Atividade antiulcerogênica e mecanismo de ação da troxerrutina: um flavonóide semissintético da rutina

Abstract

Gastric ulcer represents an ulcerative and inflammatory gastrointestinal disorder that appears as a serious public health problem worldwide. The appearance of this condition is the result of an imbalance between aggressive and protective agents of the gastric mucosa, including exacerbation of alcohol consumption. Flavonoids such as troxerutin (TRX) are highlighted in the pharmacological environment, due to their antioxidant, anti-inflammatory and cytoprotective properties. The present study aimed to determine the gastroprotective effect of TRX on ethanol-induced gastric ulcer in mice, and its role in antioxidant and anti-inflammatory mechanisms. After the induction of gastric lesions by ethanol, treatment with TRX (100 mg/kg., p.o.), N-acetylcysteine (NAC) was performed. To determine the gastroprotective effect of TRX in the gastric lesion, the following evaluations were used: percentage of ulcerated area, histopathological analysis, glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), immunohistochemistry for TNF-α and iNOS, and Molecular docking for iNOS. Our results showed that Troxerutin at a dose of 100mg/kg administered before ethanol was effective in gastroprotection, demonstrated through macroscopic and microscopic analysis where we evidenced the regression of the loss of epithelial cells, edema, inflammatory infiltrate, and decrease in the number of mast cells. We observed that (iNOS and Indomethacin) were able to reverse the gastroprotective effect of troxerutin at a dose of 100mg/kg, showing that these substances act in the mentioned pathways. Our findings suggest that Troxerutin can suppress the release of the pro-inflammatory cytokine TNF-α and iNOS, through immunostaining of tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS). We showed in our studies that troxerutin significantly increased GSH levels and reduced Malondialdehyde (MDA) levels, and reduced myeloperoxidase (MPO) enzymatic activity. Our results demonstrate that troxerutin at a dose of 100mg/kg has gastroprotective activity against ethanol-induced gastric injury, and this action apparently involves the participation of nitric oxide and prostaglandins, in addition to the potential antioxidant effect of troxerutin.