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A novel mechanistic approach for the anti-fibrotic potential of rupatadine in rat liver via amendment of PAF/NF-ĸB p65/TGF-ß1 and hedgehog/HIF-1α/VEGF trajectories.
Didamoony, Manar A; Atwa, Ahmed M; Ahmed, Lamiaa A.
Afiliação
  • Didamoony MA; Pharmacology and Toxicology Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, 11829, Egypt. manar-didamoony@eru.edu.eg.
  • Atwa AM; Pharmacology and Toxicology Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, 11829, Egypt.
  • Ahmed LA; Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. lamiaa.ahmed@pharma.cu.edu.eg.
Inflammopharmacology ; 31(2): 845-858, 2023 Apr.
Article em En | MEDLINE | ID: mdl-36811777
Hepatic fibrosis is one of the major worldwide health concerns which requires tremendous research due to the limited outcomes of the current therapies. The present study was designed to assess, for the first time, the potential therapeutic effect of rupatadine (RUP) in diethylnitrosamine (DEN)-induced liver fibrosis and to explore its possible mechanistic actions. For the induction of hepatic fibrosis, rats were treated with DEN (100 mg/kg, i.p.) once weekly for 6 consecutive weeks, and on the 6th week, RUP (4 mg/kg/day, p.o.) was administered for 4 weeks. Treatment with RUP ameliorated changes in body weights, liver indices, liver function enzymes, and histopathological alterations induced by DEN. Besides, RUP amended oxidative stress, which led to the inhibition of PAF/NF-κB p65-induced inflammation, and, subsequently, prevention of TGF-ß1 elevation and HSCs activation as indicated by reduced α-SMA expression and collagen deposition. Moreover, RUP exerted significant anti-fibrotic and anti-angiogenic effects by suppressing Hh and HIF-1α/VEGF signaling pathways. Our results highlight, for the first time, a promising anti-fibrotic potential of RUP in rat liver. The molecular mechanisms underlying this effect involve the attenuation of PAF/NF-κB p65/TGF-ß1 and Hh pathways and, subsequently, the pathological angiogenesis (HIF-1α/VEGF).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: NF-kappa B / Fator de Crescimento Transformador beta1 Limite: Animals Idioma: En Revista: Inflammopharmacology Assunto da revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Egito

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: NF-kappa B / Fator de Crescimento Transformador beta1 Limite: Animals Idioma: En Revista: Inflammopharmacology Assunto da revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Egito