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Evaluation of gastroprotective activity of PPAR agonist Lyso-07 and chlorogenic acid

Grant number: 11/01848-8
Support Opportunities:Regular Research Grants
Duration: July 01, 2011 - June 30, 2013
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Sandra Helena Poliselli Farsky
Grantee:Sandra Helena Poliselli Farsky
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Norberto Peporine Lopes

Abstract

The gastric ulcer is characterized by the gastric necrotic lesions formation, caused by an imbalance between aggressive and endogenous protective factors. The process is marked by intense neutrophil migration, which in the first instance, acts as a defense mechanism. However, its secretory activity contributes to the tissue damaging process. Current pharmacological treatments are effective; however, they cause adverse effects, which leads to the search for new therapeutic agents. In this context, recent literature has proposed that the receptor agonist peroxisome proliferator activated (PPARs) and the natural compound chlorogenic acid (CGA) can be used as antiulcer agents. Investigating the effects and action mechanisms of indole-thiazolidine molecule partial agonist of PPAR-gamma (LYSO-07), and ACG, a polyphenolic compound isolated from Lychnophora salicifolia, on the installation and healing of experimental gastric ulcer in mice, caused by various exogenous agents, is the aim of this project. Male Swiss mice will be treated with LYSO-07 (5, 25 and 50 mg/kg) or ACG (5, 25 and 50 mg/kg) one hour before the ulcer-inducer chemical treatments (60% ethanol + 0.03 M HCl or indomethacin, 100mg/kg, gavage). The effect of LYSO-07 or the ACG on the healing process in the chronic ulcerative lesion induced by acetic acid solution 20% (20 µL in the layer sub-serous stomach) will be evaluated in mice treated with LYSO-07 or ACG once a day, for 7 days, by gavage route. Circulating blood and stomach tissue will be collected to evaluate the damaged area (microscopic evaluation), oxidative enzymes activities (biochemical), the nitric oxide production (Greiss reaction), interleukins 1², 6, 4, 10, tumor necrosis factor alpha-±,, prostaglandin E2 and prostacyclin secretion (ELISA), biochemical parameters (cholesterol, triglycerides and glucose by enzymatic methods). Data obtained may contribute to the knowledge of action mechanisms of PPARs agonists and ACG, and it may provide results for further studies to possible therapeutic use of new Brazilian produced molecules. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SANTIN, JOSE ROBERTO; UCHOA, FLAVIA D. T.; LIMA, MARIA DO CARMO A.; RABELLO, MARCELO M.; MACHADO, ISABEL DAUFENBACK; HERNANDES, MARCELO Z.; AMATO, ANGELICA A.; MILTON, FLORA APARECIDA; WEBB, PAUL; ROCHA NEVES, FRANCISCO DE ASSIS; et al. Chemical synthesis, docking studies and biological effects of a pan peroxisome proliferator-activated receptor agonist and cyclooxygenase inhibitor. European Journal of Pharmaceutical Sciences, v. 48, n. 4-5, p. 689-697, . (10/17175-0, 11/01848-8)
SANTIN, JOSE ROBERTO; MACHADO, ISABEL DAUFENBACK; RODRIGUES, STEPHEN F. P.; TEIXEIRA, SIMONE; MUSCARA, MARCELO N.; GALDINO, SUELY LINS; PITTA, IVAN DA ROCHA; FARSKY, SANDRA H. P.. Role of an Indole-Thiazolidine Molecule PPAR Pan-Agonist and COX Inhibitor on Inflammation and Microcirculatory Damage in Acute Gastric Lesions. PLoS One, v. 8, n. 10, . (10/17175-0, 11/01848-8)
SHIMOYAMA, ANDRE T.; SANTIN, JOSE ROBERTO; MACHADO, ISABEL D.; DE OLIVEIRA E SILVA, ANA MARA; PEREIRA DE MELO, ILLANA L.; MANCINI-FILHO, JORGE; FARSKY, SANDRA H. P.. Antiulcerogenic activity of chlorogenic acid in different models of gastric ulcer. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. 386, n. 1, p. 5-14, . (11/01848-8, 10/18069-9)

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