Mechanism of ochratoxin A stimulated lipid peroxidation.
Lipid peroxidation, measured as malondialdehyde formation or by oxygen uptake, was stimulated markedly by the mycotoxin ochratoxin A (OTA) in a reconstituted system consisting of phospholipid vesicles, the flavoprotein NADPH-cytochrome P450 reductase, Fe3+, EDTA and NADPH. Deletion of EDTA lowered the extent of lipid peroxidation but did not eliminate it. Fluorometric and spectrophotometric studies demonstrated the formation of a 1:1 Fe3(+)-OTA complex. The rate of reduction of Fe3+ to Fe2+ was enhanced markedly in the presence of OTA, and there was a further increase in the rate when EDTA was also included. The data indicate that OTA stimulates lipid peroxidation by complexing Fe3+ and facilitating its reduction. Subsequent to oxygen binding, an iron-oxygen complex of undetermined nature initiates lipid peroxidation. Free hydroxyl radicals appear not to participate in lipid peroxidation stimulated by Fe3(+)-OTA.
Omar
R F
RF
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
Hasinoff
B B
BB
Mejilla
F
F
Rahimtula
A D
AD
D000818:Animals; D004492:Edetic Acid / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009793:Ochratoxins / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains
D009793:Ochratoxins; C025589:ochratoxin A; D008315:Malondialdehyde; D004492:Edetic Acid; D007501:Iron; D009251:NADPH-Ferrihemoprotein Reductase