI] [PubMed] [Google Scholar]
  9. Pansy F. E., Jambor W. P., Wilber-Murphy J., Gadebusch H. H. Comparative chemotherapeutic activities of heptaene macrolide antifungal antibiotics in experimental candidiasis. J Antibiot (Tokyo) 1972 Jul;25(7):405–408. doi: 10.7164/antibiotics.25.405. [DOI] [PubMed] [Google Scholar]
  10. Rosenberg E. B., McCoy J. L., Green S. S., Donnelly F. C., Siwarski D. F., Levine P. H., Herberman R. B. Destruction of human lymphoid tissue-culture cell lines by human peripheral lymphocytes in 51Cr-release cellular cytotoxicity assays. J Natl Cancer Inst. 1974 Feb;52(2):345–352. doi: 10.1093/jnci/52.2.345. [DOI] [PubMed] [Google Scholar]
  11. Rubens R. D., Dulbecco R. Augmentation of cytotoxic drug action by antibodies directed at cell surface. Nature. 1974 Mar 1;248(5443):81–82. doi: 10.1038/248081a0. [DOI] [PubMed] [Google Scholar]
  12. Sharma B., Terasaki P. I. In vitro immunization to cultured human tumor cells. Cancer Res. 1974 Jan;34(1):115–118. [PubMed] [Google Scholar]
  13. UTAHARA R., OKAMI Y., NAKAMURA S., UMEZAWA H. On a new antifungal substance, mediocidin, and other antifungal substances of Streptomyces with three characteristic absorption maxima. J Antibiot (Tokyo) 1954 Aug;7(4):120–124. [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES