title: Preventive Effects of Carnosine on Lipopolysaccharide-induced Lung Injury.
abstract: Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute lung injury, which involves neutrophilic inflammation and pulmonary cell death. Reactive oxygen species (ROS) play important roles in ARDS development. New compounds for inhibiting the onset and progression of ARDS are required. Carnosine (β-alanyl-L-histidine) is a small di-peptide with numerous activities, including antioxidant effects, metal chelation, proton buffering capacity and the inhibition of protein carbonylation and glycoxidation. We have examined the preventive effects of carnosine on tissue injury, oedema and inflammation in a murine model for ARDS. Oral administration of carnosine suppressed lipopolysaccharide (LPS)-induced vascular permeability, tissue injury and inflammation in the lung. In vivo imaging analysis revealed that LPS administration increased the level of ROS and that this increase was inhibited by carnosine administration. Carnosine also suppressed LPS-induced neutrophilic inflammation (evaluated by activation of myeloperoxidase in the lung and increased extracellular DNA in bronchoalveolar lavage fluid). Furthermore, carnosine administration suppressed the LPS-induced endoplasmic reticulum stress response in vivo. These results suggest that the oral administration of carnosine suppresses LPS-induced lung injury via carnosine's ROS-reducing activity. Therefore, carnosine may be beneficial for suppressing the onset and progression of ARDS.
authors.affiliation: Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Tanaka
authors.affiliation: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Sugizaki
authors.affiliation: Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Tamura
authors.affiliation: Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Niino
authors.affiliation: Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawahara
mesh_terms: D000818:Animals; D002336:Carnosine / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D002336:Carnosine