Deuterated Pufa Inhibit Oxidative Damage To Liposomes Upon Photodynamic Treatment

Lipid peroxidation (LPO) plays a key role in many age-related neurodegenerative disorders and other pathologies. introduction of deuterated polyunsaturated fatty acids (D-PUFA) into membrane lipids has been recently suggested as a promising approach for protection against LPO. We have previously demonstrated inhibition of the Fe2+ascorbate - initiated LPO, when about 20% of membrane lipids contained D-PUFA with deuterium atoms instead of protons at bis-allylic positions (Firsov et al. FEBS J. 2019). Here, we report on the protective action of D-PUFA upon the photodynamic induction (illumination in the presence of a photosensitizer) of LPO in liposomes via two experimental procedures: 1) sulforhodamine B leakage from liposomes, detected with an FCS setup by changes in the amplitude of autocorrelation function, and 2) formation of diene conjugates, measured by absorbance at 234 nm. Trisulfonated aluminum phthalocyanine (AlPcS3) was used as a photosensitizer in these experiments. in particular, in the case of liposomes formed from lipids without D-PUFA (dilinoleyl-sn-glycero-3-phosphatidylcholine), 1-minute illumination led to a dramatic decrease in the amplitude of the autocorrelation function (ACF) showing permeabilization of the liposomes. by contrast, no decrease in the ACF amplitude was observed in the case of 50% D-PUFA (1-palmitoyl-2-(11,11-D2-linoleyl)-sn-glycero-3-phosphatidylcholine) - containing liposomal lipids. Experiments with giant unilamellar liposomes (GUVs) confirmed the protective action of the D-PUFA on the membrane permeability compromised by photodymanic action. The light-induced changes of the GUV surface as well as phase-contrast intensity (related to sucrose leakage) were significantly decreased in the presence of D-PUFA. This work was supported by the Russian Science Foundation grant 19-74-00015.