The effect of methylprednisolone on platinum kinetics and urinary enzyme excretion following intravenous cisplatin in vivo and on the growth inhibition of LLC-PK1 cells by cisplatin in vitro.
In order to evaluate the mechanism of the protective action of methylprednisolone against cisplatin-induced nephrotoxicity, platinum kinetics and urinary enzyme excretion following intravenous cisplatin, with or without methylprednisolone, were studied in vivo. The growth inhibition of LLC-PK1 cells by cisplatin in the presence or absence of methylprednisolone was studied in vitro. Rats intravenously injected with cisplatin combined with subcutaneous methylprednisolone 4 h prior to the cisplatin injection excreted more platinum in urine than rats treated with cisplatin alone. Both plasma and kidney platinum concentrations in rats injected with both cisplatin and methylprednisolone were significantly lower than those in rats given cisplatin alone at 4 h after cisplatin injection. However, there was no significant difference in urinary excretion of lactate dehydrogenase, gamma-glutamyl transpeptidase or N-acetyl-beta-D-glucosaminidase between methylprednisolone-treated rats and control rats. Methylprednisolone did not affect the inhibitory effects of cisplatin on the cell growth of LLC-PK1. These findings indicate that methylprednisolone-induced increase in urinary platinum excretion, accompanied by a decrease in plasma and kidney platinum concentrations following cisplatin injection in rats, may be one of the mechanisms responsible for the protective action of methylprednisolone.
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J
J
Uozumi
Y
Y
Koikawa
T
T
Yasumasu
N
N
Tokuda
T
T
Ueda
J
J
Kumazawa
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002945:Cisplatin / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000652:urine; D018374:LLC-PK1 Cells; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D010984:Platinum / Q000097:blood / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D005723:gamma-Glutamyltransferase / Q000652:urine
D010984:Platinum; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D002945:Cisplatin; D008775:Methylprednisolone