Effect of echinacoside as a palliative for irinotecan-induced intestinal mucositis

Irinotecan, an anticancer drug, causes severe delayed diarrhea due to its active metabolite, SN-38, which damages the intestinal mucosa. This diarrhea may lead to the discontinuation of anticancer therapy in clinical practice. Therefore, in this study, we aimed to elucidate the pathogenesis of irinotecan-induced intestinal inflammation. We examined the effects of echinacoside, which has been reported to reduce LPS (lipopolysaccharide)-induced apoptosis and inflammation. We administered irinotecan (75 mg/kg) to seven-week-old male BALB/c mice intraperitoneally once daily for 4 d; a daily decrease in body weight, and no diarrhea was observed. Necropsies were performed 24 and 72 h after the last dose. Irinotecan caused cellular damage in the small intestine, particularly the ileum. After 72 h, a significant increase in myeloperoxidase activity was observed in the ileum. Concomitant oral administration of echinacoside (500 and 1000 mg/kg) with irinotecan significantly prevented weight loss and cellular damage in the ileal region. These results suggested the role of intestinal bacteria as previously reported with 5-FU-induced enteritis. The increased rate of deconjugation by β-glucuronidase may have increased the direct damage caused by SN-38. Additionally, irinotecan caused less histological damage to the large intestine than to the small intestine, possibly explaining the clinical absence of diarrhea. In conclusion, concomitant administration of echinacoside significantly inhibited the severity of irinotecan-induced intestinal inflammation, indicating their usefulness against irinotecan-induced enteritis.