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

The Effects of Montelukast on Antioxidant Enzymes and Proinflammatory Cytokines on the Heart, Liver, Lungs, and Kidneys in a Rat Model of Cecal Ligation and Puncture–Induced Sepsis

We investigated the potential protective effects of montelukast (MLK) on cecal ligation and puncture (CLP)–induced tissue injury in vital organs — liver, heart, kidneys, and especially lungs — through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS) in rats. The rat groups were (1) a 10-mg/kg MLK-treated CLP group; (2) a 20-mg/kg MLK-treated CLP group; (3) a 20-mg/kg MLK-treated, sham-operated group; (4) a CLP control group; and (5) a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6) cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure

An investigation of postmortem urotensin II receptor levels in brain and kidney tissues in a rat model of cardiac ischemia

This study aimed to investigate changes in postmortem urotensin II receptor (UTR) levels in brain and kidney tissues in a rat model of cardiac ischemia. The rats were divided into two groups: a control group and a cardiac ischemia-induced group. Cardiac ischemia was created by an intraperitoneal injection of a single lethal dose of isoproterenol (ISO; 850 mg/kg). Plasma UT, blood urea nitrogen, and creatinine levels were determined 0 h postmortem. Brain and kidney UTR mRNA expression levels were determined 0, 1, 3, 6, 12, 24, 48, and 72 h postmortem. The histopathological appearance of brain and kidney tissues was also evaluated. Plasma UT and plasma creatinine levels were increased in the cardiac ischemia-induced group as compared with those in the control group (P < 0.001). Ischemia resulted in histopathological changes in brain and cerebellum tissue. The morphological evaluation revealed Purkinje cell degeneration (P = 0.037) and dark neurons (P = 0.004). The UTR expression level decreased after 1 h postmortem in the brain and after 3 h postmortem in the kidneys in the cardiac ischemia-induced group as compared with that in the control group (P < 0.001). The observed changes in UTR expression levels may be valuable in clinical practice in the field of forensic medicine. These changes may be used as a marker in postmortem evaluations of sudden death caused by ischemia-induced cardiac shock

Tnf-alpha inhibition by infliximab as a new target for the prevention of glycerol-contrast-induced nephropathy

Karaman, Adem/0000-0002-3091-0609; UGAN, RUSTEM ANIL/0000-0002-4837-2343; UN, Harun/0000-0003-1772-282X; ATMACA, HASAN TARIK/0000-0001-8379-4114WOS: 000353929900011PubMed: 25682004Contrast medium-induced nephropathy (CIN) remains as a problem with high incidence and mortality rates. The aim of this study is to examine the roles of infliximab (INF) in the glycerol (GLY) and CIN model in rats. The rats were separated into five groups (n=8): Healthy, GLY, GLY+CM, GLY+CM+INF 5 mg/kg intraperitoneally (i.p.), and GLY+CM+INF 7 mg/kg (i.p.). Antioxidant levels in the therapy groups were observed to be quite similar to those in the healthy group. In this study, while the kidney TNF-alpha, TGF-1 beta and Caspase 3 gene expressions' levels increased in the nephrotoxic groups, these levels were found to have decreased in the treatment groups. Moreover, histopathologic examination showed that hyaline, haemorrhagic casts and necrosis were increased in nephrotoxicity group, whereas they decreased in the therapy group. Furthermore, TNF-alpha and NF-kappa B expression were decreased with infliximab administrated groups similar to control group. In conclusion, we suggest that infliximab have protective roles on CIN. (C) 2015 Elsevier B.V. All rights reserved.Ataturk University Scientific Experimental Project OfficeAtaturk University [2013/54]This article was supported by the Ataturk University Scientific Experimental Project Office, Project Number: 2013/5

Effects of Aliskiren, an RAAS inhibitor, on a carrageenan-induced pleurisy model of rats

Abstract Our aim is to investigate the potentially preventive effects of Aliskiren in a carrageenan-induced lung pleurisy model and to compare the standard anti-inflammatory agents, indomethacin and dexamethasone. The pleurisy model was induced through the injection of carrageenan (0.2 ml-%2) into the pleural cavity. After the experiment, serum and lung tissues were collected and biochemical, molecular and pathological examinations were performed. In our study, pleural inflammation decreased superoxide dismutase activity and the glutathione level and increased the malondialdehyde level in the lung of rats, while Aliskiren increased the superoxide dismutase activity and glutathione level and decreased the malondialdehyde level. In addition, carrageenan-induced pleurisy caused a significant increase in pro-inflammatory cytokines mRNA expressions (TNF-α, IL-1β, and NF-KB), while Aliskiren administration decreased their expressions as well as the standard treatments, indomethacin and dexamethasone, did. Aliskiren administration at the 200 mg/kg dose protected the lungs in the pathological evaluation, especially against inflammatory cell infiltration and edematous lesions. It appears that Aliskiren protects the lung from carrageenan-induced pleurisy damage by regulating inflammation and antioxidant-oxidant balance via Renin Angiotensin Aldosterone System inhibition

Does Bosentan Protect Diabetic Brain Alterations in Rats? The Role of Endothelin-1 in the Diabetic Brain

Cayir, Yasemin/0000-0001-9133-5460; UN, Harun/0000-0003-1772-282X; Yayla, Muhammed/0000-0002-0659-3084; ATMACA, HASAN TARIK/0000-0001-8379-4114WOS: 000350099600008PubMed: 25200216Diabetes mellitus (DM) is a major problem all over the world, affecting more people in recent years. Individuals with diabetes are more prone to disease than non-diabetics, especially vascular complications. The aim of this study was to examine the roles of the endothelin (ET)-1 in brain damage formed in a streptozocin (STZ)-induced diabetes model, and the effect of bosentan, which is the non-specific ET1 receptor blocker in the prevention of the diabetes-induced brain damage. To examine the effects of bosentan (50mg/kg and 100mg/kg) in this study, the rats were given the drug for 3months. The rats were divided into four groups: the sham group (n=10), the diabetic control group (n=10), the group of diabetic rats given bosentan 50mg/kg (n=10) and the group of diabetic rats given bosentan 100mg/kg (n=10). Diabetes was induced in the rats by STZ (60mg/kg i.p.). On day 91, all rats were killed. Brain tissues of the rats were measured by molecular, biochemical and histopathological methods. Antioxidant levels in the therapy groups were observed as quite near to the values in the healthy group. In this study, while the brain eNOS levels in the diabetic groups decreased, the ET1 and iNOS levels were found to be increased. However, in the diabetes group, hippocampus and cerebellum, pericellular oedema and a number of neuronal cytoretraction were increased in neuropiles, whereas these results were decreased in the therapy group. Based on all of these results, ET1 will not be ignored in diabetes-induced cerebral complications

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