Envolvimento do receptor de potencial transitório vanilóide 4 (trpv4) na lesão gástrica induzida por etanol, em camundongos

Abstract

Transient potential receptors (TRP) form a superfamily implicated in a variety of cellular functions. Among them, we can highlight the transient vanilloid potential receptors (TRPV), which are associated with the development of numerous pathologies, including gastric disorders, such as ulcers caused by the use of indomethacin, acetic acid and ethanol. Vanilloid transient potential receptor 4 (TRPV4) is part of the TRPV receptor family, is morphologically and functionally expressed in the gastric epithelium and is also associated with disorders of the gastrointestinal tract. However, there are few studies demonstrating the association of TRPV4 with the development of gastric ulcers. Taking this into consideration, our study aimed to evaluate the possible participation of this receptor in the development of these types of ulcers. For this, we used animal models of gastric lesion induction by ethanol from the use of swiss mice weighing between 25 and 30g, in groups of approximately 5 animals. The negative control group received only saline administration (0.9%) and the positive control received 50% or 30% ethanol

administration. In the two experimental groups were administered 50% ethanol- associated TRPV4 antagonists (0.5ml / 25g, vo), where one group received

ruthenium red (doses: 0.03, 0.1 or 0.3 mg / kg, ip), a nonspecific antagonist, and the other group GSK2193874 (doses: 0.1, 0.3 and 0.9 mg / kg, ip), a specific antagonist. In addition, one group of animals received administration of GSK1016790A (0.9 mg / kg, i.p), TRPV4 agonist, and soon after 30% ethanol (0.5ml / 25g). One hour after the administration the animals were euthanized, a laparatomy was performed to remove the stomach, which was opened around the greater curvature, stretched and photographed for macroscopic analysis of the gastric mucosa, which was performed by the Image J program. The best dose of TRPV4 antagonists were selected for the other tests. Stomach samples were taken for histopathological evaluation, atomic force microscopy, malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) dosages. Gastric mucus experiment, immunohistochemistry and analysis of TRPV4 mRNA expression were also performed. As a result, we found that TRPV4 blockade promoted macro and microscopic gastroprotection in the ethanol-induced injury model, leading to decreased bleeding parameters, cell loss, edema, and increased gastric integrity relative to the ethanol group. The data also showed a significant increase (p <0.05) in SOD and GSH concentrations and a reduction in MDA concentrations (p <0.05) in the gastric mucosa, demonstrating a decrease in oxidative stress caused by alcohol. The mucus experiment showed a higher amount of gastric mucus in animals pretreated with TRPV4 antagonists. On the other hand, the use of TRPV4 agonist demonstrated, through macroscopic analyzes, an exacerbation of the lesion area (p <0.05) when compared to the group that received 30% ethanol. With this we can conclude that the activation of TRPV4 is involved in the process of gastric injury induced by ethanol, and that the use of TRPV4 blockers may in future be a therapeutic alternative for the treatment of gastric ulcers.