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Titolo:
The therapeutic effects of ursodeoxycholic acid as an anti-apoptotic agent
Autore:
Rodrigues, CMP; Steer, CJ;
Indirizzi:
Univ Lisbon, Fac Farm, Ctr Patogenese Mol, P-1600083 Lisbon, Portugal UnivLisbon Lisbon Portugal P-1600083 se Mol, P-1600083 Lisbon, Portugal Univ Minnesota, Sch Med, Dept Med & Genet, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 Genet, Minneapolis, MN 55455 USA Univ Minnesota, Sch Med, Dept Cell Biol, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 l Biol, Minneapolis, MN 55455 USA Univ Minnesota, Sch Med, Dept Dev, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 pt Dev, Minneapolis, MN 55455 USA
Titolo Testata:
EXPERT OPINION ON INVESTIGATIONAL DRUGS
fascicolo: 7, volume: 10, anno: 2001,
pagine: 1243 - 1253
SICI:
1354-3784(200107)10:7<1243:TTEOUA>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
PRIMARY BILIARY-CIRRHOSIS; PRIMARY SCLEROSING CHOLANGITIS; ISOLATED RAT HEPATOCYTES; CYTOCHROME-C RELEASE; MITOCHONDRIAL PERMEABILITY TRANSITION; ELECTRON-TRANSPORT CHAIN; PLACEBO-CONTROLLED TRIAL; BILE-DUCT LIGATION; TAUROURSODEOXYCHOLIC ACID; 3-NITROPROPIONIC ACID;
Keywords:
bile acids; cholestasis; hepatoprotection; mitochondrial pathway of apoptosis; neuroprotection;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
99
Recensione:
Indirizzi per estratti:
Indirizzo: Rodrigues, CMP Univ Lisbon, Fac Farm, Ctr Patogenese Mol, Av Forcas Armadas, P-1600083 Lisbon, Portugal Univ Lisbon Av Forcas Armadas Lisbon Portugal P-1600083 al
Citazione:
C.M.P. Rodrigues e C.J. Steer, "The therapeutic effects of ursodeoxycholic acid as an anti-apoptotic agent", EXPERT OP I, 10(7), 2001, pp. 1243-1253

Abstract

The dihydroxy bile acid, ursodeoxycholic acid (UDCA), has been in widespread clinical use in the Western world since the mid 1980s, when it was initially used for gallstone dissolution ([1,2]) and subsequently for the treatment of chronic cholestatic liver diseases ([3,4]). Many clinical trials of UDCA in a variety of cholestatic disorders established biochemical and clinical improvements, and most importantly showed a significant prolongation of transplant-free survival after four years of treatment with UDCA in patients with primary biliary cirrhosis ([5]). Despite its clinical efficacy, the precise mechanism(s) by which UDCA improves liver function during cholestasis is still a matter of debate ([6]). It was initially considered that the choleretic effect of UDCA, coupled with its ability to cause a marked shift in the composition of the bile acid pool towards hydrophilicity, accounted for its mechanism of action. In recent years, however, it has become evident that UDCA and its conjugated derivatives are capable of exerting direct effects at the cellular, subcellular, and molecular levels by stabilisingcell membranes, affecting signal transduction pathways, and regulating immune responses. In addition, we have shown that UDCA plays a unique role in modulating the apoptotic threshold in both hepatic and non-hepatic cells ([7-10]). The purpose of this article is to examine the mechanism(s) by whichUDCA prevents apoptotic cell death associated with cholestasis. In addition, we will also review a potentially novel and, heretofore, unrecognised role of UDCA as a therapeutic agent in the treatment of non-liver diseases associated with increased levels of apoptosis as a pathogenesis of the disorder.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 04:07:45