NDLI: The Permeability and Cytotoxicity of Insulin-Mimetic Vanadium Compounds

Content Provider	Springer Nature Link
Author	Yang, Xiao Gai Yang, Xiao Da Yuan, Lan Wang, Kui Crans, Debbie C.
Copyright Year	2004
Abstract	Purpose. The aim of this study was to investigate the mechanism of permeation and cytotoxicity of vanadium compounds, [VO(acac)$_{2}$], [VO(ma)$_{2}$], and vanadate. Methods. Absorptive transport were carried out in Caco-2 monolayers grown on transwell inserts. Vanadium was quantified using inductively coupled plasma atomic emission spectrometry (ICP-AES). The change of Caco-2 cells in the microvilli morphology and F-actin structure was visualized by transmission electron microscopy and confocal laser scanning microscopy. Results. The three vanadium compounds were taken up by Caco-2 cells via simple passive diffusion. [VO(acac)$_{2}$] were mainly transcellularly transported and exhibited the highest apparent permeabilty coefficients (8.2 × 10$^{-6}$ cm$^{-1}$). The cell accumulation of [VO(acac)$_{2}$] was found to be greater than that of [VO(ma)$_{2}$], and vanadate caused much less accumulation than the other two compounds. Vanadium compounds induced intracellular reactive oxygen species, reduced the transepithelial electric resistance, caused morphological change in microvilli, and led to different perturbation of F-actin structure. Conclusions. The three compounds exhibited different permeability due to different diffusion process and cellular uptake. The toxicity of vanadium complexes on Caco-2 monolayer involved F-actin-related change of tight junction and impairment of microvilli. The toxicity was also related to elevated intracellular reactive oxygen species (ROS) and their cellular accumulation.
Starting Page	1026
Ending Page	1033
Page Count	8
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	21
Issue Number	6
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2004-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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