Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin.
Poly (ADP-ribose) synthabse (PARS) or polymerase (PARP) is a cytotoxic enzyme causing cellular damage. Niacinamide inhibits PARS or PARP. The present experiment tests the effects of niacinamide (NCA) on organ dysfunction and acute lung injury (ALI) following lipopolysaccharide (LPS). LPS was administered to anesthetized rats and to isolated rat lungs. In anesthetized rats, LPS caused systemic hypotension and increased biochemical factors, nitrate/nitrite (NOx), methyl guanidine (MG), tumor necrosis factoralpha (TNFalpha), and interleukin-1beta (IL-1beta). In isolated lungs, LPS increased lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, and capillary permeability. The insult also increased NOx, MG, TNFalpha, and IL-1beta in lung perfusate, while decreased adenosine triphosphate (ATP) content with an increase in PARP activity in lung tissue. Pathological examination revealed pulmonary edema with inflammatory cell infiltration. These changes were abrogated by posttreatment (30 min after LPS) with NCA. Following LPS, the inducible NO synthase (iNOS) mRNA expression was increased. NCA reduced the iNOS expression. Niacinamide exerts protective effects on the organ dysfunction and ALI caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.
Kao
Shang-Jyh
SJ
Division of Chest Medicine, Internal Medicine, Shin-Kong Wu-Ho-Su Memorial Hospital, School of Respiratory Therapy, Taipei Medical University, and College of Medicine, Fu-Jen University, Taipei, Taiwan.
Liu
Demeral David
DD
Su
Chain-Fa
CF
Chen
Hsing I
HI
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005609:Free Radicals / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009536:Niacinamide / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014803:Vitamin B Complex / Q000494:pharmacology*
D005609:Free Radicals; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; D014803:Vitamin B Complex; D009536:Niacinamide; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D052247:Nitric Oxide Synthase Type II; D011065:Poly(ADP-ribose) Polymerases