Ceftriaxone protects against tobramycin nephrotoxicity.
The effect of ceftriaxone on tobramycin-induced nephrotoxicity was investigated. Female Sprague-Dawley rats were treated during 4 and 10 days with saline (NaCl, 0.9%), ceftriaxone at a dose of 100 mg/kg of body weight/12 h subcutaneously, tobramycin at doses of 40 and 60 mg/kg/12 h intraperitoneally, or the combination ceftriaxone-tobramycin. Creatinine levels in serum were significantly higher in animals treated with tobramycin alone given at 60 mg/kg/12 h during 10 days, compared with control animals (P < 0.01) or animals receiving the combination tobramycin-ceftriaxone (P < 0.01). After 10 days of treatment, ceftriaxone did not accumulate in renal tissue but did reduce the renal intracortical accumulation of tobramycin (P < 0.05). Tobramycin given alone at either 40 or 60 mg/kg/12 h induced a significant inhibition of sphingomyelinase activity compared with control animals (P < 0.05). However, this enzyme activity was significantly less inhibited when tobramycin was injected in combination with ceftriaxone (P < 0.05). Ceftriaxone alone had no effect on the activity of this enzyme. The [3H]thymidine incorporation into the DNA of renal cortex was also significantly lower in animals treated with tobramycin-ceftriaxone compared with animals receiving tobramycin alone (P < 0.05). The 24-h urinary excretion of beta-galactosidase was significantly reduced in animals treated with the combination tobramycin-ceftriaxone compared with the administration of tobramycin alone at 40 and 60 mg/kg/12 h after 5 and 10 days (P < 0.05). Histologically, ceftriazone induced very few cellular alterations and reduced considerably the presence of typical signs of tobramycin nephrotoxicity. This investigation demonstrated that ceftriaxone protects animals against tobramycin-induced nephrotoxicity.
Laboratoire et Service d'Infectiologie, Université Laval, Sainte-Foy, Québec, Canada.
D
D
Beauchamp
G
G
Thériault
L
L
Grenier
P
P
Gourde
S
S
Perron
Y
Y
Bergeron
L
L
Fontaine
M G
MG
Bergeron
D000818:Animals; D002443:Ceftriaxone / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D003404:Creatinine / Q000652:urine; D004347:Drug Interactions; D004798:Enzymes / Q000652:urine; D005260:Female; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D013108:Sphingomyelin Phosphodiesterase / Q000652:urine; D013936:Thymidine / Q000378:metabolism; D014031:Tobramycin / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D001616:beta-Galactosidase / Q000652:urine
D004798:Enzymes; D002443:Ceftriaxone; D003404:Creatinine; D013108:Sphingomyelin Phosphodiesterase; D001616:beta-Galactosidase; D013936:Thymidine; D014031:Tobramycin