SGLT-1: A NEW THERAPEUTIC STRATEGY TO MAINTAINS INTESTINAL EPITHELIAL INTEGRITY AND BARRIER FUNCTION

Previous findings revealed that engagement of SGLT-1 by orally administered D-glucose protects the intestinal mucosa from lipopolysaccharides (LPS)-induced injury. Here, we tested whether engagement of SGLT-1 protected also from doxorubicin (DXR)/5-fluorouracil (5-FU)-induced and DSS-induced intestinal injuries using a new synthetic compound named BLF501 as SGLT-1 agonist. A large set of experiments was performed in order to assess damages induction and recovery after treatment with DXR/5-FU and DSS with or without co-treatment with BLF501 with particular attention for intestinal epithelial integrity. We evaluated the preservation of correct epithelial structure, correct formation and functionality of junctional systems, electrophisiological properties and physiological functionality of small and large intestine. In conclusion, oral administration of BLF501 greatly accelerated recovery from mucosal injury induced by DXR (alone or in combination with 5-FU) and DSS. These data suggest a novel therapeutic approach to reduce the severity of chemotherapy-induced mucositis and a new approach for IBDs treatment.