Efeito protetor do complexo de rutênio (II) (cis-[RuCl(qui)(bpy)2]PF6) contra lesão gástrica induzida por naproxeno : possível papel regulador da enzima guanilato ciclase solúvel

Abstract

Introduction: NSAIDs contribute to the pathogenesis of gastrointestinal ulcers and represent an important etiologic factor because is commonly used in clinical practice. Aim: To evaluate the protective effect of the ruthenium complex (II) (cis-[RuCl(qui)(bpy)2]PF6), against the gastric damage induced by naproxen (NPX) in mice. Methods: Swiss mice were used (18-22g). Measure the GMPc levels incubating samples of gastric tissues with DMSO, with the complex of RU (II) and with ODQ, 30 μm of each compound, for 5 minutes. The groups evaluated were: control group that received CMC, group vehicle, in which was administered NPX (300 mg/kg) and who received complex of RU (II), all by gavage. The animals were treated with the complex of RU (II), in the doses of 0.3, 3 and 30 mg/kg. After 30 minutes, was followed with the induction of the lesion with NPX. Following the same protocol, it was evaluated the effect of the compound and its precursors, in dose of 3mg/kg, by gavage. It was verified the effect of compound in accession and leukocyte bearing; following the protocols described, both the bearing for accession were evaluated 3h after the induction of gastropathy and modulation with ODQ (10 mg/kg) by gavage. It examined the effect of the complex of RU (II) in mesenteric arteries of Wistar rats (200-250 g) pre-contracted with phenylephrine (PHE) (0.3 μM). Simulated-If the connection between the compound and the enzyme GCs from resources available in the site that contains the database of proteins. Results: Tissues incubated with metallopharmaceutica had a significant increase in the production of cGMP, when compared to the recipient that contained the solvent and ODQ. Ru complex (II), inhibited the gastric lesions induced by NPX in mice, with maximum effect in dose of 3 mg/kg-1. Only integral Ru complex (II) administration reversed gastric damage. The metallopharmaceutical reduced the leukocyte adhesion and rolling, and the ODQ not reversed this gastroprotetion. The metallopharmaceutical abolished the contraction promoted by PHE, inducing the relaxation of vessel and ODQ can’t reversed this effect. It was observed that Ru complex (II) turns in a more stable in the catalytic domain of the sGC. Conclusions: This compound prevented the gastric damage induced by naproxen in mice, through increased cGMP levels, decreased leukocyte adhesion and rolling, and still due to maintenance of gastric blood flow, with the binding site independent of ODQ, in sGC.