Intruduction of ursodeoxycholic Acid
Ursodeoxycholic Acid is more acclimated for the analysis of cholestatic alarmist diseases. Experimental affirmation suggests three above mechanisms of action: (1) aegis of cholangiocytes adjoin cytotoxicity of berserk acerbity acids, consistent from accentuation of the agreement of alloyed phospholipid-rich micelles, abridgement of acerbity acerbic cytotoxicity of acerbity and, possibly, abatement of the absorption of berserk acerbity acids in the cholangiocytes; (2) dispatch of hepatobiliary secretion, putatively via Ca(2+)- and protein kinase C-alpha-dependent mechanisms and/or activation of p38(MAPK) and extracellular signal-regulated kinases (Erk) consistent in admittance of agent molecules (e.g., acerbity alkali consign pump, BSEP, and conjugate consign pump, MRP2) into the canalicular film of the hepatocyte and, possibly, activation of amid carriers; (3) aegis of hepatocytes adjoin acerbity acid-induced apoptosis, involving inhibition of mitochondrial film permeability alteration (MMPT), and possibly, dispatch of a adaptation pathway.
In primary biliary cirrhosis, Ursodeoxycholic Acid (13-15 mg/kg/d) improves serum alarmist chemistries, may adjournment ache progression to astringent fibrosis or cirrhosis, and may prolong transplant-free survival. In primary sclerosing cholangitis, UDCA (13-20 mg/kg/d) improves serum alarmist chemistries and agent markers of prognosis, but furnishings on ache progression accept to be added evaluated. Anticholestatic furnishings of UDCA accept aswell been appear in intrahepatic cholestasis of pregnancy, alarmist ache of cystic fibrosis, accelerating familial intrahepatic cholestasis, and abiding graft-versus-host disease. Future efforts will focus on analogue of added analytic uses of UDCA, on optimized dosage regimens, as able-bodied as on added comment of mechanisms of activity of UDCA at the atomic level.