Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin

Shang Jyh Kao, Demeral David Liu, Chain Fa Su, Hsing I. Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 factorα (TNFα), and interleukin-1β (IL-1β). 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, TNFα, and IL-1β 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.

Original languageEnglish
Pages (from-to)333-342
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume50
Issue number3
DOIs
Publication statusPublished - Sep 2007

Keywords

  • Free radical
  • Inducible nitric oxide synthase
  • Nitric oxide
  • Poly (ADP-ribose) polymerase
  • Proinflammatory cytokines

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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