The effects of platinum levels in plasma, urine, and kidney on blood urea nitrogen levels after cisplatin injection in rats.
To analyze the relationship between the kinetics of filterable Pt and nephrotoxicity after cisplatin injection, Sprague-Dawley rats were given 5 mg/kg of i.v. cisplatin during hypothermia (hypothermia group) or given 5 mg/kg of cisplatin preincubated with rat serum (preincubation group). Plasma Pt levels, kidney Pt contents, urinary excretion of Pt, and blood urea nitrogen (BUN) levels after cisplatin injection were then determined. These hypothermia and preincubation treatments were performed in order to change the kinetics of filterable Pt without changing the total dose of cisplatin. Plasma Pt levels were significantly changed by both hypothermia or preincubation. Urinary excretion of Pt was unaffected by hypothermia but was significantly reduced by preincubation. However, significant differences in BUN elevation were not observed either in the hypothermia group or the preincubation group relative to the control group. Kidney Pt contents were not affected by hypothermia or preincubation at 1 h, 6 h, and 24 h after cisplatin injection. When rats were injected i.v. with 5, 7, or 10 mg/kg cisplatin, dose-related increases were observed both in kidney Pt contents and in BUN levels. These results suggest that the degree of nephrotoxicity more accurately correlates with renal Pt content rather than with plasma Pt levels or urinary concentration of Pt, and that the role of filterable Pt species in producing nephrotoxicity may have to be reevaluated.
Uozumi
J
J
Division of Cancer Treatment National Cancer Institute, Bethesda, Maryland 20892.
Litterst
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CL
D000818:Animals; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000493:pharmacokinetics*; D005260:Female; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D010984:Platinum / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D010984:Platinum; D002945:Cisplatin