title: Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion.
abstract: Poly (ADP-ribose) synthase or polymerase (PARS and PARP, respectively) is a cytotoxic enzyme which causes cellular damage. Nicotinamide, a compound of vitamin B complex, has been reported to exert an inhibitory effect on PARS or PARP. The present study tests the effects of nicotinamide on acute lung injury and associated alterations following ischaemia/reperfusion (I/R) of the isolated perfused rat's lung. I/R increased the lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, pulmonary arterial pressure and capillary permeability. The insult also increased nitrate/nitrite, methyl guanidine, tumour necrosis factor-alpha and interleukin-1beta in lung perfusate, while it decreased adenosine triphosphate content with an increase in PARP activity in lung tissue. Most of the I/R-induced changes were abrogated by post-treatment (30 min after I/R) with nicotinamide (100 mg.kg(-1) body weight). However, the increase in pulmonary arterial pressure was enhanced by nicotinamide post-treatment. Following I/R, the inducible nitric oxide synthase (iNOS) mRNA expression was enhanced. Nicotinamide reduced the iNOS expression. The results suggest that nicotinamide exerted a protective effect on the acute lung injury caused by ischaemia/reperfusion. The mechanisms may be mediated through the inhibition on the poly (adenosine diphosphate-ribose) polymerase activity, inducible nitric oxide synthase expression and the subsequent suppression of nitric oxide, free radicals and pro-inflammatory cytokines with restoration of adenosine triphosphate.
authors.affiliation: Department of Neurosurgery, Tzu Chi Hospital and University, Taipei, Taiwan.
authors.forename: C-F
authors.initials: CF
authors.lastname: Su
authors.forename: D D
authors.initials: DD
authors.lastname: Liu
authors.forename: S J
authors.initials: SJ
authors.lastname: Kao
authors.forename: H I
authors.initials: HI
authors.lastname: Chen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005609:Free Radicals; D007375:Interleukin-1 / Q000378:metabolism; D007511:Ischemia / Q000473:pathology*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury; D008297:Male; D008760:Methylguanidine / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005609:Free Radicals; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D009569:Nitric Oxide; D008760:Methylguanidine; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D011065:Poly(ADP-ribose) Polymerases