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01-01-2015 | Original Article

Atrial natriuretic peptide protects against cisplatin-induced acute kidney injury

Authors: Takashi Nojiri, Hiroshi Hosoda, Toru Kimura, Koichi Miura, Shin Ishikane, Takeshi Tokudome, Yasushi Shintani, Masayoshi Inoue, Mikiya Miyazato, Meinoshin Okumura, Kenji Kangawa

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2015

Abstract

Purpose

Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide variety of malignancies. Acute kidney injury (AKI) is the major toxicity associated with cisplatin and sometimes necessitates a reduction in dose or discontinuation of treatment. Atrial natriuretic peptide (ANP) is secreted by the heart and exerts a wide range of renoprotective effects, including anti-inflammatory activity. The objective of this study was to investigate the protective effects of ANP on cisplatin-induced AKI in mice.

Methods

Mice were randomly divided into three groups: control, cisplatin (20 mg/kg, intraperitoneal)/vehicle treatment, and cisplatin/ANP (1.5 μg/kg/min via osmotic-pump, subcutaneous) treatment. At 72 h after cisplatin injection, serum blood urea nitrogen and creatinine, urine albumin/creatinine, and renal expression of mRNAs encoding tumor necrosis factor-α, interleukin (IL)-1β, IL-6, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and transforming growth factor (TGF)-β were measured using real-time polymerase chain reaction. Histological changes were also evaluated.

Results

ANP treatment significantly attenuated cisplatin-induced increases in serum blood urea nitrogen and creatinine, urine albumin/creatinine, and renal expression of IL-1β, IL-6, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 mRNAs. Cisplatin-induced renal dysfunction and renal tubular necrosis were thus attenuated by ANP treatment.

Conclusions

Our results indicate that ANP exhibits a protective effect against cisplatin-induced AKI in mice. ANP may thus be of value in prophylactic strategies aimed at mitigating the adverse effects associated with chemotherapy agents, including cisplatin.

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Title: Atrial natriuretic peptide protects against cisplatin-induced acute kidney injury
Authors: Takashi Nojiri
Hiroshi Hosoda
Toru Kimura
Koichi Miura
Shin Ishikane
Takeshi Tokudome
Yasushi Shintani
Masayoshi Inoue
Mikiya Miyazato
Meinoshin Okumura
Kenji Kangawa
Publication date: 01-01-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2624-4

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