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The Permeability and Cytotoxicity of Insulin-Mimetic Vanadium Compounds

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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.

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Authors and Affiliations

  1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100083, China

    Xiao-Gai Yang, Xiao-Da Yang & Kui Wang

  2. Analytical Center of Peking University, Beijing, 100083, China

    Lan Yuan

  3. Department of Chemistry, and Cell and Molecular Biology Program, College of Natural Sciences, Colorado State University, Fort Collins, Colorado, 80523-1872, USA

    Debbie C. Crans

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  1. Xiao-Gai Yang
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Correspondence to Xiao-Da Yang.

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Yang, XG., Yang, XD., Yuan, L. et al. The Permeability and Cytotoxicity of Insulin-Mimetic Vanadium Compounds. Pharm Res 21, 1026–1033 (2004). https://doi.org/10.1023/B:PHAM.0000029293.89113.d5

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  • DOI: https://doi.org/10.1023/B:PHAM.0000029293.89113.d5

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