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Exp Ther Med. 2018 Dec;16(6):4900-4908. doi: 10.3892/etm.2018.6753. Epub 2018 Sep 18.

The exogenous administration of CB2 specific agonist, GW405833, inhibits inflammation by reducing cytokine production and oxidative stress.

Author information

1
Department of Pharmacology, Faculty of Medicine, Adiyaman University, Adiyaman 02040, Turkey.
2
Department of Pharmacology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara 06800, Turkey.
3
Department of Histology, Faculty of Medicine, Adiyaman University, Adiyaman 02040, Turkey.
4
Department of Biostatistics, Faculty of Medicine, Adiyaman University, Adiyaman 02040, Turkey.

Abstract

The present study aimed to investigate the role of cannabinoid 2 (CB2) receptors in a rat model of acute inflammation. Therefore, the potential of anti-inflammatory effects of CB2 receptor agonist (GW405833), CB2 receptor antagonist (AM630), and diclofenac, were investigated in carrageenan induced paw oedema in rats: as were assessed by measuring paw oedema; myeloperoxidase (MPO) activity in paw tissue; malondialdehyde (MDA) concentration; glutathione (GSH) level in paw tissue for oxidant/antioxidant balance; cytokine (interleukin-1β, IL-1β; tumour necrosis factor-α, TNF-α) levels in serum; histopathology of paw tissue for inflammatory cell accumulations. The results showed that GW405833 or diclofenac significantly reduced carrageenan-induced paw oedema. GW405833 also inhibited the increase of MPO activity, the recruitment of total leukocytes and neutrophils, and MDA concentration during carrageenan-induced acute inflammation, along with reversed nearly to the normal levels the increased of TNF-α, and IL-1β in serum. AM630 did not affect inflammation alone however clearly reversed the effects of agonist when co-administered. The mechanism of GW405833's suppression of inflammation is supported by these results, which are achieved by the inhibition of neutrophil migration, which regulates the reduction of oxidative stress, TNF-α and IL-1β levels. Finally, the activation of CB2 receptor, by selective agonist, has a major role in peripheral inflammation, and in the near future, targeting the peripheral cannabinoid system as a promising alternative to treat inflammation diseases may be considered a novel pharmacologic approach.

KEYWORDS:

CB2 receptor agonist; Carrageenan; GW405833; Paw oedema; oxidative stress

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