The nociceptin/orphanin FQ-NOP receptor antagonist effects on an animal model of sepsis.
OBJECTIVE
The aim of this study was investigate the effects of nociceptin/orphanin FQ (N/OFQ) and ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2)) (UFP-101), the endogenous N/OFQ peptide receptor (NOP) ligand and a selective NOP antagonist, respectively, in the inflammatory response after cecal ligation and puncture (CLP) model of sepsis in rats.


METHODS
Prospective, controlled experiment.


METHODS
Animal basic science laboratory.


METHODS
Male Wistar rats, weighing 300-350 g.


METHODS
Rats subjected to CLP were treated with N/OFQ (0.001, 0.01 or 0.1 mg/kg) or UFP-101 (0.03, 0.03 or 0.3 mg/kg) subcutaneously administered immediately after surgery.


RESULTS
Twelve hours after surgery, blood was collected by cardiac puncture and bronchoalveolar (BAL) and peritoneal lavage were performed. In a separate set of experiments mortality was evaluated monitoring CLP rats for 10 days. Our findings showed that UFP-101 (0.03 mg/kg, sc, but not 0.003 mg/kg) modified parameters related to the systemic inflammatory response by effectively preventing cells migration, bacterial dissemination, and by modulating the release of pro-inflammatory cytokines and chemokines, and reducing animal mortality in a clinically relevant model of sepsis. By contrast, N/OFQ (0.1 mg/kg, sc) increased mortality in the CLP model.


CONCLUSIONS
Our findings point to a functional relationship between the N/OFQ-NOP receptor system and inflammatory response in the CLP model of sepsis and suggest that NOP receptor antagonists are worthy of testing as innovative drugs for the treatment of sepsis.
Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Avenida Universitária, 1105, Criciúma, SC 88806-000, Brazil.
Dickson
D
Carvalho
Fabricia
F
Petronilho
Francieli
F
Vuolo
Roberta Albino
RA
Machado
Larissa
L
Constantino
Remo
R
Guerrini
Girolamo
G
Calo
Elaine Cristina
EC
Gavioli
Emílio Luiz
EL
Streck
Felipe
F
Dal-Pizzol
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D008297:Male; D009292:Narcotic Antagonists; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000276:immunology*; D018805:Sepsis / Q000097:blood / Q000276:immunology*; D000094942:Nociceptin Receptor
D016207:Cytokines; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722285:Oprl1 protein, rat