[Prophylactic effect of methylprednisolone on cisplatin-induced nephrotoxicity].
Cis-diamminedichloroplatinum (II) (cisplatin) is an effective antitumor drug, but it has an adverse effect of nephrotoxicity. There are many reports concerning protective agents against cisplatin nephrotoxicity. However, clinically useful modalities are very few because the mechanism of action was not well evaluated. In the present study, prophylactic effects of methylprednisolone (MP) on cisplatin-induced nephrotoxicity and its mechanism were studied. Male Sprague-Dawley rats were intravenously injected with 6.5 mg/kg of cisplatin combined with a subcutaneous MP in various doses at various timing. Rats were killed 5 days after cisplatin injection to determine BUN and serum creatinine. BUN and serum creatinine levels in rats pretreated with MP 4 or 2 hours prior to cisplatin injection were significantly lower than those in rats received cisplatin alone. To evaluate the mechanism responsible for the protective action of MP against cisplatin-induced nephrotoxicity, the effects of MP on platinum kinetics and the excretion of urinary enzymes following intravenous administration of cisplatin in vivo were studied. Rats intravenously injected with cisplatin combined with a subcutaneous MP injection excreted more platinum in their urine than rats which had received cisplatin alone. Plasma and kidney platinum concentrations in rats injected with both cisplatin and MP were significantly lower than those in rats given cisplatin alone, at 4 hours after the cisplatin injection. These findings indicate that the MP-induced increase in urinary platinum excretion accompanied by a decrease in plasma and kidney platinum concentrations following cisplatin injections in rats is one of the possible mechanisms responsible for the protective action of MP.(ABSTRACT TRUNCATED AT 250 WORDS)
Koikawa
Y
Y
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka.
D000818:Animals; D002945:Cisplatin / Q000009:adverse effects* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D002945:Cisplatin; D008775:Methylprednisolone