Prevention by urinastatin of cis-diamminedichloroplatinum-induced nephrotoxicity in rabbits: comparison of urinary enzyme excretions and morphological alterations by electron microscopy.
Acute nephrotoxicity was produced by 3 mg/kg intramuscular administrations of cis-diamminedichloroplatinum (CDDP) in rabbits. Urinary enzyme excretions of arylamidase and gamma-glutamyl transpeptidase, and morphological alterations by electron microscopy were used as endpoints to quantitate the severity of nephrotoxicity. The preventive effect of urinastatin (US), a trypsin inhibitor, on CDDP-induced nephrotoxicity was evaluated. The alteration of urinary enzyme excretions did not parallel the severity of renal morphological changes. In proximal tubular cells, the morphological alterations consisting of nuclear irregularity, brush border disruption, and lysosomal membrane destruction were observed. In contrast, in rabbits treated concurrently with CDDP and 10,000 unit/kg of US, CDDP-induced morphological changes observed in rabbits without US were completely absent. The differences in urinary enzyme excretions and morphological alterations between US-treated rabbits and the US-nontreated group were enough to fully account for the drastic protective effect of US against CDDP nephrotoxicity.
Kobayashi
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H
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Ohi
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H
Terao
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T
D000818:Animals; D004798:Enzymes / Q000652:urine; D006023:Glycoproteins / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009944:Organoplatinum Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011817:Rabbits; D014361:Trypsin Inhibitors / Q000494:pharmacology
D004798:Enzymes; D006023:Glycoproteins; D009944:Organoplatinum Compounds; D014361:Trypsin Inhibitors; C055423:didimethylsulfoxide dichloroplatinum(II); C028665:urinastatin