Nebivolol hydrochloride and its impurities induce pseudo-allergic reactions via mast cell activation.
MRGPRX2
mast cells
nebivolol hydrochloride
pseudo‐allergic reactions
Journal
Journal of applied toxicology : JAT
ISSN: 1099-1263
Titre abrégé: J Appl Toxicol
Pays: England
ID NLM: 8109495
Informations de publication
Date de publication:
16 Sep 2024
16 Sep 2024
Historique:
revised:
03
09
2024
received:
28
07
2024
accepted:
05
09
2024
medline:
17
9
2024
pubmed:
17
9
2024
entrez:
17
9
2024
Statut:
aheadofprint
Résumé
Nebivolol hydrochloride is a third-generation β-blocker commonly used to treat cardiovascular diseases. However, it has been reported to induce allergic reactions in clinical use which deserves much attention. Therefore, this study focused on the ability of two isomers of nebivolol and chiral isomer impurities to induce allergic reactions. Our findings demonstrate that both nebivolol and two isomeric impurities can activate mast cell degranulation in vitro and show significant retention on Mas-related G-protein-coupled receptor X2 (MRGPRX2)-HEK293 cell membrane chromatography. These effects were further validated in vivo, where nebivolol and impurity IP-3 were observed to cause toe swelling and mast cell degranulation in mice. Molecular docking studies revealed interactions between these compounds and key amino acids of MRGPRX2, suggesting a mechanism for the induced allergic reactions. This work lays the foundation for improving the clinical safety of nebivolol.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Natural Science Basic Research Program in Shaanxi Province of China
ID : 2023-JC-YB-679
Organisme : National Natural Science Foundation of China
ID : 82373830
Organisme : National Natural Science Foundation of China
ID : 81930096
Organisme : National Natural Science Foundation of China
ID : 82304441
Informations de copyright
© 2024 John Wiley & Sons Ltd.
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