A synergistic effect of Ambroxol and Beta-Glucosylceramide in alleviating immune-mediated hepatitis: A novel immunomodulatory non-immunosuppressive formulation for treatment of immune-mediated disorders.
Ambroxol
/ pharmacology
Animals
Anti-Inflammatory Agents
/ pharmacology
Concanavalin A
Cytokines
/ blood
Disease Models, Animal
Drug Synergism
Drug Therapy, Combination
Glucosylceramides
/ pharmacology
Hepatitis
/ blood
Immunologic Factors
/ pharmacology
Inflammation Mediators
/ blood
Liver
/ drug effects
Male
Mice, Inbred C57BL
T-Lymphocytes
/ drug effects
Ambroxol
glucocerebroside
immune mediated hepatitis
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
05
09
2020
revised:
30
09
2020
accepted:
12
10
2020
pubmed:
21
10
2020
medline:
26
2
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
Ambroxol hydrochloride is being used in respiratory diseases as a broncholytic therapy. Beta-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an immune protective effect. The aim of the present study was to determine the synergistic immunomodulatory effect between these two compounds. Immune-mediated hepatitis was induced in the mice by administration of Con A. Mice were treated with either Ambroxol or GC alone or with the combination of both. Mice were followed for their effect on the liver injury, cytokine profile, and the immune system. Coadministration of Ambroxol and GC significantly alleviated the liver injury induced by ConA, as demonstrated by the decreased liver enzymes. The combined treatment had a statistically significant synergistic effect on the suppression of intrahepatic CD8+CD25+, an increase in the CD4/CD8 lymphocyte ratio and in the CD8+ intrahepatic lymphocyte trapping, as well as on change of serum in the IL4 levels. The beneficial effect was associated with the promotion of regulatory T lymphocytes subsets, and with a trend for a pro-inflammatory to an anti-inflammatory cytokine shift. Coadministration of Ambroxol with GC exerted a synergistic immunoprotective effect in a model of immune-mediated acute liver damage. Considering the high safety profile of both agents, the combination may become a novel immunomodulatory non-immunosuppressive therapeutic agent. Coadministration of Ambroxol with glucocerebroside exerted a synergistic immunoprotective effect in a model of immune-mediated acute liver damage.
Sections du résumé
BACKGROUND
BACKGROUND
Ambroxol hydrochloride is being used in respiratory diseases as a broncholytic therapy. Beta-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an immune protective effect. The aim of the present study was to determine the synergistic immunomodulatory effect between these two compounds.
METHODS
METHODS
Immune-mediated hepatitis was induced in the mice by administration of Con A. Mice were treated with either Ambroxol or GC alone or with the combination of both. Mice were followed for their effect on the liver injury, cytokine profile, and the immune system.
RESULTS
RESULTS
Coadministration of Ambroxol and GC significantly alleviated the liver injury induced by ConA, as demonstrated by the decreased liver enzymes. The combined treatment had a statistically significant synergistic effect on the suppression of intrahepatic CD8+CD25+, an increase in the CD4/CD8 lymphocyte ratio and in the CD8+ intrahepatic lymphocyte trapping, as well as on change of serum in the IL4 levels. The beneficial effect was associated with the promotion of regulatory T lymphocytes subsets, and with a trend for a pro-inflammatory to an anti-inflammatory cytokine shift.
CONCLUSIONS
CONCLUSIONS
Coadministration of Ambroxol with GC exerted a synergistic immunoprotective effect in a model of immune-mediated acute liver damage. Considering the high safety profile of both agents, the combination may become a novel immunomodulatory non-immunosuppressive therapeutic agent.
SIGNIFICANCE STATEMENT
CONCLUSIONS
Coadministration of Ambroxol with glucocerebroside exerted a synergistic immunoprotective effect in a model of immune-mediated acute liver damage.
Identifiants
pubmed: 33080465
pii: S0753-3322(20)31082-9
doi: 10.1016/j.biopha.2020.110890
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Cytokines
0
Glucosylceramides
0
Immunologic Factors
0
Inflammation Mediators
0
Concanavalin A
11028-71-0
Ambroxol
200168S0CL
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
110890Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.