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

A M Firsov; M S F Franco; D V Chistyakov; S V Goriainov; M G Sergeeva; E A Kotova; M A Fomich; A V Bekish; O L Sharko; V V Shmanai; R Itri; M S Baptista; Y N Antonenko; M S Shchepinov

doi:10.1016/j.jphotobiol.2022.112425

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

J Photochem Photobiol B. 2022 Apr:229:112425. doi: 10.1016/j.jphotobiol.2022.112425. Epub 2022 Mar 4.

Authors

A M Firsov¹, M S F Franco², D V Chistyakov¹, S V Goriainov³, M G Sergeeva¹, E A Kotova¹, M A Fomich⁴, A V Bekish⁴, O L Sharko⁴, V V Shmanai⁴, R Itri⁵, M S Baptista⁶, Y N Antonenko¹, M S Shchepinov⁷

Affiliations

¹ Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia.
² Biochemistry Department, Institute of Chemistry, University of São Paulo (IQUSP), AV. Professor Lineu Prestes avenue, 748, USP, CEP: 05508-000 São Paulo, Brazil.
³ SREC PFUR Peoples' Friendship University of Russia, Moscow, Russia.
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, 05508-090 São Paulo, Brazil.
⁶ Biochemistry Department, Institute of Chemistry, University of São Paulo (IQUSP), AV. Professor Lineu Prestes avenue, 748, USP, CEP: 05508-000 São Paulo, Brazil. Electronic address: baptista@iq.usp.br.
⁷ Retrotope, Inc., Los Altos, 94022, CA, USA. Electronic address: shchepa65@yahoo.com.

PMID: 35276579
DOI: 10.1016/j.jphotobiol.2022.112425

Abstract

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.

Keywords: AMD; Age-related diseases; D-PUFA; Lipid peroxidation; Membrane; PUFA; Photodynamic; Photosensitized oxidation; Sun protection; Synergism; Tocopherol-Mediated Peroxidation; Trolox; α-Tocopherol.

MeSH terms

Chromatography, Liquid
Fatty Acids
Fatty Acids, Unsaturated / pharmacology
Lipid Bilayers*
Lipid Peroxidation
Liposomes
Tandem Mass Spectrometry*

Substances

Fatty Acids
Fatty Acids, Unsaturated
Lipid Bilayers
Liposomes