Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin

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dc.contributor.authorAyik, Seyhan
dc.contributor.authorGunata, Mehmet
dc.contributor.authorOzhan, Onural
dc.contributor.authorYildiz, Azibe
dc.contributor.authorVardi, Nigar
dc.contributor.authorSonmez, Emre
dc.contributor.authorErmis, Necip
dc.date.accessioned2026-04-04T13:33:22Z
dc.date.available2026-04-04T13:33:22Z
dc.date.issued2024
dc.departmentİnönü Üniversitesi
dc.description.abstractBackgroundDespite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor.ObjectivesWe aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH.MethodsThe rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 mu g/kg/day ALA, 10 mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed.ResultsMonotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima-media (TIM) thickness, PCNA and alpha-SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and alpha-SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf-2 was increased in MCT-treated rats, MEL reduced it.ConclusionALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti-remodeling, antihypertrophic, anti-inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes.
dc.description.sponsorshipInonu Universitesi [TCD-2020-2275]
dc.description.sponsorshipInonu Universitesi, Grant/Award Number: TCD-2020-2275
dc.identifier.doi10.1111/fcp.13033
dc.identifier.endpage1154
dc.identifier.issn0767-3981
dc.identifier.issn1472-8206
dc.identifier.issue6
dc.identifier.orcid0000-0001-6494-8923
dc.identifier.orcid0000-0001-9018-7849
dc.identifier.orcid0000-0001-6905-4259
dc.identifier.orcid0000-0001-6781-7478
dc.identifier.orcid0000-0002-6637-9944
dc.identifier.orcid0000-0001-9497-3468
dc.identifier.orcid0000-0002-8766-9094
dc.identifier.pmid39128482
dc.identifier.scopus2-s2.0-85201022421
dc.identifier.scopusqualityQ2
dc.identifier.startpage1143
dc.identifier.urihttps://doi.org/10.1111/fcp.13033
dc.identifier.urihttps://hdl.handle.net/11616/109102
dc.identifier.volume38
dc.identifier.wosWOS:001288209600001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofFundamental & Clinical Pharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectalamandine
dc.subjectmelatonin
dc.subjectmonocrotaline
dc.subjectpulmonary arterial hypertension
dc.subjectright ventricular systolic pressure
dc.titleAlamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin
dc.typeArticle

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