Protective effects of apocynin, an inhibitor of NADPH oxidase activity, in splanchnic artery occlusion and reperfusion.
SAO shock is a severe form of circulatory shock produced by I/R of the splanchnic organs. SAO causes an enhanced formation of ROS, which contributes to the pathophysiology of shock. Apocynin is a naturally occurring, methoxy-substituted catechol, experimentally used as an inhibitor of NOX. It can decrease the production of ROS from activated neutrophils and macrophages, inhibiting the assembly of NADPH-oxidase activity. In this study, we wanted to evaluate the pharmacological action of apocynin in rats subjected to SAO shock, which was induced by clamping the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 45 min. After this period of occlusion, the clamps were removed. Administration of apocynin i.p. (5 mg/kg i.p. 10% DMSO) 5 min before reperfusion significantly reduced the (1) histological evidence of tissue injury, (2) proinflammatory cytokine production (TNF-α, IL-1β), (3) adhesion molecules (ICAM-1, P-selectin), (4) nitrotyrosine formation, (5) NF-κB expression, and (6) apoptosis (Bax, Bcl-2, Fas-L, and TUNEL). These results could imply a future use of apocynin in the treatment of I/R shock.
Paterniti
Irene
I
School of Medicine, University of Messina, Torre Biologica-Policlinico Universitario, Via C. Valeria-Gazzi, Messina, Italy.
Galuppo
Maria
M
Mazzon
Emanuela
E
Impellizzeri
Daniela
D
Esposito
Emanuela
E
Bramanti
Placido
P
Cuzzocrea
Salvatore
S
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008638:Mesenteric Arteries / Q000503:physiopathology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D012769:Shock / Q000517:prevention & control; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; C056165:acetovanillone; D019255:NADPH Oxidases