Abstract
Glycine preserves tubular cell integrity under hypoxic and toxic conditions in vitro. It also ameliorates cisplatin nephrotoxicity in vivo. We studied the effect of glycine on tubular necrosis from ischemia reflow and on inner stripe injury in an animal model of radiocontrast nephropathy. In all experiments, glycine (75 mg/100 g/h) increased tubular damage in the inner stripe. In the model of radiocontrast nephropathy, the percentage of medullary thick ascending limb (mTAL) necrosis at 24 hours increased from 22% ± 6% to 41% ± 9% or 55% ± 7% with glycine infusion of 75 or 135 minutes, respectively (mean ± SE, P < 0.05, analysis of variance [ANOVA]). Renal function was not significantly affected. In rat kidneys subjected to ischemia reflow, mTAL injury following glycine increased from 1% ± 0% to 12% ± 6% (P < 0.05) and from 8% ± 5% to 49% ± 8% (P < 0.01) 24 hours after 30 minutes and 45 minutes ischemia, respectively. Tubular injury in the inner stripe was maximal in the deep interbundle zone, typical of hypoxic, rather than reperfusion, injury. Prior uninephrectomy increased inner stripe damage, but protected the proximal tubules. Both uninephrectomy and glycine infusion were found to contribute to mTAL necrosis. The infusion of glycine for 1 hour in intact rats increased renal blood flow by 44% and tripled urine volume (P < 0.01). A parallel increase in glomerular filtration rate GFR; by 22% over 90 minutes) fell short of statistical significance. Outer medullary oxygen tension directly measured by a Clark type microelectrode decreased from 22 ± 4 to 11 ± 3 mm Hg following 40 minutes of glycine infusion (P < 0.002). We conclude that outer medullary hypoxic injury is augmented by the infusion of glycine to rats in vivo. This may result from glycine induction of medullary oxygen insufficiency that antagonizes its cytoprotective properties noted in isolated systems. By contrast, during in vivo ischemia where cellular depletion of glycine is less likely, the exogenous supplementation of this amino acid may have different effects.
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