Amitriptyline attenuates bleomycin-induced pulmonary fibrosis: modulation of the expression of NF-κβ, iNOS, and Nrf2

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dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorZaafan M.A.
dc.contributor.authorHaridy A.R.
dc.contributor.authorAbdelhamid A.M.
dc.contributor.otherPharmacology and Toxicology Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober University for Modern Sciences and Arts (MSA)
dc.contributor.other6th of October
dc.contributor.otherEgypt; Biochemistry Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober University for Modern Sciences and Arts (MSA)
dc.contributor.other6th of October
dc.contributor.otherEgypt
dc.date.accessioned2020-01-09T20:40:39Z
dc.date.available2020-01-09T20:40:39Z
dc.date.issued2019
dc.descriptionScopus
dc.description.abstractAmitriptyline is a tricyclic antidepressant that was suggested to have antifibrotic potential. The current study aimed to investigate the modulatory effects of amitriptyline on bleomycin-induced pulmonary fibrosis in rats. Rats were randomly assigned into 4 groups: normal control, bleomycin control, amitriptyline+bleomycin, and amitriptyline only treated group. Lung injury was evaluated through the histological examination and immunohistochemical detection of ?-smooth muscle actin (?-SMA) in lung tissue, in addition to the biochemical assessment of pulmonary contents of hydroxyproline and transforming growth factor beta-1 (TGF-?1). In addition, the following parameters were investigated for studying the possible mechanisms of amitriptyline antifibrotic effect: inducible nitric oxide synthase (iNOS), nuclear factor-?? (NF-??), tumor necrosis factor-alpha (TNF-?), serpine-1, p53, nuclear factor erythroid 2-related factor 2 (Nrf2), lipid peroxides, and reduced glutathione (GSH). Amitriptyline exhibited potent antifibrotic effect that was reflected upon the histopathological examination and through its ability to suppress all the fibrotic parameters. Amitriptyline successfully suppressed the expression of NF-??, Nrf2, iNOS, and p53 in lung tissues besides the inhibition of other oxidative stress and inflammatory mediators. Amitriptyline could be a promising treatment to pulmonary fibrosis. Amitriptyline not only prevents the depression and its drawbacks in patients suffering from pulmonary fibrosis but also it can suppress fibrosis through variable mechanisms mainly via inhibition of NF-??/TNF-?/TGF-? pathway in addition to inhibition of Nrf2 and iNOS expression. � 2018, Springer-Verlag GmbH Germany, part of Springer Nature.en_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=20427&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.1007/s00210-018-1586-1
dc.identifier.doiPubMed ID 30474696
dc.identifier.issn281298
dc.identifier.otherhttps://doi.org/10.1007/s00210-018-1586-1
dc.identifier.otherPubMed ID 30474696
dc.identifier.urihttps://t.ly/zNMEX
dc.language.isoEnglishen_US
dc.publisherSpringer Verlagen_US
dc.relation.ispartofseriesNaunyn-Schmiedeberg's Archives of Pharmacology
dc.relation.ispartofseries392
dc.subjectAmitriptylineen_US
dc.subjectiNOSen_US
dc.subjectNrf2en_US
dc.subjectNuclear factor-??en_US
dc.subjectPulmonary fibrosisen_US
dc.subjectalpha smooth muscle actinen_US
dc.subjectamitriptylineen_US
dc.subjectcollagenen_US
dc.subjectglutathioneen_US
dc.subjecthydroxyprolineen_US
dc.subjectimmunoglobulin enhancer binding proteinen_US
dc.subjectinducible nitric oxide synthaseen_US
dc.subjectlipid peroxideen_US
dc.subjectprotein p53en_US
dc.subjecttranscription factor Nrf2en_US
dc.subjecttransforming growth factor beta1en_US
dc.subjectamitriptylineen_US
dc.subjectbleomycinen_US
dc.subjectimmunoglobulin enhancer binding proteinen_US
dc.subjectinducible nitric oxide synthaseen_US
dc.subjectNfe2l2 protein, raten_US
dc.subjectNos2 protein, raten_US
dc.subjecttranscription factor Nrf2en_US
dc.subjectanimal experimenten_US
dc.subjectanimal modelen_US
dc.subjectanimal tissueen_US
dc.subjectantifibrotic activityen_US
dc.subjectArticleen_US
dc.subjectbleomycin-induced pulmonary fibrosisen_US
dc.subjectcell infiltrationen_US
dc.subjectcontrolled studyen_US
dc.subjectinflammatory cellen_US
dc.subjectlung parenchymaen_US
dc.subjectmaleen_US
dc.subjectnonhumanen_US
dc.subjectprotein expressionen_US
dc.subjectraten_US
dc.subjectanimalen_US
dc.subjectdrug effecten_US
dc.subjectlungen_US
dc.subjectlung fibrosisen_US
dc.subjectmetabolismen_US
dc.subjectpathologyen_US
dc.subjectWistar raten_US
dc.subjectAmitriptylineen_US
dc.subjectAnimalsen_US
dc.subjectBleomycinen_US
dc.subjectLungen_US
dc.subjectMaleen_US
dc.subjectNF-E2-Related Factor 2en_US
dc.subjectNF-kappa Ben_US
dc.subjectNitric Oxide Synthase Type IIen_US
dc.subjectPulmonary Fibrosisen_US
dc.subjectRats, Wistaren_US
dc.titleAmitriptyline attenuates bleomycin-induced pulmonary fibrosis: modulation of the expression of NF-κβ, iNOS, and Nrf2en_US
dc.typeArticleen_US
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