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Renal histological and biochemical changes induced in the rat by dibekacin
Abstract:
Among presently available aminoglycosides, dibekacin has the least toxic effect on the functions of the cochlea and the vestibule. We investigated the potential nephrotoxicity of dibekacin at various dose levels and durations of treatment. In the rat, the injection of high doses (50 mg/kg for 8 days) produced: 1) a reduction in renal function and the onset of cellular necrosis; 2) the appearance of myeloid bodies in the cells of the proximal tubule; 3) accumulation of the drug in the renal cortex at a concentration of 4.4 micrograms/mg of protein; 4) a reduction in the lysosomal latency of N-acetyl-beta-D-glucosaminidase; and 5) disorders of the activity of cortical enzymes cathepsin B and sphingomyelinase. The effect of dibekacin is similar to that of the other aminoglycosides, but it would seem to be less nephrotoxic than gentamicin.
Insights
Dibekacin, an aminoglycoside antibiotic, shows potential nephrotoxicity in rats at high doses. While it impacts renal function and causes cellular changes, it may be less kidney toxic than gentamicin.
Area of Science:
- Pharmacology
- Nephrology
- Toxicology
Background:
- Aminoglycosides are crucial antibiotics but can cause kidney damage.
- Dibekacin is noted for lower ototoxicity compared to other aminoglycosides.
Purpose of the Study:
- To evaluate the potential nephrotoxicity of dibekacin.
- To compare dibekacin's kidney toxicity with gentamicin.
Main Methods:
- Rats were administered high doses of dibekacin (50 mg/kg for 8 days).
- Renal function, cellular changes, drug accumulation, and enzyme activities were assessed.
Main Results:
- High-dose dibekacin reduced renal function and caused proximal tubule cell necrosis.
- Myeloid bodies appeared in proximal tubule cells, and drug accumulated in the renal cortex.
- Lysosomal latency and activity of cortical enzymes (cathepsin B, sphingomyelinase) were disrupted.
Conclusions:
- Dibekacin exhibits nephrotoxic effects in rats, similar to other aminoglycosides.
- Dibekacin appears to be less nephrotoxic than gentamicin.