Abstract

Xanthines such as caffeine and theobromine are among the most consumed psychoactive stimulants in the world, either as natural components of coffee, tea and chocolate, or as added ingredients. The present study assessed if xanthines affect liver sinusoidal endothelial cells (LSEC). Cultured primary rat LSEC were challenged with xanthines at concentrations typically obtained from normal consumption of xanthine-containing beverages, food or medicines; and at higher concentrations below the in vitro toxic limit. The fenestrated morphology of LSEC were examined with scanning electron and structured illumination microscopy. All xanthine challenges had no toxic effects on LSEC ultrastructure as judged by LSEC fenestration morphology, or function as determined by endocytosis studies. All xanthines in high concentrations (150 μg/mL) increased fenestration frequency but at physiologically relevant concentrations, only theobromine (8 μg/mL) showed an effect. LSEC porosity was influenced only by high caffeine doses which also shifted the fenestration distribution towards smaller pores. Moreover, a dose-dependent increase in fenestration number was observed after caffeine treatment. If these compounds induce similar changes in vivo, age-related reduction of LSEC porosity can be reversed by oral treatment with theobromine or with other xanthines using targeted delivery.

Details

Title
Effect of caffeine and other xanthines on liver sinusoidal endothelial cell ultrastructure
Author
Mao, Hong 1 ; Szafranska, Karolina 2 ; Kruse, Larissa 2 ; Holte, Christopher 2 ; Wolfson, Deanna L. 3 ; Ahluwalia, Balpreet Singh 3 ; Whitchurch, Cynthia B. 4 ; Cole, Louise 4 ; Lockwood, Glen P. 5 ; Diekmann, Robin 6 ; Le Couteur, David 5 ; Cogger, Victoria C. 5 ; McCourt, Peter A. G. 7 

 University of Tromsø, The Arctic University of Norway, Vascular Biology Research Group, Department of Medical Biology, Faculty of Health Sciences, Tromsø, Norway (GRID:grid.10919.30) (ISNI:0000 0001 2259 5234); University of Tromsø, The Arctic University of Norway, Optical Nanoscopy Research Group, Department of Physics and Technology, Faculty of Science and Technology, Tromsø, Norway (GRID:grid.10919.30) (ISNI:0000 0001 2259 5234) 
 University of Tromsø, The Arctic University of Norway, Vascular Biology Research Group, Department of Medical Biology, Faculty of Health Sciences, Tromsø, Norway (GRID:grid.10919.30) (ISNI:0000 0001 2259 5234) 
 University of Tromsø, The Arctic University of Norway, Optical Nanoscopy Research Group, Department of Physics and Technology, Faculty of Science and Technology, Tromsø, Norway (GRID:grid.10919.30) (ISNI:0000 0001 2259 5234) 
 University of Technology Sydney, Microbial Imaging Facility, The ithree Institute, Ultimo, Australia (GRID:grid.117476.2) (ISNI:0000 0004 1936 7611) 
 ANZAC Research Institute, Concord Repatriation General Hospital, Centre for Education and Research, Concord, Australia (GRID:grid.456991.6) (ISNI:0000 0004 0428 8494); University of Sydney, The Faculty of Medicine and Health, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
 European Molecular Biology Laboratory (EMBL), Cell Biology and Biophysics Unit, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X); LaVision BioTec GmbH, Bielefeld, Germany (GRID:grid.59409.31) (ISNI:0000 0004 0552 5033) 
 University of Tromsø, The Arctic University of Norway, Vascular Biology Research Group, Department of Medical Biology, Faculty of Health Sciences, Tromsø, Norway (GRID:grid.10919.30) (ISNI:0000 0001 2259 5234); ANZAC Research Institute, Concord Repatriation General Hospital, Centre for Education and Research, Concord, Australia (GRID:grid.456991.6) (ISNI:0000 0004 0428 8494); University of Sydney, The Faculty of Medicine and Health, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
Pages
13390
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2852212855
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.