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- and high-density lipoproteins was investigated by UV-vis spectroscopy, electron microscopy, electrophoresis, and size-exclusion chromatography. Two formulations of the drug were used: the commercial Fungizone and a new, less toxic, liposomal formulation, AmBisome. It was shown that 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 amphotericin B contained in Fungizone extracted cholesterol from low-density lipoproteins which sensitized them to oxidation. Both formulations of amphotericin B studied here did not bind to high-density lipoprotein and did not affect the process of its oxidation.
Barwicz
J
J
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, Canada.
Dumont
I
I
Ouellet
C
C
Gruda
I
I
D000666:Amphotericin B / Q000633:toxicity*; D002850:Chromatography, Gel; D008075:Lipoproteins, HDL / Q000187:drug effects* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008081:Liposomes; D008854:Microscopy, Electron; D010084:Oxidation-Reduction; D013054:Spectrophotometry, Atomic; D013056:Spectrophotometry, Ultraviolet
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008081:Liposomes; C068538:liposomal amphotericin B; C099252:oxidized low density lipoprotein; D000666:Amphotericin B