INVESTIGADORES
BASIGLIO Cecilia Lorena
artículos
Título:
Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications
Autor/es:
ROMA MG; TOLEDO FD; BOAGLIO AC; BASIGLIO CL; CROCENZI FA; SANCHEZ POZZI EJ
Revista:
CLINICAL SCIENCE (LONDON, ENGLAND : 1979)
Editorial:
PORTLAND PRESS LTD
Referencias:
Lugar: Londres; Año: 2011 vol. 121 p. 523 - 544
ISSN:
0143-5221
Resumen:
UDCA (ursodeoxycholic acid) is the therapeutic agent most widely used for the treatment
of cholestatic hepatopathies. Its use has expanded to other kinds of hepatic diseases, and
even to extrahepatic ones. Such versatility is the result of its multiple mechanisms of action.
UDCA stabilizes plasma membranes against cytolysis by tensioactive bile acids accumulated in
cholestasis. UDCA also halts apoptosis by preventing the formation of mitochondrial pores,
membrane recruitment of death receptors and endoplasmic-reticulum stress. In addition, UDCA
induces changes in the expression of metabolizing enzymes and transporters that reduce bile acid
cytotoxicity and improve renal excretion. Its capability to positively modulate ductular bile flow
helps to preserve the integrity of bile ducts. UDCA also prevents the endocytic internalization of
canalicular transporters, a common feature in cholestasis. Finally, UDCA has immunomodulatory
properties that limit the exacerbated immunological response occurring in autoimmune cholestatic
diseases by counteracting the overexpression of MHC antigens and perhaps by limiting the
production of cytokines by immunocompetent cells. Owing to this multi-functionality, it is difficult
to envisage a substitute for UDCA that combines as many hepatoprotective effects with such
efficacy. We predict a long-lasting use of UDCA as the therapeutic agent of choice in cholestasis.