Bile acids: regulation of apoptosis by ursodeoxycholic acid.
Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been related to membrane damage, but also to nondetergent effects, such as oxidative stress and apoptosis. Strikingly, hydrophilic ursodeoxycholic acid (UDCA), and its taurine-conjugated form (TUDCA), show profound cytoprotective properties. Indeed, these molecules have been described as potent inhibitors of classic pathways of apoptosis, although their precise mode of action remains to be clarified. UDCA, originally used for cholesterol gallstone dissolution, is currently considered the first choice therapy for several forms of cholestatic syndromes. However, the beneficial effects of both UDCA and TUDCA have been tested in other experimental pathological conditions with deregulated levels of apoptosis, including neurological disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Here, we review the role of bile acids in modulating the apoptosis process, emphasizing the anti-apoptotic effects of UDCA and TUDCA, as well as their potential use as novel and alternate therapeutic agents for the treatment of apoptosis-related diseases.
Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
Joana D
JD
Amaral
Ricardo J S
RJ
Viana
Rita M
RM
Ramalho
Clifford J
CJ
Steer
Cecília M P
CM
Rodrigues
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D014580:Ursodeoxycholic Acid / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid