Effects of oxidative and free radical stress on cell membrane: potential markers and therapeutic/nutraceutical strategies

Cell membrane plays a crucial role in several biological processes and fatty acids, as structural membrane components and lipid mediators, have well-known protective and regulatory effects. Stress and inappropriate lifestyle, with enhanced free radical production, can induce membrane modifications that can be monitored by fatty acid lipidomics, a powerful diagnostic tool for the follow-up of membrane fatty acid remodeling that can be correlated with different physiological and pathological conditions. The experimental work described in this thesis was initially focused on the fatty acid analysis and the hyperspectral characterization of erythrocytes membranes of autistic and healthy children, leading to an important result of membrane-based diagnostics with high predictive value for autism. In the frame of the Marie Curie “ClickGene” network, the membrane fatty acid remodeling induced by two apolipoprotein isoforms, ApoE3 and ApoE4, being ApoE4 allele the major risk factor for Alzheimer’s disease, was also investigated. The results showed consistent differences in the membrane fatty acid profiles, opening a debate about the role of nutritional and metabolic adaptations as epigenetic determinants over genetic predisposition. Additionally, the biophysical role of trans fatty acids (TFAs), which can be formed by cis-trans isomerization in the presence of sulfur-centered radicals, was evaluated using liposomes as membrane models. Consistent differences in the membrane properties were established, foreseeing the insertion of toxic trans fatty acids in tumor cell membranes to achieve a synergic antitumoral effect; Finally, the full characterization of the mono-trans isomers of DHA achieved by a dual synthetic approach, was carried out. These experiments were useful for the identification of trans isomer contaminants in commercially available nutraceutical formulations. Taken together, these results could better clarify the role of fatty acids in the cell membrane composition, providing a palette of methodologies for the examination of membrane changes linked with the fatty acid geometry and types.