A Novel Role for Ursodeoxycholic Acid in Inhibiting Apoptosis by Modulating Mitochondrial Membrane Perturbation

The hydrophilic bile salt ursodeoxycholic acid (UDCA) pro-tects against the membrane-damaging effects associated with hydrophobic bile acids. This study was undertaken to (a) determine if UDCA inhibits apoptosis from deoxycholic acid (DCA), as well as from ethanol, TGF-b1, Fas ligand, and okadaic acid; and to (b) determine whether mitochon-drial membrane perturbation is modulated by UDCA. DCA induced significant hepatocyte apoptosis in vivo and in iso-lated hepatocytes determined by terminal transferase-medi-ated dUTP-digoxigenin nick end–labeling assay and nu-clear staining, respectively (P, 0.001). Apoptosis in isolated rat hepatocytes increased 12-fold after incubation with 0.5 % ethanol (P, 0.001). HuH-7 cells exhibited in-creased apoptosis with 1 nM TGF-b1 (P, 0.001) or DCA a