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Insulin and Brain Gangliosides Prevent Metabolic Disorders Caused by Activation of Free Radical Reactions after Two-Vessel Ischemia–Reperfusion Injury to the Rat Forebrain

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Abstract

The ability of insulin and gangliosides, administered separately or jointly, to increase the viability of cultured brain cortical neurons under conditions of oxidative stress and to normalize metabolic disorders in the rat brain cortex caused by the activation of free radical reactions after forebrain ischemia and subsequent reperfusion were studied. Preincubation of brain cortical neurons with insulin and/or brain ganglioside GM1 significantly increased the viability of the cells when exposed to hydrogen peroxide. Two-vessel forebrain ischemia–reperfusion caused an oxidative inactivation of Na+,K+-ATPase and significant elevation in various lipid peroxidation products. Both separate and joint administration of insulin (0.25 IU/rat, i.n.) or brain gangliosides (15 mg/kg, i.v.) prevented the accumulation of Schiff bases and significantly increased Na+,K+-ATPase activity in the ischemized and reperfused rat brain cortex. Co-administration of insulin and gangliosides at the above, relatively low, doses led to no reciprocal enhancement of the effects of both neuroprotectors. At the same time, the effect of intranasal insulin administration at a dose of 0.5 IU/rat was more pronounced than at 0.25 IU/rat. Insulin administration at a dose of 0.5 IU/rat normalized the levels of conjugated di- and trienes and Schiff bases, as well as Na+,K+-ATPase activity, in the ischemized and reperfused rat brain cortex. These findings indicate the ability of insulin and brain gangliosides to prevent or diminish a reduction in the number of survived cultured neurons under conditions of oxidative stress and metabolic disorders in the brain cortex caused by the activation of free radical reactions in the ischemized and reperfused rat forebrain, with no additivity observed in insulin and ganglioside effects.

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Funding

This work was supported by the assignment of the Ministry of Science and Higher Education of the Russian Federation to the Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (AAAA-A18-118012290427-7).

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  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    I. O. Zakharova, L. V. Bayunova, I. I. Zorina, A. O. Shpakov & N. F. Avrova

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  1. I. O. Zakharova
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  2. L. V. Bayunova
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  3. I. I. Zorina
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Contributions

Conceptualization (A.O.S., N.F.A., I.O.Z.); methodology (N.F.A., A.O.S., L.V.B.); validation (L.V.B.); investigation (I.O.Z., L.V.B., I.I.Z.); writing and editing (N.F.A., I.O.Z., A.O.S., L.V.B.).

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Correspondence to N. F. Avrova.

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The authors declare that they have neither evident nor potential conflict of interest in relation with the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 2, pp. 262–278https://doi.org/10.31857/S086981392202011X.

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Zakharova, I.O., Bayunova, L.V., Zorina, I.I. et al. Insulin and Brain Gangliosides Prevent Metabolic Disorders Caused by Activation of Free Radical Reactions after Two-Vessel Ischemia–Reperfusion Injury to the Rat Forebrain. J Evol Biochem Phys 58, 279–291 (2022). https://doi.org/10.1134/S0022093022010240

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