Efeito gastroprotetor de isoflavonas em modelos experimentais de úlcera gástrica

Abstract

Introduction: Peptic ulcers affect a significant portion of the world's population. Pharmacological treatment is mainly carried out with proton pump inhibitors and H2 antagonists, which can cause significant adverse reactions. New therapeutic approaches are needed, given the adverse effects that current therapy brings to patients, in addition to the high number of disease recurrences. In this context, natural products stand out as sources of new molecules. Among these products, some studies highlight the potential impact of isoflavones in experimental models of gastric lesions. Objectives: To evaluate the scientific evidence on the therapeutic potential of isoflavones in preclinical models of gastric ulcer and the gastroprotective effect of daidzein in an acute model of gastric ulcer. Methods: The systematic review encompassed studies obtained through searches in Web of Science, ScienceDirect, Scopus, and MEDLINE/PubMed, which investigated the effects of isoflavones, tested in isolation, in models of gastric or duodenal ulcer in animals. The risk of bias was assessed using the SYRCLE platform tool. For the experimental study, male Swiss mice (25-35 g) were used. Gastric lesions were induced by acidified ethanol (60% ethanol/0.3 M HCl) in animals pre-treated with Daidzein (10, 30, and 100 mg/kg, p.o.), vehicle (saline + 2% Tween 80), or standard drug (ranitidine 100 mg/kg, p.o.) 60 minutes before induction. The control group (without ulcers) received water instead of acidified ethanol. After 60 min, the percentage of relative ulcerative lesion area (corrected for total stomach area) was measured. Results: Thirteen studies were included out of the 3005 identified with rodents, in models of ulcers induced by ethanol, acetic acid, indomethacin, or stress, in which isoflavones were tested in isolation. The results indicated important benefits associated with the administration of isoflavones, especially as a pretreatment. Most studies demonstrated the effects of genistein and formononetin, but studies with daidzein, osajine, pormiferin, and puerarin were also found. These studies associated the gastroprotective effects of these isoflavones mainly with their ability to reduce oxidative damage and positively regulate the activity of antioxidant enzymes, such as superoxide dismutase and catalase, and reduced glutathione concentrations. Another common characteristic observed in the studies was the reduction in the concentration of pro-inflammatory cytokines, mainly TNF-α and IL-1β, and myeloperoxidase activity. In the experimental study, it was observed that acidified ethanol caused ulcerative lesions (p<0.01 vs. the group that received water) and that pretreatment with ranitidine, but not with daidzein doses, prevented the induction of ulcers (p<0.01). Conclusion: From the review, it was possible to conclude that the studies provide evidence that isoflavones play a protective role against damage to the gastric mucosa caused by various aggressive agents, by producing anti-inflammatory and antioxidant responses. The literature supports the hypothesis that daidzein has a gastroprotective effect; however, its effects have only been investigated at very high doses. Therefore, there are no reports on its action at lower doses, which does not diminish the potential of the isoflavone class as gastroprotective agents.