title: β-Nicotinamide adenine dinucleotide attenuates lipopolysaccharide-induced inflammatory effects in a murine model of acute lung injury.
abstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) occur in approximately 200,000 patients per year. Studies indicate that lung endothelium plays a significant role in ALI. The authors' recent in vitro studies demonstrate a novel mechanism of β-nicotinamide adenine dinucleotide (β-NAD)-induced protection against gram-positive (pneumolysin, PLY) and gram-negative (lipopolysaccharide, LPS) toxin-induced lung endothelial cell (EC) barrier dysfunction. The objective of the current study was to evaluate the protective effect of β-NAD against LPS-induced ALI in mice. C57BL/6J mice were randomly divided into 4 groups: vehicle, β-NAD, LPS, and LPS/β-NAD. After surgery, mice were allowed to recover for 24 hours. Evans blue dye-albumin (EBA) was given through the internal jugular vein 2 hours prior to the termination of the experiments. Upon sacrificing the animals, bronchoalveolar lavage fluid (BALF) was collected and the lungs were harvested. β-NAD treatment significantly attenuated the inflammatory response by means of reducing the accumulation of cells and protein in BALF, blunting the parenchymal neutrophil infiltration, and preventing capillary leak. In addition, the histological examination demonstrated decreased interstitial edema in the LPS/β-NAD specimens, as compared to the LPS-only specimens. The mRNA levels of the anti-inflammatory cytokines were up-regulated in the LPS group treated with β-NAD compared to the LPS-only-treated group. β-NAD treatment down-regulated the mRNA levels of the proinflammatory cytokines. These findings suggest that β-NAD could be investigated as a therapeutic option against bacterial toxin-induced lung inflammation and ALI in mice.
authors.affiliation: Vascular Biology Center and Section of Pulmonary and Critical Care Medicine, Georgia Health Sciences University, Augusta, Georgia 30912, USA. usiddaramappa@georgiahealth.edu
authors.forename: Nagavedi Siddaramappa
authors.initials: NS
authors.lastname: Umapathy
authors.forename: Joyce
authors.initials: J
authors.lastname: Gonzales
authors.forename: Sadanand
authors.initials: S
authors.lastname: Fulzele
authors.forename: Kyung-mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Rudolf
authors.initials: R
authors.lastname: Lucas
authors.forename: Alexander Dimitrievich
authors.initials: AD
authors.lastname: Verin
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D009243:NAD / Q000494:pharmacology*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D009195:Peroxidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009243:NAD; D009195:Peroxidase