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Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model
Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chi...
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/PMC8398565/ https://www.ncbi.nlm.nih.gov/pubmed/34451889 http://dx.doi.org/10.3390/ph14080792 |
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author | Kim, Seong-Jun Ko, Wan-Kyu Han, Gong-Ho Lee, Daye Lee, Yuhan Sheen, Seung-Hun Hong, Je-Beom Sohn, Seil |
author_facet | Kim, Seong-Jun Ko, Wan-Kyu Han, Gong-Ho Lee, Daye Lee, Yuhan Sheen, Seung-Hun Hong, Je-Beom Sohn, Seil |
author_sort | Kim, Seong-Jun |
collection | PubMed |
description | Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases. |
format | Online Article Text |
id | pubmed-8398565 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83985652021-08-29 Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model Kim, Seong-Jun Ko, Wan-Kyu Han, Gong-Ho Lee, Daye Lee, Yuhan Sheen, Seung-Hun Hong, Je-Beom Sohn, Seil Pharmaceuticals (Basel) Article Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases. MDPI 2021-08-12 /pmc/articles/PMC8398565/ /pubmed/34451889 http://dx.doi.org/10.3390/ph14080792 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 Kim, Seong-Jun Ko, Wan-Kyu Han, Gong-Ho Lee, Daye Lee, Yuhan Sheen, Seung-Hun Hong, Je-Beom Sohn, Seil Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model |
title | Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model |
title_full | Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model |
title_fullStr | Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model |
title_full_unstemmed | Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model |
title_short | Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model |
title_sort | chirality-dependent anti-inflammatory effect of glutathione after spinal cord injury in an animal model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398565/ https://www.ncbi.nlm.nih.gov/pubmed/34451889 http://dx.doi.org/10.3390/ph14080792 |
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