Diamine oxidase knockout mice are not hypersensitive to orally or subcutaneously administered histamine.
Acute kidney injury
Amine oxidase (copper-containing)
Body temperature
Histamine N-methyltransferase
Metabolism
Metoprine
Tacrine
Journal
Inflammation research : official journal of the European Histamine Research Society ... [et al.]
ISSN: 1420-908X
Titre abrégé: Inflamm Res
Pays: Switzerland
ID NLM: 9508160
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
06
12
2021
accepted:
04
03
2022
revised:
21
02
2022
pubmed:
19
3
2022
medline:
12
4
2022
entrez:
18
3
2022
Statut:
ppublish
Résumé
To evaluate the contribution of endogenous diamine oxidase (DAO) in the inactivation of exogenous histamine, to find a mouse strain with increased histamine sensitivity and to test the efficacy of rhDAO in a histamine challenge model. Diamine oxidase knockout (KO) mice were challenged with orally and subcutaneously administered histamine in combination with the β-adrenergic blocker propranolol, with the two histamine-N-methyltransferase (HNMT) inhibitors metoprine and tacrine, with folic acid to mimic acute kidney injury and treated with recombinant human DAO. Core body temperature was measured using a subcutaneously implanted microchip and histamine plasma levels were quantified using a homogeneous time resolved fluorescence assay. Core body temperature and plasma histamine levels were not significantly different between wild type (WT) and DAO KO mice after oral and subcutaneous histamine challenge with and without acute kidney injury or administration of HNMT inhibitors. Treatment with recombinant human DAO reduced the mean area under the curve (AUC) for core body temperature loss by 63% (p = 0.002) and the clinical score by 88% (p < 0.001). The AUC of the histamine concentration was reduced by 81%. Inactivation of exogenous histamine is not driven by enzymatic degradation and kidney filtration. Treatment with recombinant human DAO strongly reduced histamine-induced core body temperature loss, histamine concentrations and prevented the development of severe clinical symptoms.
Identifiants
pubmed: 35303133
doi: 10.1007/s00011-022-01558-2
pii: 10.1007/s00011-022-01558-2
pmc: PMC8989821
doi:
Substances chimiques
Histamine
820484N8I3
Amine Oxidase (Copper-Containing)
EC 1.4.3.21
Histamine N-Methyltransferase
EC 2.1.1.8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
497-511Subventions
Organisme : Austrian Science Fund
ID : SFB54-04
Organisme : Austrian Science Fund
ID : T1135
Informations de copyright
© 2022. The Author(s).
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