[Effect of cytochrome P-450 inhibitors on oxidative modification of low-density lipoproproteins by macrophages].
Unlike other cytochrome P450-dependent oxygenase inhibitors, ketoconazole has been shown to suppress the murine macrophage-mediated oxidative modification of human low-density lipoproteins (LDL) in a dose-dependent manner. The benzo[alpha]pyrene-induced microsomal monooxygenase activity was accomplished by a 1,5-fold increase in LDL oxidation by macrophages, ketokonazole (20 mu), methoxalene (20 mu), and alpha-naphthaflavone (50 mu). Ketoconazole was also effective in inhibiting macrophageal NADPH oxidase and LDL autooxidation induced by Fe2+ rather than Cu+, which is likely to be associated with its ability to act as a chelator of free and heme-bound iron ions.
Dushkin
M I
MI
Zenkov
N K
NK
Men'shikova
E B
EB
Pivovarova
E N
EN
Liubimov
G Iu
GIu
Vol'skiĭ
N N
NN
D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008163:Luminescent Measurements; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008730:Methoxsalen / Q000494:pharmacology; D051379:Mice; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction
D001571:Benzoflavones; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D008077:Lipoproteins, LDL; D001564:Benzo(a)pyrene; C011512:alpha-naphthoflavone; D003300:Copper; D019255:NADPH Oxidases; D007654:Ketoconazole; D008730:Methoxsalen
Vliianie ingibitorov tsitokhroma P-450 na okislitel'nuiu modifikatsiiu lipoproteinov nizkoĭ plotnosti makrofagami.