Adverse effects of oseltamivir phosphate therapy on the liver of LDLR-/- mice without any benefit on atherosclerosis and thrombosis.
Fiche publication
Date publication
février 2021
Journal
Journal of cardiovascular pharmacology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BLAISE Sébastien, Dr BOULAGNON-ROMBI Camille, Dr SCHNEIDER Christophe, Dr BENNASROUNE Amar
Tous les auteurs :
Bocquet O, Wahart A, Sarazin T, Vincent E, Schneider C, Fougerat A, Gayral S, Henry A, Blaise S, Romier-Crouzet B, Boulagnon C, Jaisson S, Gillery PP, Bennasroune A, Sartelet H, Laffargue M, Martiny PL, Duca PL, Maurice P
Lien Pubmed
Résumé
Desialylation, governed by sialidases or neuraminidases, is strongly implicated in a wide range of human disorders, and accumulative data show that inhibition of neuraminidases, such as NEU1 sialidase, may be useful for managing atherosclerosis. Several studies have reported promising effects of oseltamivir phosphate, a widely used anti-influenza sialidase inhibitor, on human cancer cells, inflammation and insulin resistance. In this study, we evaluated the effects of oseltamivir phosphate on atherosclerosis and thrombosis and potential liver toxicity in LDLR-/- mice fed with high fat diet. Our results showed that oseltamivir phosphate significantly decreased plasma levels of LDL-cholesterol and elastin fragmentation in aorta. However, no effect was observed on both atherosclerotic plaque size in aortic roots and chemically-induced thrombosis in carotid arteries. Importantly, oseltamivir phosphate administration had adverse effects on the liver of mice and significantly increased mRNA expression levels of F4/80, IL-1β, TGF-β1, MMP-12 and collagen. Taken together, our findings suggest that oseltamivir phosphate has limited benefits on atherosclerosis and carotid thrombosis and may lead to side effects in the liver with increased inflammation and fibrosis.
Référence
J Cardiovasc Pharmacol. 2021 Feb 25;: