The Flavonoid Troxerutin Prevents Tissue Damage and the Alteration of Cellularity Residing in Intestinal Mucositis by 5‐Fluorouracil

Abstract

Intestinal mucositis, characterized by inflammatory and/or ulcerative processes, occurs due to cellular and tissue damage following treatment with 5‐fluorouracil (5‐FU). Troxerutin (TRX), a semi‐synthetic flavonoid extracted from Dimorphandra gardneriana, has been reported as a potent anti‐inflammatory agent. The present study aimed to evaluate the effect of TRX on 5‐fluorouracil‐induced intestinal mucositis in Swiss mice. The mice (25‐30g) were separated into 3 groups (n = 6): Saline group (NaCl 0.9%), 5‐FU group, TRX group (100mg/kg TRX, orally). All animals, except the Saline group, received 5‐FU at the concentration of 450 mg/kg in the first experimental protocol. Duodenal portions were removed for evaluation of mucositis by analysis of histopathological damage and cellularity of resident cells of the intestinal mucosa (mast cells and goblet cells). The results of the histopathological analysis demonstrated that 5‐FU promoted structural alterations of the intestinal mucosa (p <0.05), evidenced by the reduction of villi height, deepening of the crypts, and TRX treatment (100 mg/kg) prevented the 5‐FU‐induced histopathological changes (p <0.05). Regarding cellularity, TRX decreases 5‐FU‐induced mast cell infiltration (p <0.05), as well as decreases cell lineage degranulation and, regarding goblet cell count, mucus‐producing cells, TRX prevented the decrease of these cells (p <0.05), which is a problem promoted by the 5‐FU. Our findings suggest that TRX at a concentration of 100 mg/kg had chemopreventive effects on 5‐FU‐induced intestinal mucositis due to the prevention of histological damage and maintenance of resident cellularity in the intestinal mucosa.