AMPHOTERICIN-B TOXICITY AS RELATED TO THE FORMATION OF OXIDATIVELY MODIFIED LOW-DENSITY LIPOPROTEINS

The effect of amphotericin B on the oxidation and degradation of low-a nd high-density lipoproteins was investigated by UV-vis spectroscopy, electron microscopy, electrophoresis, and size-exclusion chromatograph y. Two formulations of the drug were used: the commercial Fungizone an d a new, less toxic, liposomal formulation, AmBisome. It was shown tha t Fungizone strongly enhanced the oxidative deformation of low-density lipoprotein structure while AmBisome did not bind to this lipoprotein fraction and did not affect its oxidation. It was shown that amphoter icin B contained in Fungizone extracted cholesterol from low-density l ipoproteins which sensitized them to oxidation. Both formulations of a mphotericin B studied here did not bind to high-density lipoprotein an d did not affect the process of its oxidation. (C) 1998 John Wiley & S ons, Inc.