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- Title
Ambrisentan improves the outcome of rats with liver transplantation partially through reducing nephrotoxicity.
- Authors
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.
- Abstract
OBJECTIVE: Tacrolimus is a potent immunosuppressive agent mainly used for al logeneic sol id 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 ET1 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-γ 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.
- Subjects
TACROLIMUS; ENDOTHELINS; HOMOGRAFTS; AMINOTRANSFERASES; LIVER transplantation
- Publication
European Review for Medical & Pharmacological Sciences, 2014, Vol 18, Issue 17, p2575
- ISSN
1128-3602
- Publication type
Article