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A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration

Oxidative stress (OS) plays a key role in retinal dysfunctions and acts as a major trigger of inflammatory and neurodegenerative processes in several retinal diseases. To prevent OS-induced retinal damage, approaches based on the use of natural compounds are actively investigated. Recently, structur...

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Autores principales: Rossino, Maria Grazia, Amato, Rosario, Amadio, Marialaura, Rosini, Michela, Basagni, Filippo, Cammalleri, Maurizio, Dal Monte, Massimo, Casini, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389314/
https://www.ncbi.nlm.nih.gov/pubmed/34439544
http://dx.doi.org/10.3390/antiox10081296
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author Rossino, Maria Grazia
Amato, Rosario
Amadio, Marialaura
Rosini, Michela
Basagni, Filippo
Cammalleri, Maurizio
Dal Monte, Massimo
Casini, Giovanni
author_facet Rossino, Maria Grazia
Amato, Rosario
Amadio, Marialaura
Rosini, Michela
Basagni, Filippo
Cammalleri, Maurizio
Dal Monte, Massimo
Casini, Giovanni
author_sort Rossino, Maria Grazia
collection PubMed
description Oxidative stress (OS) plays a key role in retinal dysfunctions and acts as a major trigger of inflammatory and neurodegenerative processes in several retinal diseases. To prevent OS-induced retinal damage, approaches based on the use of natural compounds are actively investigated. Recently, structural features from curcumin and diallyl sulfide have been combined in a nature-inspired hybrid (NIH1), which has been described to activate transcription nuclear factor erythroid-2-related factor-2 (Nrf2), the master regulator of the antioxidant response, in different cell lines. We tested the antioxidant properties of NIH1 in mouse retinal explants. NIH1 increased Nrf2 nuclear translocation, Nrf2 expression, and both antioxidant enzyme expression and protein levels after 24 h or six days of incubation. Possible toxic effects of NIH1 were excluded since it did not alter the expression of apoptotic or gliotic markers. In OS-treated retinal explants, NIH1 strengthened the antioxidant response inducing a massive and persistent expression of antioxidant enzymes up to six days of incubation. These effects resulted in prevention of the accumulation of reactive oxygen species, of apoptotic cell death, and of gliotic reactivity. Together, these data indicate that a strategy based on NIH1 to counteract OS could be effective for the treatment of retinal diseases.
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spelling pubmed-83893142021-08-27 A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration Rossino, Maria Grazia Amato, Rosario Amadio, Marialaura Rosini, Michela Basagni, Filippo Cammalleri, Maurizio Dal Monte, Massimo Casini, Giovanni Antioxidants (Basel) Article Oxidative stress (OS) plays a key role in retinal dysfunctions and acts as a major trigger of inflammatory and neurodegenerative processes in several retinal diseases. To prevent OS-induced retinal damage, approaches based on the use of natural compounds are actively investigated. Recently, structural features from curcumin and diallyl sulfide have been combined in a nature-inspired hybrid (NIH1), which has been described to activate transcription nuclear factor erythroid-2-related factor-2 (Nrf2), the master regulator of the antioxidant response, in different cell lines. We tested the antioxidant properties of NIH1 in mouse retinal explants. NIH1 increased Nrf2 nuclear translocation, Nrf2 expression, and both antioxidant enzyme expression and protein levels after 24 h or six days of incubation. Possible toxic effects of NIH1 were excluded since it did not alter the expression of apoptotic or gliotic markers. In OS-treated retinal explants, NIH1 strengthened the antioxidant response inducing a massive and persistent expression of antioxidant enzymes up to six days of incubation. These effects resulted in prevention of the accumulation of reactive oxygen species, of apoptotic cell death, and of gliotic reactivity. Together, these data indicate that a strategy based on NIH1 to counteract OS could be effective for the treatment of retinal diseases. MDPI 2021-08-16 /pmc/articles/PMC8389314/ /pubmed/34439544 http://dx.doi.org/10.3390/antiox10081296 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rossino, Maria Grazia
Amato, Rosario
Amadio, Marialaura
Rosini, Michela
Basagni, Filippo
Cammalleri, Maurizio
Dal Monte, Massimo
Casini, Giovanni
A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration
title A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration
title_full A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration
title_fullStr A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration
title_full_unstemmed A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration
title_short A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration
title_sort nature-inspired nrf2 activator protects retinal explants from oxidative stress and neurodegeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389314/
https://www.ncbi.nlm.nih.gov/pubmed/34439544
http://dx.doi.org/10.3390/antiox10081296
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