title: Effect of NADPH-oxidase inhibitors in the experimental model of zymosan-induced shock in mice.
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.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000188:drug therapy; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009861:Onium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species; D012769:Shock / Q000139:chemically induced / Q000188:drug therapy*; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced / Q000188:drug therapy; D015054:Zymosan
chemical_list: D000098:Acetophenones; D016207:Cytokines; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009861:Onium Compounds; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; D015054:Zymosan; C056165:acetovanillone; D019255:NADPH Oxidases