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Background/aim: Multidrug Resistance Protein 3 (MRP3) transports bile salts and glucuronide conjugates in vitro and is postulated to protect the liver in cholestasis. Whether the absence of Mrp3 affects these processes in vivo is tested.
Methods: Mrp3-deficient mice were generated and the contribution of Mrp3 to bile salt and glucuronide conjugate transport was tested in (1): an Ussing-chamber set-up with ileal explants (2), the liver during bile-duct ligation (3), liver perfusion experiments, and (4) in vitro vesicular uptake experiments.
Results: The Mrp3((-/-)) mice show no overt phenotype. No differences between WT and Mrp3-deficient mice were found in the trans-ileal transport of taurocholate. After bile-duct ligation, there were no differences in histological liver damage and serum bile salt levels between Mrp3((-/-)) and WT mice, but Mrp3-deficient mice had lower serum bilirubin glucuronide concentrations. Glucuronide conjugates of hyocholate and hyodeoxycholate are substrates of MRP3 in vitro and in livers that lack Mrp3, there is reduced sinusoidal secretion of hyodeoxycholate-glucuronide after perfusion with hyodeoxycholate.
Conclusions: Mrp3 does not have a major role in bile salt physiology, but is involved in the transport of glucuronidated compounds, which could include glucuronidated bile salts in humans.
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http://dx.doi.org/10.1016/j.jhep.2005.07.022 | DOI Listing |
Korean J Gastroenterol
December 2024
Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Korea.
Vanishing bile duct syndrome (VBDS) is characterized by the progressive loss and destruction of the intrahepatic bile ducts, leading to bile stasis and associated symptoms such as jaundice. This condition is commonly associated with drug side effects, infections, neoplasms, and autoimmune diseases, but the precise mechanism of its development is unclear. Although VBDS can be diagnosed based on the patient's symptoms and disease progression, a liver biopsy is essential for confirmation, and the prognosis can vary significantly.
View Article and Find Full Text PDFDaru
December 2024
Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, POB 11795, Egypt.
Background: Bile salts enriched nanovesicles (bilosomes) have been attention worthy in the past few years due to their distinctive effect on the enhancement of drug delivery through various physiological administration routes. Oral delivery of multifunctioning phytochemical curcumin has faced a lot of difficulties due to its scarce solubility and poor oral bioavailability.
Objective: The current investigation aimed to develop curcumin loaded bilosomes for improvement of oral curcumin bioavailability with maximum efficiency and safety.
Photochem Photobiol Sci
December 2024
Department of Chemistry, Indian Institute of Technology Madras, Chennai, 600036, Tamil Nadu, India.
The present work focuses on the photophysical behavior of meso-N-butylcarbazole-substituted BODIPY (CBZ-BDP) in different organized media towards exploring the possible use of the dye as a molecular sensor and imaging agent. The molecule shows an appreciable change in absorption and emission spectra at 75% water-acetonitrile mixture compared to pure acetonitrile. In water-acetonitrile mixture, it displays aggregate-induced emission (AIE) bands.
View Article and Find Full Text PDFJ Transl Med
December 2024
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Background: Yes-associated protein 1 (YAP1) regulates the survival, proliferation, and stemness of cells, and contributes to the development of metabolic dysfunction associated fatty liver disease (MAFLD). However, the regulatory role of intestinal YAP1 in MAFLD still remains unclear.
Methods: Terminal ileal specimens were used to compare intestinal YAP1 activation in patients with and without MAFLD.
J Transl Med
December 2024
Department of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Introduction: Severe acute pancreatitis (SAP) is a crucial gastrointestinal disease characterized by systemic inflammatory responses and persistent multiple organ failure. The role of bile acids (BAs) in diverse inflammatory diseases is increasingly recognized as crucial, but the underlying role of BA conjugation remains elusive.
Objectives: Our study aim to investigate the potential role of conjugated bile acids in SAP and reveal the molecular mechanisms underlying its regulatory effects.
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