title: Myeloprotective effects of C-type natriuretic peptide on cisplatin-induced bone marrow granulocytopenia in mice.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  CNP exerts myeloprotective effects in cisplatin-induced granulocytopenia and decreases CXCR4 expression.
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan.|Department of Pediatric Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Zenitani
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan. nojiri@ri.ncvc.go.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nojiri
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hino
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Nakahata
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Uehara
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan.
authors.forename: Mikiya
authors.initials: M
authors.lastname: Miyazato
authors.affiliation: Department of Pediatric Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Oue
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Okuyama
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D000380:Agranulocytosis / Q000517:prevention & control*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000235:genetics; D002945:Cisplatin / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000235:genetics
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D020011:Protective Agents; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D020098:Natriuretic Peptide, C-Type; D002945:Cisplatin
keywords: CNP; CXCR4; Chemotherapy; Myelosuppression