L-Carnitine Ameliorates the Decrease of Aquaporin 2 Levels in Rats with Cisplatin-Induced Kidney Injury.
BACKGROUND
It has been found that L-carnitine ameliorated cisplatin-induced acute kidney injury (AKI) in rats. However, the detailed role of L-carnitine in improving the renal urinary concentration function in cisplatin-induced AKI is not fully understood.


METHODS
In this study, 30 Sprague-Dawley rats were divided randomly into 5 groups: control, cisplatin (CIS), L-carnitine (CAR), L-carnitine plus cisplatin (CAR + CIS), and cisplatin plus L-carnitine (CIS + CAR) groups. Cisplatin (7 mg/kg) and L-carnitine (300 mg/kg) were injected intraperitoneally. Urine (24 h) and blood samples were collected to analyze renal urinary concentrating function. Immunoblotting, confocal laser microscopy, and enzyme-linked immunosorbent assays were used to assess the level and localization of the water channel aquaporin (AQP) 2, and levels of stimulatory G protein α subunit (GSα protein), arginine vasopressin (AVP) receptor 2, adenylyl cyclase and serum AVP.


RESULTS
Renal urinary concentrating function was improved by L-carnitine in rats with cisplatin-induced AKI. AQP2 expression, which decreased after cisplatin treatment, was improved by L-carnitine in different regions of the kidney. Moreover, our data indicated that L-carnitine could increase AQP2 accumulation at the apical plasma membranes of the renal-collecting ducts. Finally, intervention with L-carnitine effectively improved the expression of AQP2 upstream signaling proteins, such as GSα protein, adenylyl cyclase, and serum AVP levels in rats with cisplatin-induced AKI.


CONCLUSIONS
L-carnitine resolves the cisplatin-induced urinary concentration defect, which may occur by increasing AVP/cyclic adenosine monophosphate/AQP2 levels, indicating the potential use of L-carnitine to ameliorate the renal urinary concentration effect in cancer patients treated with cisplatin.
Department of Nephrology, The 306th Hospital of Chinese PLA, Beijing, China.
Jianjun
J
Gao
Zhaoyan
Z
Gu
Min
M
Li
Yongxing
Y
Xu
Yuehua
Y
Gao
Jiamei
J
Wei
Boran
B
Liang
Yu
Y
Na
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000097:blood; D002331:Carnitine / Q000627:therapeutic use*; D002945:Cisplatin / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000097:blood
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D003404:Creatinine; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6; D002945:Cisplatin; D002331:Carnitine