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This Article Full Text Full Text (PDF) All Versions of this Article: iovs.09-3525v1 50/11/5300    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Pereira, D. V. Articles by Dal-Pizzol, F. PubMed PubMed Citation Articles by Pereira, D. V. Articles by Dal-Pizzol, F.

Effects of an Antagonist of the Gastrin-Releasing Peptide Receptor in an Animal Model of Uveitis

From the ¹Laboratório 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; ²Programa de Pós Graduação em Ciências Biológicas—Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; ³Grupo de Pesquisa em Neurofarmacologia Celular e Molecular, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; and ⁴Laboratório de Pesquisas em Câncer, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Corresponding author: Felipe Dal-Pizzol, Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806–000 Criciúma, SC, Brazil; piz{at}unesc.net.

Purpose. 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-, 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- 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.