Background: In Brazil, 57.7% of the adult population is overweight and 19.8% is obese. Obesity causes a low-grade inflammatory condition that can result in other comorbidities such as type 2 diabetes mellitus, hypertension, hepatic steatosis and atherosclerosis. In addition, in cases of gastrointestinal tract disorders, there is an increase in the severity of gastric lesions and greater difficulty in the healing process, intensified by the use of medications that further aggravate gastric mucosal lesions in obese individuals. Thus, the literature has reported that obesity delays processes such as the healing of gastric lesions and metalloproteinases are intimately related to this difference. These enzymes play a crucial role in ulcer healing, in the initial phase, the role of MMP-9 is highlighted, and in the later phase, MMP-2. Studies conducted by our group showed that Citral is able to promote healing acceleration through the modulation of inflammatory mediators in ulcers induced by acetic acid in rats, but its healing action associated with obesity condition is still unknown.
Aim: Evaluate the pharmacological effects of Citral on healing process of gastric lesions in eutrophic and obese mice
Material and methods: For induction of obesity, C57Bl-J6 male mice were divided into 2 groups: Standard diet (SD) and high-fat diet (HFD), with 60% of calories from lipids and after 12 weeks of dietary intake, the animals underwent gastric ulcer induction surgery by acetic acid. For injury induction, the animals were anesthetized with isoflurane via inhalation, then they were laparatomized, stomachs exposed to 80% acetic acid application for 20 seconds. For evaluation of the action of Citral, three doses were orally administrated: 25, 100 or 300 mg/kg for 10 subsequent days and the following groups were included: negative control treated with vehicle (Tween 80 at 1%, 10 mL/kg) and positive control treated with Lansoprazole (30 mg/kg). All protocols were approved by the animal use ethics committee of the Institute under the number 1208. All stomachs were collected for macroscopic morphological and zymographic analysis. The macroscopic analysis of the lesions was performed by quantifying the area of regeneration tissue and the ulcer in mm2. In addition, we quantified matrix metalloproteinases 2 and 9 by zymography. For statistical analysis, two-way analysis of variance was used, followed by the Tukey or Dunnett test. The minimum significance level adopted for this study was p < 0.05.
Results and discussion: In the group of animals fed with SD, we observed that 10 days after the induction of gastric injury by acetic acid, the treatment of animals with 3 doses of citral did not promote macroscopic changes in gastric lesions compared to the negative control group. There was no difference between the groups in the MMP-2 activity either. However, in animals fed with HFD, there was a significant increase in MMP-9 activity in its intermediate (50%, p < 0.05) and active (13%, p < 0.05) forms in animals treated with the dose of 100 mg/kg of Citral compared to the group treated with vehicle. Since MMP-9 is an enzyme that operates in the early phase of ulcer healing and there was no difference between the areas of lesion, the reduction of its activity may indicate that healing process in the group that received the intermediate dose of Citral was in a more advanced stage of healing.
Conclusion: Although we did not detect macroscopic changes, we found that in obese animals, treatment for 10 days with Citral at a dose of 100 mg/kg reduced MMP-9 activity, indicating that the healing process may be accelerated in this group.
