국가연구개발성과

논문 (학술지)
Pravastatin Attenuates Acute Radiation-Induced Enteropathy and Improves Epithelial Cell Function

저자, 논문 구분, 저자, 학술지명, ISSN, SCI(SCIE포함) 구분, 학술지 출판 일자, 볼륨, 페이지, 학술지 임팩트 팩터, 학술대회명, 학술대회 개최국, 키워드 항목으로 구성된 논문 상세조회를 제공하고 데이터가 없는 항목에 대해서는 출력
등록번호 RPMS-2019-0190759435 SCI 구분
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 ※구분 : SCI(SCIE포함), 비SCI

SCI
저자명 (주·공동저자) Jang Hyosun; Lee Janet; Park Sunhoo; Myung Hyunwook; Kang Jihoon; Kim Kyuchang; Kim Hyewon; Jang Won-Suk; Lee Sun-Joo; Shim Sehwan; Myung Jae K.
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동일저자 논문보기
논문구분 국외전문학술지 학술지명 FRONTIERS IN PHARMACOLOGY
ISSN 1663-9812 학술지 출판일자 -
학술지 볼륨번호 9 논문페이지 0 ~ -
학술지 임팩트팩터 0.0 기여율 100 %
DOI 10.3389/fphar.2018.01215
초록 Background and Aim: Radiation-induced enteropathy is frequently observed after radiation therapy for abdominal and pelvic cancer or occurs secondary to accidental radiation exposure. The acute effects of irradiation on the intestine might be attributed to inhibition of mitosis in the crypts, as the loss of proliferative functions impairs development of the small intestinal epithelium and its barrier function. Especially, oxidative damage to intestinal epithelial cells is a key event in the initiation and progression of radiation-induced enteropathy. Pravastatin is widely used clinically to lower serum cholesterol levels and has been reported to have anti-inflammatory effects on endothelial cells. Here, we investigated the therapeutic effects of pravastatin on damaged epithelial cells after radiation-induced enteritis using in vitro and in vivo systems. Materials and Methods: To evaluate the effects of pravastatin on intestinal epithelial cells, we analyzed proliferation and senescence, oxidative damage, and inflammatory cytokine expression in an irradiated human intestinal epithelial cell line (InEpC). In addition, to investigate the therapeutic effects of pravastatin in mice, we performed histological analysis, bacterial translocation assays, and intestinal permeability assays, and also assessed inflammatory cytokine expression, using a radiation-induced enteropathy model. Results: Histological damage such as shortening of villi length and impaired intestinal crypt function was observed in whole abdominal-irradiated mice. However, damage was attenuated in pravastatin-treated animals, in which normalization of intestinal epithelial cell differentiation was also observed. Using in vitro and in vivo systems, we also showed that pravastatin improves the proliferative properties of intestinal epithelial cells and decreases radiation-induced oxidative damage to the intestine. In addition, pravastatin inhibited levels of epithelial-derived inflammatory cytokines including IL-6, IL-1β, and TNF-α in irradiated InEpC cells. We also determined that pravastatin could rescue intestinal barrier dysfunction via anti-inflammatory effects using the mouse model. Conclusion: Pravastatin has a therapeutic effect on intestinal lesions and attenuates radiation-induced epithelial damage by suppressing oxidative stress and the inflammatory response

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