Biomimetic Chemistry: Radiation-induced modification of lipids by thiyl radicals

Lipid peroxidation is generally considered to be the major mechanism of cell injury in organisms subject to oxidative stress. Many medical aspects of cellular damage related peroxidation of unsaturated lipids have motivated the interest in studies on the lipid peroxidation processes in model membrane systems such as micelles and vesicles. Lipid micelles are structurally much simpler than bilayers of phospholipids, thus fatty acids provide reasonable model compounds susceptible to undergo processes associated with oxidative modifications of lipids. Thiols and other sulfur compounds play an important role in the protection of lipids from their degradation pathways by scavenging the primary oxidizing species or by repairing molecules damaged by their reactions. However, oxidation of polyunsaturated fatty acids (PUFA) by thiyl radicals from thiols is believed to be responsible for some of the biological damage resulting from lipid oxidation. At the same time, thiyl radicals can cause the isomerization of the PUFA double bonds with the formation of trans isomers. In this study, radiation-induced peroxidation of PUFA was investigated in mixed micelles formed from nonionic surfactant (Tween 20) and PUFA under conditions of higher acidity, in the absence and in the presence of 2-mercaptoethanol. We measured the formation of hydroperoxides of PUFA in micelles, exposed to radicals generated by gamma radiation from thiol. The geometrical isomerization of PUFA was simultaneously analyzed by gas chromatography. The effects of dose and dose rate on both lipid modification processes were studied. The results suggest that lower dose rates were more efficient in producing lipid hydroperoxidation and isomerization, respectively. The dose rate dependence of peroxidation found in our model system indicated the validity of the inverse square-root relationship with dose rate. The support and sponsorship by COST Action CM0603 on “Free Radicals in Chemical Biology (CHEMBIORADICAL) are kindly acknowledged.