title: Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs.
abstract: BACKGROUND
  Phorbol myristate acetate (PMA) is a strong neutrophil activator and has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC) on the PMA-induced ALI and associated changes.
  
  
  METHODS
  The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 μg/g), PMA 4 μg/g (lung weight), cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight). There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc) were determined in isolated lungs. ATP (adenotriphosphate) and PARP [poly(adenosine diphophate-ribose) polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS). The neutrophil-derived mediators in lung perfusate were determined.
  
  
  RESULTS
  PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent.
  
  
  CONCLUSIONS
  Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental role in the PMA-induced lung injury. ATP is beneficial, while PARP plays a deteriorative effect on the PMA-induced ALI. NAC exerts protective effects on the inflammatory cascade leading to pulmonary injury. This B complex compound may be applied for clinical usage and therapeutic regimen.
authors.affiliation: Department of Physical Education and Kinesiology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Chia-Chih
authors.initials: CC
authors.lastname: Lin
authors.forename: Nan-Kuang
authors.initials: NK
authors.lastname: Hsieh
authors.forename: Huey Ling
authors.initials: HL
authors.lastname: Liou
authors.forename: Hsing I
authors.initials: HI
authors.lastname: Chen
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D009536:Niacinamide / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*
chemical_list: D009536:Niacinamide; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D013755:Tetradecanoylphorbol Acetate