Effect of the estrogen receptor antagonist fulvestrant on the cirrhotic rat lung.
Fiche publication
Date publication
mars 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr AGIN Arnaud, Pr SCHINI-KERTH Valérie, Pr GENY Bernard
Tous les auteurs :
Oswald-Mammosser M, Rashid S, Boehm N, Agin A, Geny B, Kerth VS, Charloux A
Lien Pubmed
Résumé
It has been postulated that cirrhosis-related lung vasodilatation and the subsequent hepatopulmonary syndrome is partly explained by an increased estradiol level through an enhanced endothelial formation of nitric oxide (NO). In this study we assessed whether the estrogen receptor antagonist fulvestrant (F) improves cirrhosis-related lung abnormalities. Cirrhosis was induced in rats by chronic bile duct ligation (CBDL). Four groups were studied: CBDL, CBDL+F, sham, sham+F. Histological, immunohistochemical and western blot analyses were performed on lung samples. In the lung, the endothelial nitric oxide synthase (eNOS), and the nitrotyrosine protein expressions were increased in CBDL as compared to sham rats. Both parameters were significantly reduced by fulvestrant in the CBDL rats. Surprisingly, the level of pVASP (an indirect marker of NO formation and action) was decreased in CBDL rats and fulvestrant had no effect on this parameter. The level of the vascular endothelial growth factor, the diameter of small lung vessels and the number of macrophages were increased in CBDL lungs in comparison to sham lungs and these parameters were unaffected by fulvestrant treatment. In conclusion, fulvestrant may not be relevant to improve lung abnormalities in cirrhosis since NO may not be biologically active and since key events contributing to the lung abnormalities are not affected by fulvestrant. This article is protected by copyright. All rights reserved.
Référence
Fundam Clin Pharmacol. 2015 Mar 7