Deuterated polyunsaturated fatty acids inhibit photoirradiation-induced lipid peroxidation in lipid bilayers

Lipid peroxidation (LPO) plays a key role in many age-related neurodegenerative conditions and other disorders. Light irradiation can initiate LPO through various mechanisms and is of importance in retinal and dermatological pathologies. The introduction of deuterated polyunsaturated fatty acids (D-PUFA) into membrane lipids is a promising approach for protection against LPO. Here, we report the protective effects of D-PUFA against the photodynamically induced LPO, using illumination in the presence of the photosensitizer trisulfonated aluminum phthalocyanine (AlPcS3) in liposomes and giant unilamellar vesicles (GUV), as assessed in four experimental models: 1) sulforhodamine B leakage from liposomes, detected with fluorescence correlation spectroscopy (FCS); 2) formation of diene conjugates in liposomal membranes, measured by absorbance at 234 nm; 3) membrane leakage in GUV assessed by optical phase-contrast intensity observations; 4) UPLC-MS/MS method to detect oxidized linoleic acid (Lin)-derived metabolites. Specifically, in liposomes or GUV containing H-PUFA (dilinoleyl-sn-glycero-3-phosphatidylcholine), light irradiation led to an extensive oxidative damage to bilayers. By contrast, no damage was observed in lipid bilayers containing 20% or more D-PUFA (D2-Lin or D10-docosahexanenoic acid). Remarkably, addition of tocopherol increased the dye leakage from liposomes in H-PUFA bilayers compared to photoirradiation alone, signifying tocopherol's pro-oxidant properties. However, in the presence of D-PUFA the opposite effect was observed, whereby adding tocopherol increased the resistance to LPO. These findings suggest a method to augment the protective effects of D-PUFA, which are currently undergoing clinical trials in several neurological and retinal diseases that involve LPO. © 2022 Elsevier B.V.

Firsov A.M.1 , Franco M.S.F.2 , Chistyakov D.V. 1 , Goriainov S.V. 3 , Sergeeva M.G. 1 , Kotova E.A.1 , Fomich M.A.4 , Bekish A.V.4 , Sharko O.L.4 , Shmanai V.V.4 , Itri R.5 , Baptista M.S.2 , Antonenko Y.N.1 , Shchepinov M.S.6
Elsevier B.V.
  • 1 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russian Federation
  • 2 Biochemistry Department, Institute of Chemistry, University of São Paulo (IQUSP), AV. Professor Lineu Prestes avenue, 748, USP, São Paulo, CEP: 05508-000, Brazil
  • 3 SREC PFUR Peoples' Friendship University of Russia, Moscow, Russian Federation
  • 4 Institute of Physical Organic Chemistry, National Academy of Science, Minsk, Belarus
  • 5 Applied Physics Department, Institute of Physics, University of São Paulo, Rua do Matão, 1371 (217-B.Jafet), Butantã, USP, São Paulo, 05508-090, Brazil
  • 6 Retrotope, Inc., Los Altos, CA 94022, United States
Ключевые слова
Age-related diseases; AMD; D-PUFA; Lipid peroxidation; Membrane; Photodynamic; Photosensitized oxidation; PUFA; Sun protection; Synergism; Tocopherol-Mediated Peroxidation; Trolox; α-Tocopherol
Дата создания
Дата изменения
Постоянная ссылка

Другие записи