title: [Nephrotoxicity of aminoglycosides and cephalosporins. Value of examining the isoenzyme profile of N-acetyl-beta-D-glucosaminidase].
abstract: It is a well known fact that aminoglycosides increase urinary action of N-acetyl-beta-D-glucosaminidase (NAG) but the significance of this fact remains, as yet, nuclear. The aim of this study is firstly to attempt to form an explanation of the enzymatic effects of aminoglycosides by studying the excretion of A, B, I isoenzymes and by calculating the ratio A/B + I during gentamicin, tobramycin and amikacin therapy and secondly, by using this method, to try to propose a marker for evaluating nephrotoxicity. Our results indicate that all three antibiotics induce an increase in the excretion of the A-form, which is present freely in the lysosomes and in physiological urines, but that only gentamicin and tobramycin bring about an increase in the B-form associated with the lysosomal membrane. Since excretion of the B-form is associated with renal failure, it can be proposed as a good marker for evaluating nephrotoxicity. These observations allow us to advance the hypothesis that aminoglycosides determine an enzymatic inducing effect on the NAG synthesis with urinary excretion of the A-form by exocytosis whilst the excretion of the B-form, associated with the lysosomal membrane, would result from a rupture of this membrane. This lesion would bring about an excretion of toxic aminoside into the cytoplasm, causing damage to the mitochondrial apparatus. On the other hand isoenzymatic profiles, observed during cephalosporin treatment suggest a process of cellular necrosis.
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine*; D000617:Aminoglycosides / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002511:Cephalosporins / Q000009:adverse effects*; D002848:Chromatography, DEAE-Cellulose; D004359:Drug Therapy, Combination; D006596:Hexosaminidases / Q000652:urine*; D006801:Humans; D007527:Isoenzymes / Q000652:urine; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D007527:Isoenzymes; D006596:Hexosaminidases; D000118:Acetylglucosaminidase
vernacular_title: Néphrotoxicité des aminosides et céphalosporines. Intérêt de l'étude des profils iso-enzymatiques de la N-acétyl-bêta-D-glucosaminidase (NAG).