Enhanced Bioavailability of Polyaromatic Hydrocarbons in the Form of Mucin Complexes
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- 作者：Eyal Drug ; Dalit Landesman-Milo ; Bogdan Belgorodsky ; Natalia Ermakov ; Moran Frenkel-Pinter ; Ludmila Fadeev ; Dan Peer ; Michael Gozin
- 刊名：Chemical Research in Toxicology
- 出版年：2011
- 出版时间：March 21, 2011
- 年：2011
- 卷：24
- 期：3
- 页码：314-320
- 全文大小：888K
- 年卷期：v.24,no.3(March 21, 2011)
- ISSN：1520-5010
文摘
Increasing exposure of biological systems to large amounts of polycyclic aromatic hydrocarbons is of great public concern. Organisms have an array of biological defense mechanisms, and it is believed that mucosal gel (which covers the respiratory system, the gastrointestinal tract, etc.) provides an effective chemical shield against a range of toxic materials. However, in this work, we demonstrate, for the first time, that, upon complexation of polyaromatic hydrocarbons with mucins, enhanced bioavailability and, therefore, toxicity are obtained. This work was aimed to demonstrate how complexation of various highly hydrophobic polycyclic aromatic hydrocarbons with representative mucin glycoprotein could lead to the formation of previously undescribed materials, which exhibit increased toxicity versus pristine polycyclic aromatic hydrocarbons. In the present work, we show that a representative mucin glycoprotein, bovine submaxillary mucin, has impressive and unprecedented capabilities of binding and solubilizing water-insoluble materials in physiological solution. The complexes formed between the mucin and a series of polycyclic aromatic hydrocarbons were comprehensively characterized, and their toxicity was evaluated by both in vivo and in vitro assays. In addition, the bioavailability and membrane-penetration capabilities were tested using an internalization assay. Our results provide, for the first time, evidence of an unknown route by which hydrophobic materials may achieve higher bioavailability, penetrating some of the biological defense systems, in the form of water-soluble complexes with mucosal proteins.