Modification mechanism of methylmercury toxicokinetics and toxicity under diabetic status

• Project/Area Number: 16K09121
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: National Institute for Minamata Disease
• Principal Investigator: Yamamoto Megumi 国立水俣病総合研究センター, その他部局等, 部長 (70344421)
• Co-Investigator(Kenkyū-buntansha): 中村 政明 国立水俣病総合研究センター, その他部局等, 部長 (50399672)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: メチル水銀 / 毒物動態 / 糖代謝異常 / マウス / 糖尿病 / 体内動態 / 神経毒性 / 糖代謝 / 水銀

Outline of Final Research Achievements

We compared the toxicokinetics of MeHg in KK-Ay type 2 diabetic mice and C57BL/6J mice to evaluate how metabolic changes associated with diabetes affect MeHg toxicokinetics. A single dose of MeHg (0.2, 1, or 5 mg mercury/kg) was orally administered to 12-week-old KK-Ay and C57BL/6J male mice. Total mercury concentrations in plasma, blood cells, whole blood, and tissues (brain, kidney, liver, and pancreas) were measured after 4, 7, 11, and 14 days, and the toxicokinetics was analyzed using pharmacokinetic parameters (Vd/F, Kel, t1/2, AUC, CL/F, Kp, Kp’). The results indicate that MeHg is more rapidly absorbed in and eliminated from blood cells, brain, liver, kidney, and pancreas in KK-Ay mice under the experimental conditions.

Academic Significance and Societal Importance of the Research Achievements

2型糖尿病マウスと正常マウスにおけるMeHgの体内動態に関する初めての比較研究である。糖代謝異常の病態下におけるMeHgの各組織への移行や排出のされやすさの解明につながる。MeHgの標的器官への選択的な分布と、病態下におけるMeHg曝露に対する感受性の理解に役立つ知見であると考えられる。