EFFECT OF N-ACYLETHANOLAMIDES ON PLASMA LIPID PEROXIDATION AND PARAOXONASE ACTIVITY: AN IN VITRO STUDY

N-acylethanolamides (NAEs) are naturally occurring hydrophobic molecules, present in mammalian tissues and biological fluids, such as plasma. Previous studies showed that some of these molecules have protective properties against oxidative stress in some cell models. The present study was designed to determine whether NAEs, differing for acyl chain length and unsaturation, can have a protective effect on the oxidative susceptibility of plasma lipids, that is considered a factor contributing to atherogenic risk. To study the effect of three different NAEs on free-radical induced damage of plasma lipids, conjugated dienes and lipid hydroperoxides formation was investigated by incubating unfractionated plasma with radical generators (Cu2+ and/or AAPH). Moreover, the effect of these NAEs on the in vitro induced oxidative degradation of PON1 activity was measured, in unfractionated plasma. PON1, an enzyme associated with plasma high density lipoproteins, plays an important role against oxidative damage of lipoproteins and in protection against atherosclerosis. Results obtained demonstrated that the NAEs used oleoylethanolamide, palmitoylethanolamide and anandamide) elicited a significant protection against both AAPH and copper-induced plasma lipid hydroperoxides increase or oxidative decrease of PON1 activity. The protective effect was shown also on the conjugated dienes formation induced by incubation of diluted plasma with CuSO4. Among the three NAEs used, the largest protective effect was shown by 1 µM anandamide (AEA) that induced a 32.6% decrease of lipid hydroperoxides concentration, with respect to control sample, in undiluted plasma incubated with 20 µM CuSO4. Our results suggest a possible protective role of NAEs in the pathogenesis of diseases associated with oxidative stress.