title: Ambrisentan improves the outcome of rats with liver transplantation partially through reducing nephrotoxicity.
abstract: 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.
  
  
  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-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.
authors.affiliation: Department of Surgery, Organ Transplant Center, Shanghai Changzheng Hospital, Shanghai Second Military Medical University, Shanghai, China. wenyguo@yeah.net.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Zou
authors.forename: S-H
authors.initials: SH
authors.lastname: Song
authors.forename: Z-X
authors.initials: ZX
authors.lastname: Wang
authors.forename: G-S
authors.initials: GS
authors.lastname: Ding
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Ni
authors.forename: H
authors.initials: H
authors.lastname: Fu
authors.forename: X-M
authors.initials: XM
authors.lastname: Shi
authors.forename: X-G
authors.initials: XG
authors.lastname: Gao
authors.forename: Q-C
authors.initials: QC
authors.lastname: Han
authors.forename: W-Y
authors.initials: WY
authors.lastname: Guo
authors.forename: Z-R
authors.initials: ZR
authors.lastname: Fu
mesh_terms: D000818:Animals; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016559:Tacrolimus / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010666:Phenylpropionates; D011724:Pyridazines; C467894:ambrisentan; D016559:Tacrolimus