Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia.
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.



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.



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.



ANP has protective effects in cisplatin-induced granulocytopenia, with increased G-CSF production.
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan. nojiri@ri.ncvc.go.jp.|Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan. nojiri@ri.ncvc.go.jp.
Takashi
T
Nojiri
Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita-City, Osaka, Japan.
Hiroshi
H
Hosoda
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan.
Masahiro
M
Zenitani
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan.
Takeshi
T
Tokudome
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan.|Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Toru
T
Kimura
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan.
Koichi
K
Miura
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan.
Mikiya
M
Miyazato
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Meinoshin
M
Okumura
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan.
Kenji
K
Kangawa
D000380:Agranulocytosis / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage* / Q000494:pharmacology; D002945:Cisplatin / Q000633:toxicity*; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D055014:Granulocyte-Macrophage Progenitor Cells / Q000378:metabolism; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor; D009320:Atrial Natriuretic Factor; D002945:Cisplatin
Atrial natriuretic peptide; Cisplatin; G-CSF; Granulocytopenia