Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury

Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effectiv...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Irina O. Zakharova, Liubov V. Bayunova, Inna I. Zorina, Tatiana V. Sokolova, Alexander O. Shpakov, Natalia F. Avrova
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	insulin α-tocopherol protection cortical neurons oxidative stress brain cortex Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/860e5497ce8a4f2db16e093cdfd4d935
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:860e5497ce8a4f2db16e093cdfd4d935
record_format	dspace
spelling	oai:doaj.org-article:860e5497ce8a4f2db16e093cdfd4d9352021-11-11T17:13:22ZInsulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury10.3390/ijms2221117681422-00671661-6596https://doaj.org/article/860e5497ce8a4f2db16e093cdfd4d9352021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11768https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effective dose. Our aim was thus to study the efficiency of combined use of insulin and α-tocopherol (α-T) to increase the viability of cultured cortical neurons under oxidative stress conditions and to normalize the metabolic disturbances caused by free radical reaction activation in brain cortex of rats with two-vessel forebrain ischemia/reperfusion injury. Immunoblotting, flow cytometry, colorimetric, and fluorometric techniques were used. α-T enhanced the protective and antioxidative effects of insulin on neurons in oxidative stress, their effects were additive. At the late stages of oxidative stress, the combined action of insulin and α-T increased Akt-kinase activity, inactivated GSK-3beta and normalized ERK1/2 activity in cortical neurons, it was more effective than either drug action. In the brain cortex, ischemia/reperfusion increased the lipid peroxidation product content and caused Na<sup>+</sup>,K<sup>+</sup>-ATPase oxidative inactivation. Co-administration of insulin (intranasally, 0.25 IU/rat) and α-T (orally, 50 mg/kg) led to a more pronounced normalization of the levels of Schiff bases, conjugated dienes and trienes and Na<sup>+</sup>,K<sup>+</sup>-ATPase activity than administration of each drug alone. Thus, α-T enhances the protective effects of insulin on cultured cortical neurons in oxidative stress and in the brain cortex of rats with cerebral ischemia/reperfusion injury.Irina O. ZakharovaLiubov V. BayunovaInna I. ZorinaTatiana V. SokolovaAlexander O. ShpakovNatalia F. AvrovaMDPI AGarticleinsulinα-tocopherolprotectioncortical neuronsoxidative stressbrain cortexBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11768, p 11768 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	insulin α-tocopherol protection cortical neurons oxidative stress brain cortex Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	insulin α-tocopherol protection cortical neurons oxidative stress brain cortex Biology (General) QH301-705.5 Chemistry QD1-999 Irina O. Zakharova Liubov V. Bayunova Inna I. Zorina Tatiana V. Sokolova Alexander O. Shpakov Natalia F. Avrova Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury
description	Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effective dose. Our aim was thus to study the efficiency of combined use of insulin and α-tocopherol (α-T) to increase the viability of cultured cortical neurons under oxidative stress conditions and to normalize the metabolic disturbances caused by free radical reaction activation in brain cortex of rats with two-vessel forebrain ischemia/reperfusion injury. Immunoblotting, flow cytometry, colorimetric, and fluorometric techniques were used. α-T enhanced the protective and antioxidative effects of insulin on neurons in oxidative stress, their effects were additive. At the late stages of oxidative stress, the combined action of insulin and α-T increased Akt-kinase activity, inactivated GSK-3beta and normalized ERK1/2 activity in cortical neurons, it was more effective than either drug action. In the brain cortex, ischemia/reperfusion increased the lipid peroxidation product content and caused Na<sup>+</sup>,K<sup>+</sup>-ATPase oxidative inactivation. Co-administration of insulin (intranasally, 0.25 IU/rat) and α-T (orally, 50 mg/kg) led to a more pronounced normalization of the levels of Schiff bases, conjugated dienes and trienes and Na<sup>+</sup>,K<sup>+</sup>-ATPase activity than administration of each drug alone. Thus, α-T enhances the protective effects of insulin on cultured cortical neurons in oxidative stress and in the brain cortex of rats with cerebral ischemia/reperfusion injury.
format	article
author	Irina O. Zakharova Liubov V. Bayunova Inna I. Zorina Tatiana V. Sokolova Alexander O. Shpakov Natalia F. Avrova
author_facet	Irina O. Zakharova Liubov V. Bayunova Inna I. Zorina Tatiana V. Sokolova Alexander O. Shpakov Natalia F. Avrova
author_sort	Irina O. Zakharova
title	Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury
title_short	Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury
title_full	Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury
title_fullStr	Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury
title_full_unstemmed	Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury
title_sort	insulin and α-tocopherol enhance the protective effect of each other on brain cortical neurons under oxidative stress conditions and in rat two-vessel forebrain ischemia/reperfusion injury
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/860e5497ce8a4f2db16e093cdfd4d935
work_keys_str_mv	AT irinaozakharova insulinandatocopherolenhancetheprotectiveeffectofeachotheronbraincorticalneuronsunderoxidativestressconditionsandinrattwovesselforebrainischemiareperfusioninjury AT liubovvbayunova insulinandatocopherolenhancetheprotectiveeffectofeachotheronbraincorticalneuronsunderoxidativestressconditionsandinrattwovesselforebrainischemiareperfusioninjury AT innaizorina insulinandatocopherolenhancetheprotectiveeffectofeachotheronbraincorticalneuronsunderoxidativestressconditionsandinrattwovesselforebrainischemiareperfusioninjury AT tatianavsokolova insulinandatocopherolenhancetheprotectiveeffectofeachotheronbraincorticalneuronsunderoxidativestressconditionsandinrattwovesselforebrainischemiareperfusioninjury AT alexanderoshpakov insulinandatocopherolenhancetheprotectiveeffectofeachotheronbraincorticalneuronsunderoxidativestressconditionsandinrattwovesselforebrainischemiareperfusioninjury AT nataliafavrova insulinandatocopherolenhancetheprotectiveeffectofeachotheronbraincorticalneuronsunderoxidativestressconditionsandinrattwovesselforebrainischemiareperfusioninjury
_version_	1718432128822149120

Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury

Ejemplares similares