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

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          Abstract

          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.

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          This assay for superoxide dismutase (SOD, EC 1.15.1.1) activity involves inhibition of nitroblue tetrazolium reduction, with xanthine-xanthine oxidase used as a superoxide generator. By using a reaction terminator, we can determine 40 samples within 55 min. One unit of activity of pure bovine liver Cu,ZnSOD and chicken liver MnSOD was expressed by 30 ng and 500 ng of protein, respectively. The mean concentrations of Cu,ZnSOD as measured by this method in blood from normal adults were 242 (SEM 4) mg/L in erythrocytes, 548 (SEM 20) micrograms/L in serum, and 173 (SEM 11) micrograms/L in plasma. The Cu,ZnSOD concentrations in serum and plasma of patients with cancer of the large intestine tended to be less and greater than these values, respectively, but not statistically significantly so.
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            Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs.

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              Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker.

              We examined the hypothesis that myeloperoxidase (MPO), a plentiful constituent of neutrophils, might serve as a marker for tissue neutrophil content. To completely extract MPO from either neutrophils or skin, hexadecyltrimethylammonium bromide (HTAB) was used to solubilize the enzyme. With this detergent treatment, 97.8 +/- 0.2% of total recoverable MPO was extracted from neutrophils with a single HTAB treatment; 93.1 +/- 1.0% was solubilized with a single treatment of skin. Neutrophil MPO was directly related to neutrophil number; with the dianisidine-H2O2 assay as few as 10(4) neutrophils could be detected. The background level of MPO within uninflamed tissue was 0.385 +/- 0.018 units per gram of tissue, equivalent to only 7.64 +/- 0.36 X 10(5) neutrophils. In experimental staphylococcal infection, skin specimens contained 34.8 +/- 3.8 units MPO per gram, equivalent to 8.55 +/- 0.93 X 10(7) neutrophils. These studies demonstrate that MPO can be used as a marker for skin neutrophil content: it is recoverable from skin in soluble form, and is directly related to neutrophil number. Further, normal skin possesses a low background of MPO compared to that of inflamed skin.
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                Author and article information

                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi Publishing Corporation
                0962-9351
                1466-1861
                2012
                14 May 2012
                : 2012
                : 438912
                Affiliations
                1Department of Physical Medicine and Rehabilitation, Erzurum Regional Training and Research Hospital, 25240 Erzurum, Turkey
                2Department of Pharmacology, Faculty of Pharmacy, Atatürk University, 25240 Erzurum, Turkey
                3Department of Pharmacology, Faculty of Medicine, Atatürk University, 25240 Erzurum, Turkey
                4Department of Biochemistry, Faculty of Pharmacy, Atatürk University, 25240 Erzurum, Turkey
                Author notes

                Academic Editor: Tânia Fröde

                Article
                10.1155/2012/438912
                3361306
                22665951
                cdd70447-f09b-4f8c-beb1-a407daaf897b
                Copyright © 2012 Hulya Uzkeser et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 December 2011
                : 28 February 2012
                : 28 February 2012
                Categories
                Research Article

                Immunology
                Immunology

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