Kátia Duarte Vital, Luiz Octavio Pires, Bruno Gallotti, Janayne Luihan Silva, Luís Cláudio Lima de Jesus, Jacqueline Isaura Alvarez-Leite, Ênio Ferreira, Vasco Ariston de Carvalho Azevedo, Flaviano Santos Martins, Valbert Nascimento Cardoso, Simone Odília Antunes Fernandes
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引用次数: 0
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.
期刊介绍：
The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy.
The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs.
Specific areas of focus include, but are not limited to:
· Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents;
· Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy;
· Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents;
· The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs;
· Drug interactions in single or combined applications;
· Drug resistance to antimicrobial and anticancer drugs;
· Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research;
· Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs;
· Pharmacogenetics and pharmacogenomics;
· Precision medicine in infectious disease therapy and in cancer therapy;
· Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.
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