Disease relevance of URSODEOXYCHOLIC ACID

• RESULTS: The incidence of cirrhosis after 5 years of UDCA treatment was 4%, 12%, and 59% among patients followed-up from stages I, II, and III, respectively [1].
• BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) slows the progression of primary biliary cirrhosis (PBC) [1].
• BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) improves liver function in patients with chronic cholestatic liver diseases by an unknown mechanism [2].
• The therapeutic effects of UDCA may be caused in part by stimulation of canalicular transporter expression in the absence of hepatocellular toxicity [3].
• Therefore, UDCA and its taurine conjugate tauroursodeoxycholic acid (TUDCA) were administered in vivo to rats simultaneously subjected to bile duct ligation and vagotomy, a model that induces cholestasis and loss of bile ducts by apoptosis of cholangiocytes [4].

High impact information on URSODEOXYCHOLIC ACID

• CONCLUSIONS: This study provides new data about the time course of PBC under UDCA and constitutes a rationale for the design and evaluation of clinical trials aimed to assess the efficacy of drugs associated with UDCA [1].
• Neither UDCA nor CA affected Mdr2 expression [3].
• Previous work suggested that UDCA stimulates biliary exocytosis via Ca(++)- and protein kinase C (PKC)-dependent mechanisms [5].
• The administration of UDCA or TUDCA prevented the induction of apoptosis and the loss of proliferative and functional responses observed in the bile duct ligation-vagotomized rats [4].
• UDCA and TUDCA enhanced intracellular Ca2+ and IP3 levels, together with increased phosphorylation of protein kinase C-alpha [4].

Anatomical context of URSODEOXYCHOLIC ACID

• However, many studies have subsequently confirmed that UDCA improves liver function by three major mechanisms of action, including protection of cholangiocytes against the cytotoxicity of hydrophobic bile acids, stimulation of hepatobiliary secretion, and inhibition of liver cell apoptosis [6].

Associations of URSODEOXYCHOLIC ACID with other chemical compounds

• Here, we review the anti-apoptotic mechanisms of UDCA in hepatic cells, and discuss a potential involvement of nuclear steroid receptors in mediating the survival effects of UDCA [6].
• This study was undertaken (a) to characterize further the mechanism by which 3-NP induces apoptosis in rat neuronal RN33B cells and (b) to determine if and how the taurine-conjugated UDCA, tauroursodeoxycholic acid (TUDCA), inhibits apoptosis induced by 3-NP [7].
• Moreover, TUDCA, as well as UDCA and its glycine-conjugated form, glycoursodeoxycholic acid, prevented mitochondrial release of cytochrome c (p < 0.001), which probably accounts for the observed inhibition of DEVD-specific caspase activity and poly(ADP-ribose) polymerase cleavage [7].
• Lithocholic acid and its precursor CDCA are toxic when fed to the rabbit, rhesus monkey, and baboon, but not when CDCA, as well as UDCA, is used for therapeutic purposes in man [8].
• The results showed that UDCA had no effect on the tryptophan fluorescence of Bax [9].

Gene context of URSODEOXYCHOLIC ACID

• UDCA acts as a potent inhibitor of the classical mitochondrial pathway of apoptosis, but also interferes with alternate and upstream molecular targets such as the E2F-1/p53 pathway [6].
• After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF-alpha levels and progression risk score compared to placebo-treated patients [10].
• TNF-alpha and TGF-beta levels were significantly reduced compared to baseline levels in the UDCA-treated group after 2 years, while there was no significant change in the levels of placebo-treated patients [10].
• METHODS: A Markov model was used to describe the progression toward cirrhosis in 183 UDCA-treated patients with PBC [1].
• In this study, the preventive effect of UDCA on HCC was examined in patients with early-stage HCV-LC [11].

Analytical, diagnostic and therapeutic context of URSODEOXYCHOLIC ACID

• RESULTS: Twenty-eight patients originally assigned to UDCA and 42 patients originally assigned to placebo have died or undergone transplantation [12].

References