title: The therapeutic effect and mechanism of niacin on acute lung injury in a rat model of hemorrhagic shock: Down-regulation of the reactive oxygen species-dependent nuclear factor κB pathway.
abstract: BACKGROUND
  The purpose of the current study was to investigate the protective effect of niacin on acute lung injury by the down-regulation of the nuclear factor κB (NF-κB) pathway in hemorrhagic shock (HS) rats.
  
  
  METHODS
  HS was induced in male Sprague-Dawley rats by withdrawing blood to maintain a mean arterial pressure of 20 mm Hg to 25 mm Hg for 40 minutes. The rats were resuscitated by the reinfusion of the drawn blood, and a vehicle (HS), a low-dose of niacin (360 mg/kg, HS + LD-NA), or a high dose of niacin (1,080 mg/kg, HS + HD-NA) were administered orally. The survival of the subjects was observed for 72 hours, and a separate set of animals was killed at 6 hours after HS induction. We measured cytoplasmic phosphorylated inhibitor κB-α and inhibitor κB-α expressions, nuclear NF-κB p65 expression, NF-κB p65 DNA-binding activity, MEK partner 1 activity, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-8, nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione, glutathione disulfide, malondialdehyde levels, and histologic damage in the lung tissue. We also measured TNF-α, IL-6, and IL-8 levels in the serum.
  
  
  RESULTS
  The survival rates of the sham, HS, HS + LD-NA, and HS + HD-NA groups were 6 of 6 (100%), 0 of 9 (0%), 1 of 9 (11.1%), and 3 of 9 (33.3%), respectively. A high dose of niacin increased lung NAD+, nicotinamide adenine dinucleotide phosphate levels, and glutathione-glutathione disulfide ratios; decreased lung malondialdehyde levels; down-regulated the NF-κB pathway; suppressed TNF-α, IL-6, and IL-8 levels in the lung tissue and serum; and attenuated histologic lung damage.
  
  
  CONCLUSIONS
  A high dose of niacin attenuated lung inflammation, suppressed proinflammatory cytokine release, reduced histologic lung damage, and improved survival after HS in rats. Its therapeutic benefits were associated with the down-regulation of the reactive oxygen species-dependent NF-κB pathway.
authors.affiliation: From the Department of Emergency Medicine (K.Y.J., Y.S.J.), National Medical Center; Department of Emergency Medicine (G.J.S., W.Y.K., K.S.K.), Seoul National University Hospital; and Department of Emergency Medicine (Y.C.K.), Veterans Health Service Medical Center, Seoul, Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Jeong
authors.forename: Gil Joon
authors.initials: GJ
authors.lastname: Suh
authors.forename: Woon Yong
authors.initials: WY
authors.lastname: Kwon
authors.forename: Kyung Su
authors.initials: KS
authors.lastname: Kim
authors.forename: Yoon Sun
authors.initials: YS
authors.lastname: Jung
authors.forename: Yu Chan
authors.initials: YC
authors.lastname: Kye
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015536:Down-Regulation; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000150:complications*
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009525:Niacin