Protective effects of C-type natriuretic peptide on cisplatin-induced nephrotoxicity in Mice

Purpose 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..

Medienart:

E-Artikel

Erscheinungsjahr:

2015

Erschienen:

2015

Enthalten in:

Zur Gesamtaufnahme - volume:75

Enthalten in:

Cancer chemotherapy and pharmacology - 75(2015), 5 vom: 27. März, Seite 1057-1063

Sprache:

Englisch

Beteiligte Personen:

Kimura, Toru [VerfasserIn]
Nojiri, Takashi [VerfasserIn]
Hosoda, Hiroshi [VerfasserIn]
Ishikane, Shin [VerfasserIn]
Shintani, Yasushi [VerfasserIn]
Inoue, Masayoshi [VerfasserIn]
Miyazato, Mikiya [VerfasserIn]
Okumura, Meinoshin [VerfasserIn]
Kangawa, Kenji [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

Themen:

Anti-inflammatory
C-type natriuretic peptide
Cisplatin
Nephrotoxicity

RVK:

RVK Klassifikation

Anmerkungen:

© Springer-Verlag Berlin Heidelberg 2015

doi:

10.1007/s00280-015-2734-7

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2091756490

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