Integrity of the Blood-Brain Barrin Barrier System against Methylmercury Acute Toxicity

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To examine the possibility of methylmercury (MeHg)-induced damage at the bloodbrain barrier system, male C57BL/6N mice were orally administered MeHg chloride at doses from 40 to 200 μmol/kg of body weight. Although the Hg levels in plasma and blood at 24 h after the administration increased linearly with dosed amount, the increase in the brain levels exceeded that in the circulation levels. The ratio of the brain Hg to the dosed amount increased from 0.443±0.026% in the 40 μmol/kg dosed group to 0.667±0.062% in the 200 μmol/kg dosed group. The Hg concentration ratio of brain to plasma also increased from 1.26 to 1.90. Although some disturbance was expected in the brain uptake system of MeHg for the accelerated accumulation of the brain Hg, brain uptake of ^<125> I-labeled bovine serum albumin and ^<14>C-L-methionine was not affected by MeHg treatment at all. This indicated that transport systems for albumin- and cysteine-conjugate of MeHg in the brain remained unchanged under the present circumstances. Ultrafiltration analysis revealed that Hg distribution rates in low molecular weight fraction of plasma markedly increased with dose. Glutathione and cysteine conjugates of MeHg were dominant constituents in this fraction. Although plasma cysteine levels increased after MeHg administration, glutathione levels remained unchanged. In contrast, albumin and total SH contents in plasma were markedly decreased in a dose-dependent manner by MeHg treatment. Furthermore, affinity of MeHg for albumin, a dominant MeHg carrier in mouse plasma, was suggested to be lowered by MeHg treatment. These results appeared to indicate that the mouse blood-brain barrier system was strongly protected from MeHg acute toxicity, as indicated by the unchanged protein and amino acid uptake rates and its γ-glutamyltranspeptidase activity. Plasma albumin, however, was shown to be liable to undergo quantitative and qualitative changes by MeHg treatment, thereby resulting in dose-dependent acceleration of the uptake of the low molecular weight Hg conjugate (s) in the brain.
社団法人日本薬学会の論文
1991-10-31

Integrity of the Blood-Brain Barrin Barrier System against Methylmercury Acute Toxicity

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