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Kidney ectopeptidases in gentamicin and mercuric chloride-induced acute renal failure
V Stefanović1, P Vlahović, V Savić
1Institute of Nephrology and Hemodialysis, University School of Medicine, Nis, Yugoslavia.
Abstract:
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.
Insights
Gentamicin treatment significantly reduces kidney ectopeptidase activity, potentially impairing peptide handling and contributing to nephrotoxicity and acute renal failure (ARF). This study clarifies biochemical events underlying gentamicin-induced kidney injury.
Area of Science:
- Nephrology
- Biochemistry
- Toxicology
Background:
- Gentamicin use causes nephrotoxicity in over 10% of patients.
- The precise biochemical mechanisms of gentamicin-induced proximal tubular injury and acute renal failure (ARF) remain unclear.
Purpose of the Study:
- To investigate the effects of gentamicin on rat kidney cortex ectopeptidases.
- To compare gentamicin's effects with those of mercuric chloride, a known nephrotoxin.
Main Methods:
- Rats received daily intraperitoneal injections of gentamicin (100 mg/kg) for up to 6 days.
- A separate group received a single intraperitoneal injection of mercuric chloride (2.5 mg/kg) and was studied after 3 days.
- Activities of kidney cortex aminopeptidase N, angiotensinase A, and dipeptidylpeptidase IV were measured.
Main Results:
- Gentamicin significantly decreased aminopeptidase N activity after 3 and 6 days.
- Angiotensinase A activity decreased significantly after 3 days and more markedly after 6 days of gentamicin treatment.
- Dipeptidylpeptidase IV activity was significantly reduced only after 6 days of gentamicin exposure.
- Mercuric chloride-induced ARF resulted in a significant decrease in all three peptidase activities.
Conclusions:
- Gentamicin-induced reduction in ectopeptidase activities may impair the handling of vasoactive and other biologically active peptides.
- This compromised peptide metabolism could have significant consequences for renal function and metabolism, contributing to nephrotoxicity.
- The findings provide insight into the biochemical basis of gentamicin-induced kidney injury.