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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...

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Autores principales: Kim, Seong-Jun, Ko, Wan-Kyu, Han, Gong-Ho, Lee, Daye, Lee, Yuhan, Sheen, Seung-Hun, Hong, Je-Beom, Sohn, Seil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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