THE NANOMICELLAR COMPLEX OF Α-LIPOIC ACID AND CARNOSINE, WHICH HAS ANTIOXIDANT ACTIVITY: A STUDY IN VITRO AND IN VIVO

Issue: 
11
Year: 
2016

S.L. Stvolinskiy
Dr.Sc. (Biol.), Leading Research Scientist, Research Center of Neurology (Moscow)
E-mail: slstvolinsky@mail.ru
V.N. Prozorovskiy
Dr.Sc. (Biol.), Research Scientist, V.N. Orekhovich Research Institute of Biomedical Chemistry (Moscow)
D.S. Berezhnoy
Ph.D. (Biol.), Junior Research Scientist, Research Center of Neurology (Moscow)
O.I. Kulikova
Junior Research Scientist, Research Center of Neurology (Moscow)
D.A. Abaimov
Ph.D. (Biol.), Chief Research Scientist, Research Center of Neurology (Moscow)
T.N. Fedorova
Dr.Sc. (Biol.), Head of Laboratory, Research Center of Neurology (Moscow)

The water-soluble nanomicellar complex of carnosine and α-lipoic acid (C/LA-complex), a stable compound that retains its properties when stored in a lyophilized form, was obtained. Carnosine within the C/LA-complex showed enhanced resistance to hydrolysis by serum carnosinase compared to molecular carnosine: 44,9% of carnosine was hydrolyzed in 1 hour instead of 61,4%, 57,3% instead of 71,7% in 2 hours, and 72,2% instead of 83,3% in 3 hours accordingly. C/LA-complex is characterized by a higher direct antioxidant activity in iron-induced peroxidation of lipoproteins compared to the components constituting it. The direct antioxidant effect of C/LA-complex was registered at a concentration of 0,025 mM, and at 1 mM lipoprotein peroxidation was completely suppressed. 0,5 mM C/LA-complex increased lipoprotein resistance to oxidation by 36% and decreased oxidation rate by 35% which is more effective in comparison to carnosine. According to MTT assay, 0,25 mM C/LA-complex increased the viability 2 times in 6-hydroxydopamine (6- ОНDA) and 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) intoxication of SH-SY5Y neuroblastoma cells, differentiated to the dopaminergic cell-type, while α-lipoic acid and carnosine showed no protective effect. In the conditions of acute hypobaric hypoxia in rats the complex showed protective action comparable to carnosine efficiency. The obtained complex may be of interest for the development of highly efficient combined antioxidant drugs.

Keywords: 
Key words: carnosine
carnosine/α-lipoic acid complex
carnosinase
total antioxidant activity
human neuroblastoma SH-SY5Y
cytoprotection.