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Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice †
Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199319/ https://www.ncbi.nlm.nih.gov/pubmed/34206048 http://dx.doi.org/10.3390/ijms22115995 |
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author | Davuljigari, Chand Basha Ekuban, Frederick Adams Zong, Cai Fergany, Alzahraa A. M. Morikawa, Kota Ichihara, Gaku |
author_facet | Davuljigari, Chand Basha Ekuban, Frederick Adams Zong, Cai Fergany, Alzahraa A. M. Morikawa, Kota Ichihara, Gaku |
author_sort | Davuljigari, Chand Basha |
collection | PubMed |
description | Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity. |
format | Online Article Text |
id | pubmed-8199319 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81993192021-06-14 Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice † Davuljigari, Chand Basha Ekuban, Frederick Adams Zong, Cai Fergany, Alzahraa A. M. Morikawa, Kota Ichihara, Gaku Int J Mol Sci Article Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity. MDPI 2021-06-01 /pmc/articles/PMC8199319/ /pubmed/34206048 http://dx.doi.org/10.3390/ijms22115995 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 Davuljigari, Chand Basha Ekuban, Frederick Adams Zong, Cai Fergany, Alzahraa A. M. Morikawa, Kota Ichihara, Gaku Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice † |
title | Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice † |
title_full | Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice † |
title_fullStr | Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice † |
title_full_unstemmed | Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice † |
title_short | Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice † |
title_sort | nrf2 activation attenuates acrylamide-induced neuropathy in mice † |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199319/ https://www.ncbi.nlm.nih.gov/pubmed/34206048 http://dx.doi.org/10.3390/ijms22115995 |
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