Ceftriaxone protects against tobramycin nephrotoxicity
Autor: | Michel G. Bergeron, Louis Grenier, Denis Beauchamp, Yves Bergeron, Sylvie Perron, Guy Thériault, L Fontaine, Pierrette Gourde |
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Rok vydání: | 1994 |
Předmět: |
Kidney Cortex
medicine.medical_treatment Renal cortex Pharmacology Nephrotoxicity Rats Sprague-Dawley chemistry.chemical_compound medicine Tobramycin Animals Pharmacology (medical) Drug Interactions Saline Antibacterial agent Creatinine business.industry Ceftriaxone beta-Galactosidase Enzymes Rats carbohydrates (lipids) Microscopy Electron Infectious Diseases medicine.anatomical_structure Sphingomyelin Phosphodiesterase chemistry Immunology Toxicity Female Kidney Diseases business medicine.drug Thymidine Research Article |
Zdroj: | Antimicrobial agents and chemotherapy. 38(4) |
ISSN: | 0066-4804 |
Popis: | 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. |
Databáze: | OpenAIRE |
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