Ethylacetate fractional extract of Mentha spicata attenuates irinotecan‐induced mucositis in mice

Abstract

Irinotecan induced‐mucositis is an inflammatory event of intestine that has negative impact on patient health and affect treatment efficacy. Irinotecan first metabolized in the liver by a carboxylesterase (CES) to the active cytotoxic metabolite (SN‐38), which subsequently glucuronidated by hepatic enzymes to the inactive metabolite SN38G. The SN‐38G undergo deconjugation in the intestine liberating the active SN‐38 via β‐glucuronidase produced by the intestinal bacterial flora. Consequently, SN‐38 triggers inflammation events characterized by delayed intestinal mucositis and diarrhea. This study aims to ameliorate irinotecan‐induced mucositis and diarrhea in mice model using ethylacetate fractional extraction of Mentha spicata(EAEMS), an edible widley consumed plant. Mice model of irinotecan‐induced mucositis and diarrhea produced by I.P injection of irinotecan (75mg/Kg/day) for 4 days. EAEMS administered orally (160mg/kg) twice daily for 7 days starting one day before irinite can dose. Diarrhae scores and mice body weight variation measured to assess the severity of mucositis and diarrhea. Jejunal IL‐1β and MPO measured as markers of intestinal inflammation. β‐glucuronidase activity in fecal pelletes were measured also. Compared to model control mice, results revealed that animals received EAEMS presented with significantly lower diarrhea scores and body weight loss. Furthermore, jejunal IL‐1β and MPO significantly reduced and associated with significant inhibition of fecal β‐glucuronidase activity in animals received EAEMS compared to model control mice. In conclusion, we showed for the first time that EAEMS has a protective effect against irinotecan‐induced mucositis and diarrhea, an effect suggested to be mediated by inhibition of bacterial β‐glucuronidase activity. This promising result might have a therapeutic application in cancer patients suffering from delayed‐onset diarrhea due to irinotecan treatment.Support or Funding InformationUniversity of Baghdad, College of PharmacyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.