Ursodeoxycholic acid
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Ursodeoxycholic acid is a bile acid used for the treatment of primary biliary cirrhosis (PBC).
Ursodeoxycholic acid is a bile acid used for the treatment of primary biliary cirrhosis (PBC).
Endogenous hydrophobic bile acids such as deoxycholic acid and chenodeoxycholic acid can exert hepatotoxic effects. Ursodeoxycholic acid is a hydrophilic bile acid that mediates its biological effects via several mechanisms. Ursodeoxycholic acid (UDCA) protects hepatocytes and cholangiocytes from bile acid-induced damage, such as reactive oxygen species (ROS)-induced inflammation and mitochondrial dysfunction. UDCA was shown to reserve hepatocyte cell structures and stimulate anti-apoptotic pathways. It was also shown to prevent the production of ROS by Kupffer cells and resident macrophages in the liver, thus attenuating oxidative stress in the liver. UDCA can also change the hydrophobicity index of the bile acid pool: following oral administration, UDCA forms a major fraction of the human bile acid pool and competitively displaces the hydrophobic or more toxic bile acids. It increases the absorption of hydrophilic bile acids. There are several proposed mechanisms of choleretic actions of UDCA: UDCA increases intracellular calcium levels, stimulating transport proteins and vesicular exocytosis in cholestatic hepatocytes. UDCA may also upregulate the expression of membrane transport proteins like the chloride-bicarbonate anion exchanger (AE2), which is involved in biliary secretion and is often observed to be defective in primary biliary cholangitis. In rats, UDCA reduced hepatic expression of major histocompatibility complex (MHC) class I antigens, suggesting immunomodulating effects. UDCA acts as a partial agonist at the bile acid receptor, also known as the farnesoid X receptor (FXR), and has negligible effects on cholesterol and lipid synthesis.
Ursodeoxycholic acid is indicated for the treatment of patients with primary biliary cholangitis. It is used for the short-term treatment of radiolucent, noncalcified gallbladder stones in patients selected for elective cholecystectomy. It is also used to prevent gallstone formation in obese patients experiencing rapid weight loss.
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