INHIBITION BY LITHIUM OF NEOMYCIN-INDUCED RELEASE OF N-ACETYL-BETA-GLUCOSAMINIDASE IN THE RAT-HEART

The effects of neomycin, lithium and concurrent therapy of these drugs on subcellular distribution of lysosomal enzyme, N-acetyl-beta-glucos aminidase (NAG) in the heart was studied. Released activity of NAG was used as a marker for assessing myocardial lysosomal integrity. The ac tivity of NAG was determined in non-sedimentable and sedimentable frac tions after centrifugation of the tissue extracted for assessment of t he subcellular distribution of the lysosomal enzyme. Daily intraperito neal injection of 100 mg/kg/day of neomycin increased the ratio of the non-sedimentable activity (free) to the non-sedimentable plus sedimen table activities (total) of NAG. Daily intraperitoneal injection of li thium decreased the total activity of NAG but did not affect the ratio of free: total activities of the enzyme. Lithium in doses of 2 and 4 mM/kg/day one hour prior to neomycin reduced the neomycin-induced enha ncement of the ratio of free: total activity of NAG. Neomycin like oth er aminoglycosides altered the acidic phospholipid metabolism in lysos omal membranes and/or impairment of some important lysosomal functions . In this regard, the protective effects of lithium may be due to inte rference of this ion with phosphoinositide cycle.