title: Hydrophilic but not hydrophobic bile acids prevent gallbladder muscle dysfunction in acute cholecystitis.
abstract: The pathogenesis of acute cholecystitis (AC) is controversial. Bile acids may be involved in the pathogenesis of AC because the hydrophobic chenodeoxycholic acid (CDCA) reproduced in vitro the muscle dysfunction observed in AC and was prevented by the hydrophilic ursodeoxycholic acid (UDCA). The present study examined the in vivo effects of UDCA or CDCA on gallbladder muscle dysfunction caused by AC. Guinea pigs were treated with placebo, UDCA, or CDCA for 2 weeks before sham operation or induction of AC by bile duct ligation (BDL) for 3 days. Pretreatment with oral UDCA prevented the defective contraction in response to agonists (acetylcholine [ACh], cholecystokinin 8 [CCK-8], and KCl) that occurs after BDL. Prostaglandin (PG) E(2)-induced contraction remained normal in the placebo and UDCA-treated groups but was impaired in the CDCA-treated group. Treatment with UDCA also prevented the expected increase in the levels of H(2)O(2), lipid peroxidation, and PGE(2) content in the placebo-treated AC group, whereas CDCA caused further increases in these oxidative stress markers. The binding capacity of PGE(2) to its receptors and the activity of catalase were reduced after treatment with CDCA. Treatment with UDCA enriched gallbladder bile acids with its conjugates and reduced the percentage of CDCA conjugates. In contrast, treatment with CDCA significantly decreased the percentage of UDCA in bile. In conclusion, oral treatment with UDCA prevents gallbladder muscle damage caused by BDL, whereas oral treatment with CDCA worsens the defective muscle contractility and the oxidative stress.
authors.affiliation: Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, RI, USA.
authors.forename: Zuo-Liang
authors.initials: ZL
authors.lastname: Xiao
authors.forename: Piero
authors.initials: P
authors.lastname: Biancani
authors.forename: Martin C
authors.initials: MC
authors.lastname: Carey
authors.forename: Jose
authors.initials: J
authors.lastname: Behar
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D001652:Bile Ducts; D015415:Biomarkers / Q000032:analysis; D002374:Catalase / Q000037:antagonists & inhibitors; D002635:Chenodeoxycholic Acid / Q000378:metabolism / Q000494:pharmacology*; D002764:Cholecystitis / Q000209:etiology / Q000503:physiopathology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D005704:Gallbladder / Q000187:drug effects / Q000503:physiopathology*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors; D008026:Ligation; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology; D014580:Ursodeoxycholic Acid / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D008054:Lipid Peroxides; D018078:Receptors, Prostaglandin E; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D015232:Dinoprostone; D012844:Sincalide; D000109:Acetylcholine