Meconic acid is a possible neuroprotector: justification on in vitro experiments and its physico-chemical properties

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Main representatives of gamma pyronic acid are meconic, comenic, chelidonic and kojic acid. It was found that comenic acid exerts a neuroprotective effect, and chelidonic acid has a pronounced anti-inflammatory effect. It was not studied whether meconic acid exhibits neuroprotective effects. The aim of this work was to assess the neuroprotective potential of meconic acid, taking into accout its physicochemical properties, using an in vitro model of ischemic stroke. Primary neuroglial culture was obtained from the cerebellum of 7-8-day-old Wistar rat pups by mechanical tissue dissociation. The protective effect of meconic acid on the culture of cerebellar neurons was studied using the model of glutamate toxicity and oxygen-glucose deprivation. Quantum mechanical calculations were used and experiments in the model system citrate-phosphate-luminol were conducted by the method of chemiluminescent analysis to investigate the antioxidant activity of meconic acid. The chelating properties of meconic acid with respect to Fe3+ in solutions were studied using Job's method. Meconic acid has been found to have a protective effect in in vitro models of ischemia. Its action leads to a decrease in the level of intracellular calcium and the restoration of the membrane potential of mitochondria in a culture of cerebellar neurons under glutamate exposure, resulting in an increase in the percentage of living cells under oxygen-glucose deprivation. Meconic acid has a high calculated antioxidant potential, confirmed experimentally. With an increase in the pH of the medium, stepwise binding of meconic acid with Fe3+ occurs with the formation of complexes with different ligand/metal ratios. At physiological pH, the composition of the resulting complex is 1:3. The obtained antioxidant, chelating, and cytoprotective action of meconic acid provides a basis for further study of the possible neuroprotective properties of this compound in in vivo experiments, and the data obtained in the work on its physicochemical properties can be useful for the synthesis and study of new coordination compounds based on meconic acid.

作者简介

S. Kozin

Kuban State University;Federal Research Center "Southern Scientific Center of the Russian Academy of Sciences"

Krasnodar, Russia;Rostov-on-Don, Russia

L. Ivashchenko

Kuban State University

Krasnodar, Russia

A. Kravtsov

Kuban State University;Federal Research Center "Southern Scientific Center of the Russian Academy of Sciences"

Krasnodar, Russia;Rostov-on-Don, Russia

L. Vasilyeva

Kuban State University

Krasnodar, Russia

A. Vasiliev

Kuban State University

Krasnodar, Russia

N. Bukov

Kuban State University

Krasnodar, Russia

A. Dorohova

Kuban State University;Federal Research Center "Southern Scientific Center of the Russian Academy of Sciences"

Email: 013194@mail.ru
Krasnodar, Russia;Rostov-on-Don, Russia

O. Lyasota

Kuban State University;Federal Research Center "Southern Scientific Center of the Russian Academy of Sciences"

Krasnodar, Russia;Rostov-on-Don, Russia

A. Bespalov

Kuban State University

Krasnodar, Russia

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