Toxicokinetics of methylmercury in diabetic KK-Ay mice and C57BL/6 mice

被引:3
作者
Yamamoto, Megumi [1 ]
Yanagisawa, Rie [2 ]
Sakai, Atsushi [3 ]
Mogi, Masaki [4 ]
Shuto, Satoshi [5 ]
Shudo, Masachika [6 ]
Kashiwagi, Hazuki [1 ]
Kudo, Megumi [1 ]
Nakamura, Masaaki [7 ]
Sakamoto, Mineshi [1 ]
机构
[1] Natl Inst Minamata Dis, Dept Environm & Publ Hlth, 4058-18 Hama, Minamata, Kumamoto 8670008, Japan
[2] Natl Inst Environm Studies, Ctr Hlth & Environm Risk Res, Tsukuba, Ibaraki, Japan
[3] Nippon Medac Co Ltd, Tokyo, Japan
[4] Ehime Univ, Grad Sch Med, Dept Pharmacol, Toon, Japan
[5] Hokkaido Univ, Fac Pharmaceut Sci, Dept Mol Pharmaceut Sci, Sapporo, Hokkaido, Japan
[6] Ehime Univ, Adv Res Support Ctr, Matsuyama, Ehime, Japan
[7] Natl Inst Minamata Dis, Dept Clin Med, Minamata, Japan
关键词
diabetes; methylmercury; mouse; susceptibility; toxicokinetics; METHYL MERCURY; IN-VIVO; GLUTATHIONE SYNTHESIS; DOSAGE ADJUSTMENT; PHARMACOKINETICS; CYSTEINE; MODEL; METABOLISM; EXPOSURE; CHLORIDE;
D O I
10.1002/jat.4078
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:928 / 940
页数:13
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