title: Protective effects of C-type natriuretic peptide on cisplatin-induced nephrotoxicity in mice.
abstract: OBJECTIVE
  Cisplatin is a highly effective chemotherapeutic agent used to treat various malignancies, but its utility is compromised by its nephrotoxicity. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, exhibits anti-inflammatory effects by activating its specific receptor, guanylyl cyclase (GC)-B. CNP and GC-B receptor are known to be expressed in both the vascular endothelium and the kidney. The objective of this study was to investigate the renoprotective effects of CNP in a mouse model of cisplatin-induced nephrotoxicity.
  
  
  METHODS
  C57BL/6 mice were divided into three groups: normal control mice; cisplatin (20 mg/kg, intraperitoneal) mice treated with vehicle; and cisplatin mice treated with CNP (2.5 µg/kg/min, subcutaneous). At 72 h after cisplatin injection, urine, blood and kidney samples were collected. Urine and blood samples were examined biochemically. Histological findings and gene expression in kidney tissue were evaluated.
  
  
  RESULTS
  CNP reduced histological renal tubular damage and apoptosis induced by cisplatin and suppressed plasma blood urea nitrogen and creatinine levels, which were elevated by cisplatin administration. CNP treatment decreased the expression of kidney injury molecule-1 and monocyte chemoattractant protein-1, which were elevated in the kidney by cisplatin administration. CNP treatment attenuated the decrease in GC-B expression in cisplatin-induced kidney injury.
  
  
  CONCLUSIONS
  The present study is the first to show that CNP inhibits nephrotoxicity and kidney cell damage induced by cisplatin. The mechanism of action may involve down-regulation of inflammatory cytokine expression in cisplatin-induced kidney injury and attenuation of apoptosis in renal tubular cells.
authors: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan, kimura@thoracic.med.osaka-u.ac.jp.
authors: Toru
authors: T
authors: Kimura
authors: Takashi
authors: T
authors: Nojiri
authors: Hiroshi
authors: H
authors: Hosoda
authors: Shin
authors: S
authors: Ishikane
authors: Yasushi
authors: Y
authors: Shintani
authors: Masayoshi
authors: M
authors: Inoue
authors: Mikiya
authors: M
authors: Miyazato
authors: Meinoshin
authors: M
authors: Okumura
authors: Kenji
authors: K
authors: Kangawa
mesh_terms: D000419:Albuminuria / Q000652:urine; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D020098:Natriuretic Peptide, C-Type; D003404:Creatinine; D002945:Cisplatin