title: RC-3095, a selective gastrin-releasing peptide receptor antagonist, does not protect the lungs in an experimental model of lung ischemia-reperfusion injury.
abstract: RC-3095, a selective GRPR antagonist, has been shown to have anti-inflammatory properties in different models of inflammation. However, its protective effect on lungs submitted to lung ischemia-reperfusion injury has not been addressed before. Then, we administrated RC-3095 intravenously before and after lung reperfusion using an animal model of lung ischemia-reperfusion injury (LIRI) by clamping the pulmonary hilum. Twenty Wistar rats were subjected to an experimental model in four groups: SHAM, ischemia-reperfusion (IR), RC-Pre, and RC-Post. The final mean arterial pressure significantly decreased in IR and RC-Pre compared to their values before reperfusion (P < 0.001). The RC-Post group showed significant decrease of partial pressure of arterial oxygen at the end of the observation when compared to baseline (P = 0.005). Caspase-9 activity was significantly higher in the RC-Post as compared to the other groups (P < 0.013). No significant differences were observed in eNOS activity among the groups. The groups RC-Pre and RC-Post did not show any significant decrease in IL-1β (P = 0.159) and TNF-α (P = 0.260), as compared to IR. The histological score showed no significant differences among the groups. In conclusion, RC-3095 does not demonstrate a protective effect in our LIRI model. Additionally, its use after reperfusion seems to potentiate cell damage, stimulating apoptosis.
authors.affiliation: Department of Research Group and Post-Graduation, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Sala 2227, 90.035-903 Porto Alegre, RS, Brazil.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Oliveira-Freitas
authors.affiliation: Lung and Airway Laboratory, Federal University of Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Sala 21313, 90.035-903 Porto Alegre, RS, Brazil.
authors.forename: Leonardo Dalla Giacomassa Rocha
authors.initials: LD
authors.lastname: Thomaz
authors.affiliation: Lung and Airway Laboratory, Federal University of Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Sala 21313, 90.035-903 Porto Alegre, RS, Brazil.
authors.forename: Lucas Elias Lise
authors.initials: LE
authors.lastname: Simoneti
authors.affiliation: Laboratory of Translational Physiology, Universidade Nove de Julho, Rua Vergueiro 235/249, 3 Subsolo, 01.504-000 São Paulo, SP, Brazil.
authors.forename: Christiane
authors.initials: C
authors.lastname: Malfitano
authors.affiliation: Laboratory of Translational Physiology, Universidade Nove de Julho, Rua Vergueiro 235/249, 3 Subsolo, 01.504-000 São Paulo, SP, Brazil.
authors.forename: Kátia
authors.initials: K
authors.lastname: De Angelis
authors.affiliation: Department of Pathology, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, 90.035-903 Porto Alegre, RS, Brazil.
authors.forename: Jane Maria
authors.initials: JM
authors.lastname: Ulbrich
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Federal University of Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 3° Leste, 90.035-903 Porto Alegre, RS, Brazil.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.affiliation: Department of Thoracic Surgery, Hospital de Clínicas de Porto Alegre and Hospital da Criança Santo Antônio, Ramiro Barcelos 2.350, 90035-903 Porto Alegre, RS, Brazil.
authors.forename: Cristiano Feijó
authors.initials: CF
authors.lastname: Andrade
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D010446:Peptide Fragments; D018004:Receptors, Bombesin; D014409:Tumor Necrosis Factor-alpha; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D001839:Bombesin