PANCREAS AND BILIARY TRACT

Ursodeoxycholic acid improves muscle contractility and inflammation in symptomatic gallbladders with cholesterol gallstones

Michele Pier Luca Guarino¹, Ping Cong², Michele Cicala¹, Rossana Alloni¹, Simone Carotti¹, Jose Behar²

¹ Department of Digestive Disease, Campus Bio Medico University of Rome, Rome, Italy
² Rhode Island Hospital and Brown University Medical School, Providence, Rhode Island, USA

Correspondence to:
Dr M P Luca Guarino
Dipartimento di Malattie dell’Apparato Digerente, Università Campus Bio-Medico, Via Longoni, 83 - 00155 Rome, Italy;m.guarino{at}unicampus.it

Objective: To examine the mechanisms of action of ursodeoxycholic acid (UDCA) on gallbladder (GB) muscle cells in patients with symptomatic cholesterol gallstones (GSs) as it reduces the incidence of acute cholecystitis.

Design and patients: A double-blind study was performed on 15 patients, 7 randomised to UDCA and 8 to placebo, treated for 4 weeks before cholecystectomy. Muscle contraction induced by cholecystokinin (CCK)-8, acetylcholine (ACh) and potassium chloride (KCl) was determined in enzymatically isolated GB muscle cells, and cholesterol levels were determined in plasma membranes. H₂O₂, lipid peroxidation, platelet-activating factor (PAF)-like lipids, prostaglandin E₂ (PGE₂) and catalase activity were determined as biochemical markers of oxidative stress and inflammation in muscle cells.

Results: UDCA significantly increased GB muscle cell contraction induced by all concentrations of CCK-8, ACh and KCl, and reduced the plasma membrane cholesterol (mean (SD) 0.32 (0.16) vs 0.72 (0.5) µmol/mg of protein) compared with placebo. In GB muscle cells, UDCA treatment significantly decreased the levels of H₂O₂ (4.4 (1.9) vs 13.7 (5.3) µmol/mg of protein), lipid peroxidation (malondialdehyde levels 1.3 (0.4) vs 2.52 (0.7) nmol/100 mg of protein), PAF-like lipids (8.9 (4.9) vs 29.6 (7.1) pg/mg of protein) as well as the production of PGE₂ (142 (47) vs 365 (125) pg/mg of protein) and catalase activity (14.5 (9.4) vs 35.8 (12.7) units/mg of protein) when compared with placebo.

Conclusion: These studies suggest that UDCA treatment improves GB muscle contractility by decreasing the cholesterol content in the plasma membrane of muscle cells, and the biochemical parameters of oxidative stress, thus explaining its possible therapeutic mechanisms in patients with symptoms of cholesterol GSs.

Abbreviations: AC, acute cholecystitis; ACh, acetylcholine; BDL, bile duct ligation; CCK, cholecystokinin; EIA, enzyme immunoassay; GB, gallbladder; GS, gallstone; KCl, potassium chloride; PAF, platelet-activating factor; PGE₂, prostaglandin E₂; ROS, reactive oxygen species; SPA, scintillation proximity assay; TCDC, taurochenodeoxycholic acid; UDCA, ursodeoxycholic acid

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