Atorvastatin improves intestinal mucositis induced by 5-fluorouracil in mice by modulating the and epithelial barrier and inflammatory signaling pathways

Author:

Vital Kátia Duarte1,Pires Luiz Octavio1,Gallotti Bruno1,Silva Janayne Luihan1,Jesus Luís Cláudio Lima1,Alvarez-Leite Jacqueline Isaura1,Ferreira Ênio1,Azevedo Vasco Ariston Carvalho1,Martins Flaviano Santos1,Cardoso Valbert Nascimento1,Fernandes Simone Odília Antunes1

Affiliation:

1. Federal University of Minas Gerais

Abstract

Abstract Chemotherapy-induced intestinal mucositis is a major side effect of cancer treatment. Statins are 3-hydroxy-3-methyl glutaryl coenzyme reductase inhibitors used to treat hypercholesterolemia and atherosclerotic diseases. Recent studies have demonstrated that atorvastatin (ATV) has antioxidant, anti-inflammatory, and resulting from the regulation of different molecular pathways. In the present study, we investigated the effects of ATV on intestinal homeostasis in 5-fluorouracil (5-FU)-induced mucositis. Our results showed that ATV protected the intestinal mucosa from epithelial damage caused by 5-FU mainly due to inflammatory infiltrate and intestinal permeability reduction, downregulation of inflammatory markers, such as Tlr4, MyD88, NF-κB, Tnf-a, Il1β, and Il6 dose-dependent. ATV also improved epithelial barrier function by upregulating the mRNA transcript levels of mucin 2 (MUC2), and ZO-1 and occludin tight junction proteins. The results suggest that the ATV anti-inflammatory and protective effects on 5-FU-induced mice mucositis involve the inhibition of the TLR4/MYD88/NPRL3/NF-κB, iNos, and caspase 3 signaling pathways.

Publisher

Research Square Platform LLC

Reference109 articles.

1. Oral Mucositis Induced By Anticancer Therapies;Al-Ansari S;Curr Oral Health Rep,2015

2. Mucositis: pathobiology and management;Villa A;Curr Opin Oncol,2015

3. Pathobiology of mucositis;Sonis ST;Semin Oncol Nurs,2004

4. New frontiers in the pathobiology and treatment of cancer regimen-related mucosal injury;Cinausero M;Front Pharmacol,2017

5. Oral mucositis;Raber-Durlacher JE;Oral Oncol. 2010 Jun

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3