Diosmin enhances the anti-angiogenic activity of sildenafil and pentoxifylline against hepatopulmonary syndrome via regulation of TNF-α/VEGF, IGF-1/PI3K/AKT, and FGF-1/ANG-2 signaling pathways.
Eur J Pharmacol
; 873: 173008, 2020 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-32050083
ABSTRACT
Hepatopulmonary syndrome (HPS) is a severe complication of hepatic cirrhosis, which is characterized by hypoxia, intrapulmonary vasodilation, inflammation, and angiogenesis. In this study, we aimed to investigate the regulatory effects of diosmin (DS) on selected phosphodiesterase inhibitors against chronic bile duct ligation (CBDL)-induced HPS. Experimentally, Wistar Albino rats were used and HPS was induced by CBDL for 28 days. DS (100 mg/kg, daily, P.O.), sildenafil (Sild; 10 mg/kg, twice daily, P.O.), and pentoxifylline (PTX; 50 mg/kg, daily, P.O.) were evaluated either alone or in combinations for their anti-angiogenic activity. CBDL significantly altered oxidative stress biomarkers and up-regulated pulmonary mRNA expressions of VEGF, IGF-1, ET-1, iNOS, eNOS, and ANG-2 as well as the protein expressions of vWF, FGF-1, PI3K, AKT, p-AKT, TGF-ß, HYP, MPO activity and circulating TNF-α. Treatment with DS, Sild, PTX, and their combinations significantly attenuated molecular and cellular changes due to CBDL. Improvement of histopathological changes was also observed after drug treatment which further supported our results. Furthermore, DS combination with Sild or PTX exhibited an improvement in HPS in comparison to each drug alone. Collectively, DS can augment the anti-angiogenic activity of Sild and PTX during HPS through regulation of TNF-α/VEGF, IGF-1/PI3K/AKT, and FGF-1/ANG-2 signaling pathways.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pentoxifilina
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Transdução de Sinais
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Síndrome Hepatopulmonar
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Inibidores da Angiogênese
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Diosmina
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Citrato de Sildenafila
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Egito
País de publicação:
HOLANDA
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HOLLAND
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NETHERLANDS
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NL
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PAISES BAJOS
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THE NETHERLANDS