Kidney Ectopeptidases in Gentamicin and Mercuric Chloride-Induced Acute Renal Failure

The clinical use of gentamicin is associated by nephrotoxicity in over 10% of patients. However, the biochemical events responsible for proximal tubular injury and acute renal failure (ARF) are still unclear. In the present study, effects of gentamicin and, comparatively, of mercuric chloride upon rat kidney cortex ectopeptidases were studied. Gentamicin was given i.p., 100 mg/kg daily for up to 6 days, mercuric chloride i.p. once 2.5 mg/kg to rats studied after 3 days. Kidney cortex aminopeptidase N decreased significantly after 3 and 6 days' treatment (p < 0.01), however, angiotensinase A significantly decreased after 3 (p < 0.01), and much more after 6 days of gentamicin treatment (p < 0.001). Dipeptidylpeptidase IV activity was significantly decreased only after 6 days of treatment with gentamicin. In mercuric chloride-induced ARF all three peptidase activities were markedly decreased (p < 0.001). These results suggest that gentamicin-induced decrease in ectopeptidase activities could compromise vasoactive and other biologically active peptides handling, with important consequences upon renal function and metabolism.