التفاصيل البيبلوغرافية
| العنوان: |
Sodium glucose cotransporter 1 ligand BLF501 as a novel tool for management of gastrointestinal mucositis |
| المؤلفون: |
Cardani, Diego, Sardi, Claudia, La Ferla, Barbara, D’Orazio, Giuseppe, Sommariva, Michele, Marcucci, Fabrizio, Olivero, Daniela, Tagliabue, Elda, Koepsell, Hermann, Nicotra, Francesco, Balsari, Andrea, Rumio, Cristiano |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2014 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
Gastrointestinal mucositis, SGLT-1, Synthetic D-glucose analogs, Chemotherapy, Inflammation |
| الوصف: |
Background Recent studies demonstrated that engagement of sodium glucose transporter 1 (SGLT-1) by orally administered D-glucose protects the intestinal mucosa from lipopolysaccharide (LPS)-induced injury. We tested whether SGLT-1 engagement might protect the intestinal mucosa from doxorubicin (DXR)- and 5-fluorouracil (5-FU)-induced injury in animal models mimicking acute or chronic mucositis. Methods Mice were treated intraperitoneally with DXR, alone or in combination with 5-FU, and orally with BLF501, a glucose-derived synthetic compound with high affinity for SGLT-1. Intestinal mucosal epithelium integrity was assessed by histological analysis, cellular proliferation assays, real-time PCR gene expression assays and Western blot assays. Student’s t-test (paired two-tailed) and χ 2 analyses were used for comparisons between groups. Differences were considered significant at p < 0.05. Results BLF501 administration in mice treated with DXR and/or 5-FU decreased the injuries to the mucosa in terms of epithelial integrity and cellular proliferative ability. Co-treatment with BLF501 led to a normal expression and distribution of both zonula occludens-1 (ZO-1) and beta-catenin, which were underexpressed after treatment with either chemotherapeutic agent alone. BLF501 administration also restored normal expression of caspase-3 and ezrin/radixin/moesin (ERM), which were overexpressed after treatment with DXR and 5-FU. In SGLT1-/- mice, BLF501 had no detectable effects. BLF501 administration in wild-type mice with growing A431 tumors did not modify antitumor activity of DXR. Conclusions BLF501-induced protection of the intestinal mucosa is a promising novel therapeutic approach to reducing the severity of chemotherapy-induced mucositis. |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| العلاقة: |
http://www.molecular-cancer.com/content/13/1/23Test |
| الإتاحة: |
http://www.molecular-cancer.com/content/13/1/23Test |
| حقوق: |
Copyright 2014 Cardani et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.DAC14325 |
| قاعدة البيانات: |
BASE |
