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 ironoxygen complex of undetermined nature initiates lipid peroxidation. Free hydroxyl radicals appear not to participate in lipid peroxidation stimulated by Fe3+-OTA. © 1990.