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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Mast cells play a vital role in hypersensitivity reactions. Rocuronium is known to cause mast cell mobilization, hypersensitivity, and pancreatitis. The aim of this study was to investigate the effects of sugammadex on pancreatic changes due to rocuronium. A total of 42 Sprague-Dawley male rats were divided into six equal groups to receive either rocuronium 1 mg/kg intravenously (i.v., R group), rocuronium 1 mg/kg + sugammadex 16 mg/kg i.v. (RS16 group), rocuronium 1 mg/kg + sugammadex 96 mg/kg i.v. (RS96 group), sugammadex 16 mg/kg (S16), sugammadex 96 mg/kg i.v. (S96 group), or 0.9% sodium chloride (control group). Sugammadex was administered 5s later following rocuronium. In R group, mast count was higher, and the distribution rate of granules and nuclear changes were different compared with other groups. Distribution rate of granules in groups S16 and S96 were similar to the control group and lower compared with other groups. The amount of mast cells and granule density in groups RS16 and RS96 was lower compared with R group. The amount of mast cells in groups RS16 and RS96 was significantly lower compared with other treatment groups. These results suggest that sugammadex may have an inhibitory effect on mobilization and morphological changes in pancreatic mast cells induced by administration of rocuronium and sugammadex in rats.

Rocuronium, sugammadex, and rocuronium-sugammadex complexes cause histopathological changes and immunoreactivity to calcineurin in muscle cells.

Introduction: Methotrexate (MTX) causes hepatotoxicity by producing oxidative stress. Benfotiamine and irisin have protective effects against oxidative stress. The aim of this study was to investigate the changes in irisin activity in the liver as a result of toxicity produced by MTX and the protective role of benfotiamine in the hepatotoxicity. Material and methods: Rats were divided into 4 groups as follows: control, benfotiamine (50 mg/kg, oral gavage (o.g.), for 14 days), MTX (MTX 20 mg/kg intraperitoneally (i.p.) on day 1), MTX + benfotiamine (MTX 20 mg/kg (i.p.) on day 1, then 50 mg/kg (o.g.) benfotiamine for 14 days). Liver tissue was used to examine histopathological and immunohistochemical changes. Serum was used to look for oxidative stress markers (total antioxidant status (TAS) and total oxidant status (TOS)). Results: Administration of MTX caused a significant TOS increase and TAS decrease in the serum as compared to the control group. Immunohistochemically, irisin was significantly increased in immunoreactivity in the MTX group as compared to the control group (p < 0.05). Significant histopathological improvement and decrease in serum TOS levels were observed in the MTX + benfotiamine group compared to the MTX group (p < 0.05). In addition, an increase in TAS level and a decrease in irisin immunoreactivity were observed but they were not statistically significant (p > 0.05). Conclusions: Our results showed that MTX caused an increase in the activity of irisin after producing toxicity in the liver. In addition, we found that benfotiamine was effective in preventing damage caused by MTX in the liver.