Publication:
The protective effect of vitamin U on valproic acid-induced lung toxicity in rats via amelioration of oxidative stress

dc.contributor.coauthorOztay, Fusun
dc.contributor.coauthorTunali, Sevim
dc.contributor.coauthorYanardag, Refiye
dc.contributor.departmentKUTTAM (Koç University Research Center for Translational Medicine)
dc.contributor.kuauthorKayalar, Özgecan
dc.contributor.schoolcollegeinstituteResearch Center
dc.date.accessioned2024-11-09T23:37:14Z
dc.date.issued2020
dc.description.abstractVitamin U (Vit U) is a novel free-radical scavenger. The protective effect of Vit U on valproic acid (VPA)-induced lung damage was examined. Rats were divided into four groups: control rats; rats given Vit U (50 mg/kg/d, by gavage) for 15 days; rats treated with VPA (500 mg/kg/d, intraperitoneally) for 15 days; and rats were given VPA + Vit U (in same dose and time). On the 16th day of the experiment, the lungs were collected from rats. Lung structure, pulmonary oxidant/antioxidant parameters and Nrf2, alpha-SMA, and collagen-1 were evaluated by microscopic and biochemical analysis. Additionally, it was determined the interactions of Vit U with Nrf2 and Keap1 by in silico analysis. VPA administration increased lipid peroxidation and the activity of lactate dehydrogenase and myeloperoxidase. However, it decreased the glutathione level, and the activities of glutathione peroxidase, glutathione-S-transferase, catalase, and superoxide dismutase. VPA-mediated oxidative stress prompted structural distortion and fibrotic alterations in the lung. Vit U supplementation reversed structural and biochemical alterations, induced antioxidant system through Nrf2 activation, and attenuated fibrosis by reducing collagen expression in VPA-administered rats. However, Vit U pretreatment was unable to reduce alpha-SMA levels in the lung of VPA-treated rats. Molecular docking analysis showed the binding of Vit U to ETGE motif leads to dissociation of Nrf2 from the Nrf2/Keap1 complex and its transfer to nuclei. In conclusion, Vit U attenuated VPA-induced tissue damage by restoring antioxidative systems through amelioration of Nrf2 activity in the lung under oxidative stress.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue12
dc.description.openaccessNO
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipBilimsel Arastirma Projeleri Birimi, Istanbul Universitesi [3319] Bilimsel Arastirma Projeleri Birimi, Istanbul Universitesi, Grant/Award Number: 3319
dc.description.volume34
dc.identifier.doi10.1002/jbt.22602
dc.identifier.eissn1099-0461
dc.identifier.issn1095-6670
dc.identifier.scopus2-s2.0-85089986946
dc.identifier.urihttps://doi.org/10.1002/jbt.22602
dc.identifier.urihttps://hdl.handle.net/20.500.14288/12771
dc.identifier.wos562469500001
dc.keywordsFibrosis
dc.keywordsNrf2
dc.keywordsPulmonary antioxidant system
dc.keywordsS-methyl methionine
dc.keywordsValproic acid
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofJournal Of Biochemical And Molecular Toxicology
dc.subjectBiochemistry
dc.subjectMolecular biology
dc.subjectToxicology
dc.titleThe protective effect of vitamin U on valproic acid-induced lung toxicity in rats via amelioration of oxidative stress
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorKayalar, Özgecan
local.publication.orgunit1Research Center
local.publication.orgunit2KUTTAM (Koç University Research Center for Translational Medicine)
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relation.isOrgUnitOfPublication.latestForDiscovery91bbe15d-017f-446b-b102-ce755523d939
relation.isParentOrgUnitOfPublicationd437580f-9309-4ecb-864a-4af58309d287
relation.isParentOrgUnitOfPublication.latestForDiscoveryd437580f-9309-4ecb-864a-4af58309d287

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