Compositions and methods for hepatoprotection and treatment of cholestasis
Methods for the treatment of cholestatic liver disease and reduction and prevention of hepatic injury resulting from cholestasis via administration of a FXR ligand are provided.
1. A method of treating cholestasis in a mammalian subject comprising administering to said subject a therapeutically effective amount of an FXR agonist having Formula (II)
wherein X 1 is CH or N; X 2 is O or NH; R and R 1 are independently H, lower alkyl, halogen, or CF 3 ; R 2 is lower alkyl; R 3 and R 4 are independently H, lower alkyl, halogen, CF 3 , OH, O-alkyl, or O-polyhaloalkyl.
2. The method of claim 1 wherein the FXR agonist comprises a compound of Formula (I):
3. A method for treating cholestasis-induced liver damage in a mammalian subject comprising administering to the subject a therapeutically effective amount of a Famesoid X Receptor (FXR) agonist having Formula (II)
wherein X 1 is CH or N; X 2 is O or NH; R and R 1 are independently H, lower alkyl, halogen, or CF 3 ; R 2 is lower alkyl; R 3 and R 4 are independently H, lower alkyl, halogen, CF 3 , OH; O-alkyl, or O-polyhaloalkyl.
4. The method of claim 3 wherein the FXR agonist comprises a compound of Formula (I):
5. A method according to claim 3 where said treatment results in a decrease in a serum marker of liver disease selected from the group consisting of alanine aminotransferase (ALT), asparate aminotransferase (AST), γ-glutamyl transferase (GGT), total serum bilirubin, and serum bile acids.