Atrial natriuretic peptide protects against cisplatin-induced acute kidney injury.
OBJECTIVE
Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide variety of malignancies. Acute kidney injury (AKI) is the major toxicity associated with cisplatin and sometimes necessitates a reduction in dose or discontinuation of treatment. Atrial natriuretic peptide (ANP) is secreted by the heart and exerts a wide range of renoprotective effects, including anti-inflammatory activity. The objective of this study was to investigate the protective effects of ANP on cisplatin-induced AKI in mice.


METHODS
Mice were randomly divided into three groups: control, cisplatin (20 mg/kg, intraperitoneal)/vehicle treatment, and cisplatin/ANP (1.5 μg/kg/min via osmotic-pump, subcutaneous) treatment. At 72 h after cisplatin injection, serum blood urea nitrogen and creatinine, urine albumin/creatinine, and renal expression of mRNAs encoding tumor necrosis factor-α, interleukin (IL)-1β, IL-6, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and transforming growth factor (TGF)-β were measured using real-time polymerase chain reaction. Histological changes were also evaluated.


RESULTS
ANP treatment significantly attenuated cisplatin-induced increases in serum blood urea nitrogen and creatinine, urine albumin/creatinine, and renal expression of IL-1β, IL-6, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 mRNAs. Cisplatin-induced renal dysfunction and renal tubular necrosis were thus attenuated by ANP treatment.


CONCLUSIONS
Our results indicate that ANP exhibits a protective effect against cisplatin-induced AKI in mice. ANP may thus be of value in prophylactic strategies aimed at mitigating the adverse effects associated with chemotherapy agents, including cisplatin.
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.
Takashi
T
Nojiri
Hiroshi
H
Hosoda
Toru
T
Kimura
Koichi
K
Miura
Shin
S
Ishikane
Takeshi
T
Tokudome
Yasushi
Y
Shintani
Masayoshi
M
Inoue
Mikiya
M
Miyazato
Meinoshin
M
Okumura
Kenji
K
Kangawa
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004343:Drug Implants; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D009336:Necrosis; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004343:Drug Implants; C090509:Icam1 protein, mouse; D018836:Inflammation Mediators; D020011:Protective Agents; D018799:Intercellular Adhesion Molecule-1; D009320:Atrial Natriuretic Factor; D002945:Cisplatin