Protective effect of ceftriaxone against the nephrotoxicity of isepamicin administered once daily in rats.
The protective effect of ceftriaxone on isepamicin-induced nephrotoxicity was investigated. For 14 d, Wistar rats were administered either ceftriaxone 100 mg/kg intraperitoneally, isepamicin 300 mg/kg subcutaneously, or ceftriaxone isepamicin in combination. The animals given 300 mg/kg of isepamicin showed a significant increase in urine NAG (N-acetyl-beta-D-glucosaminidase) levels as compared with the control animals which received saline (p<0.01). However, the increase in NAG level was markedly less when isepamicin was administered in combination with ceftriaxone (p<0.01). Ceftriaxone alone had no effect on urine NAG activity. Serum creatinine levels were significantly higher in animals treated with isepamicin alone than in control animals (p<0.01) or animals receiving the isepamicin ceftriaxone combination (p<0.01). After 14 d of treatment, ceftriaxone had not accumulated in renal tissue, but it did reduce the renal intracortical accumulation of isepamicin (p<0.01). Histopathologically, ceftriaxone induced very few cellular alterations and considerably reduced the manifestation of typical signs of isepamicin nephrotoxicity. This investigation demonstrates that ceftriaxone protects animals against isepamicin-induced nephrotoxicity.
Yoshiyama
Y
Y
Division of Clinical Pharmacy, Kyoritsu College of Pharmacy, Tokyo, Japan.
Yazaki
T
T
Beauchamp
D
D
Kanke
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002443:Ceftriaxone / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D005839:Gentamicins / Q000037:antagonists & inhibitors / Q000633:toxicity; D006596:Hexosaminidases / Q000652:urine; D007672:Kidney Cortex / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005839:Gentamicins; D002443:Ceftriaxone; D003404:Creatinine; D006596:Hexosaminidases; C016927:isepamicin