Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress.

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.

Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway.

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.