EFFECT OF DEPLETION OF REDUCED GLUTATHIONE AND ITS SUPPLEMENTATION BYGLUTATHIONE MONOESTER ORE RENAL OXALATE RETENTION IN HYPEROXALURIA

The effect of glutathione (GSH) depletion followed by administration o f glutathione monoester (GME) on the metabolism of oxalate in hyperoxa luric condition was investigated Renal GSH was depleted by intraperito neal administration of buthionine sulfoximine (BSO, 4 mmol/kg b.w) twi ce a: day for 20 days to rats with or without hyperoxaluria induced by adding 0.75% ethylene glycol (EG) in drinking water. GME was administ ered intraperitoneally (5 m mol in water/kg body weight) simultaneousl y. Tissue GSH was depleted by 47% and 58% by treatment with BSO and BS O + 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 o nly in the kidney of BSO- + EG-treated rats. GME treatment brought dow n kidney oxalate and calcium content dramatically and reduced calcium oxalate retention. However GME did not have any effect on urinary oxal ate level. The observed decreased creatinine clearance, elevated urina ry excretion of lactate dehydrogenase (LDH) and gamma-glutamyl transpe ptidase (gamma-GT), and decreased tissue nonenzymatic and enzymatic an tioxidants, and thiol status in BSO + EG treated rats were all restore d 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. (C) Elsevier S cience Inc. 1997.