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Protection against gentamicin nephrotoxicity by daptomycin in nephrectomized rats
N Thibault1, L Grenier, M Simard
1Laboratoire et Service d'Infectiologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada.
Life Sciences
|January 1, 1995
Summary
Daptomycin (DAP) reduces gentamicin (GEN) induced kidney toxicity in rats. While DAP offers protection, it is less effective in nephrectomized rats compared to normal rats, indicating kidney function influences its protective effect.
Area of Science:
- Pharmacology
- Nephrology
- Toxicology
Background:
- Gentamicin is an antibiotic with known nephrotoxicity.
- Daptomycin has demonstrated protective effects against gentamicin-induced renal damage in prior studies.
- The impact of daptomycin on gentamicin toxicity in nephrectomized models requires further investigation.
Purpose of the Study:
- To evaluate the protective effect of daptomycin against gentamicin nephrotoxicity in normal and nephrectomized rats.
- To assess the pharmacokinetic profiles of daptomycin and gentamicin in different rat models.
- To investigate the cellular localization and biochemical markers of renal damage.
Main Methods:
- Ninety-six female Sprague-Dawley rats were used, divided into normal and nephrectomized groups.
- Treatment groups included saline, gentamicin, daptomycin, and a combination of daptomycin and gentamicin.
- Drug levels, sphingomyelinase activity, serum creatinine, and histopathology were analyzed over 4 and 10 days.
Main Results:
- Daptomycin significantly reduced gentamicin-induced renal toxicity, evidenced by fewer histopathological changes and lower serum creatinine levels.
- Cortical drug levels were higher in nephrectomized rats receiving both daptomycin and gentamicin.
- Daptomycin's protective effect was less pronounced in nephrectomized rats compared to normal rats.
- Both drugs were localized in the lysosomes of proximal tubular cells.
Conclusions:
- Daptomycin confers protection against gentamicin nephrotoxicity in rats.
- Kidney function status influences the extent of daptomycin's protective efficacy.
- Daptomycin represents a potential co-administered agent to mitigate gentamicin-induced kidney damage.