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.