Adverse Effects of Oseltamivir Phosphate Therapy on the Liver of LDLR-/- Mice Without Any Benefit on Atherosclerosis and Thrombosis.
Animals
Antiviral Agents
/ toxicity
Aorta
/ drug effects
Aortic Diseases
/ drug therapy
Atherosclerosis
/ drug therapy
Carotid Artery Thrombosis
/ drug therapy
Chemical and Drug Induced Liver Injury
/ etiology
Diet, High-Fat
Disease Models, Animal
Female
Liver
/ drug effects
Liver Cirrhosis
/ chemically induced
Mice, Knockout
Oseltamivir
/ toxicity
Plaque, Atherosclerotic
Receptors, LDL
/ deficiency
Risk Assessment
Journal
Journal of cardiovascular pharmacology
ISSN: 1533-4023
Titre abrégé: J Cardiovasc Pharmacol
Pays: United States
ID NLM: 7902492
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
received:
04
09
2020
accepted:
10
02
2021
pubmed:
25
3
2021
medline:
15
12
2021
entrez:
24
3
2021
Statut:
ppublish
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 neuraminidases 1 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 messenger RNA expression levels of F4/80, interleukin-1β, transforming growth factor-β1, matrix metalloproteinase-12, and collagen. Taken together, our findings suggest that oseltamivir phosphate has limited benefits on atherosclerosis and carotid thrombosis and may lead to adverse side effects on the liver with increased inflammation and fibrosis.
Identifiants
pubmed: 33760798
doi: 10.1097/FJC.0000000000001002
pii: 00005344-202105000-00016
doi:
Substances chimiques
Antiviral Agents
0
Receptors, LDL
0
Oseltamivir
20O93L6F9H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
660-672Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
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