Effects of an antagonist of the gastrin-releasing peptide receptor in an animal model of uveitis.
OBJECTIVE
Some studies have shown the role of gastrin-releasing peptide (GRP) on the production and release of cytokines both in animal models and in humans with inflammatory diseases, but there are no reports on the effects of GRP in ocular inflammatory disease, mainly uveitis. The authors report on the effects of the GRP receptor (GRPR) antagonist RC-3095 in a well-established model for uveitis induced by the administration of lipopolysaccharide (LPS), comparing its effects with those of glucocorticoids.


METHODS
Adult male Wistar rats (weight range, 250-300 g; n = 6 per group) were randomly divided into four groups: saline, LPS + saline, LPS + dexamethasone, LPS + RC-3095. Two hours after LPS administration, RC-3095 (0.3 mg/kg, single dose, subcutaneously) or dexamethasone (1 mg/kg, each 6 hours, subcutaneously) was administered. After 24 and 48 hours, rats were anesthetized, aqueous humor was sampled, and the irides were removed. Aqueous humor tumor necrosis factor-alpha, monocyte chemoattractant protein-1 concentration, myeloperoxidase activity were determined. In addition, oxidative damage to the irides was determined by the measure of thiobarbituric acid reactive substances and protein carbonyl content.


RESULTS
The acute administration of RC-3095 exhibited anti-inflammatory actions, characterized by a reduction of myeloperoxidase activity and a decrease in tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels, to a greater extent than dexamethasone. In addition, RC-3095 elicits important action against irides oxidative damage.


CONCLUSIONS
These findings suggest that GRP participates in the inflammatory response in an animal model of uveitis, making GRPR a target for new therapeutic options in the treatment of uveitis.
Pereira
David Valter
DV
Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Steckert
Amanda Valnier
AV
Mina
Franciele
F
Petronilho
Fabricia
F
Roesler
Rafael
R
Schwartsmann
Gilberto
G
Ritter
Cristiane
C
Dal-Pizzol
Felipe
F
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000378:metabolism; D001839:Bombesin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D019886:Gastrin-Releasing Peptide / Q000502:physiology; D005938:Glucocorticoids / Q000627:therapeutic use; D007498:Iris / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D050050:Protein Carbonylation; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D016588:Anticarcinogenic Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D018004:Receptors, Bombesin; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D003907:Dexamethasone; D019886:Gastrin-Releasing Peptide; D009195:Peroxidase; D001839:Bombesin