Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg) effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO) activity and lipid peroxidation (LPO) level and increased the activity of superoxide dismutase (SOD) and level of glutathione (GSH) during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions

Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis

Karaman, Adem/0000-0002-3091-0609; UGAN, RUSTEM ANIL/0000-0002-4837-2343; POLAT, Beyzagul/0000-0003-2042-5949; ATMACA, HASAN TARIK/0000-0001-8379-4114; UN, Harun/0000-0003-1772-282XWOS: 000368422100001PubMed: 26562095Objective: Contrast media (CM) are a major cause of nephropathy in high-risk patients. The aim of this study was to examine the effects of carnitine (CAR) in advanced nephrotoxicity due to CM administration in rats with glycerol-induced renal functional disorder. Methods: 40 rats were divided randomly into five groups (n=8): (1) healthy group; (2) glycerol only (GLY); (3) glycerol and CM (GLY1CM); (4) glycerol, CM and 200 mg kg(-1) carnitine (CAR200, Carnitene (R); Sigma-tau/Santa Farma, Istanbul, Turkey); and (5) glycerol, CM and 400 mg kg(-1) carnitine (CAR400). Kidney injury was induced with a single-dose, intramuscular injection of 10 ml kg(-1) body weight (b.w.) of GLY. CAR was administered intraperitoneally. CM (8 ml kg(-1) b.w. iohexol, Omni-paque (TM) T; Opakim Medical Products, Istanbul, Turkey) was infused via the tail vein to the rats in Groups 3-5. Results: L-carnitine administration significantly decreased serum creatinine and blood urea nitrogen levels. Superoxide dismutase and glutathione activity increased significantly in the treatment groups compared with the nephrotoxic groups. CAR400 significantly reduced malondialdehyde levels to healthy levels. In the treatment groups, tumour necrosis factor (TNF)-beta, transforming growth factor 1 beta, interleukin 1 beta and caspase-3 gene expression decreased compared with the nephrotoxic groups. TNF-alpha and nuclear factor kappa-beta (NF-kappa B) protein expression increased after CM and CAR administration reduced both TNF-alpha and NF-kappa B expressions. Histopathologically, hyaline and haemorrhagic casts and necrosis in proximal tubules increased in the nephrotoxicity groups and decreased in the CAR groups. Conclusion: The results reveal that L-carnitine protects the oxidant/antioxidant balance and decreases proinflammatory cytokines and apoptosis in CM-induced nephrotoxicity in rats with underlying pathology. Advances in knowledge: Depending on the underlying kidney pathologies, the incidence of CM-induced nephropathy (CIN) increases. Therefore, this is the best model to represent clinically observed CIN. Advances in knowledge: Depending on the underlying kidney pathologies, the incidence of CM-induced nephropathy (CIN) increases. Therefore, this is the best model to represent clinically observed CIN.Ataturk University Scientific Experimental Project OfficeAtaturk University [2013/52]This work was supported by the Ataturk University Scientific Experimental Project Office through project number: 2013/52

The effect of metyrosine/prednisolone combination to oophorectomy-induced osteoporosis

Background: Osteoporosis is a chronic disease characterized by a decrease in bone mineral density (BMD) and corruption of the microarchitectural structure of bone tissue.Objective: It was investigated whether methylprednisolone had a favorable effect on osteoporotic bone tissue in Oophorectomy induced osteoporotic rats whose endogenous adrenaline levels are suppressed with metyrosine.Materials and Methods: Bone Mineral Density, number of osteoblast-osteoclast, bone osteocalcin levels and alkaline phosphatase (ALP) measurements were performed. Obtained results were compared with that of alendronate.Results: Oophorectomy induced osteoporosis was exacerbated by methylprednisolone. Alentronate prevented ovariectomised induced osteoporosis, but it couldn’t prevent methylprednisolone +ovariectomised induced osteoporosis in rats.Conclusion: Combined treatment with methylprednisolon and metyrosine was the best treatment for preventing osteoporosis but metyrosine alone couldn’t prevent osteoporosis in ovariectomised rats