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Atrial natriuretic peptide protects against cisplatin-induced acute kidney injury

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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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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research (26861136) and a Grant from the Takeda Science Foundation, Japan Research Foundation for Clinical Pharmacology, Osaka Cancer Society, and Kobayashi Foundation for Cancer Research, Japan.

Conflict of interest

All authors have nothing to declare.

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Authors and Affiliations

  1. Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita-City, Osaka, 565-8565, Japan

    Takashi Nojiri, Toru Kimura, Shin Ishikane, Takeshi Tokudome, Mikiya Miyazato & Kenji Kangawa

  2. Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan

    Takashi Nojiri, Toru Kimura, Yasushi Shintani, Masayoshi Inoue & Meinoshin Okumura

  3. Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita-City, Osaka, Japan

    Hiroshi Hosoda & Koichi Miura

Authors
  1. Takashi Nojiri
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  2. Hiroshi Hosoda
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  3. Toru Kimura
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  4. Koichi Miura
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  5. Shin Ishikane
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  6. Takeshi Tokudome
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  7. Yasushi Shintani
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  8. Masayoshi Inoue
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  9. Mikiya Miyazato
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  10. Meinoshin Okumura
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  11. Kenji Kangawa
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Corresponding author

Correspondence to Takashi Nojiri.

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Nojiri, T., Hosoda, H., Kimura, T. et al. Atrial natriuretic peptide protects against cisplatin-induced acute kidney injury. Cancer Chemother Pharmacol 75, 123–129 (2015). https://doi.org/10.1007/s00280-014-2624-4

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  • DOI: https://doi.org/10.1007/s00280-014-2624-4

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