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

Michele Pier Luca Guarino ^1*, Ping Cong ², Michele Cicala ¹, Rossana Alloni ¹, Simone Carotti ¹ and Jose' Behar ³

¹ Campus Bio Medico University, Italy
² Rhode Island Hospital and Brown University Medical School, Providence, United States
³ Rhode Island Hospital, Providence, United States

^* To whom correspondence should be addressed. E-mail: m.guarino{at}unicampus.it.

Accepted 8 December 2006

Abstract

Objective: Aim of this study was to examine the mechanisms of action of Ursodeoxycholic acid (UDCA) on on gallbladder muscle cells in symptomatic cholesterol gallstones patients since it reduces the incidence of acute cholecystitis.

Design and Patients: A double blind study was performed on 15 patients, 7 randomized to UDCA and 8 to placebo, treated for 4 weeks prior to cholecystectomy. Muscle contraction induced by CCK-8, Ach and KCl was determined in enzymatically isolated gallbladder muscle cells and cholesterol levels were determined in plasma membranes. H2O2, lipid peroxidation, PAF-like lipids, PGE2 and catalase activity were determined as biochemical markers of oxidative stress and inflammation in muscle cells.

Results: UDCA significantly increased gallbladder muscle cell contraction induced by all concentrations of CCK-8, Ach and KCl and reduced the plasma membrane cholesterol (0.32±0.16 vs 0.72±0.5 µmol/mg of protein, mean±SD) compared to placebo. UDCA treatment significantly decreased the gallbladder muscle cell levels of H2O2 (4.4±1.9 vs 13.7±5.3 µmol/mg of protein), lipid per-oxidation (MDA levels: 1.3±0.4 vs 2.52±0.7 nmol/100mg 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 to placebo. In conclusion, these studies suggest that UDCA improves gallbladder muscle contractility by decreasing muscle cell cholesterol content in the plasma membranes and the biochemical parameters of oxidative stress explaining possible therapeutic mechanisms in symptomatic cholesterol gallstone patients.

Keywords: CCK, Gallbladder muscle cells, oxidative stress, plasma membranes

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