Comparative nephrotoxicity of ribostamycin and gentamicin in rats evaluated by urinalysis.
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.
Kitasato
I
I
Research & Development, Meiji Seika Kaisha Ltd., Tokyo, Japan.
Niizato
T
T
Inouye
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004798:Enzymes / Q000652:urine; D005839:Gentamicins / Q000378:metabolism / Q000633:toxicity*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007672:Kidney Cortex / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology / Q000652:urine; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D011141:Polyuria / Q000139:chemically induced; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D012271:Ribostamycin / Q000378:metabolism / Q000633:toxicity*; D014556:Urine / Q000166:cytology
D000900:Anti-Bacterial Agents; D004798:Enzymes; D005839:Gentamicins; D012271:Ribostamycin