Skip to main content
Log in

RETRACTED ARTICLE: Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

This article was retracted on 21 December 2023

This article has been updated

Abstract

Purpose

Granulocytopenia is the major toxicity associated with cisplatin treatment. Atrial natriuretic peptide (ANP) is a cardiac hormone used clinically for the treatment of acute heart failure in Japan. ANP exerts a wide range of protective effects on various organs, including the heart, blood vessels, lungs, and kidneys. This study’s objective was to investigate the protective effects of ANP on cisplatin-induced granulocytopenia in mice.

Methods

The mice were divided into two groups: cisplatin with vehicle and cisplatin with ANP. ANP (1.5 μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started 1 day before cisplatin injection until the mice were killed. At 0, 2, 4, 8, and 14 days after cisplatin injection (16 mg/kg, intraperitoneally as a single dose), the white blood cell, red blood cell, and platelet counts were measured in the peripheral blood in both groups. The numbers of total and live cells and colony-forming unit-granulocyte–macrophage (CFU-GM) colonies in the bone marrow of the mice were also examined. In addition, at 0, 0.5, 1, and 2 days after cisplatin injection, serum granulocyte colony-stimulating factor (G-CSF) levels were measured.

Results

ANP significantly attenuated the white blood cell count decrease in the peripheral blood 2 and 4 days after cisplatin injection. ANP also attenuated the decrease in the number of live cells and CFU-GM colonies in bone marrow 2, 4, and 8 days after cisplatin injection. ANP significantly increased serum G-CSF levels 1 day after cisplatin injection.

Conclusions

ANP has protective effects in cisplatin-induced granulocytopenia, with increased G-CSF production.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Change history

References

  1. Montoya L (2007) Managing hematologic toxicities in the oncology patient. J Infus Nurs 30:168–172

    Article  PubMed  Google Scholar 

  2. Shelton BK (2003) Evidence-based care for the neutropenic patient with leukemia. Semin Oncol Nurs 19:133–141

    Article  PubMed  Google Scholar 

  3. Demetri GD, Griffin JD (1991) Granulocyte colony-stimulating factor and its receptor. Blood 78:2791–2808

    Article  CAS  PubMed  Google Scholar 

  4. Franzke A (2006) The role of G-CSF in adaptive immunity. Cytokine Growth Factor Rev 17:235–244

    Article  CAS  PubMed  Google Scholar 

  5. Panopoulos AD, Watowich SS (2008) Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and ‘emergency’ hematopoiesis. Cytokine 42:277–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Xu S, Höglund M, Venge P (1996) The effect of granulocyte colony-stimulating factor (G-CSF) on the degranulation of secondary granule proteins from human neutrophils in vivo may be indirect. Br J Haematol 93:558–568

    Article  CAS  PubMed  Google Scholar 

  7. Bennett CL, Djulbegovic B, Norris LB, Armitage JO (2013) Colony-stimulating factors for febrile neutropenia during cancer therapy. N Engl J Med 368:1131–1139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kishimoto I, Tokudome T, Horio T, Garbers DL, Nakao K, Kangawa K (2009) Natriuretic peptide signaling via guanylyl cyclase (GC)-A: an endogenous protective mechanism of the heart. Curr Cardiol Rev 5:45–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kasama S, Furuya M, Toyama T, Ichikawa S, Kurabayashi M (2008) Effect of atrial natriuretic peptide on left ventricular remodelling in patients with acute myocardial infarction. Eur Heart J 29:1485–1494

    Article  CAS  PubMed  Google Scholar 

  10. Nojiri T, Hosoda H, Kimura T, Miura K, Ishikane S, Tokudome T, Shintani Y, Inoue M, Miyazato M, Okumura M, Kangawa K (2015) Atrial natriuretic peptide protects against cisplatin-induced acute kidney injury. Cancer Chemother Pharmacol 75:123–129

    Article  CAS  PubMed  Google Scholar 

  11. Ventura GJ, Reading CL, Hester JP, Vadhan-Raj S (1990) Circulating myeloid progenitor cell kinetics during hematologic recovery from chemotherapy and subsequent recombinant human granulocyte-macrophage colony-stimulating factor administration. Acta Haematol 84:175–181

