Bacterial conversion of UDCA to chenodeoxycholic acid may be the mechanism for this side effect. Right upper quadrant abdominal pain and exacerbation of pruritus was occasionally reported in trials in patients with PBC. Additional symptoms may include bloating, weight gain, and occasionally, thinning of hair. Mechanisms of action
Choleretic effects
Primary bile acids are produced by the liver and stored in the gall bladder. When secreted into the intestine, primary bile acids can be metabolized into secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest fats. Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which the intestine absorbs cholesterol molecules while breaking up micelles containing cholesterol. The drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery. There are multiple mechanisms involved in cholestatic liver diseases. Immunomodulating effects
Ursodeoxycholic acid has also been shown experimentally to suppress immune response such as immune cell phagocytosis. Prolonged exposure and/or increased quantities of systemic (throughout the body, not just in the digestive system) ursodeoxycholic acid can be toxic. Anti-inflammatory effects
Ursodeoxycholic acid has been shown to exert anti-inflammatory and protective effects in human epithelial cells of the gastrointestinal tract. It has been linked to regulation of immunoregulatory responses by regulation of cytokines, antimicrobial peptides defensins, and take an active part in increased restitution of wound in the colon. Moreover, UDCAs effects has been shown to have exert actions outside the epithelial cells.While some bile acids are known to be colon tumor promoters (e.g.
deoxycholic acid), others such as ursodeoxycholic acid are thought to be chemopreventive, perhaps by inducing cellular differentiation and/or cellular senescence in colon epithelial cells. Chemistry
Ursodeoxycholic acid is an epimer of chenodeoxycholic acid, which has similar choleretic effects and a wider species distribution. However, CDCA is not as well-tolerated in humans and it does not show immunomodulating or chemoprotective effects. Both are 7-hydroxyl derivatives of deoxycholic acid, but UDCA has the group in the beta instead of the alpha orientation. Biosynthesis
Among mammals, only bears (Ursidae; excluding giant pandas) produce UDCA at useful amounts (>30%). It is produced in the bear liver, but the pathway remains unknown.Other vertebrates produce UDCA in much smaller amounts by gut bacteria. CDCA is oxidized into 7-oxo-CDCA then reduced into UDCA. Industrial production
UDCA is most commonly produced from cholic acid (CA) derived from bovine bile, a by-product of the beef industry. The current yield of this semisynthesis is about 30%. Society and culture
Names
The term is from the Latin noun ursus meaning bear, as bear bile contains the substance.Ursodeoxycholic acid can be chemically synthesized and is marketed under multiple trade names, including Ursetor, Udikast, Actibile, Actigall, Biliver, Deursil, Egyurso, Udcasid, Udiliv, Udinorm, Udoxyl, Urso, Urso Forte, Ursocol, Ursoliv, Ursofalk, Ursosan, Ursoserinox, Udimarin, Ursonova, and Stener. History
Bear bile, a natural source of UDCA, is used in traditional Chinese medicine since the seventh century. Japanese scientists successfully synthesized UDCA chemically in 1955.