Although
glycine prevents renal tubular cell injury in vitro, its effect in vivo is not clear. The purpose of this study was to investigate whether a bolus injection of
glycine given before reperfusion plus continuous dietary supplementation afterward would reduce renal injury caused by
ischemia-reperfusion. Female Sprague-Dawley rats received a semisynthetic powdered diet containing 5%
glycine and 15%
casein (
glycine group) or 20%
casein (control group). Two days later, renal
ischemia was produced by cross-clamping the left renal vessels for 15 min, followed by reperfusion. The right kidney was removed before reperfusion. The postischemic glomerular filtration rate (GFR) showed that renal function was less impaired and recovered more quickly in rats receiving
glycine. For example, at day 7, GFR in controls (0.31 +/- 0.03 ml x min(-1) x 100 g(-1)) was about one-half that of
glycine-treated rats (0.61 +/- 0.06 ml x min(-1) x 100 g(-1), P < 0.05). Furthermore, tubular injury and cast formation observed in controls was minimized by
glycine (pathology score, 3.2 +/- 0.4 vs. 1.0 +/- 0.4, P < 0.05). Urinary
lactate dehydrogenase (LDH) concentration was elevated by
ischemia-reperfusion in the control group (260 +/- 22 U/l), but values were significantly lower by about fourfold (60 +/- 30 U/l) in
glycine-fed rats. Similarly,
free radical production in urine was significantly lower in
glycine-treated animals. Importantly, on postischemic day 1, binding of
pimonidazole, an in vivo
hypoxia marker, was increased in the outer medulla in controls; however, this phenomenon was prevented by
glycine. Two weeks later, mild leukocyte infiltration and interstitial
fibrosis were still observed in controls, but not in kidneys from
glycine-treated rats. In conclusion, these results indicate that administration of
glycine indeed reduces mild
ischemia-reperfusion injury in the kidney in vivo, in part by decreasing initial damage and preventing chronic
hypoxia.