Intravenous anesthetic ketamine attenuates complete Freund's adjuvant-induced arthritis in rats via modulation of MAPKs/NF-κB.
Administration, Intravenous
Animals
Apoptosis
/ drug effects
Arthritis, Experimental
/ chemically induced
Cytokines
/ antagonists & inhibitors
Edema
/ drug therapy
Excitatory Amino Acid Antagonists
/ administration & dosage
Foot
Freund's Adjuvant
/ administration & dosage
I-kappa B Proteins
/ drug effects
Joints
/ pathology
Ketamine
/ administration & dosage
Male
Mitogen-Activated Protein Kinases
/ drug effects
NF-kappa B
/ drug effects
Phosphorylation
Rats
Rats, Sprague-Dawley
Signal Transduction
/ drug effects
Arthritis
Inflammation
IκBα
NF-κB
Pro-inflammatory cytokines
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:
Feb 2019
Feb 2019
Historique:
received:
21
09
2018
accepted:
15
11
2018
revised:
13
11
2018
pubmed:
7
12
2018
medline:
16
5
2019
entrez:
4
12
2018
Statut:
ppublish
Résumé
The current study was intended to investigate the effect of ketamine (KET) on complete Freund's adjuvant (CFA)-induced arthritis in rats. The CFA was administered in the hind paw of the rats for the induction of adjuvant-induced arthritis. The paw swelling of experimental animals was measured as hind paw volume. Hematoxylin and eosin staining was estimated and pathological changes in the joint tissues were observed under a light microscope. Furthermore, the bicinchoninic acid assay was used for protein quantification. The antibody-reactive bands were visualized using enhanced chemiluminescence. The present study showed that KET significantly reduces the severity of arthritis in CFA mice. The therapeutic effects were linked with reduced joint swelling and destruction, as evidenced by analyzing rat paws. The KET also revealed to attenuate the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In western blot analysis, KET inhibit phosphorylation of MAPKs, IκBα and nuclear translocation NF-κB in the inflammatory joints of AIA rats. Moreover, KET showed to induce apoptosis via mitochondrial signalling pathways (Bcl2, Bax, cytochrome C, cleaved caspase-3 and cleaved caapse-9). Taken together, KET show significant anti-rheumatoid arthritis activity via multiple mechanisms and may thus have therapeutic benefits for RA.
Sections du résumé
BACKGROUND
BACKGROUND
The current study was intended to investigate the effect of ketamine (KET) on complete Freund's adjuvant (CFA)-induced arthritis in rats.
METHODS
METHODS
The CFA was administered in the hind paw of the rats for the induction of adjuvant-induced arthritis. The paw swelling of experimental animals was measured as hind paw volume. Hematoxylin and eosin staining was estimated and pathological changes in the joint tissues were observed under a light microscope. Furthermore, the bicinchoninic acid assay was used for protein quantification. The antibody-reactive bands were visualized using enhanced chemiluminescence.
RESULTS
RESULTS
The present study showed that KET significantly reduces the severity of arthritis in CFA mice. The therapeutic effects were linked with reduced joint swelling and destruction, as evidenced by analyzing rat paws. The KET also revealed to attenuate the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In western blot analysis, KET inhibit phosphorylation of MAPKs, IκBα and nuclear translocation NF-κB in the inflammatory joints of AIA rats. Moreover, KET showed to induce apoptosis via mitochondrial signalling pathways (Bcl2, Bax, cytochrome C, cleaved caspase-3 and cleaved caapse-9).
CONCLUSION
CONCLUSIONS
Taken together, KET show significant anti-rheumatoid arthritis activity via multiple mechanisms and may thus have therapeutic benefits for RA.
Identifiants
pubmed: 30506262
doi: 10.1007/s00011-018-1202-3
pii: 10.1007/s00011-018-1202-3
doi:
Substances chimiques
Cytokines
0
Excitatory Amino Acid Antagonists
0
I-kappa B Proteins
0
NF-kappa B
0
Ketamine
690G0D6V8H
Freund's Adjuvant
9007-81-2
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
147-155Subventions
Organisme : Hunan Provincial Natural Science Foundation
ID : 2017JJ3445
Organisme : Hunan Provincial Natural Science Foundation
ID : 2014JJ3040
Organisme : Hunan science and technology project
ID : 2015SK2085
Organisme : Natural Science Foundation of China
ID : 81500658
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