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-glucosaminidase (NAG) in the heart was studied. Released activity of NAG was used as a marker for assessing myocardial lysosomal integrity. The activity of NAG was determined in non-sedimentable and sedimentable fractions after centrifugation of the tissue extracted for assessment of the subcellular distribution of the lysosomal enzyme. Daily intraperitoneal injection of 100 mg/kg/day of neomycin increased the ratio of the non-sedimentable activity (free) to the non-sedimentable plus sedimentable activities (total) of NAG. Daily intraperitoneal injection of lithium 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 enhancement of the ratio of free: total activity of NAG. Neomycin like other aminoglycosides altered the acidic phospholipid metabolism in lysosomal membranes and/or impairment of some important lysosomal functions. In this regard, the protective effects of lithium may be due to interference of this ion with phosphoinositide cycle.
Dehpour
A R
AR
Department of Pharmacology, School of Medicine, University of Tehran, Iran.
Samini
M
M
Ghafourifar
P
P
Kyani
H
H
D000118:Acetylglucosaminidase / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D006321:Heart / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology*; D008247:Lysosomes / Q000737:chemistry; D008297:Male; D009206:Myocardium / Q000737:chemistry* / Q000648:ultrastructure; D009355:Neomycin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats
D008094:Lithium; D000118:Acetylglucosaminidase; D009355:Neomycin