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Gentamicin-induced nephrotoxicity in mice: protection by loop diuretics
Abstract:
Gentamicin, at doses of 50 or 100 mg/kg body wt administered daily to healthy male MF1 mice by i.p. injection for either 7 or 10 days caused proximal tubular cell damage shown both by the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and by electron microscopy. The tubular damage was maximal at 7 days. Concomitant administration of any of 3 diuretics-frusemide, bumetanide or piretanide at 5,0.5 and 1 mg/kg body wt/day respectively-resulted in less tubular damage than that caused by gentamicin alone. This finding of protection by diuretics contrasts with those of previous studies of combination gentamicin-diuretic therapy.
Insights
Gentamicin causes kidney damage in mice, but co-administering certain diuretics reduces this toxicity. This protective effect of diuretics against gentamicin nephrotoxicity was unexpected.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Gentamicin is a widely used antibiotic with known nephrotoxic potential, primarily affecting proximal tubular cells.
- Assessing and mitigating gentamicin-induced kidney damage is crucial for patient safety and effective treatment.
Purpose of the Study:
- To investigate the effect of concomitant administration of specific diuretics on gentamicin-induced nephrotoxicity in a mouse model.
- To evaluate the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and electron microscopy findings as indicators of tubular damage.
Main Methods:
- Healthy male MF1 mice were administered gentamicin (50 or 100 mg/kg/day) via intraperitoneal injection for 7 or 10 days.
- Three diuretics (frusemide, bumetanide, piretanide) were co-administered at specific doses.
- Renal tubular damage was assessed by measuring urinary NAG excretion and through electron microscopy.
Main Results:
- Gentamicin administration led to significant proximal tubular cell damage, peaking at 7 days.
- Co-administration of frusemide, bumetanide, or piretanide with gentamicin resulted in reduced tubular damage compared to gentamicin alone.
- Urinary NAG levels and electron microscopy confirmed the protective effect of the diuretics.
Conclusions:
- The study demonstrates a protective effect of frusemide, bumetanide, and piretanide against gentamicin-induced nephrotoxicity in mice.
- This finding contrasts with previous research and suggests a potential therapeutic strategy for mitigating gentamicin-related kidney injury.