Protection from cisplatin nephrotoxicity by A68828, an atrial natriuretic peptide.

Deegan PM, Ryan MP, Basinger MA, Jones MM, Hande KR
Ren Fail. 1995 17 (2): 117-23

PMID: 7644762 · DOI:10.3109/08860229509026248

The ability of a 13 amino-acid analog of atrial natriuretic peptide (ANP), A68828, to prevent development of cisplatin toxicity was evaluated in a rat model. ANP (1 microgram/kg/min), A68828 (10 micrograms/kg/min), A68828 (50 micrograms/kg/min), or peptide buffer was given as an intravenous infusion over 1 h beginning 15 min prior to an infusion of 5 mg/kg cisplatin. Animals receiving cisplatin plus peptide buffer vehicle developed predictable renal failure, with mean plasma creatinine and blood urea nitrogen concentrations of 1.09 +/- 0.09 mg/dL and 50.13 +/- 5.96 mg/dL, 72 h after treatment. ANP and A68828 (10 micrograms/kg/min) attenuated the increase in these indices of nephrotoxicity (mean plasma creatinine 0.86 +/- .06 mg/dL and 0.76 +/- 0.11 mg/dL, respectively). Surprisingly, the higher dose of A68828 (50 micrograms/kg/min) did not reduce cisplatin nephrotoxicity (72-h plasma creatinine 1.61 +/- 0.34 mg/dL). These results indicate that a short-term infusion of ANP or the analog A68828 can reduce the severity of cisplatin toxicity. At high doses of A68828 the beneficial effects of treatment may be lost.

MeSH Terms (15)

Animals Atrial Natriuretic Factor Blood Urea Nitrogen Cisplatin Creatinine Disease Models, Animal Dose-Response Relationship, Drug Drug Interactions Humans Infusions, Intravenous Kidney Function Tests Male Nephrosis Rats Rats, Sprague-Dawley

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