Protection from Glycine at Low Doses in Ischemia-Reperfusion Injury of the Rat Small Intestine

Abstract

Background: Glycine at high doses is known to protect the small intestine against ischemia-reperfusion (I/R) injury. Here, we studied whether glycine at low clinically applicable doses has a protective effect. Methods: In series 1, intestinal I/R was induced in male Wistar rats by occlusion (90 min)/reopening (120 min) of the superior mesenteric artery. Glycine was intravenously infused for 30 min before ischemia (pre-ischemic infusion), and once again from 30 min before until 60 min after reperfusion. Total glycine doses applied over the 120-min infusion were 5, 10, 20, and 75 mg glycine/kg. In series 2, pre-ischemic blood plasma glycine concentrations were determined under the conditions of series 1. Results: In series 1, attenuation of I/R injury was comparable at 10, 20, and 75 mg glycine/kg, but less at 5 mg/kg (as indicated by less intestinal hemorrhages and better preserved mean arterial blood pressure, among other signs). In series 2, pre-ischemic blood plasma glycine concentrations increased with increasing glycine doses from 280 to 330, 340, 380, and 680 µM, respectively. Conclusion: These results demonstrate that even at a dose 50 times lower than previously applied – and at only slightly elevated plasma concentrations – glycine provides full protection against I/R injury of the small intestine.