Bile duct ligation-induced cirrhosis does not alter the blood-brain barrier permeability to sucrose in rats.

Autor: Miah MK; Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, Texas, USA.; Clinical Pharmacology & Quantitative Pharmacology, CPSS, AstraZeneca, Boston, Massachusetts, USA., Bickel U; Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, Texas, USA.; Center for Blood-Brain Barrier Research, Texas Tech University Health Sciences Center, Amarillo, Texas, USA., Mehvar R; Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, Texas, USA. mehvar@chapman.edu.; Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, 9401 Jeronimo Road, Irvine, California, USA. mehvar@chapman.edu.
Jazyk: angličtina
Zdroj: Metabolic brain disease [Metab Brain Dis] 2024 Dec 05; Vol. 40 (1), pp. 53. Date of Electronic Publication: 2024 Dec 05.
DOI: 10.1007/s11011-024-01486-6
Abstrakt: Contradictory results have been reported about the effects of liver diseases on the blood-brain barrier (BBB) permeability to markers. For instance, both an increase and no change in the BBB permeability to BBB markers sodium fluorescein and Evans blue have been reported in experimental cholestasis induced by bile duct ligation (BDL) in rats. These contradictory effects might be due to inherent limitations of these markers and/or methodological issues. Here, we investigated the time course of the impact of BDL in rats on BBB permeability using a recently developed stable isotope labeled marker [ 13 C]sucrose, which is expected to be devoid of limitations of other markers, such as sodium fluorescein. At various times (five days, two weeks, and four weeks) after BDL or sham surgery, the brain uptake clearance (K in ) of [ 13 C]sucrose was estimated using quantitation of the marker in plasma, blood, and brain by a specific LC-MS/MS analytical method. BDL caused substantial increases in the plasma concentrations of liver biochemical markers (bilirubin, total bile acids, ammonia, and cholesterol) and reduced liver cytochrome P450 content and metabolic activities. However, compared with the sham group, the plasma or blood AUC, brain concentrations, and K in of [ 13 C]sucrose in BDL animals remained unchanged at all the studied times. Additionally, we observed a negative correlation between the sucrose K in and plasma total bile acids concentrations in the BDL animals. It is concluded that cholestatic liver disease, induced by BDL surgery in rats, does not significantly affect the BBB permeability to sucrose up to 4 weeks after the surgery.
Competing Interests: Declarations. Ethics approval: All the animal procedures used in this study were approved by Texas Tech University Health Sciences Center’s Institutional Animal Care and Use Committee and were consistent with the guidelines set by the National Research Council (USA) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (8th edition, 2011). Consent to participate: Not applicable. Consent for publication: All authors have read and approved the manuscript. Conflict of interest: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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