[Influence of aminoglycosides on the activity of urinary N-acetyl-beta-D-glucosaminidase (NAG) and its isoenzymes].

Lysosomal enzyme activities can be modified by aminoglycosides. In this study, we have investigated the "in vitro" effect of gentamicin (G), tobramycin (T), dibekacin (D), netilmicin (N) and amikacin (AK) on urinary N-acétyl-beta-D-glucosaminidase (NAG) and its isoenzymatic forms. G, D and N are activators of this enzyme, specifically of the B isoenzymatic form, while T inhibits slightly the A, I1 and I2 forms. At usual therapeutical urinary concentration of AK during antibiotherapy, NAG and its isoenzymes are very strongly inhibited (more than 65%). Dixon plot indicates that the nature of inhibition is "competitive apparent", without binding of inhibitor to the active site of the enzyme. This binding of aminoglycosides to NAG as to other lysosomal enzymes may represent one of the accumulation mechanisms of aminoglycosides in tubular cells. It can explain the specific alteration of lysosomes during nephrotoxic antibiotherapy. Consequently, when urinary NAG determination is used as indicator of nephrotoxicity during therapy, the activation or inhibition of the enzyme by aminoglycosides could lead to false assay results.