Ivan Tikhonov
P.G. Demidov Yaroslavl State university, Yaroslavl, Russia
Title: Nitroxyl radicals as antioxidants against lipid peroxidation: an in vitro study
Biography
Biography: Ivan Tikhonov
Abstract
Nitroxyl radicals (>NO·) exhibit a set of unique properties (ease of single-electron transfer, paramagnetic properties, cell permeability, antioxidant activity), which makes them attractive for use as drug components. It is known that >NO· catalytically dismute the superoxide anion, inhibit the oxidation of lipids, protect DNA from radicals. We investigated the mechanism of antioxidant action of nitroxyl radicals using a simplified model of lipid membrane (methyl linoleate (LH) in micelles). It has been established that >NO· effectively inhibit azo-initiated LH oxidation even at concentrations of ~10–6 M. Antioxidant activity of >NO· increases with increasing its lipophilicity. Each >NO· radical breaks 2-5 oxidation chains, i.e. the regeneration of antioxidant takes place. This effect is explained by the reaction >NO· + HO2· ® >NOH + O2, while HO2· radical is formed upon the LH oxidation in micelles. This conclusion is confirmed by the results of superoxide dismutase enzyme effect on the kinetics of the process: the antioxidant activity of >NO· decreases, and one >NO· radical terminates one oxidation chain, since the >NO· and HO2· interaction is eliminated. The piperidine-based radicals with a low reduction potential of the oxoammonium cation / nitroxyl radical pair, in particular 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), have the greatest antioxidant activity during the oxidation of LH in the presence of a source of O2·–/HO2· radicals. This results can be useful for the selection of >NO· structures for testing as drug components to protect against the oxidative stress.
The research is supported by RSF grant No. 14-23-00018.