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


METHODS
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. H(2)O(2), lipid peroxidation, platelet-activating factor (PAF)-like lipids, prostaglandin E(2) (PGE(2)) 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) micromol/mg of protein) compared with placebo. In GB muscle cells, UDCA treatment significantly decreased the levels of H(2)O(2) (4.4 (1.9) vs 13.7 (5.3) micromol/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 PGE(2) (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.


CONCLUSIONS
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.
Guarino
Michele Pier Luca
MP
Department of Digestive Disease, Campus Bio Medico University of Rome, Rome, Italy. m.guarino@unicampus.it
Cong
Ping
P
Cicala
Michele
M
Alloni
Rossana
R
Carotti
Simone
S
Behar
Jose
J
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D041881:Cholecystitis, Acute / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology; D002784:Cholesterol / Q000032:analysis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D042882:Gallstones / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D010446:Peptide Fragments; C410885:cholecystokinin 8; D011189:Potassium Chloride; D014580:Ursodeoxycholic Acid; D002766:Cholecystokinin; D002784:Cholesterol; D000109:Acetylcholine