Effect of NADPH-oxidase inhibitors in the experimental model of zymosan-induced shock in mice

Free Radic Res. 2011 Jul;45(7):820-34. doi: 10.3109/10715762.2011.581667. Epub 2011 May 31.

Abstract

The aim of this study was to investigate the effects of NADPH-oxidase inhibitors, in a mouse model of zymosan. Zymosan-induced shock was induced in mice by administration of zymosan (500 mg/kg, i.p.). The pharmacological treatment was the administration of apocynin (5 mg/kg 10% DMSO i.p.) and diphenylene iodonium chloride (DPI) (1 mg/kg i.v.) 1 h and 6 h after zymosan administration. MOF and systemic inflammation in mice was assessed 18 h after administration of zymosan. NADPH-oxidase inhibitors caused a significant reduction of the (1) peritoneal exudate formation, (2) neutrophil infiltration, (3) multiple organ dysfunction syndrome, (4) nitrotyrosine, (5) poly (ADP-ribose) (PAR), (6) cytokine formation, (7) adhesion molecule expression, (8) nuclear factor (NF-κB) expression and (9) apoptosis induced by zymosan. Moreover, NADPH-oxidase inhibitors treatment significantly reduced the systemic toxicity, the loss in body weight and the mortality caused by zymosan. This study has shown that NADPH-oxidase inhibitors attenuate the degree of zymosan-induced non-septic shock in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Cytokines / biosynthesis
  • Enzyme Inhibitors / therapeutic use*
  • Male
  • Mice
  • Multiple Organ Failure / chemically induced
  • Multiple Organ Failure / drug therapy
  • NADPH Oxidases / antagonists & inhibitors*
  • Nitrates / blood
  • Nitrites / blood
  • Onium Compounds / pharmacology
  • Reactive Oxygen Species
  • Shock / chemically induced
  • Shock / drug therapy*
  • Systemic Inflammatory Response Syndrome / chemically induced
  • Systemic Inflammatory Response Syndrome / drug therapy
  • Zymosan

Substances

  • Acetophenones
  • Cytokines
  • Enzyme Inhibitors
  • Nitrates
  • Nitrites
  • Onium Compounds
  • Reactive Oxygen Species
  • diphenyleneiodonium
  • Zymosan
  • acetovanillone
  • NADPH Oxidases