Phlorizin attenuates postoperative gastric ileus in rats

Postoperative ileus (POI) is a major complication of abdominal surgery (AS). Impaired gut barrier mediated via Toll-like receptor 4 (TLR4) and interleukin-1 (IL-1) receptor is involved in the development of POI. Phlorizin is a nonselective inhibitor of sodium-linked glucose transporters (SGLTs) and is known to improve lipopolysaccharide (LPS)-induced impaired gut barrier. This study aimed to clarify our hypothesis that AS-induced gastric ileus is mediated via TLR4 and IL-1 signaling, and phlorizin improves the ileus.AS consisted of a celiotomy and manipulation of the cecum for 1 min. Gastric emptying (GE) in 20 min with liquid meal was determined 3 h after the surgery in rats. The effect of subcutaneous (s.c.) injection of LPS (1 mg kg-1 ) was also determined 3 h postinjection.AS delayed GE, which was blocked by TAK-242, an inhibitor of TLR4 signaling and anakinra, an IL-1 receptor antagonist. LPS delayed GE, which was also mediated via TLR4 and IL-1 receptor. Phlorizin (80 mg kg-1 , s.c.) significantly improved delayed GE induced by both AS and LPS. However, intragastrical (i.g.) administration of phlorizin did not alter it. As gut mainly expresses SGLT1, SGLT2 may not be inhibited by i.g. phlorizin. The effect of phlorizin was blocked by ghrelin receptor antagonist in the LPS model.AS-induced gastric ileus is mediated via TLR4 and IL-1 signaling, which is simulated by LPS. Phlorizin improves the gastric ileus via activation of ghrelin signaling, possibly by inhibition of SGLT2. Phlorizin may be useful for the treatment of POI.