Protective effect of piperacillin against the nephrotoxicity of cisplatin in rats.
The protective effect of piperacillin against the nephrotoxicity of cisplatin was compared with that of fosfomycin in Fischer 344 rats. Blood urea nitrogen, serum creatinine, and morphological changes were evaluated as the renal toxicological parameters. Rats receiving 2 mg of cisplatin per kg of body weight for 5 days showed significant (P less than 0.01 by multiple-comparison test) elevation of blood urea nitrogen and serum creatinine concentrations compared with rats receiving saline alone and also exhibited development of cell lesions in the pars recta of the tubules in the outer stripe of the outer medulla. However, piperacillin (250 and 1,000 mg/kg) significantly (P less than 0.01 by multiple-comparison test) reduced these toxicological parameters in comparison with results for cisplatin alone. The protective effect of piperacillin was superior to that of fosfomycin, although platinum levels in the kidney were higher with the combination of cisplatin and piperacillin than with cisplatin plus fosfomycin. Although the nephrotoxicity of cisplatin was also reduced when cisplatin was administered concomitantly with sodium chloride in mole-equivalents to 250 and 1,000 mg of piperacillin per kg, its protective effect was less than that of the corresponding piperacillin dose. These results suggest that piperacillin may have a role as a protective agent against the nephrotoxicity of cisplatin.
Hayashi
T
T
Research Laboratory, Toyama Chemical Co., Ltd., Toyama, Japan.
Watanabe
Y
Y
Kumano
K
K
Kitayama
R
R
Muratani
T
T
Yasuda
T
T
Saikawa
I
I
Katahira
J
J
Kumada
T
T
Shimizu
K
K
D000818:Animals; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D005578:Fosfomycin / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007939:Leukemia L1210 / Q000378:metabolism; D008297:Male; D010878:Piperacillin / Q000627:therapeutic use*; D010984:Platinum / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D005578:Fosfomycin; D010984:Platinum; D002945:Cisplatin; D010878:Piperacillin