| Pathophysiological preconditions promoting mixed "black" pigment plus cholesterol gallstones in a DeltaF508 mouse model of cystic fibrosis. | |
| | |
MedLine Citation:
|
PMID: 20430874 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Gallstones are frequent in patients with cystic fibrosis (CF). These stones are generally "black" pigment (i.e., Ca bilirubinate) with an appreciable cholesterol admixture. The pathophysiology and molecular mechanisms for this "mixed" gallstone in CF are unknown. Here we investigate in a CF mouse model with no overt liver or gallbladder disease whether pathophysiological changes in the physical chemistry of gallbladder bile might predict the occurrence of "mixed" cholelithiasis. Employing a DeltaF508 mouse model with documented increased fecal bile acid loss and induced enterohepatic cycling of bilirubin (Am J Physiol Gastrointest Liver Physiol 294: G1411-G1420, 2008), we assessed gallbladder bile chemistry, morphology, and microscopy in CF and wild-type mice, with focus on the concentrations and compositions of the common biliary lipids, bilirubins, Ca(2+), and pH. Our results demonstrate that gallbladder bile of CF mice contains significantly higher levels of all bilirubin conjugates and unconjugated bilirubin with lower gallbladder bile pH values. Significant elevations in Ca bilirubinate ion products in bile of CF mice increase the likelihood of supersaturating bile and forming black pigment gallstones. The risk of potential pigment cholelithogenesis is coupled with higher cholesterol saturations and bile salt hydrophobicity indexes, consistent with a proclivity to cholesterol phase separation during pigment gallstone formation. This is an initial step toward unraveling the molecular basis of CF gallstone disease and constitutes a framework for investigating animal models of CF with more severe biliary disease, as well as the human disease. |
| | |
Authors:
|
Folke Freudenberg; Monika R Leonard; Shou-An Liu; Jonathan N Glickman; Martin C Carey |
Related Documents
:
|
1576744 - Activity of cholesterol in human gallbladder bile in relation to nucleation of choleste... 11446434 - Metabolism of chylomicron cholesterol is delayed by estrogen. an in vivo study in the rat. 22466924 - Early nutrition impact on the insulin-like growth factor axis and later health conseque... 20118264 - Flagellated but not hyperfimbriated salmonella enterica serovar typhimurium attaches to... 1390604 - Nutritional implications of l-arabinose in pigs. 2377394 - Development of the neonatal rat small intestinal barrier to nonspecific macromolecular ... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-29 |
Journal Detail:
|
Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 299 ISSN: 1522-1547 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2010 Jul |
Date Detail:
|
Created Date: 2010-06-16 Completed Date: 2010-07-12 Revised Date: 2012-05-02 |
Medline Journal Info:
|
Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: G205-14 Citation Subset: IM |
Affiliation:
|
Department of Medicine, Harvard Medical School and Harvard Digestive Diseases Center; Department of Medicine, Gastroenterology Division, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Bile / metabolism* Bilirubin / metabolism* Cholelithiasis / etiology*, genetics, metabolism, pathology, physiopathology Cholesterol / metabolism* Cystic Fibrosis / complications*, genetics, metabolism, pathology, physiopathology Disease Models, Animal Enterohepatic Circulation Feces / chemistry Female Gallbladder / metabolism, pathology, physiopathology* Gallstones / etiology*, genetics, metabolism, pathology, physiopathology Hydrogen-Ion Concentration Hydrophobic and Hydrophilic Interactions Male Mice Mice, Inbred CFTR Mucins / metabolism Risk Factors |
| Grant Support | |
ID/Acronym/Agency:
|
DK-036588/DK/NIDDK NIH HHS; DK-073687/DK/NIDDK NIH HHS; R01 DK073687/DK/NIDDK NIH HHS; R01 DK073687-03/DK/NIDDK NIH HHS; R37 DK036588/DK/NIDDK NIH HHS; R37 DK036588-24/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Mucins; 57-88-5/Cholesterol; 635-65-4/Bilirubin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Monochloramine-induced toxicity and dysregulation of intracellular Zn2+ in parietal cells of rabbit ...
Next Document: Expression of cannabinoid CB1 receptors by vagal afferent neurons: kinetics and role in influencing ...