Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from Dimorphandra gardneriana, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis.

Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU), a chemotherapeutic agent used for cancer treatment. Troxerutin (TRX), a semi-synthetic flavonoid extracted from Dimorphandra gardneriana, has been reported as a potent antioxidant and anti-inflammatory agent. In the present study, we aimed to evaluate the effect of TRX on 5-FU-induced intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, TRX-50, TRX-100, TRX-150, Celecoxib (CLX), and CLX + TRX-100. The weight of mice was measured daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis), levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), mast and goblet cell counts, immunohistochemical analysis, and cyclooxygenase-2 (COX-2) activity. Compared to the saline treatment, the 5-FU treatment induced intense weight loss and reduction in villus height. TRX treatment (100 mg/kg) prevented the 5-FU-induced histopathological changes and decreased oxidative stress by decreasing the MDA levels and increasing GSH concentration. TRX attenuated inflammatory process by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. TRX also reversed the depletion of goblet cells. Our findings suggest that TRX at a concentration of 100 mg/kg had chemopreventive effects on 5-FU-induced intestinal mucositis via COX-2 pathway.

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Intestinal mucositis is a frequent complication in the treatment of cancer with 5‐fluorouracil (5‐FU) chemotherapeutic agent. Rutin bioflavonoid extracted from Dimorphandra gardneriana has been reported as a potent anti‐inflammatory and antioxidant agent. Therefore, this study aims to investigate whether rutin reverses morphological elevations and oxidative stress promoted by 5‐fluorouracil in an experimental model of intestinal mucositis in mice. Swiss mice stratified into the following groups were used: Saline group (0.9% NaCl), 5‐FU group, Rutin group (RUT) (200 mg/kg Rutin, vo). For the oxidative damage evaluation, the levels of the reduced antioxidant glutathione and the lipid peroxidation product, malondylaldehyde, of the duodenal segments were determined. To investigate the morphological changes, hematoxylin and eosin staining was performed. The 5‐FU group showed a significant increase in MDA levels (8127 ± 561.5, p <0.05) when compared to the saline group (4587 ± 367.5, p <0.05). For GSH levels, 5‐FU (20.48 ± 4.89, p <0.05) promoted a significant decrease in duodenum antioxidant levels when compared to the saline group (112.8 ± 19.45, p <0.05). Pretreatment with RUT 200 mg/kg decreased MDA levels (3750 ± 405.3, p <0.05) and increased GSH levels (74.67 ± 12.73, p <0.05) when compared to the 5‐FU injury group. The results of the histopathological analysis showed that 5‐FU promoted structural alterations of the intestinal mucosa, reduction of villus height, deepening of the crypts and inflammatory infiltrate, compared to the Saline group, characterized by the integrity of the villi and crypts and absence of inflammatory infiltrate. Rutin‐treated animals showed a significant reversal of antineoplastic‐induced morphological changes. From the results we found that rutin promotes attenuation of oxidative stress by reducing the levels of Malonylaldehyde and increasing the levels of the antioxidant glutathione. In addition, we found that rutin reverses antineoplastic‐induced morphological changes.

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