Protective Effects of Functional Amino Acids on Apoptosis, Inflammatory Response, and Pulmonary Fibrosis in Lipopolysaccharide-Challenged Mice.

Lung injury is a complicated and lethal condition characterized by alveolar barrier disruption, pulmonary edema, enhanced inflammation, and apoptosis in alveoli. However, therapeutic strategies to ameliorate lung injury without exerting side effects are not available. Functional amino acids have been shown to have anti-inflammatory and anti-apoptotic effects under various conditions. The objective of this study was to test the hypothesis that arginine, glutamine, or glycine supplementation ameliorated lipopolysaccharide (LPS)-induced lung injury in mice. Mice pretreated with aerosolized arginine, glutamine, or glycine were exposed to aerosolized LPS to induce lung injury. Results showed that arginine or glycine pretreatment beneficially reduced LPS-induced collagen deposition, apoptosis of alveolar cells, expression of inflammatory cytokines and chemokines, and accumulation of neutrophils and macrophages in lung tissues of mice, thus contributing to improved alveolar integrity and function. Glutamine administration reduced LPS-induced collagen deposition and inflammatory cytokines without affecting any other parameters examined in the study. Our findings indicated that arginine or glycine pretreatment effectively alleviated LPS-induced lung injury by inhibiting the accumulation of lymphocytes, the release of inflammatory cytokines and chemokines, and the apoptosis of alveolar cells. Supplementation of arginine or glycine may be a novel nutritional strategy to reduce deleterious effects of bacterial infection on alveolar function.