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Antimicrob Agents Chemother. 1980 October; 18(4): 586-592

Permeabilizing and hemolytic action of large and small polyene antibiotics on human erythrocytes.

ABSTRACT

The effects of large polyenes (heptaenes and the "degenerate heptaene" nystatin) on human erythrocytes were found to occur in three separate stages. Stage I was a reversible increase in cell membrane permeability to monovalent cations and occurred at low antibiotic concentrations. At intermediate antibiotic concentrations, an irreversible increase in cell membrane permeability to cations (stage II) occurred, which then led to swelling of cells and hemolysis (stage III). Hemolysis could be prevented by sucrose, mannitol, or melezitose, but stages I and II still occurred under these conditions. The effects of the small polyenes (pentaenes and a tetraene) occurred in only one stage. Changes in cell membrane permeability (stages I and II) were not noted before hemolysis (stage III) even in the presence of carbohydrate. Carbohydrates gave only weak, transient protection from the hemolytic action of small polyenes, probably because the membrane damage induced by these antibiotics was more extensive than that induced by the large polyenes. In the presence of sucrose, large polyenes were able to inhibit the hemolytic action of small polyenes, implying that both antibiotics have the same binding sites.

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