Ambrisentan improves the outcome of rats with liver transplantation partially through reducing nephrotoxicity

作者：Zhang, L.; Zou, Y.; Song, S. -H.; Wang, Z. -X.; Ding, G. -S.; Ma, J.; Ni, Z. -J.; Fu, H.; Shi, X. -M.; Gao, X. -G.; Han, Q. -C.; Guo, W. -Y.^*; Fu, Z. -R.

来源：European Review for Medical and Pharmacological Sciences, 2014, 18(17): 2575-2583.

• Tacrolimus
• Ambrisentan
• Liver transplantation
• Endotheline
• Nephrotoxicity

OBJECTIVE: Tacrolimus is a potent immunosuppressive agent mainly used for allogeneic solid organ transplantation. Although usage of tacrolimus led to a significant increase in short-term allograft survival, the long-term morbidity remains high. Endothelin-1 (ET-1) is reported to be associated with increased vascular resistance, CNI-induced nephrotoxicity and chronic rejection. MATERIALS AND METHODS: In the present study, we first detected the serum and renal ET-1 level of rats treated by tacrolimus and found strong positive correlations were existed between the ET-1 level and the tacrolimus dosage and treated time. Furthermore, we studied the protective effect of ambrisentan in liver transplantation rats when co-administrated with tacrolimus. Healthy inbred male Wistar and Sprague-Dawley (SD) rats were used in this study. The post-operative general condition, transplantation survival time, hepatic aminotransferase, serum IFN-gamma and level kidney injury biochemical index were recorded and compared to evaluate the immune response and outcomes in the recipient rats after liver transplantation. RESULTS: Our results indicate that ambrisentan prevents the changes of ET-1 content in rats of non-operative treatment group and reduced the nephrotoxicity in the rats with liver transplantation. Rats from ambrisentan co-administration group exhibited good postoperative condition and prolonged survival. CONCLUSIONS: Ambrisentan reverted some effects induced by tacrolimus in the kidney and indicated a positive potential for therapeutic benefit.

• 出版日期2014-9
• 单位中国人民解放军第二军医大学; 天津市中医药研究院附属医院