Vildagliptin ameliorates intrapulmonary vasodilatation and angiogenesis in chronic common bile duct ligation-induced hepatopulmonary syndrome in rat - 26/06/24
, Khaled A. Khalaf d, Mohamed Abdelhakim Mahdy eHighlights |
• | Hepatopulmonary syndrome is a frequent pulmonary complication of hepatic diseases with increased risk of mortality that was reproduced in male Wistar rats by common bile duct ligation. |
• | The potential effectiveness of vildagliptin in attenuating the experimental hepatopulmonary syndrome was evaluated. |
• | This is particularly important since no curative treatments for hepatopulmonary syndrome are proved to be effective till now, hence, new pharmaceutical molecules are required. |
• | Vildagliptin decreased intrapulmonary vasodilation and pulmonary angiogenesis through ET-1/NOS/NO and TNF-α/IL-6/VEGF-A signaling pathways regulation. |
• | These protective effects were attained, at least in part, via GLP-1R-dependent mechanisms. |
Abstract |
Introduction |
Experimental hepatopulmonary syndrome (HPS) is best reproduced in the rat common bile duct ligation (CBDL) model. Vildagliptin (Vild) is an anti-hyperglycemic drug that exerts beneficial anti-inflammatory, anti-oxidant and anti-fibrotic effects. Therefore, the present search aimed to explore the possible effectiveness of Vild in CBDL-induced HPS model.
Methods |
Four groups of male Wistar rats which weigh 220–270 g were used, including the normal control group, the sham control group, the CBDL group and CBDL+Vild group. The first three groups received i.p. saline, while the last group was treated with i.p. Vild (10 mg/kg/day) from the 15th to 28th day of the experiment.
Results |
CBDL decreased the survivability and body weight of rats, increased diameter of the pulmonary vessels, and altered the arterial blood gases and the liver function parameters. Additionally, it increased the pulmonary expressions of endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) mRNA as well as endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor-A (VEGF-A) proteins. The CBDL rats also exhibited elevation of the pulmonary interleukin-6 (IL-6), dipeptidyl peptidase-4 (DPP-4) and nitric oxide (NO) levels along with reduction of the pulmonary total anti-oxidant capacity and glucagon-like peptide-1 (GLP-1) levels. Vild mitigated these alterations and improved the histopathological abnormalities caused by CBDL.
Conclusion |
Vild effectively attenuated CBDL-induced HPS through its anti-oxidant and anti-inflammatory effects along with its modulatory effects on ET-1/NOS/NO and TNF-α/IL-6/VEGF-A signaling implicated in the regulation of intrapulmonary vasodilatation and angiogenesis, respectively.
Le texte complet de cet article est disponible en PDF.Keywords : Hepatopulmonary syndrome, Common bile duct ligation, Vildagliptin, Nitric oxide, Endothelin-1, Vascular endothelial growth factor-A
Abbreviations : ALP, ALT, AST, CBDL, DPP-4, eNOS, ET-1, ET-B, GGT, GLP-1, GLP-1R, HSI, HPS, IL-6, iNOS, NO, P(A-a)O2, PaCO2, PaO2, qRT-PCR, ROS, TNF-α, VEGF-A, Vild
Plan
Vol 48 - N° 7
Article 102408- août 2024 Retour au numéro
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