We compared the toxicokinetics of methylmercury (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 administered orally to 12‐week‐old KK‐Ay and C57BL/6J male mice. Total mercury concentrations in plasma, blood cells, whole blood, and tissues (brain, kidneys, liver, and pancreas) were measured after 4, 7, 11, and 14 days. The volume of distribution/bioavailability and the elimination rate constant per day were higher in KK‐Ay mice, while the terminal elimination half‐life was lower in almost all samples of KK‐Ay mice. The area under the curve was lower in all blood and almost all tissue samples from KK‐Ay mice. Total clearance/bioavailability was lower in all blood and tissue samples of KK‐Ay mice at all MeHg doses. These results indicate that MeHg is more rapidly absorbed by, and eliminated from, the blood cells, brain, liver, kidney, and pancreas of KK‐Ay mice under the experimental conditions. Different patterns of tissue‐to‐plasma and tissue‐to‐whole blood partition coefficients suggest that notable differences in MeHg transfer between plasma and blood cells affect its distribution in tissues of the two mouse strains. These findings are useful to understand the selective distribution of MeHg to target organs and the sensitivity to MeHg in pathological states.

中文翻译：

---

甲基汞在糖尿病 KK-Ay 小鼠和 C57BL/6 小鼠中的毒代动力学

我们在 KK-Ay 2 型糖尿病小鼠和 C57BL/6J 小鼠中比较了甲基汞 (MeHg) 的毒代动力学，以评估与糖尿病相关的代谢变化如何影响甲基汞的毒代动力学。给 12 周大的 KK-Ay 和 C57BL/6J 雄性小鼠口服单剂量的甲基汞（0.2、1 或 5 毫克汞/千克）。在 4、7、11 和 14 天后测量血浆、血细胞、全血和组织（大脑、肾脏、肝脏和胰腺）中的总汞浓度。KK-Ay 小鼠的分布容积/生物利用度和每天的消除速率常数较高，而几乎所有 KK-Ay 小鼠样品的终末消除半衰期都较低。曲线下面积在 KK-Ay 小鼠的所有血液和几乎所有组织样本中都较低。在所有甲基汞剂量下，KK-Ay 小鼠的所有血液和组织样本的总清除率/生物利用度较低。这些结果表明，在实验条件下，MeHg 更快地被 KK-Ay 小鼠的血细胞、脑、肝、肾和胰腺吸收和清除。组织-血浆和组织-全血分配系数的不同模式表明，血浆和血细胞之间 MeHg 转移的显着差异影响其在两种小鼠品系的组织中的分布。这些发现有助于了解甲基汞向靶器官的选择性分布以及病理状态下对甲基汞的敏感性。组织-血浆和组织-全血分配系数的不同模式表明，血浆和血细胞之间 MeHg 转移的显着差异影响其在两种小鼠品系的组织中的分布。这些发现有助于了解甲基汞向靶器官的选择性分布以及病理状态下对甲基汞的敏感性。组织-血浆和组织-全血分配系数的不同模式表明，血浆和血细胞之间 MeHg 转移的显着差异影响其在两种小鼠品系的组织中的分布。这些发现有助于了解甲基汞向靶器官的选择性分布以及病理状态下对甲基汞的敏感性。