title: Treatment with N-methyl-D-aspartate receptor antagonist (MK-801) protects against oxidative stress in lipopolysaccharide-induced acute lung injury in the rat.
abstract: Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are common syndromes that affect both clinical and surgical patients. This study describes the effects of a potent and specific N-methyl-d-aspartate receptor antagonist (MK-801) against oxidative stress in acute lung injury induced by intratracheal lipopolysaccharide (LPS) injection. This study was performed using male Wistar rats weighing 200-250g. Rats were randomly divided into four groups: control with isotonic saline instillation (n=6); LPS (100μg/100g of body weight) treated with saline (n=6); LPS treated with MK-801 (0.3mg/kg, intraperitoneally; n=6); LPS treated with MK-801 (0.3mg/kg, intratracheally; n=6). Twelve hours after the LPS instillation, rats were anesthetized and a bronchoalveolar lavage (BAL) was performed in order to determine the alveolar-capillary membrane alterations and the inflammatory infiltrate level. Blood and lung samples were isolated and assayed for oxidative stress variables and histopathologic analysis. The use of MK-801 decreased bronchoalveolar lavage fluid protein, LDH activity and inflammatory cells. Indeed, the treatment with MK-801 significantly attenuated lung oxidative damage and histopathologic alterations after LPS instillation. Our data provide the first experimental demonstration that MK-801 decreases oxidative stress and limits inflammatory response and alveolar disarray in lipopolysaccharide-induced acute lung injury.
authors.affiliation: Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Aline Andrea
authors.initials: AA
authors.lastname: da Cunha
authors.forename: Fernanda Bordignon
authors.initials: FB
authors.lastname: Nunes
authors.forename: Adroaldo
authors.initials: A
authors.lastname: Lunardelli
authors.forename: Vânia
authors.initials: V
authors.lastname: Pauli
authors.forename: Robson Henrich
authors.initials: RH
authors.lastname: Amaral
authors.forename: Luciana Mello
authors.initials: LM
authors.lastname: de Oliveira
authors.forename: Vasyl Custódio
authors.initials: VC
authors.lastname: Saciura
authors.forename: Gabriela Lucas
authors.initials: GL
authors.lastname: da Silva
authors.forename: Melissa Guerra Simões
authors.initials: MG
authors.lastname: Pires
authors.forename: Márcio Vinícius Fagundes
authors.initials: MV
authors.lastname: Donadio
authors.forename: Denizar Alberto da Silva
authors.initials: DA
authors.lastname: Melo
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.forename: Guilherme Antonio
authors.initials: GA
authors.lastname: Behr
authors.forename: Carlos Luiz
authors.initials: CL
authors.lastname: Reichel
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Rosa
authors.forename: Jarbas Rodrigues
authors.initials: JR
authors.lastname: de Oliveira
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D018893:Bronchoalveolar Lavage; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase