Sodium hydrosulfide moderately alleviates the hallmark symptoms of Duchenne muscular dystrophy in mdx mice

2023
journal article
article
dc.abstract.enDuchenne muscular dystrophy (DMD) is an incurable disease caused by mutations in the X-linked DMD gene that encodes a structural muscle protein, dystrophin. This, in turn, leads to progressive degeneration of the skeletal muscles and the heart. Hydrogen sulfide ($H_{2}S$), the pleiotropic agent with antioxidant, anti-inflammatory, and pro-angiogenic activities, could be considered a promising therapeutic factor for DMD. In this work, we studied the effect of daily intraperitoneal administration of the $H_{2}S$ donor, sodium hydrosulfide (NaHS, 100 μmol/kg/day for 5 weeks) on skeletal muscle (gastrocnemius, diaphragm and tibialis anterior) pathology in dystrophin-deficient mdx mice, characterized by decreased expression of $H_{2}S$-generating enzymes. NaHS reduced the level of muscle damage markers in plasma (creatine kinase, lactate dehydrogenase and osteopontin). It lowered oxidative stress by affecting the GSH/GSSG ratio, up-regulating the level of cytoprotective heme oxygenase-1 (HO-1) and down-regulating the NF-$\kappa$B pathway. In the gastrocnemius muscle, it also increased angiogenic vascular endothelial growth factor (Vegf) and its receptor (Kdr) expression, accompanied by the elevated number of $\alpha$-SMA/CD31/lectin-positive blood vessels. The expression of fibrotic regulators, like Tgf$\beta$, Col1a1 and Fn1 was decreased by NaHS in the tibialis anterior, while the level of autophagy markers (AMPK$\alpha$ signalling and Atg genes), was mostly affected in the gastrocnemius. Histological and molecular analysis showed no effect of $H_{2}S$ donor on regeneration and the muscle fiber type composition. Overall, the $H_{2}S$ donor modified the gene expression and protein level of molecules associated with the pathophysiology of DMD, contributing to the regulation of oxidative stress, inflammation, autophagy, and angiogenesis.pl
dc.affiliationSzkoła Doktorska Nauk Ścisłych i Przyrodniczychpl
dc.affiliationWydział Biochemii, Biofizyki i Biotechnologii : Zakład Biotechnologii Medycznejpl
dc.contributor.authorMyszka, Małgorzata - 260835 pl
dc.contributor.authorMucha, Olga - 206879 pl
dc.contributor.authorPodkalicka, Paulina - 201153 pl
dc.contributor.authorWaśniowska, Urszulapl
dc.contributor.authorDulak, Józef - 127818 pl
dc.contributor.authorŁoboda, Agnieszka - 130081 pl
dc.date.accessioned2023-08-09T07:46:44Z
dc.date.available2023-08-09T07:46:44Z
dc.date.issued2023pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.versionostateczna wersja wydawcy
dc.description.volume955pl
dc.identifier.articleid175928pl
dc.identifier.doi10.1016/j.ejphar.2023.175928pl
dc.identifier.eissn1879-0712pl
dc.identifier.issn0014-2999pl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/317609
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeinne
dc.subject.enDMDpl
dc.subject.enDuchenne muscular dystrophypl
dc.subject.enhydrogen sulfidepl
dc.subject.enNaHSpl
dc.subject.ensodium hydrosulfidepl
dc.subject.enmdxpl
dc.subtypeArticlepl
dc.titleSodium hydrosulfide moderately alleviates the hallmark symptoms of Duchenne muscular dystrophy in mdx micepl
dc.title.journalEuropean Journal of Pharmacologypl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
Duchenne muscular dystrophy (DMD) is an incurable disease caused by mutations in the X-linked DMD gene that encodes a structural muscle protein, dystrophin. This, in turn, leads to progressive degeneration of the skeletal muscles and the heart. Hydrogen sulfide ($H_{2}S$), the pleiotropic agent with antioxidant, anti-inflammatory, and pro-angiogenic activities, could be considered a promising therapeutic factor for DMD. In this work, we studied the effect of daily intraperitoneal administration of the $H_{2}S$ donor, sodium hydrosulfide (NaHS, 100 μmol/kg/day for 5 weeks) on skeletal muscle (gastrocnemius, diaphragm and tibialis anterior) pathology in dystrophin-deficient mdx mice, characterized by decreased expression of $H_{2}S$-generating enzymes. NaHS reduced the level of muscle damage markers in plasma (creatine kinase, lactate dehydrogenase and osteopontin). It lowered oxidative stress by affecting the GSH/GSSG ratio, up-regulating the level of cytoprotective heme oxygenase-1 (HO-1) and down-regulating the NF-$\kappa$B pathway. In the gastrocnemius muscle, it also increased angiogenic vascular endothelial growth factor (Vegf) and its receptor (Kdr) expression, accompanied by the elevated number of $\alpha$-SMA/CD31/lectin-positive blood vessels. The expression of fibrotic regulators, like Tgf$\beta$, Col1a1 and Fn1 was decreased by NaHS in the tibialis anterior, while the level of autophagy markers (AMPK$\alpha$ signalling and Atg genes), was mostly affected in the gastrocnemius. Histological and molecular analysis showed no effect of $H_{2}S$ donor on regeneration and the muscle fiber type composition. Overall, the $H_{2}S$ donor modified the gene expression and protein level of molecules associated with the pathophysiology of DMD, contributing to the regulation of oxidative stress, inflammation, autophagy, and angiogenesis.
dc.affiliationpl
Szkoła Doktorska Nauk Ścisłych i Przyrodniczych
dc.affiliationpl
Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Biotechnologii Medycznej
dc.contributor.authorpl
Myszka, Małgorzata - 260835
dc.contributor.authorpl
Mucha, Olga - 206879
dc.contributor.authorpl
Podkalicka, Paulina - 201153
dc.contributor.authorpl
Waśniowska, Urszula
dc.contributor.authorpl
Dulak, Józef - 127818
dc.contributor.authorpl
Łoboda, Agnieszka - 130081
dc.date.accessioned
2023-08-09T07:46:44Z
dc.date.available
2023-08-09T07:46:44Z
dc.date.issuedpl
2023
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
955
dc.identifier.articleidpl
175928
dc.identifier.doipl
10.1016/j.ejphar.2023.175928
dc.identifier.eissnpl
1879-0712
dc.identifier.issnpl
0014-2999
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/317609
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
inne
dc.subject.enpl
DMD
dc.subject.enpl
Duchenne muscular dystrophy
dc.subject.enpl
hydrogen sulfide
dc.subject.enpl
NaHS
dc.subject.enpl
sodium hydrosulfide
dc.subject.enpl
mdx
dc.subtypepl
Article
dc.titlepl
Sodium hydrosulfide moderately alleviates the hallmark symptoms of Duchenne muscular dystrophy in mdx mice
dc.title.journalpl
European Journal of Pharmacology
dc.typepl
JournalArticle
dspace.entity.type
Publication

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