title: In-vivo evaluation of the permeability of the blood-brain barrier to arsenicals, molybdate, and methylmercury by use of online microdialysis-packed minicolumn-inductively coupled plasma mass spectrometry.
abstract: To study the permeability of the blood-brain barrier (BBB) to arsenates, arsenite, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), molybdate, and methylmercury, and the transfer behavior of these species, we constructed an automatic online analytical system comprising a microdialysis sampling device, a minicolumn packed with nonfunctionalized poly(vinyl chloride) beads, and an inductively coupled plasma mass spectrometer for continuous in-vivo measurement of their dynamic variation in the extracellular space of the brains of living rats. By using ion-polymer interactions as a novel working mechanism for sample pretreatment of volume-limited microdialysate, we simplified the operating procedure of conventional solid-phase extraction and reduced the contribution to the blank of the chemicals used. After optimizing this hyphenated system, we measured its performance by analysis of NIST standard reference materials 1640a (trace elements in natural water) and 2672a (trace elements in human urine) and by in-vivo monitoring of the dynamic variation of the compounds tested in the extracellular fluid (ECF) of rat brain. We found that intraperitoneal administration led to observable BBB permeability of arsenates, arsenite, DMA, MMA, and molybdate. Nevertheless, the limited sensitivity of the system and the size of microdialysis samples meant that detection of MeHg in ECF remained problematic, even when we administered a dose of 20 mg MeHg kg(-1) body weight. On the basis of these practical demonstrations, we suggest that our analytical system could be used not only for dynamic monitoring of the transfer kinetics of the four arsenicals and molybdate in the rat brain but also to describe associated neurotoxicity in terms of exposure to toxic metals and their species.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013, Hsinchu, Taiwan.
authors.forename: Cheng-Kuan
authors.initials: CK
authors.lastname: Su
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Yang
authors.forename: Cheng-Hsing
authors.initials: CH
authors.lastname: Lin
authors.forename: Yuh-Chang
authors.initials: YC
authors.lastname: Sun
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000378:metabolism* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D002101:Cacodylic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D002199:Capillary Permeability; D004567:Electrodes, Implanted; D007274:Injections, Intraperitoneal; D008297:Male; D008767:Methylmercury Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D017551:Microdialysis; D008982:Molybdenum / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D013238:Stereotaxic Techniques
chemical_list: D001152:Arsenicals; D008767:Methylmercury Compounds; C044659:molybdate; C030957:methylmercury II; D008982:Molybdenum; D002101:Cacodylic Acid; C020300:monomethylarsonic acid