Tyrosol attenuates lipopolysaccharide-induced acute lung injury by inhibiting the inflammatory response and maintaining the alveolar capillary barrier

Abstract

Acute lung injury (ALI) is a life-threatening disease characterized by increased pulmonary vascular permeability because of alveolar capillary barrier dysfunction and increased immune responses. This study determined the anti-inflammatory effect of tyrosol on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms of action. BALB/c mice were orally administered with tyrosol (0.1, 1, and 10 mg/kg) 1 h before an intratracheal injection of LPS (25 mu g/50 mu L). Oral treatment with tyrosol inhibited lung vascular permeability, histopathological changes, wet/dry lung weight ratio, and pulmonary vascular cell infiltration. The LPS-induced imbalance in the activity of enzymes, such as superoxide dismutase and myeloperoxidase, was regulated by tyrosol. Pro inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6, were reduced by tyrosol in bronchoalveolar lavage fluid and lung tissue. The activation of inflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and phosphorylated-I kappa B alpha, was suppressed by the presence of tyrosol in the lung tissue. In addition, tyrosol attenuated the production of NO, the expression of pro inflammatory cytokines, the expression of iNOS and COX-2, and the nuclear translocation of nuclear factor-kappa B in LPS-stimulated RAW 264.7 macrophages. These results suggested that tyrosol is a potential therapeutic agent for treating inflammatory lung diseases.