TY - JOUR
T1 - Myeloprotective effects of C-type natriuretic peptide on cisplatin-induced bone marrow granulocytopenia in mice
AU - Zenitani, Masahiro
AU - Nojiri, Takashi
AU - Kimura, Toru
AU - Hosoda, Hiroshi
AU - Miura, Koichi
AU - Hino, Jun
AU - Nakahata, Kengo
AU - Uehara, Shuichiro
AU - Miyazato, Mikiya
AU - Oue, Takaharu
AU - Okuyama, Hiroomi
AU - Kangawa, Kenji
N1 - Funding Information:
We are grateful to K. Shioya for helping us care for the mice. This work was supported in part by research grants to T. Nojiri from the Ministry of Education, Culture, Sports, Science and Technology of Japan (26861136); the Osaka Cancer Society; the Japan Research Foundation for Clinical Pharmacology; the Kobayashi Foundation for Cancer Research; the Mochida Memorial Foundation for Medical and Pharmaceutical Research; the Uehara Memorial Foundation; the Senri Life Science Foundation; the Kato Memorial Bioscience Foundation; and the Takeda Science Foundation.
Publisher Copyright:
© 2017, Springer-Verlag Berlin Heidelberg.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Purpose: Cisplatin is an effective chemotherapeutic agent used to treat a variety of malignant tumors. The major toxicity associated with cisplatin treatment is granulocytopenia. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, protects against toxicity in many organs, including the heart, blood vessels, lung, and kidney. The objective of this study was to investigate the myeloprotective effects of CNP in a mouse model of cisplatin-induced granulocytopenia. Methods: The mice were divided into two groups: cisplatin with vehicle and cisplatin with CNP. CNP (2.5 μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started two day before cisplatin injection, and continued until the mice were killed. At 0, 2, 4, 8, and 14 days after cisplatin injection (16 mg/kg, intraperitoneally as a single dose), we counted total and living cells and granulocyte/macrophage colony-forming units (CFU-GM) in bone marrow. In addition, at 0, 1, 2, and 4 days after cisplatin injection, we measured mRNA levels of CXC chemokine receptor 4 (CXCR4) and chemokine CXC ligand 12 (CXCL12) in bone marrow. Results: CNP significantly attenuated the reduction in bone marrow nucleated cell count and CFU-GM in bone marrow at 4 days after cisplatin injection. Four days after cisplatin injection, CNP significantly decreased the CXCR4 mRNA level in bone marrow, but had no effect on the level of CXCL12 mRNA. Conclusions: CNP exerts myeloprotective effects in cisplatin-induced granulocytopenia and decreases CXCR4 expression.
AB - Purpose: Cisplatin is an effective chemotherapeutic agent used to treat a variety of malignant tumors. The major toxicity associated with cisplatin treatment is granulocytopenia. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, protects against toxicity in many organs, including the heart, blood vessels, lung, and kidney. The objective of this study was to investigate the myeloprotective effects of CNP in a mouse model of cisplatin-induced granulocytopenia. Methods: The mice were divided into two groups: cisplatin with vehicle and cisplatin with CNP. CNP (2.5 μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started two day before cisplatin injection, and continued until the mice were killed. At 0, 2, 4, 8, and 14 days after cisplatin injection (16 mg/kg, intraperitoneally as a single dose), we counted total and living cells and granulocyte/macrophage colony-forming units (CFU-GM) in bone marrow. In addition, at 0, 1, 2, and 4 days after cisplatin injection, we measured mRNA levels of CXC chemokine receptor 4 (CXCR4) and chemokine CXC ligand 12 (CXCL12) in bone marrow. Results: CNP significantly attenuated the reduction in bone marrow nucleated cell count and CFU-GM in bone marrow at 4 days after cisplatin injection. Four days after cisplatin injection, CNP significantly decreased the CXCR4 mRNA level in bone marrow, but had no effect on the level of CXCL12 mRNA. Conclusions: CNP exerts myeloprotective effects in cisplatin-induced granulocytopenia and decreases CXCR4 expression.
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U2 - 10.1007/s00280-016-3221-5
DO - 10.1007/s00280-016-3221-5
M3 - Article
C2 - 28101584
AN - SCOPUS:85009802450
SN - 0344-5704
VL - 79
SP - 363
EP - 368
JO - Cancer chemotherapy and pharmacology
JF - Cancer chemotherapy and pharmacology
IS - 2
ER -
