Attenuation of intestinal ischemia-reperfusion-injury by β-alanine: a potentially glycine-receptor mediated effect

• Published in: The Journal of surgical research 2017-05, Vol.211, p.233-241
• Main Authors: Brencher, Lisa, Verhaegh, Rabea, Kirsch, Michael
• Format: Article
• Language: English
• Subjects: Animals; beta-Alanine - metabolism; beta-Alanine - pharmacology; beta-Alanine - therapeutic use; Biomarkers - metabolism; Dose-Response Relationship, Drug; Glycine; Glycine receptor; Inflammation; Injections, Intravenous; Injury; Intestine; Intestines - blood supply; Intestines - drug effects; Intestines - pathology; Ischemia; Male; Protective Agents - metabolism; Protective Agents - pharmacology; Protective Agents - therapeutic use; Rats; Rats, Wistar; Receptors, Glycine - metabolism; Reperfusion; Reperfusion Injury - prevention & control; β-Alanine
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2016.12.023

Acute mesenteric ischemia is often caused by embolization of the mesenteric arterial circulation. Coherent intestinal injury due to ischemia and following reperfusion get visible on macroscopic and histologic level. In previous studies, application of glycine caused an ameliorated intestinal damage after ischemia-reperfusion in rats. Because we speculated that glycine acted here as a signal molecule, we investigated whether the glycine-receptor agonist β-alanine evokes the same beneficial effect in intestinal ischemia-reperfusion. β-alanine (10, 30, and 100 mg/kg) was administered intravenously. Ischemia/reperfusion of the small intestine was initiated by occluding and reopening the superior mesenteric artery in rats. After 90 min of ischemia and 120 min of reperfusion, the intestine was analyzed with regard to macroscopic and histologic tissue damage, the activity of the saccharase, and accumulation of macrophages. In addition, systemic parameters and metabolic ones (e.g., acid-base balance, electrolytes, and blood glucose) were measured at certain points in time. All three dosages of β-alanine did not change systemic parameters but prevent from hyponatremia during the period of reperfusion. Most importantly, application of 100-mg β-alanine clearly diminished intestinal tissue damage, getting visible on macroscopic and histologic level. In addition, I/R-mediated decrease of saccharase activity and accumulation of macrophages in the small intestine were ameliorated. The present study demonstrated that β-alanine was a potent agent to ameliorate I/R-induced injury of the small intestine. Due to its diminishing effect on the accumulation of macrophages, β-alanine is strongly expected to mediate its beneficial effect via glycine receptors.