    Article  CAS  PubMed  Google Scholar 

  12. Mehta HM, Malandra M, Corey SJ (2015) G-CSF and GM-CSF in neutropenia. J Immunol 195:1341–1349

    Article  CAS  PubMed  Google Scholar 

  13. Cooper KL, Madan J, Whyte S, Stevenson MD, Akehurst RL (2011) Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis. BMC Cancer 11:404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bohlius J, Reiser M, Schwarzer G, Engert A (2003) Impact of granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF in patients with malignant lymphoma: a systematic review. Br J Haematol 122:413–423

    Article  CAS  PubMed  Google Scholar 

  15. Nishida M, Fujimoto S, Toiyama K, Sato H, Hamaoka K (2004) Effect of hematopoietic cytokines on renal function in cisplatin-induced ARF in mice. Biochem Biophys Res Commun 324:341–347

    Article  CAS  PubMed  Google Scholar 

  16. Iwasaki M, Adachi Y, Minamino K, Suzuki Y, Zhang Y, Okigaki M, Nakano K, Koike Y, Wang J, Mukaide H, Taketani S, Mori Y, Takahashi H, Iwasaka T, Ikehara S (2005) Mobilization of bone marrow cells by G-CSF rescues mice from cisplatin-induced renal failure, and M-CSF enhances the effects of G-CSF. J Am Soc Nephrol 16:658–666

    Article  CAS  PubMed  Google Scholar 

  17. Nojiri T, Yamamoto K, Maeda H, Takeuchi Y, Funakoshi Y, Inoue M, Okumura M (2012) Effect of low-dose human atrial natriuretic peptide on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer: a double-blind, placebo-controlled study. J Thorac Cardiovasc Surg 143:488–494

    Article  CAS  PubMed  Google Scholar 

  18. Nojiri T, Inoue M, Yamamoto K, Maeda H, Takeuchi Y, Funakoshi Y, Okumura M (2012) Effects of low-dose human atrial natriuretic peptide for preventing post-operative cardiopulmonary complications in elderly patients undergoing pulmonary resection for lung cancer. Eur J Cardiothorac Surg 41:1330–1334

    Article  PubMed  Google Scholar 

  19. Nojiri T, Inoue M, Maeda H, Takeuchi Y, Sawabata N, Shintani Y, Yamamoto K, Okumura M (2013) Low-dose human atrial natriuretic peptide for the prevention of postoperative cardiopulmonary complications in chronic obstructive pulmonary disease patients undergoing lung cancer surgery. Eur J Cardiothorac Surg 44:98–103

    Article  PubMed  Google Scholar 

  20. Nojiri T, Hosoda H, Tokudome T, Miura K, Ishikane S, Otani K, Kishimoto I, Shintani Y, Inoue M, Kimura T, Sawabata N, Minami M, Nakagiri T, Funaki S, Takeuchi Y, Maeda H, Kidoya H, Kiyonari H, Shioi G, Arai Y, Hasegawa T, Takakura N, Hori M, Ohno Y, Miyazato M, Mochizuki N, Okumura M, Kangawa K (2015) Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells. Proc Natl Acad Sci USA 112:4086–4091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Alderson MR, Tough TW, Ziegler SF, Grabstein KH (1991) Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes. J Exp Med 173:923–930

    Article  CAS  PubMed  Google Scholar 

  22. Arai KI, Lee F, Miyajima A, Miyatake S, Arai N, Yokota T (1990) Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem 59:783–836

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to M. Fukui for her technical assistance and to K. Shioya for helping us to care for the mice. This work was supported in part by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (26861136); Osaka Cancer Society, Japan Research Foundation for Clinical Pharmacology, Kobayashi Foundation for Cancer Research, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Uehara Memorial Foundation, the Senri Life Science Foundation, Kato Memorial Bioscience Foundation, and Takeda Science Foundation to T. Nojiri.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takashi Nojiri.

Ethics declarations

Conflict of interest

None declared.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nojiri, T., Hosoda, H., Zenitani, M. et al. RETRACTED ARTICLE: Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia. Cancer Chemother Pharmacol 78, 191–197 (2016). https://doi.org/10.1007/s00280-016-3075-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-016-3075-x

Keywords

Navigation