Protection from Cisplatin Nephrotoxicity by A68828, an Atrial Natriuretic Peptide

Abstract

The ability of a 13 amino acid analog of atrial natriuretic peptide (ANP), A68828, to prevent development of cisplatin toxiciry was evaluated in a rat model. ANP (1 μg/kg/min), A68828 (10 μg/kg/min), A68828 (50 μg/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 μg/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 μg/kg/min) did not reduce cisplatin nephrotoxicity (72-h plasma creatinine 1.61 ± 0.34 mg/dL). These results indicate that a shortterm 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.