Ursodeoxycholic acid for primary sclerosing cholangitis

Chazouillères, Olivier; Poupon, Raoul; Capron, Jean‐Pierre; Metman, Étienne-Henry; Dhumeaux, Daniel; Amouretti, M; Couzigou, Patrice; Labayle, D; Trinchet, Jean–Claude

doi:10.1016/0168-8278(90)90281-u

Cited by 156 publications

(54 citation statements)

References 10 publications

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“…In contrast, hydrophilic bile acids such as ursodeoxycholic acid (UDCA) 1 and its taurine and glycine conjugates appear to protect against cholestasis and the toxicity induced by the hydrophobic bile acids (2,6). Although the mechanism of action is not entirely understood, the oral administration of UDCA markedly improves clinical and biochemical indices in a variety of chronic liver diseases (7)(8)(9). This protective effect appears to result from mechanisms beyond simply displacing toxic bile acids from the liver.…”

Section: Introductionmentioning

confidence: 99%

A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation.

Rodrigues¹,

Gao²,

Ma³

et al. 1998

J. Clin. Invest.

494

383

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The hydrophilic bile salt ursodeoxycholic acid (UDCA) protects against the membrane-damaging effects associated with hydrophobic bile acids. This study was undertaken to (a) determine if UDCA inhibits apoptosis from deoxycholic acid (DCA), as well as from ethanol, TGF-␤1, Fas ligand, and okadaic acid; and to (b) determine whether mitochondrial membrane perturbation is modulated by UDCA. DCA induced significant hepatocyte apoptosis in vivo and in isolated hepatocytes determined by terminal transferase-mediated dUTP-digoxigenin nick end-labeling assay and nuclear staining, respectively (P Ͻ 0.001). Apoptosis in isolated rat hepatocytes increased 12-fold after incubation with 0.5% ethanol (P Ͻ 0.001). HuH-7 cells exhibited increased apoptosis with 1 nM TGF-␤1 (P Ͻ 0.001) or DCA at Ն 100 M (P Ͻ 0.001), as did Hep G2 cells after incubation with anti-Fas antibody (P Ͻ 0.001). Finally, incubation with okadaic acid induced significant apoptosis in HuH-7, Saos-2, Cos-7, and HeLa cells. Coadministration of UDCA with each of the apoptosis-inducing agents was associated with a 50-100% inhibition of apoptotic changes (P Ͻ 0.001) in all the cell types. Also, UDCA reduced the mitochondrial membrane permeability transition (MPT) in isolated mitochondria associated with both DCA and phenylarsine oxide by Ͼ 40 and 50%, respectively (P Ͻ 0.001). FACS ® analysis revealed that the apoptosis-inducing agents decreased the mitochondrial transmembrane potential and increased reactive oxygen species production (P Ͻ 0.05). Coadministration of UDCA was associated with significant prevention of mitochondrial membrane alterations in all cell types. The results suggest that UDCA plays a central role in modulating the apoptotic threshold in both hepatocytes and nonliver cells, and inhibition of MPT is at least one pathway by which UDCA protects against apoptosis.

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Section: Introductionmentioning

confidence: 99%

A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation.

Rodrigues¹,

Gao²,

Ma³

et al. 1998

J. Clin. Invest.

494

383

View full text Add to dashboard Cite

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“…Ursodexoycholic acid (UDCA) is the single most extensively studied agent in PSC. Several controlled and uncontrolled clinical trials have shown significant improvement in liver biochemistries when PSC patients were treated with UDCA (10)(11)(12)(13)(14)(15). However, large randomized and controlled prospective clinical trials have failed to demonstrate that UDCA can positively affect the clinical outcomes of patients with PSC (13,15).…”

Section: Introductionmentioning

confidence: 99%

Current research on the treatment of primary sclerosing cholangitis

Ali

Carey

Lindor

2015

IRDR

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“…Although these criteria need prospective validation, they may be useful for prognostic purposes. However, it is important to emphasize that late responses can occur (even after two years of therapy) and that the suspension of UDCA may lead to significant clinical and laboratory worsening (79,87) . Thus there is no evidence that UDCA should be stopped in the absence of significant biochemical response, except in cases of suspected UDCA-related disease progression.…”

Section: Pharmacological Treatment Of Pscmentioning

confidence: 99%

“…However, ursodeoxycholic acid (UDCA), an epimer of chenodeoxycholic acid, has been widely used for the management of patients with for more than 30 years (79) . Potential mechanisms of action of UDCA in cholestatic liver diseases involve: 1) increased hydrophilicity of the circulating bile acid (BA) pool; 2) stimulation of hepatobiliary secretion of BA, organic and inorganic anions and adenosine triphosphate (ATP); 3) reduction of BA-induced and cytokine-induced cytotoxicity against hepatocytes and colangiocytes; and 4) immunomodulatory and antiinflammatory effects (80) .…”

Section: Pharmacological Treatment Of Pscmentioning

confidence: 99%

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

Bittencourt

Cançado

Couto

et al. 2015

Arq. Gastroenterol.

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-In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.

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Ursodeoxycholic acid for primary sclerosing cholangitis

Cited by 156 publications

References 10 publications

A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation.

A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation.

Current research on the treatment of primary sclerosing cholangitis

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

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