ATTENUATION OF GENTAMICIN-INDUCED NEPHROTOXICITY IN RATS BY FLEROXACIN

The effect of fleroxacin on gentamicin-induced nephrotoxicity was eval uated with female Sprague-Dawley rats. Animals were injected during 4 or 10 days with saline (NaCl; 0.9%), gentamicin alone at doses of 10 a nd 40 mg/kg of body weight/12 h (subcutaneously), fleroxacin alone at a dose of 25 mg/kg/12 h (intraperitoneally), or the combination gentam icin-fleroxacin in the same regimen. Gentamicin induced a dose- and ti me-dependent renal toxicity as evaluated by gentamicin cortical levels , sphingomyelinase activity in the renal cortex, histopathologic and m orphometric analysis, blood urea nitrogen and serum creatinine levels, and cellular regeneration ([H-3]thymidine incorporation into DNA of c ortical cells). The extent of these changes was significantly reduced when gentamicin was given in combination with fleroxacin. Although the mechanisms by which fleroxacin reduces the nephrotoxic potential of g entamicin are unknown, we propose that the fleroxacin-gentamicin combi nation enhances exocytosis activity in proximal tubular cells, as sugg ested by the higher excretion of urinary enzymes and lower cortical le vels of gentamicin observed in animals treated with the combination fl eroxacin-gentamicin compared with those treated with gentamicin alone. The protective effect of fleroxacin on gentamicin nephrotoxicity shou ld be investigated further.