Nephrotoxicity and pharmacokinetics of cisplatinum in young and adult rats.
Wistar rats (10 and 55 days old) were administered a single dose of 0.6 mg cisplatinum (CP) 100 g body wt. intraperitoneally. Urinary volume, p-aminohippurate and total protein excretion were determined. Separation of urinary proteins was performed by sodium dodecylsulfate polyacrylamide gel electrophoresis. Significant symptoms of nephrotoxicity (oliguria, reduced PAH-excretion, heavy proteinuria, changes in urinary protein composition) were detected in adult rats 72 h after CP. At that time young rats did not show distinct signs of nephrotoxicity. Experiments on time dependence of nephrotoxicity showed that in young rats symptoms occurred already 6 h after CP-administration, and 72 h after CP the damage was nearly completely repaired. Pt-determination in serum, kidney tissue, and urine showed a shorter t1/2 in serum, lower concentrations in kidney tissue as well as higher Pt-concentrations in urine of young compared with adult rats.
Appenroth
D
D
Institute of Pharmacology and Toxicology, Friedrich Schiller University, DDR, Jena.
Winnefeld
K
K
Bräunlich
H
H
D000375:Aging; D000419:Albuminuria; D000818:Animals; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000473:pathology*; D008297:Male; D011507:Proteinuria; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D002945:Cisplatin