EPOXIDATION OF TRANS-4-HYDROXY-2-NONENAL BY FATTY-ACID HYDROPEROXIDESAND HYDROGEN-PEROXIDE

In this study, we reported that fatty acid hydroperoxides and hydrogen peroxide are capable of epoxidizing 4-hydroxy-2-nonenal, a lipid pero xidation product, to the mutagenic epoxide. The evidence of its format ion is provided (i) by trapping with [8-H-3]deoxyadenosine for the for mation of (1',2'-dihydroxyheptyl)-1,N-6-ethenodeoxyadenosine as a pair of diastereomers, (ii) by derivatization with (2,4-dinitrophenyl)hydr azine in acidic methanol, and (iii) by comparing its H-1-nuclear magne tic resonance and mass spectra to those of the authentic standard. Aft er incubating 4-hydroxy-2-nonenal with 9- or 13-linoleic acid hydroper oxide at 37 degrees C for 24 h, the epoxide was produced in 13.4% or 1 2.5% yield, and with hydrogen peroxide, the yield was 21.5%. In the pr esence of fatty acid (linoleic acid, gamma-linolenic acid, or arachido nic acid) and lipoxygenase, the epoxide of 4-hydroxy-2-nonenal was for med in 15.3%, 7.2%, or 6.2% yield, respectively. The xanthine/xanthine oxidase/superoxide dismutase system generated the epoxide in 1.2% yie ld. These yields are estimated on the basis of a standard curve obtain ed from reactions of deoxyadenosine and epoxide. These results show th at 4-hydroxy-2-nonenal is epoxidized by biological oxidants, suggestin g a plausible endogenous pathway for the in vivo formation of etheno a dducts.