Intravenous anesthetic ketamine attenuates complete Freund's adjuvant-induced arthritis in rats via modulation of MAPKs/NF-κB.

Lin, H ; Wang, Z ; et al.

In: Inflammation research : official journal of the European Histamine Research Society ... [et al.], Jg. 68 (2019-02-01), Heft 2, S. 147-155

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Background: The current study was intended to investigate the effect of ketamine (KET) on complete Freund's adjuvant (CFA)-induced arthritis in rats.

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: 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: Taken together, KET show significant anti-rheumatoid arthritis activity via multiple mechanisms and may thus have therapeutic benefits for RA.

Titel:	Intravenous anesthetic ketamine attenuates complete Freund's adjuvant-induced arthritis in rats via modulation of MAPKs/NF-κB.
Autor/in / Beteiligte Person:	Lin, H ; Wang, Z ; Shen, J ; Xu, J ; Li, H
Link:	Full Text Finder (Volltext)
Zeitschrift:	Inflammation research : official journal of the European Histamine Research Society ... [et al.], Jg. 68 (2019-02-01), Heft 2, S. 147-155
Veröffentlichung:	Basel, Switzerland : Birkhäuser, c1995-, 2019
Medientyp:	academicJournal
ISSN:	1420-908X (electronic)
DOI:	10.1007/s00011-018-1202-3
Schlagwort:	Administration, Intravenous Animals Apoptosis drug effects Arthritis, Experimental chemically induced Arthritis, Experimental pathology Cytokines antagonists & inhibitors Cytokines blood Edema drug therapy Edema pathology Excitatory Amino Acid Antagonists administration & dosage Foot Freund's Adjuvant administration & dosage I-kappa B Proteins drug effects Joints pathology Ketamine administration & dosage Male Phosphorylation Rats Rats, Sprague-Dawley Arthritis, Experimental drug therapy Excitatory Amino Acid Antagonists therapeutic use Ketamine therapeutic use Mitogen-Activated Protein Kinases drug effects NF-kappa B drug effects Signal Transduction drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Inflamm Res] 2019 Feb; Vol. 68 (2), pp. 147-155. <i>Date of Electronic Publication: </i>2018 Nov 30. MeSH Terms: Arthritis, Experimental / drug therapy ; Excitatory Amino Acid Antagonists / therapeutic use ; Ketamine / therapeutic use ; Mitogen-Activated Protein Kinases / drug effects ; NF-kappa B / drug effects ; Signal Transduction / drug effects ; Administration, Intravenous ; Animals ; Apoptosis / drug effects ; Arthritis, Experimental / chemically induced ; Arthritis, Experimental / pathology ; Cytokines / antagonists & inhibitors ; Cytokines / blood ; Edema / drug therapy ; Edema / pathology ; Excitatory Amino Acid Antagonists / administration & dosage ; Foot ; Freund's Adjuvant / administration & dosage ; I-kappa B Proteins / drug effects ; Joints / pathology ; Ketamine / administration & dosage ; Male ; Phosphorylation ; Rats ; Rats, Sprague-Dawley References: J Immunol. 1999 Aug 1;163(3):1521-8. (PMID: 10415055) ; Nurs Times. 2004 Jun 15-21;100(24):40-4. (PMID: 15224492) ; Toxicol Lett. 2004 Dec 1;154(1-2):69-80. (PMID: 15475180) ; World J Gastroenterol. 2006 Dec 7;12(45):7350-4. (PMID: 17143955) ; Expert Opin Ther Pat. 2008 Jul;18(7):723-738. (PMID: 19578469) ; Rheumatol Int. 2010 Jun;30(8):1025-33. (PMID: 19697035) ; JAMA. 2011 May 4;305(17):1824. (PMID: 21540429) ; J Med Econ. 2011;14(6):709-19. (PMID: 21899486) ; Br J Clin Pharmacol. 2014 Feb;77(2):357-67. (PMID: 23432384) ; Int J Gen Med. 2013 May 24;6:383-6. (PMID: 23737674) ; Clin Med Insights Arthritis Musculoskelet Disord. 2013 Aug 08;6:35-43. (PMID: 23997576) ; Arthritis Care Res (Hoboken). 2014 Apr;66(4):523-31. (PMID: 24023001) ; Rheumatology (Oxford). 2014 Sep;53(9):1560-9. (PMID: 24402580) ; Biochim Biophys Acta. 2014 Nov;1843(11):2563-2582. (PMID: 24892271) ; Autoimmun Rev. 2015 Jun;14(6):490-7. (PMID: 25636595) ; Chem Biol Interact. 2015 Jul 5;236:41-6. (PMID: 25935278) ; Front Immunol. 2015 Jul 27;6:384. (PMID: 26284069) ; Mol Med Rep. 2016 Jun;13(6):5013-20. (PMID: 27109206) ; Arthritis Res Ther. 2017 Jun 30;19(1):146. (PMID: 28666464) ; Oncotarget. 2017 Jul 24;8(33):55384-55393. (PMID: 28903427) ; Bone Res. 2018 Apr 27;6:15. (PMID: 29736302) Grant Information: 2017JJ3445 Hunan Provincial Natural Science Foundation; 2014JJ3040 Hunan Provincial Natural Science Foundation; 2015SK2085 Hunan science and technology project; 81500658 Natural Science Foundation of China Contributed Indexing: Keywords: Arthritis; Inflammation; IκBα; NF-κB; Pro-inflammatory cytokines Substance Nomenclature: 0 (Cytokines) ; 0 (Excitatory Amino Acid Antagonists) ; 0 (I-kappa B Proteins) ; 0 (NF-kappa B) ; 690G0D6V8H (Ketamine) ; 9007-81-2 (Freund's Adjuvant) ; EC 2.7.11.24 (Mitogen-Activated Protein Kinases) Entry Date(s): Date Created: 20181204 Date Completed: 20190515 Latest Revision: 20200225 Update Code: 20240513

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