Isoquercitrin Alleviates 5‐Fluorouracil‐Induced Intestinal Mucositis in Mice by Modulating Inflammation and Oxidative Stress

This study aimed to evaluate the role of isoquercitrin (ISO) in 5-fluorouracil-induced intestinal mucositis. The animals (6 animals/group) were divided into: vehicle (2% DMSO), 5-fluorouracil (5-FU) and groups receiving ISO (10, 50, or 100 mg/kg). ISO at 100 mg/kg (ISO-100) (232.5 ± 3.8 µm) attenuated the reduction in villus height induced by 5-FU (125.3 ± 1.5 µm) and the reduction in crypt depth in the intestine (ISO-100: 101.7 ± 3.5 µm vs 5-FU: 70.8 ± 1.6 µm; p < 0.05). The jejunum was chosen for assays involving oxidative stress and inflammation. ISO-100 attenuated the mastocytosis (ISO-100: 7.6 ± 0.1 mast cells/field vs 5-FU: 12.5 ± 0.2 mast cells/field; p < 0.05) and goblet cell depletion (ISO-100: 11.0 ± 0.5 cells/field vs 5-FU: 8.0 ± 0.6 cells/field; p < 0.05). The treatment with ISO-100 showed lower levels of MDA and MPO, and increased GSH levels. Administration of celecoxib (selective COX-2 inhibitor) + ISO-100 increased the villus height and the immunohistochemistry showed that ISO-100 + CLX (7.4% ± 0.1%) attenuates the expression of COX-2 in jejunum induced by 5-FU (22.5% ± 0.1%). These results show that ISO-100 attenuates 5-FU-induced intestinal mucositis by modulating the inflammatory process and reducing oxidative stress.