Glutamine Alleviates I/R-Induced Intestinal Injury and Dysmotility Via the Downregulation of Xanthine Oxidase/Uric Acid Signaling and Lactate Generation in Wistar Rats

Introduction: Disruption of intestinal histoarchitecture and intestinal dysmotility is critical to intestinal ischemia/reperfusion (IR) injury and xanthine oxidase (XO)/uric acid (UA) signaling and increased lactate generation have been reported to play a role. More so, glutamine treatment has been demonstrated to inhibit XO/UA signaling. However, the role of glutamine in intestinal IR injury-induced intestinal dysmotility and the associated mechanisms of action are unclear. Therefore, this study was to investigate the mechanisms underlying the role of glutamine in intestinal IR injury. Methods: Forty male Wistar rats were acclimatized for two weeks and then randomized into four groups. The sham-operated, glutamine-treated, intestinal IR, and IR + glutamine groups.Results: Glutamine therapy attenuated the IR-induced increase in intestinal weight, disruption of intestinal histoarchitecture, and intestinal dysmotility. In addition, glutamine ameliorated IR-induced intestinal oxidative stress (increased malondialdehyde, reduced glutathione and super -oxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities), inflammation (increased TNF-a and IL-1b), and apoptosis (increased caspase three activity). These events were accompanied by glutamine alleviation of IR-induced upregulation of intestinal nuclear factor kappa B, XO/UA, and lactate generation. Conclusions: In conclusion, XO/UA signaling and lactate levels are key factors in IR-induced intestinal injury and dysmotility, and glutamine-mediated XO/UA/lactate modulation may attenuate IR-induced intestinal injury and dysmotility.(c) 2023 Elsevier Inc. All rights reserved.