Abstract

Background and Aims: Radiation-induced intestinal injury occurred in application of radiotherapy for abdominal and pelvic cancers or in nuclear accidents. Radiation-induced enteritis may be considered an ideal model of gastrointestinal inflammation. The endothelium is a crucial component of inflammation, and the endothelial dysfunction following radiation exposure induces the intestinal proinflammatory response and progression of radiation enteritis. Baicalein (5,6,7-trihydroxyflavonoid) is a flavonoid from Scutellaria baicalensis used in oriental herbal medicine. Baicalein has been found to have multiple beneficial properties including antioxidant, anti-inflammatory, anti-allergic, and anti-cancer activities. Here, we investigated the therapeutic effects of baicalein on endothelial dysfunction in radiation-induced intestinal inflammation. Materials and Methods: We performed histological analysis, bacterial translocation, and intestinal permeability assays and also assessed infiltration of leukocytes and inflammatory cytokine expression using a mouse model of radiation-induced enteritis. In addition, to investigate the effect of baicalein in endothelial dysfunction, we analyzed endothelial-derived adherent molecules in human umbilical vein endothelial cells (HUVECs) and irradiated intestinal tissue. Results: Histological damage such as shortening of villi length and impaired intestinal crypt function was observed in the radiation-induced enteritis mouse model. Intestinal damage was attenuated in baicalein-treated groups with improvement of intestinal barrier function. Baicalein inhibited the expression of radiation-induced adherent molecules in HUVECs and intestine of irradiated mouse and decreased leukocyte infiltration in the radiation-induced enteritis. Conclusions: Baicalein could accelerate crypt regeneration via recovery of endothelial damage. Therefore, baicalein has a therapeutic effect on radiation-induced intestinal inflammation by attenuating endothelial damage.

Highlights

  • The intestine is one of the most radiosensitive organs in the body

  • Baicalein inhibited the expression of radiation-induced adherent molecules in human umbilical vein endothelial cells (HUVECs) and intestine of irradiated mouse and decreased leukocyte infiltration in the radiation-induced enteritis

  • Baicalein has a therapeutic effect on radiation-induced intestinal inflammation by attenuating endothelial damage

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Summary

Introduction

The intestine is one of the most radiosensitive organs in the body. Exposure to high doses of radiation, for example, following a nuclear accident or a dirty bomb explosion can cause severe intestinal damage with a high rate of mortality (Kavanagh et al, 2010). Acute bowel toxicity by irradiation is primarily a result of cell death in the proliferating crypt epithelium and an inflammatory reaction in the intestine. Hauer-Jensen et al recently proposed that radiation-induced enteritis is a useful model to explore mucosal inflammation, and the mechanisms related to radiation-induced intestinal inflammation could critically advance the understanding of gastrointestinal injury, such as inflammatory bowel disease (IBD) (Hauer‐Jensen et al, 2014; Toullec et al, 2017). Radiation-induced intestinal injury occurred in application of radiotherapy for abdominal and pelvic cancers or in nuclear accidents. The endothelium is a crucial component of inflammation, and the endothelial dysfunction following radiation exposure induces the intestinal proinflammatory response and progression of radiation enteritis. We investigated the therapeutic effects of baicalein on endothelial dysfunction in radiation-induced intestinal inflammation

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