Effect of PPAR agonist LYSO-07 on installation and healing of gastric ulcers in mice

Abstract

Gastric ulcer affects a lot of people in the world population. It is caused by the imbalance between aggressive and protective factors, characterized by lesioned areas and necrosis on the gastric tissues. The process is characterized by intense neutrophil migration, which at the beginning ; acts as a defense mechanism, although a variety of chemicals secreted by it contribute to the injurious process. The currently available pharmacological treatments are effective, however, cause a adverse effects, which leads to find out new lesser toxic agents. In this context, recent literature has proposed that receptor agonist peroxisome proliferator activated (PPARs) can be used as antiulcer agents. Therefore, this project aims to investigate the action of partial agonist of PPAR-g LYSO-07 ([5-(5-bromo-1H-indole-3-metieleno)-3-(4-chloro-benzyl)-thiazolidine-2,4-dione)]), an indole-thiazolidine molecule, synthesized by the Synthesis Group and Planning Drugs the Pernambuco University on the installation and healing of experimental gastric ulcer in mice evoked by three different exogenous agents and investigate the possible mechanisms involved in the pharmacological and toxicological effects. Male Swiss mice, will be treated with LYSO-07 (5, 25 and 50 mg/kg) one hour before gastric ulcer induction (60% ethanol + 0.03 M HCl or indomethacin, 100mg/kg, gavage) . To evaluate the effect of LYSO-07 on the healing process, chronic ulcerative lesion will be induced by acetic acid (20 µL, 20% solution in the layer sub-serous stomach) and LYSO-07 will be administered once a day, oral route during 7 days, . Peripheral blood and stomach tissue will be collected to evaluate the lesioned area (optical microscopy associated to image analysis); oxidative enzymes activities (biochemical approaches); nitric oxide production (Greiss reaction); secretion of pro or anti-inflammatory cytokines (interleukins 1², 6, 4,10 and tumor necrosis factor alpha (TNF-±, ELISA); prostaglandin E2 (PGE2; ELISA) and prostacyclin (PGI2; ELISA); cholesterol, triglycerides and glucose ( enzymatic methods). Data here obtained may contribute to the knowledge of the mechanisms of action of PPARs agonists and will provide the basis for further studies focused to the employment of therapeutic molecules synthesized in Brazil.