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Comparative nephrotoxicity of ribostamycin and gentamicin in rats evaluated by urinalysis
I Kitasato1, T Niizato, S Inouye
1Research & Development, Meiji Seika Kaisha Ltd., Tokyo, Japan.
Abstract:
The nephrotoxicity of ribostamycin and gentamicin was compared by urinalysis using 18 parameters. When a dose of 40 mg/kg per day was administered intramuscularly to Fischer rats for 14 days, ribostamycin caused little change of parameters in urine volume, urine osmolality, urine protein, maltase and beta 2-microglobulin. A slight increase with ribostamycin was observed in alpha-fucosidase, beta-N-acetylglucosaminidase, leucine aminopeptidase, lactic dehydrogenase (LDH) and potassium, and a moderate increase was observed in acid phosphatase and alkaline phosphatase. On the other hand, gentamicin caused a large alteration in most parameters. Both antibiotics caused a change of the isoenzyme pattern of LDH1-5, but the pattern with ribostamycin was much closer to the normal pattern than with gentamicin. When a dose of 80 mg/kg of ribostamycin was compared with 10 mg/kg of gentamicin, alteration of urinary parameters was almost comparable. Histopathological observations of the kidney specimens of rats given 40 mg/kg per day showed no histological damage with ribostamycin except for a slight increase and enlargement of lysosomes of the proximal epithelial cells. However, significant histological damage was observed with gentamicin, consistent with the results obtained from urinalysis. Renal accumulation of ribostamycin at a single dose of 20 mg/kg was three times less than that of gentamicin. Ribostamycin caused slightly less nephrotoxicity in rats than kanamycin and far less than dibekacin at an equal dosage of 40 mg/kg per day for 14 days.
Insights
Ribostamycin exhibits lower nephrotoxicity than gentamicin in rats, showing minimal urinary changes and no significant kidney damage. This suggests ribostamycin is a safer alternative antibiotic.
Area of Science:
- Pharmacology
- Nephrology
- Toxicology
Background:
- Aminoglycoside antibiotics are crucial for treating bacterial infections.
- Nephrotoxicity is a significant adverse effect limiting the use of certain aminoglycosides.
- Comparing the renal safety profiles of different aminoglycosides is essential for clinical practice.
Purpose of the Study:
- To compare the nephrotoxicity of ribostamycin and gentamicin in a rat model.
- To evaluate the effects of these antibiotics on renal function using urinalysis and histopathology.
- To assess the comparative renal accumulation and toxicity of ribostamycin against other aminoglycosides like kanamycin and dibekacin.
Main Methods:
- Fischer rats were administered daily intramuscular doses of ribostamycin and gentamicin for 14 days.
- Urinalysis was performed using 18 parameters to assess renal function.
- Kidney histopathology was conducted to evaluate structural damage.
- Renal accumulation of antibiotics was measured after a single dose.
- Comparative toxicity was assessed against kanamycin and dibekacin.
Main Results:
- Ribostamycin caused minimal changes in most urinary parameters compared to gentamicin, which induced significant alterations.
- Histopathological examination revealed no significant kidney damage with ribostamycin, unlike gentamicin.
- Ribostamycin showed a renal accumulation three times lower than gentamicin.
- Ribostamycin demonstrated less nephrotoxicity than kanamycin and significantly less than dibekacin at equivalent doses.
Conclusions:
- Ribostamycin exhibits a significantly better nephrotoxic profile than gentamicin in rats.
- Urinalysis and histopathology confirm the lower renal toxicity of ribostamycin.
- Ribostamycin represents a potentially safer aminoglycoside antibiotic option with reduced risk of kidney damage.