Protective effects of relaxin against cisplatin-induced nephrotoxicity in rats.
BACKGROUND
Cisplatin (CDDP)-induced acute kidney injury (AKI) involves pro-inflammatory responses, apoptosis of renal tubular epithelial cells and vascular damage. AKI increases the risk of chronic kidney disease. Relaxin (RLX) has anti-apoptotic and anti-fibrosis properties. The aim of this study was to investigate the effects of RLX on CDDP-induced nephrotoxicity.


METHODS
We investigated the mitigating effects of RLX based on the etiopathology of AKI induced by CDDP, and also the anti-fibrotic effect of RLX on renal fibrosis after AKI. In the short-term experiments, rats were divided into the control group, CDDP group, and CDDP+RLX group. In the latter group, RLX was infused for 5 or 14 days using an implanted osmotic minipump. CDDP was injected intraperitoneally (6 mg/kg) after RLX or saline infusion. At 5 and 14 days post-CDDP, the kidneys were removed for analysis. The effect of RLX on renal fibrosis after AKI was evaluated at 6 weeks post-CDDP.


RESULTS
In short-term experiments, CDDP transiently increased plasma creatinine and blood urea nitrogen with peaks at day 5, and RLX prevented such rises. Semiquantitative analysis of the histological lesions indicated marked structural damage and apoptotic cells in the CDDP group, with the lesions being reduced by RLX treatment. Overexpression of Bax, interleukin-6 and tumor necrosis factor-α observed in the kidneys of the CDDP group was reduced in the CDDP+RLX group. In the long-term experiments, RLX significantly reduced renal fibrosis compared with the CDDP group.


CONCLUSIONS
The results suggested that RLX provided protection against CDDP-induced AKI and subsequent fibrosis by reducing apoptosis and inflammation.
Department of Clinical Nutrition, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.
Takuya
T
Yoshida
Hiromichi
H
Kumagai
Tetsuya
T
Kohsaka
Naoki
N
Ikegaya
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis; D015918:Infusion Pumps, Implantable; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012065:Relaxin; D003404:Creatinine; D002945:Cisplatin