Effect of depletion of reduced glutathione and its supplementation by glutathione monoester on renal oxalate retention in hyperoxaluria

The effect of glutathione (GSH) depletion followed by administration of glutathione monoester (GME) on the metabolism of oxalate in hyperoxaluric condition was investigated. Renal GSH was depleted by intraperitoneal administration of buthionine sulfoximine (BSO, 4 mmol/kg b.w.) twice a day for 20 days to rats with or without hyperoxaluria induced by adding 0.75% ethylene glycol (EG) in drinking water GME was administered intraperitoneally (5 m mol in water/kg body weight) simultaneously. Tissue GSH was depleted by 47% and 58% by a treatment with BSO and BSO + EG, respectively. Oxalate content was enhanced maximally (125% of control) only in BSO + EG treated group. A polarized light microscopic examination showed prominent deposition of calcium oxalate crystals only in the kidney of BSO- + EG-treated rats. GME treatment brought down kidney oxalate and calcium content dramatically and reduced calcium oxalate retention. However, GME did not have any effect on urinary oxalate level. The observed decreased creatinine clearance, elevated urinary excretion of lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT), and decreased tissue nonenzymatic and enzymatic antioxidants, and thiol status in BSO + EG treated rats were all restored to normal values on GME supplementation. GSH depletion increases the retention of calcium oxalate in renal cells and normalization of GSH by administration of glutathione monoester prevents it.