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

Parlar,Ali; Arslan,Seyfullah  Oktay; Doğan,Muhammed  Fatih; Çam,Saliha  Ayşenur; Yalçin,Alper; Elibol,Ebru; Özer,Mehmet Kaya; Üçkardeş,Fatih; Kara,Halil

doi:10.3892/etm.2018.6753

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

Authors:
- Ali Parlar
- Seyfullah Oktay Arslan
- Muhammed Fatih Doğan
- Saliha Ayşenur Çam
- Alper Yalçin
- Ebru Elibol
- Mehmet Kaya Özer
- Fatih Üçkardeş
- Halil Kara
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Affiliations: Department of Pharmacology, Faculty of Medicine, Adiyaman University, Adiyaman 02040, Turkey, Department of Pharmacology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara 06800, Turkey, Department of Histology, Faculty of Medicine, Adiyaman University, Adiyaman 02040, Turkey, Department of Biostatistics, Faculty of Medicine, Adiyaman University, Adiyaman 02040, Turkey
Published online on: September 18, 2018 https://doi.org/10.3892/etm.2018.6753
Pages: 4900-4908

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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.

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