Can gastric healing be altered in obese animals? Evaluation of the antiulcerogenic effect of citral in mice treated with a high-fat diet

Abstract

Obesity is worrying and very prevalent in the world and in Brazil. The presence of comorbidities is very characteristic in obese patients, such as type 2 diabetes mellitus. During obesity, pro-inflammatory mediators are released by adipocytes, such as tumor necrosis factor (TNF) -±, interleukin (IL) -1², IL-6 and leptin, which promote a chronic inflammatory condition. In addition, there is also an imbalance of the redox system, which increases the susceptibility to the development of dyspepsia and gastric ulcers. These are characterized as lesions in the gastric mucosa that occur, mainly, due to the imbalance between the protective and aggressive factors (such as the use of non-steroidal anti-inflammatory drugs). And its healing is a complex process that involves different molecular factors, such as the hypoxia-induced factor (HIF) -1±; vascular endothelial (VEGF) and epidermal (EGF) growth factors; cyclooxygenases (COX); metalloproteinases (MMP), as well as leptin and other inflammatory mediators (TNF-±, IL-1², IL-6). These factors contribute to the re-epithelialization of the gastric mucosa and to the remodeling of the extracellular matrix, prevents the recurrence of gastric lesions and fights local inflammation. Citral is a monoterpenoid present in essential oils from medicinal plants. Previous laboratory studies have already demonstrated its effectiveness in resolving gastric ulcers induced by acetic acid in adult male rats, however it is unknown how healing occurs in obesity. For this, gastric lesions will be implanted in obese mice and treatments will be carried out in the different experimental groups for the evaluation of two doses of citral in two consecutive treatment periods. The area of injury and the biochemical and pro-inflammatory parameters in the healing process will be analyzed. Based on the evaluation of the pharmacological effects of citral on the healing of gastric ulcers in eutrophic and obese mice, it is intended to obtain scientific support to suggest a new therapeutic option for the treatment of this disease.