Protective effect of fosfomycin on the experimental nephrotoxicity induced by dibekacin.
Protection by fosfomycin of the nephrotoxicity of dibekacin was studied using Fischer 344 rats and urinary parameters such as volume, osmolality, protein, N-acetyl-beta-D-glucosaminidase, leucine aminopeptidase, lactate dehydrogenase and nucleated cells were determined as markers of nephrotoxicity. The duration of treatment was 11 d. Fosfomycin reduced polyuria, proteinuria, enzymuria and cyturia induced by dibekacin best by the concomitant administration, followed by pre-treatment, but not by post-treatment. Protection was effective in the dose ratio of dibekacin: fosfomycin = 1:2 - 1:32, regardless of administration routes. As judged from urinalysis, protection by fosfomycin (320 mg/kg) was almost complete for the experimental nephrotoxicity induced by 10 mg/kg of dibekacin, and still significant for that by 40 mg/kg. This was supported by the histo-pathological and ultrastructural improvement of proximal tubules and by suppressed blood urea nitrogen and creatinine values. Protective activity of fosfomycin was more potent than that of cephalothin, when compared on the weight basis.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors* / Q000627:therapeutic use* / Q000633:toxicity; D002512:Cephalothin / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D003982:Dibekacin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005578:Fosfomycin / Q000008:administration & dosage / Q000627:therapeutic use*; D007612:Kanamycin / Q000031:analogs & derivatives*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control* / Q000652:urine; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D003982:Dibekacin; D007612:Kanamycin; D002512:Cephalothin