Platelet-activating factor antagonist, BN-52021 protects against cis-diamminedichloroplatinum nephrotoxicity in the rat

The protective effect of the platelet-activating factor (PAF) antagonist, BN 52021, was assessed on cis-diammine-dichloroplatinum (CDDP)-induced nephrotoxicity. Wistar male rats were treated with either a single dose of CDDP (10 mg/kg b.w. ip) alone or in association with 7 daily doses of BN 52021 (...

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Bibliographic Details
Published inRenal failure Vol. 12; no. 3; p. 171
Main Authors Pirotzky, E, Guilmard, C, Sidoti, C, Ivanow, F, Principe, P, Braquet, P
Format Journal Article
LanguageEnglish
Published England 1990
Subjects
Acute Kidney Injury - chemically induced
Acute Kidney Injury - physiopathology
Animals
Blood Urea Nitrogen
Body Weight - drug effects
Cisplatin - antagonists & inhibitors
Cisplatin - pharmacokinetics
Cisplatin - toxicity
Creatinine - metabolism
Diterpenes
Ginkgolides
Glomerular Filtration Rate - drug effects
Lactones - pharmacology
Male
Platelet Activating Factor - antagonists & inhibitors
Rats
Rats, Inbred Strains
Renal Circulation - drug effects
Tumor Cells, Cultured - drug effects
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Summary:The protective effect of the platelet-activating factor (PAF) antagonist, BN 52021, was assessed on cis-diammine-dichloroplatinum (CDDP)-induced nephrotoxicity. Wistar male rats were treated with either a single dose of CDDP (10 mg/kg b.w. ip) alone or in association with 7 daily doses of BN 52021 (10 mg/kg b.w. ip). At the end of the experiment, the CDDP-treated rats lost 25% of body weight and serum creatinine and urea increased from 0.041 +/- 0.006 mmol/l and 0.165 +/- 0.007 g/l for the control group to 0.202 +/- 0.019 mmol/l and 1.51 +/- 0.131 g/l versus CDDP respectively. Body weight, serum creatinine, serum urea and creatinine clearances were similar to the control group in animals treated with CDDP and BN 52021. CDDP caused proximal tubular necrosis and dilatation of cortical collecting tubes, changes that were markedly less in the BN 52021-protected animals. The concomitant administration of BN 52021 with CDDP did not modify the plasma pharmacokinetic of CDDP. In addition, BN 52021 did not interfere with the antiproliferative and antitumoral actions of CDDP in cultured human tumor cells. BN 52021 therefore could prevent the nephrotoxicity of CDDP.
ISSN:0886-022X
DOI:10.3109/08860229009065560