Influence of muzolimine, a new diuretic, on experimental gentamicin nephrotoxicity.
The administration of diuretic drugs increases the nephrotoxicity of aminoglycosides. Muzolimine is a new diuretic which acts on the ascending limb of the loop of Henle and on the distal tubule. It differs from frusemide in its strong lipid binding and in its action at the antiluminal cellular pole. We attempted to determine whether muzolimine increases the nephrotoxicity of gentamicin. Four groups of Wistar rats were studied: one control group, one group treated with muzolimine (15 mg/kg), one group treated with gentamicin (20 mg/kg), and one group treated with gentamicin and muzolimine. Muzolimine induced a moderate but significant decrease in creatinine clearance, increased urinary excretion of n-acetyl-beta-D-glucosaminidase, and a slight decrease in lysosomal latency. The action of muzolimine did not reduce enzyme activities of the renal cortex (AAP, NAG, sphingomyelinase). Gentamicin induced functional renal modifications known to characterise nephrotoxicity of aminoglycosides. The association of muzolimine and gentamicin did not provoke a greater decrease of creatinine clearance or a greater decrease in enzyme activities of the renal cortex. In conclusion, muzolimine does not seem to potentiate the nephrotoxic action of gentamicin. However, we note that the association of muzolimine and gentamicin provoked a greater decrease in mitochondrial oxygen consumption than that provoked by gentamicin alone. It also induced more marked reduction of the activity of renal sphingomyelinase. This point is important when it is considered that the appearance of myelin bodies in the renal cortex is secondary to the decrease of this enzyme.
D000818:Animals; D004357:Drug Synergism; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D009156:Muzolimine / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005839:Gentamicins; D011720:Pyrazoles; D009156:Muzolimine