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.

Purpose; The current study aimed to investigate the oxidative stress in diabetic rat liver as well as the protective effects of N-acetylcysteine (NAC)on irisin expression. Methods; Twenty-eight male Wistar rats were divided into four groups, 7 rats in each group and 30-d regimens of experimental or control groups. NAC treated group: 100mg/kg once daily was administered intraperitoneally (i.p.). Diabetes-induced group: Single dose intraperitoneal injection of streptozotocin (STZ) (50mg/kg B.W.) was used to induce diabetes mellitus in overnight fasting Wistar rats. By determining blood glucose concentration in STZ-induced rats 72 hours after injection of STZ, diabetes was assessed. DM+NAC group: STZ-induced DM plus NAC as described previously. Serial and liver samples were collected on the 30-day and after overnight fasting. Biochemical analyses were performed to measure total antioxidant status (TAS), total oxidant status (TOS), and Malondialdehyde (MDA)levels. Each liver sample was weighed, then prepared for histopathologic evaluation by light microscopy. Results; There was a statistically significant decrease in TAS levels and an increase in TOS and MDA levels in the DM group compared to the control group. In contrast, TOS and MDA levels were found significantly decreased, and TAS levels increased in the serum and liver tissues of the DM+NAC group compared to the DM group. Liver samples were also used for histopathological examination using hematoxylin-eosin and immunohistochemical staining. STZ-induced liver injury via increasing oxidative stress, sinusoidal dilatation, degeneration of hepatocytes, and in irisin, and immunoreactivity. NAC significantly reduced the STZ-induced hepatotoxicity. Conclusion; In the early period of diabetes, due to the antioxidant properties of irisin related to the sudden response of liver tissue to oxidative stress, it is thought that the immunoreactivity in the tissue increases in the early period. As a result, NAC in diabetic rat liver tissue was found to suppress oxidative damage and irisin immunoreactivity.

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Artemisinin, an antimalarial drug, has anticancer activity and possesses protective effects against several tissue injuries. The aim of the present study was to investigate the effects of artemisinin on doxorubicin-induced renal and testicular toxicity in rats. Doxorubicin was administered to rats at a single dose of 10 mg/kg body weight (b.w.) as a single intraperitoneal injection. Application of artemisinin was by using oral gavage feeding needle for 14 days at different specified doses (7 mg/kg and 35 mg/kg b.w.). At the end of the experiments, kidney and testis samples were collected and used for histopathological and immunohistochemical examinations. At histopathological examination, while hyperemia was the marked finding in kidney and testis of rats treated with doxorubicin only, no evidence of structural abnormalities showed in other groups. Immunohistochemical examination of the testes and kidneys demonstrated significantly increased expression of caspase-3, TNF-α, iNOS and NF-κB in rats treated with doxorubicin only. Artemisinin decreased the doxorubicin-induced overexpression of NF-κB, iNOS, TNFα and caspase-3 in these tissues of rats. Artemisinin can protect the kidney and testis against doxorubicin-induced nephrotoxicity and testotoxicity, probably through a decrease of caspase-3, TNF-α, iNOS and NF-κB expressions. It may be concluded that artemisinin has a potential for clinical use in the treatment of kidney and testis damage induced by doxorubicin. Further researches are required to determine the appropriate combination of artemisinin with doxorubicin.