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Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice

Metabolites/impurities (MIs) of penicillin are normally considered to be the main substances inducing immediate hypersensitivity reactions in penicillin treatment. Our previous research found that penicillin can cause non-allergic hypersensitivity reactions (NAHRs) by directly triggering vascular hy...

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Autores principales: Wang, Dunfang, Han, Jiayin, Pan, Chen, Li, Chunying, Zhao, Yong, Liu, Suyan, Zhang, Yushi, Tian, Jingzhuo, Yi, Yan, Zhu, Jingjing, Liu, Chenyue, Wang, Yuan, Xian, Zhong, Meng, Jing, Qin, Shasha, Tang, Xuan, Wang, Fang, Liang, Aihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9443931/
https://www.ncbi.nlm.nih.gov/pubmed/36071842
http://dx.doi.org/10.3389/fphar.2022.874486
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author Wang, Dunfang
Han, Jiayin
Pan, Chen
Li, Chunying
Zhao, Yong
Liu, Suyan
Zhang, Yushi
Tian, Jingzhuo
Yi, Yan
Zhu, Jingjing
Liu, Chenyue
Wang, Yuan
Xian, Zhong
Meng, Jing
Qin, Shasha
Tang, Xuan
Wang, Fang
Liang, Aihua
author_facet Wang, Dunfang
Han, Jiayin
Pan, Chen
Li, Chunying
Zhao, Yong
Liu, Suyan
Zhang, Yushi
Tian, Jingzhuo
Yi, Yan
Zhu, Jingjing
Liu, Chenyue
Wang, Yuan
Xian, Zhong
Meng, Jing
Qin, Shasha
Tang, Xuan
Wang, Fang
Liang, Aihua
author_sort Wang, Dunfang
collection PubMed
description Metabolites/impurities (MIs) of penicillin are normally considered to be the main substances inducing immediate hypersensitivity reactions in penicillin treatment. Our previous research found that penicillin can cause non-allergic hypersensitivity reactions (NAHRs) by directly triggering vascular hyperpermeability and exudative inflammation. However, the chief culprits and underlying mechanisms involved in penicillin-induced NAHRs have not yet been fully elucidated. In this study, we used a combination of approaches including a mouse non-allergic hypersensitivity reaction model, UPLC-MS/MS analyses of arachidonic acid metabolites (AAMs), immunoblotting technique, and molecular docking, etc to investigate the culprits involved in penicillin-induced hypersensitivity reactions. We found penilloic acid, one of the main MIs of penicillin, could trigger NAHRs via inducing increased vascular permeability, while the other MIs did no exhibit similar effect. Penilloic acid-induced reactions were not IgE-dependent. Significantly increased arachidonic acids and cascade metabolites in lungs, and activation of RhoA/ROCK signaling pathway in the ears and lungs of mice were noticed after once administration of penilloic acid. This study revealed that penilloic acid was the chief culprit involved in penicillin-induced immediate NAHRs in mice, which mainly associated with direct stimulation of vascular hyperpermeability and exudative inflammation. The activations of AAMs and RhoA/ROCK signaling pathway played important roles in these reactions.
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spelling pubmed-94439312022-09-06 Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice Wang, Dunfang Han, Jiayin Pan, Chen Li, Chunying Zhao, Yong Liu, Suyan Zhang, Yushi Tian, Jingzhuo Yi, Yan Zhu, Jingjing Liu, Chenyue Wang, Yuan Xian, Zhong Meng, Jing Qin, Shasha Tang, Xuan Wang, Fang Liang, Aihua Front Pharmacol Pharmacology Metabolites/impurities (MIs) of penicillin are normally considered to be the main substances inducing immediate hypersensitivity reactions in penicillin treatment. Our previous research found that penicillin can cause non-allergic hypersensitivity reactions (NAHRs) by directly triggering vascular hyperpermeability and exudative inflammation. However, the chief culprits and underlying mechanisms involved in penicillin-induced NAHRs have not yet been fully elucidated. In this study, we used a combination of approaches including a mouse non-allergic hypersensitivity reaction model, UPLC-MS/MS analyses of arachidonic acid metabolites (AAMs), immunoblotting technique, and molecular docking, etc to investigate the culprits involved in penicillin-induced hypersensitivity reactions. We found penilloic acid, one of the main MIs of penicillin, could trigger NAHRs via inducing increased vascular permeability, while the other MIs did no exhibit similar effect. Penilloic acid-induced reactions were not IgE-dependent. Significantly increased arachidonic acids and cascade metabolites in lungs, and activation of RhoA/ROCK signaling pathway in the ears and lungs of mice were noticed after once administration of penilloic acid. This study revealed that penilloic acid was the chief culprit involved in penicillin-induced immediate NAHRs in mice, which mainly associated with direct stimulation of vascular hyperpermeability and exudative inflammation. The activations of AAMs and RhoA/ROCK signaling pathway played important roles in these reactions. Frontiers Media S.A. 2022-08-22 /pmc/articles/PMC9443931/ /pubmed/36071842 http://dx.doi.org/10.3389/fphar.2022.874486 Text en Copyright © 2022 Wang, Han, Pan, Li, Zhao, Liu, Zhang, Tian, Yi, Zhu, Liu, Wang, Xian, Meng, Qin, Tang, Wang and Liang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wang, Dunfang
Han, Jiayin
Pan, Chen
Li, Chunying
Zhao, Yong
Liu, Suyan
Zhang, Yushi
Tian, Jingzhuo
Yi, Yan
Zhu, Jingjing
Liu, Chenyue
Wang, Yuan
Xian, Zhong
Meng, Jing
Qin, Shasha
Tang, Xuan
Wang, Fang
Liang, Aihua
Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice
title Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice
title_full Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice
title_fullStr Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice
title_full_unstemmed Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice
title_short Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice
title_sort penilloic acid is the chief culprit involved in non-ige mediated, immediate penicillin-induced hypersensitivity reactions in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9443931/
https://www.ncbi.nlm.nih.gov/pubmed/36071842
http://dx.doi.org/10.3389/fphar.2022.874486
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