Effects of halogenated antibacterials on the erythrocyte membrane.
The influence of halogenated antibacterials on membrane structure and function was investigated using the human erythrocyte membrane as a model. Measurements of hemolysis in isotonic solution, altered membrane permeability, and stabilization against hypotonic hemolysis resulting from exposure of erythrocytes to halogenated antibacterials served as criteria of membrane-related effects. The hemolytic potency of the compounds studied differed widely, decreasing in the order hexachlorophene (HCP) greater than 2,2'-methylenebis(3,5-dichlorophenol) (3,5-TCP) greater than 2,2'-methylenebis(3,4-dichlorophenol) (3,4-TCP) approximately equal to 2,2'-methylenebis(4,6-dichlorophenol) (4,6-TCP) greater than 2,2'-methylenebis(4-chlorophenol) (DCP) greater than 3,4'-tribromosalicylanilide (TBS) approximately equal to 3,3',4',5-tetrachlorosalicylanilide (TCSA). Each of the antibacterials tested stabilized the erythrocyte against hypotonic hemolysis, although there were marked differences in the concentrations required to afford maximum stabilization as well as in the extent of protection. The observed order of protective effectiveness was HCP greater than 3,4-TCP greater than 4,6-TCP greater than DCP approximately equal to TCS greater than TBS. As shown by measurements of the first-order rate constant for K+ efflux, the permeability of the erythrocyte membrane to K+ was increased upon exposure to the antibacterials, with the effect of HCP greater than 3,4-TCP greater than 4,6-TCP approximately equal to 3,4-TCP greater than DCP approximately equal to TCS greater than TBS. These results indicate that halogenated antibacterials are capable of perturbing mammalian membranes, a feature which may account in part for their mammalian toxicity.
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002733:Chlorophenols / Q000097:blood / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects; D006582:Hexachlorophene / Q000097:blood / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008566:Membranes / Q000187:drug effects*; D009996:Osmotic Fragility / Q000187:drug effects; D011188:Potassium / Q000097:blood
D000890:Anti-Infective Agents; D002733:Chlorophenols; D006582:Hexachlorophene; D011188:Potassium