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Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve

Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal demyelination in the brain and spinal cord. Studies showed that iron released during the course of myelin breakdown exacerbates tissue damage, which is in agreement with the features of iron-dependent cell death, ferropt...

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Autores principales: Rayatpour, Atefeh, Foolad, Forough, Heibatollahi, Motahareh, Khajeh, Khosro, Javan, Mohammad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668997/
https://www.ncbi.nlm.nih.gov/pubmed/36385152
http://dx.doi.org/10.1038/s41598-022-24152-2
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author Rayatpour, Atefeh
Foolad, Forough
Heibatollahi, Motahareh
Khajeh, Khosro
Javan, Mohammad
author_facet Rayatpour, Atefeh
Foolad, Forough
Heibatollahi, Motahareh
Khajeh, Khosro
Javan, Mohammad
author_sort Rayatpour, Atefeh
collection PubMed
description Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal demyelination in the brain and spinal cord. Studies showed that iron released during the course of myelin breakdown exacerbates tissue damage, which is in agreement with the features of iron-dependent cell death, ferroptosis. Here, we aimed to investigate the possible contribution of ferroptosis in the demyelinated optic nerve, and to explore the effectiveness of ferroptosis inhibitor, deferiprone (DFP), on the extent of demyelination, inflammation and axonal damage. For this purpose, focal demyelination was induced by injection of lysolecithin (LPC), into the optic nerve of male C57BL/6J mice. Afterward, optic nerves were harvested at different time points from as early as 6 h up to 7 days post-LPC injection. Next, to evaluate the effectiveness of DFP two groups of animals received daily intraperitoneal injection of DFP for 3 or 7 continuous days. Vehicle groups received saline. Iron deposition was observed at different time points post-LPC injection from 6 h to 7 days post injection. Examining ferroptosis markers showed a significant reduction in glutathione content along with increased level of malondialdehyde and upregulated ferroptosis marker genes at early time points after injection. Besides, DFP treatment during the inflammatory phase of the model resulted in decreased microgliosis and inflammation. Reduced demyelination, microgliosis and astrogliosis was shown in mice that received DFP for 7 days. Moreover, DFP protected against axonal damage and retinal ganglion cells loss. Our results suggest the possible contribution of ferroptosis pathway in the process of demyelination. The therapeutic strategies targeting iron deposition, e.g. DFP treatment might thus represent a promising therapeutic target for patients with MS.
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spelling pubmed-96689972022-11-18 Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve Rayatpour, Atefeh Foolad, Forough Heibatollahi, Motahareh Khajeh, Khosro Javan, Mohammad Sci Rep Article Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal demyelination in the brain and spinal cord. Studies showed that iron released during the course of myelin breakdown exacerbates tissue damage, which is in agreement with the features of iron-dependent cell death, ferroptosis. Here, we aimed to investigate the possible contribution of ferroptosis in the demyelinated optic nerve, and to explore the effectiveness of ferroptosis inhibitor, deferiprone (DFP), on the extent of demyelination, inflammation and axonal damage. For this purpose, focal demyelination was induced by injection of lysolecithin (LPC), into the optic nerve of male C57BL/6J mice. Afterward, optic nerves were harvested at different time points from as early as 6 h up to 7 days post-LPC injection. Next, to evaluate the effectiveness of DFP two groups of animals received daily intraperitoneal injection of DFP for 3 or 7 continuous days. Vehicle groups received saline. Iron deposition was observed at different time points post-LPC injection from 6 h to 7 days post injection. Examining ferroptosis markers showed a significant reduction in glutathione content along with increased level of malondialdehyde and upregulated ferroptosis marker genes at early time points after injection. Besides, DFP treatment during the inflammatory phase of the model resulted in decreased microgliosis and inflammation. Reduced demyelination, microgliosis and astrogliosis was shown in mice that received DFP for 7 days. Moreover, DFP protected against axonal damage and retinal ganglion cells loss. Our results suggest the possible contribution of ferroptosis pathway in the process of demyelination. The therapeutic strategies targeting iron deposition, e.g. DFP treatment might thus represent a promising therapeutic target for patients with MS. Nature Publishing Group UK 2022-11-16 /pmc/articles/PMC9668997/ /pubmed/36385152 http://dx.doi.org/10.1038/s41598-022-24152-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rayatpour, Atefeh
Foolad, Forough
Heibatollahi, Motahareh
Khajeh, Khosro
Javan, Mohammad
Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve
title Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve
title_full Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve
title_fullStr Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve
title_full_unstemmed Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve
title_short Ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve
title_sort ferroptosis inhibition by deferiprone, attenuates myelin damage and promotes neuroprotection in demyelinated optic nerve
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668997/
https://www.ncbi.nlm.nih.gov/pubmed/36385152
http://dx.doi.org/10.1038/s41598-022-24152-2
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