title: Experimental study of renal disorder caused by oxaliplatin in rat renal cortical slices.
abstract: BACKGROUND
  Oxaliplatin is a newly developed antitumor platinum complex that is known to have low nephrotoxicity. The inhibitory effects of oxaliplatin on several tubular functions were compared with those of cisplatin and carboplatin, using a renal cortical slice system.
  
  
  RESULTS
  Rat renal cortical slices were incubated with 0.25 mM to 2.0 mM of oxaliplatin, cisplatin, on carboplatin at 37 degrees C for 120 min. Para-amino hippuric acid (PAH) accumulation, gluconeogenesis, and ATP content in the rat renal slices were determined. PAH accumulation was not inhibited by carboplatin, but it was significantly inhibited by oxaliplatin and cisplatin. Inhibition of PAH accumulation by cisplatin was greater than that by oxaliplatin. Gluconeogenesis was not decreased by carboplatin, but it was suppressed by oxaliplatin and cisplatin in a dose-dependent manner. The decrease in gluconeogenesis induced by oxaliplatin was significantly greater than that induced by cisplatin. ATP content in the renal slices was decreased by oxaliplatin, cisplatin, and carboplatin to almost the same extent. As an in vivo experiment, 21.6 mmole/kg of oxaliplatin, cisplatin, or carboplatin was injected into rats; then blood urea nitrogen (BUN) and serum creatinine were determined on day 4. Significantly elevated levels of BUN and serum creatinine were observed only in the rats injected with cisplatin.
  
  
  CONCLUSIONS
  Oxaliplatin did not cause nephrotoxicity in the in vivo study; however, the nephrotoxic pattern of oxaliplatin observed in the renal cortical-slice system resembled that of cisplatin. The reason why oxaliplatin is less nephrotoxic than cisplatin in vivo could not be fully elucidated in the present experiment using the renal cortical-slice system.
authors.affiliation: Department of Urology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kanou
authors.forename: Jiro
authors.initials: J
authors.lastname: Uozumi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Soejima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tokuda
authors.forename: Zenjiro
authors.initials: Z
authors.lastname: Masaki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D016190:Carboplatin / Q000737:chemistry / Q000494:pharmacology; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D005943:Gluconeogenesis / Q000502:physiology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000473:pathology; D008297:Male; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D000077150:Oxaliplatin; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin