Effect of cisplatin treatment on the urinary excretion of guanidinoacetic acid, creatinine and creatine in patients with urinary tract neoplasm, and on superoxide generation in human neutrophils.
Production of guanidinoacetic acid, a precursor of creatinine is known to be reduced by metabolic disturbance when kidney function is damaged, and thus it may be a sensitive marker of renal damage. Therefore, the urinary levels of guanidinoacetic acid, creatinine and creatine from patients with urinary tract neoplasm who received cisplatin treatment were measured by liquid chromatography-mass spectrometry. Following the administration of cisplatin, the urinary excretion of guanidinoacetic acid decreased significantly, and the low concentration was maintained for at least five days. The concentrations of creatinine and creatine gradually decreased until the third day after cisplatin administration, and slightly increased on the fifth day. As superoxide might be concerned in renal damage by cisplatin, the effect of cisplatin on superoxide generation was also investigated using human neutrophils. Cisplatin significantly enhanced phorbol 12-myristate 13-acetate-induced superoxide generation in a concentration-dependent manner, but had no effect on the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine and arachidonic acid. The superoxide generation increased by cisplatin was inhibited by staurosporine, an inhibitor of protein kinase C, but was rather enhanced by genistein, an inhibitor of protein tyrosine kinase.
Yasuda
M
M
Department of Urology, Kochi Medical School, Kochi 783-8505, Japan.
Sugahara
K
K
Zhang
J
J
Shuin
T
T
Kodama
H
H
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D003401:Creatine / Q000652:urine*; D003404:Creatinine / Q000652:urine*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014571:Urologic Neoplasms / Q000652:urine*
D000970:Antineoplastic Agents; D013481:Superoxides; D003404:Creatinine; C004946:glycocyamine; D003401:Creatine; D002945:Cisplatin; D005998:Glycine