INHIBITION BY LITHIUM OF GENTAMICININDUCED RELEASE OF N-ACETYL--DGLUCOSAMINIDASE IN ISOLATED PERFUSED RAT KIDNEY

N-Acetyl--d-glucosaminidase (NAG) is one of the sensitive hydrolytic lysosomal enzymes that is released after renal tubular damage. We have studied gentamicin-induced nephrotoxicity by determining the NAG release in a perfused rat kidney model. Gentamicin at 100 ug/ml caused a time-dependent increase in enzymuria. The effect of pretreatment with 5 or 10 mmol/kg of lithium chloride, administered subcutaneously 24 h prior to perfusion with gentamicin, was also studied through the measurement of NAG activity. Lithium at 5 mmol/kg absolutely inhibited NAG release; 10 mmol/kg lithium significantly diminished the release of enzyme. The inhibitory effect of 5 mmol/kg of lithium may be due to its interference with phosphoinositide cycle in renal tubular lysosomal membrane.