title: Effect of a gastrin-releasing peptide receptor antagonist and a proton pump inhibitor association in an animal model of gastritis.
abstract: It has been proposed that reactive oxygen species play a causative role of gastric mucosal damage induced by increased gastric secretion. Gastrin-releasing peptide is a typical neuropeptide that stimulates acid secretion by release of gastrin. In the present work we have investigated the mechanism of indomethacin (IDM)-induced gastric ulcer caused by ROS and determined the effects of a selective gastrin-releasing peptide receptor antagonist, RC-3095, alone and in association with omeprazole (OM) and compared it with an established antioxidant compound N-acetyl cysteine (NAC). Adult male Wistar rats were pre-treated for 7 days with OM, RC-3095, NAC, both drugs and water (control). The animals were then submitted to fasting for 24h; IDM was administered. Rats were killed 6h after that and the stomachs were used for evaluation of macroscopic damage and oxidative stress parameters. Our results showed that IDM increased mitochondrial superoxide production; OM and RC-3095 alone did not prevent such effect, but the combination of these drugs was effective. TBARS assay revealed that IDM-induced lipid peroxidation in gastric tissue and that OM and RC-3095, alone or in combination, prevented this effect with superior action that NAC. Finally, we verified that IDM increased protein carbonyl content and that this effect was prevented RC-3095, alone or in combination with OM, being similar to standard antioxidant. The present results support the view that, besides the inhibition of acid secretion, the protective effects exerted by OM and RC-3095 against IDM-induced gastric damage can be ascribed to a reduction of gastric oxidative injury.
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
authors.forename: Fabricia
authors.initials: F
authors.lastname: Petronilho
authors.forename: João H
authors.initials: JH
authors.lastname: Araújo
authors.forename: Amanda V
authors.initials: AV
authors.lastname: Steckert
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Ferreira
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007213:Indomethacin / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D013481:Superoxides / Q000378:metabolism; D013858:Thiobarbiturates / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D054328:Proton Pump Inhibitors; D018004:Receptors, Bombesin; D013858:Thiobarbiturates; D013481:Superoxides; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D009853:Omeprazole; C029684:thiobarbituric acid; D001839:Bombesin; D007213:Indomethacin