Irisin attenuates intestinal injury, oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis.

Abstract

BACKGROUNDAcute pancreatitis (AP) is often associated with intestinal injury, which in turn exaggerates the progression of AP. Our recent study has shown that a low level of serum irisin, a novel exercise-induced hormone, is associated with poor outcomes in patients with AP and irisin administration protects against experimental AP. However, the role of irisin in intestinal injury in AP has not been evaluated.AIMTo investigate the effect of irisin administration on intestinal injury in experimental AP.METHODSAP was induced in male adult mice by two hourly intraperitoneal injections of L-arginine. At 2 h after the last injection of L-arginine, irisin (50 or 250 μg/kg body weight) or 1 mL normal saline (vehicle) was administered through intraperitoneal injection. The animals were sacrificed at 72 h after the induction of AP. Intestinal injury, apoptosis, oxidative and endoplasmic reticulum (ER) stress were evaluated.RESULTSAdministration of irisin significantly mitigated intestinal damage, reduced apoptosis, and attenuated oxidative and ER stress in AP mice. In addition, irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas, liver and lung of AP mice.CONCLUSIONIrisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP. Irisin has a great potential to be further developed as an effective treatment for patients with AP.