EVALUATION OF MECHANISMS OF ACTION INVOLVED IN ANTIULCER ACTIVITY OF CITRAL AGAINST PEPTIC ULCER DISEASE

Abstract

This work is a subproject of FAPESP n. 2009/54603-2, entitled "Effects of monoterpenes on peptic ulcer disease" and its objective is continue the studies with the monoterpene Citral against peptic ulcers from the observation of its antiulcer action at doses below those used for current pharmacotherapy (FAPESP n. 2010/00420-1). To this purpose, we will characterize the pharmacological action of Citral, by the analysis of mechanisms of action and influence of this on DNA and protein synthesis. In this context, we will analyze the action and antiulcer mechanisms possible involvement of anti-inflammatory and antioxidant Citral induced ulcers in an acute (ischemia and reperfusion) and chronic (contact of gastric or duodenal mucosa with acetic acid). To monitor the pathophysiological conditions of the gastric mucosa, concentrations of antioxidant enzymes such as glutathione and superoxide dismutase, and pro-oxidants such as myeloperoxidase are measures. We also determine the levels of cytokines pro-inflammatory (tumor necrosis factor and interleukin-1) and anti-inflammatory (interleukin-10) of the injured region. A comparative analysis of the mechanisms of action and quality of protection and healing gastroduodenal of Citral in relation to one of the most widely used drugs today, lansoprazole, will also be evaluated. We will study the gene and protein expression of some protective factors of the mucosa, they were, epidermal growth factor (EGF), fibroblast growth factor (VGF), enzymes cyclooxygenase-1 (COX-1) and 2 (COX-2), and as involvement with the levels of prostaglandin E2 (PGE2) in the recovery of the gastroduodenal mucosa. Another important parameter to be investigated is the involvement of Citral in the regulation of gastric acid secretion. In this context, we will analyze the parameters of gastric juice (pH, H+, and volume of gastric juice), the mechanisms of action antisecretory by examining the involvement of channels ATP-sensitive K+, adrenergic ±-2 or afferents sensitive capsaicin, and quantify the serum levels of gastrin and somatostatin.