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. Conclusion: 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.