4,4-Di-isothiocyanostilbene-2,2'-disulphonic acid inhibition of taurocholate efflux from canalicular vesicles was used to demonstrate that potential driven and 'carrier'-mediated canalicular excretion of taurocholate occur via a common, rather than two separate, pathways. This electrogenic canalicular bile acid 'carrier' preferentially transports trihydroxylated and conjugated dihydroxylated bile acids, but not the unphysiological oxo bile acids, and possibly extends its substrate specificity to other amphipathic molecules such as sulphobromophthalein.
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http://dx.doi.org/10.1042/bj2420465 | DOI Listing |
Arch Toxicol
March 2025
Experimental Hepatology Unit, Health Research Institute La Fe (IISLAFE), Torre A. Instituto Investigación Sanitaria La Fe Av Fernando Abril Martorell 106, 46026, Valencia, Spain.
Drug-induced cholestasis is one of the major mechanisms implicated in drug-induced hepatotoxicity that poses a serious problem in terms of patient morbidity and mortality, healthcare system expenses and efficacy of newly developed drugs. Impaired bile acid homeostasis due to transporter alterations, hepatocellular injury or canalicular abnormalities is the most characteristic feature of cholestasis. Given the complexity of cholestasis and the different underlying mechanisms, new models and technologies that span a variety of biological processes are needed to accurately predict drugs' cholestatic potential.
View Article and Find Full Text PDFGastroenterol Rep (Oxf)
March 2025
Department of Gastroenterology, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, P. R. China.
Niemann-Pick C1-like 1 (NPC1L1) is distributed in the human liver and intestine but only slightly expressed in the mouse liver. While it is well established that intestinal NPC1L1 is crucial for the absorption of exogenous cholesterol, the physiological and pathological roles of canalicular membrane-localized NPC1L1 in human hepatic cholesterol transport remain unclear. In this review, we discussed the potential function of human hepatic NPC1L1 and proposed that the disparity in NPC1L1 abundance between humans and mice in the liver may be attributable to their distinct bile hydrophobicity.
View Article and Find Full Text PDFACG Case Rep J
March 2025
Division of Digestive Diseases, University of Cincinnati Medical Center, Cincinnati, OH.
Recurrent cholestasis poses diagnostic challenges and necessitates repeated testing. The (adenosine triphosphate-binding cassette, subfamily B, member 4) gene encodes a protein that removes phospholipids from the hepatic canalicular membrane through bile salts. Mutations lead to a spectrum of clinical syndromes that cause recurrent cholestasis, pruritus, and jaundice.
View Article and Find Full Text PDFPediatr Dev Pathol
February 2025
Department of Pediatric Hepatology, Gastroenterology and Nutrition, National Liver Institute, Menoufia University, Menoufia, Egypt.
Background: Bile acids in the ileum act as a feedback regulator of their own synthesis by inducing the release of ileal fibroblast growth factor 19 (FGF19), which inhibits the cholesterol-7-alpha hydroxylase enzyme. In cholestasis, this feedback mechanism is dysregulated. FGF19 is not expressed in the healthy liver.
View Article and Find Full Text PDFJ Vet Diagn Invest
February 2025
San Bernardino branches, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
spp. can cause gastroenteritis, hepatitis, bacteremia, and abortions in domestic animals and humans. Some spp.
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