Ebselen Attenuates Lung Injury in Experimental Model of Carrageenan-Induced Pleurisy in Rats

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Ebselen Attenuates Lung Injury in Experimental Model of Carrageenan-Induced Pleurisy in Rats Fabricia Petronilho,1,3,6 Drielly Florentino,1 Fernanda Silvestre,1 Lucineia Gainski Danielski,1 Diego Zapelini Nascimento,1 Andriele Vieira,1 Luiz Alberto Kanis,2 Jucelia Jeremias Fortunato,1 Marwa Badawy,3 Tatiana Barichello,3,4 and Joao Quevedo3,5

Abstract—The study evaluates the role of Ebselen (Eb), an organoselenium compound in animal model of acute lung injury induced by carrageenan (CG). Wistar rats received saline or 2 % λ-carrageenan in the pleural cavity, and treatment with Eb (50 mg/kg intragastrically) or dexamethasone (Dx) (0.5 mg/kg intraperitoneal) after CG administration. After 4 h, rats were euthanized and the pleural exudate removed for analysis of the total cell count, total protein, lactate dehydrogenase, and nitrite/nitrate. Moreover, lung tissue were removed to verify the myeloperoxidase activity and oxidative damage. Eb showed antiinflammatory activity by inhibiting leukocyte influx, myeloperoxidase activity, and nitrite/nitrate concentration. Eb presented with an anti-inflammatory activity similar to Dx and an antioxidant activity better than Dx. This study suggests that Eb plays an important role against the oxidative damage associated with anti-inflammatory activity in animal model of acute lung injury, proving to be similar or potentially more effective than Dx. KEY WORDS: acute lung injury; pleurisy; ebselen; inflammation; oxidative damage.

INTRODUCTION Pleurisy induced by carrageenan (CG) is a wellcharacterized model of experimental inflammation, which

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Laboratory of Clinical and Experimental Pathophysiology, Postgraduate Program in Health Sciences, University of South Santa Catarina, Tubarao, SC, Brazil 2 Group of Research in Pharmaceutical Technology TECFARMA, Postgraduate Program in Health Sciences, University of South Santa Catarina, Tubarao, SC, Brazil 3 Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA 4 Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil 5 Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil 6 To whom correspondence should be addressed at Laboratory of Clinical and Experimental Pathophysiology, Postgraduate Program in Health Sciences, University of South Santa Catarina, Tubarao, SC, Brazil. Email: [email protected]

allows the quantification of mediators involved in cell changes during the inflammatory process [1]. This model is characterized by infiltration of neutrophils, followed by lung injury by reactive oxygen species (ROS) and reactive nitrogen species (RNS) such as hydrogen peroxide (H2O2), superoxide anion (O2−), hydroxyl radical (OH−), and peroxynitrite (ONOO−), as well as the liberation of other chemical mediators derived from act