RESUMO
The gastroprotective effects of N-acylarylhydrazone derivatives on ethanol-induced gastric lesions in mice were investigated with respect to the NO/cGMP/KATP pathway. To investigate our hypothesis, the mice were intraperitoneally pretreated with glibenclamide, L-NAME, or ODQ 30â¯min before treatment with DMSO, LASSBio-294 (1, 2, and 4â¯mg/kg, p.o.), LASSBio-897 (0.5, 1, and 2â¯mg/kg, p.o.), or omeprazole. After 1â¯h, the mice received absolute ethanol (4â¯ml/kg) by gavage to induce gastric mucosal lesions, and the microscopic and macroscopic parameters were evaluated. GSH (non-protein sulfhydryl groups) and MDA (malondialdehyde) concentrations, hemoglobin levels, nitric oxide production, myeloperoxidase (MPO) activity, and TNF-α and IL-1ß levels were also analyzed in the stomach after absolute ethanol administration. Pretreatment with LASSBio-294 or LASSBio-897 significantly reduced the microscopic and macroscopic lesion area. The compounds restored the GSH, MDA, and hemoglobin levels and reduced MPO activity. Moreover, the compounds significantly reduced nitrate and nitrite concentrations in the stomach samples after ethanol administration. Molecular docking studies revealed that LASSBio-294 and LASSBio-897 interact with active sites of the eNOS (endothelial nitric oxide synthase) enzymes through hydrogen bonds. LASSBio-294 and LASSBio-897 also reduced TNF-α and IL-1ß levels. It was observed that a NO synthase inhibitor, an ATP-sensitive potassium channel blocker, and a guanylate cyclase inhibitor significantly reversed the gastroprotective effects of these compounds. Thus, the gastroprotective effect of LASSBio-294 and LASSBio-897 against gastric lesions is mediated through the NO/cGMP cascade, followed by blocking of the KATP channels.
Assuntos
GMP Cíclico/fisiologia , Mucosa Gástrica/efeitos dos fármacos , Hidrazonas/farmacologia , Canais KATP/fisiologia , Óxido Nítrico/fisiologia , Tiofenos/farmacologia , Animais , Etanol/toxicidade , Mucosa Gástrica/patologia , Glutationa/metabolismo , Canais KATP/antagonistas & inibidores , Masculino , Camundongos , Simulação de Acoplamento Molecular , Peroxidase/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Galactomannans are neutral polysaccharides isolated from the endosperm of some Leguminosae seeds. They consist of a (1â¯ââ¯4) linked ß-mannopyranosyl backbone partially substituted at O-6 with α-d-galactopyranosyl side groups. C. pulcherrima have anti-inflammatory and muco-adhesive proprieties. Acute gastritis is an inflammatory disease triggered by use of non-steroidal anti-inflammatory drugs. We investigated the gastroprotective effect of galactomannan obtained from the seeds of Caesalpinia pulcherrima L. (GM-CP) in acute gastritis model induced by indomethacin. Gastritis was induced with indomethacin (30â¯mg/kg, P.·O.) in female Swiss mice. Animal groups (nâ¯=â¯7) were pretreated with saline-dissolved GM-CP (3â¯mg/kg, 10â¯mg/kg, 30â¯mg/kg, P.O.) or vehicle 1â¯h before gastritis induction. Mice were euthanized seven hours after the induction. The stomach and blood samples were collected for analysis. At 10â¯mg/kg, GP-CP reduced the extension of macroscopic lesion and the loss of superficial cells by alleviating inflammatory symptoms (neutrophil infiltration, migration and adhesion of mesenteric leukocytes, production of TNF-α and thiobarbituric acid reactive species (TBARS) and helping to maintain mucin labeling of the tissue. Thus, the findings of the study suggest that GM-CP exhibits gastroprotective effects.