Increased methylmercury toxicity related to obesity in diabetic KK-Ay mice.
Increased methylmercury toxicity related to obesity in diabetic KK-Ay mice.
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糖尿病 KK-Ay 小鼠中与肥胖相关的甲基汞毒性增加。
DOI：
10.1002/jat.2954
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Eto K.
中科院分区：
文献类型：
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作者：
Yamamoto M;Yanagisawa R;Motomura E;Nakamura M;Sakamoto M;Takeya M;Eto K.
我们研究了甲基汞（MeHg）对KK‐Ay 2型糖尿病小鼠的毒性作用，以阐明与2型糖尿病相关的代谢变化如何影响甲基汞的毒性。4周龄雄性KK‐Ay和C57BL/6J （BL/6）小鼠每周3次给予MeHg (5mg Hg kg-1day-1p.o)，持续6周。在实验的第一天，BL/6和KK - Ay小鼠的平均体重（BW）分别为16.3和16.4 g，在实验的最后一天分别为24.8和42.3 g。MeHg处理的KK - Ay小鼠在MeHg给药后约5周开始体重减轻。7只经MeHg处理的KK - Ay小鼠中有6只在实验的最后阶段出现后肢扣合。MeHg处理的KK - Ay小鼠的平均血汞水平在治疗10天后最高达到9.8µg ml-1，而MeHg处理的BL/6小鼠的平均血汞水平为2.8µg ml-1。BL/6小鼠的大脑和附睾脂肪垫的平均总汞浓度分别为7.4和0.57µg - 1， KK‐Ay小鼠的平均总汞浓度分别为27和1.6µg - 1。在MeHg治疗的KK - Ay神经症状小鼠中，在脑、肾和脾脏中观察到CD204阳性巨噬细胞，表明CD204可能是损伤组织的标志物。其他各组小鼠未见体重下降和明显的病理改变。这些结果表明，在相同剂量的MeHg / BW下，2型糖尿病患者的体脂增加和脂肪组织中的低汞积累增加了KK‐Ay小鼠器官中的MeHg浓度，并增强了毒性。版权所有©2013 John Wiley & Sons， Ltd
We examined the toxic effects of methylmercury (MeHg) in KK‐Ay type 2 diabetic mice to clarify how metabolic changes associated with type 2 diabetes mellitus affect MeHg toxicity. MeHg (5 mg Hg kg–1day–1p.o.) was given to 4‐week‐old male KK‐Ay and C57BL/6J (BL/6) mice three times per week for 6 weeks. Average body weights (BW) of vehicle‐treated BL/6 and KK‐Ay mice were 16.3 and 16.4 g respectively on the first day, and 24.8 and 42.3 g respectively on the last day of the experiment. MeHg‐treated KK‐Ay mice began to lose weight about 5 weeks after MeHg administration. Six of seven MeHg‐treated KK‐Ay mice showed hind‐limb clasping in the final stage of the experiment. The mean blood mercury level of MeHg‐treated KK‐Ay mice reached a maximum of 9.8 µg ml–1, whereas that of the MeHg‐treated BL/6 mice was 2.8 µg ml–1after 10 days of treatment. The average total mercury concentrations in the cerebrum and epididymal fat pad were 7.4 and 0.57 µg g–1, respectively, for BL/6 mice and 27 and 1.6 µg g–1, respectively, for KK‐Ay mice. In MeHg‐treated KK‐Ay mice with neurological symptoms, CD204‐positive macrophages were observed in the brain, kidney and spleen, indicating CD204 could be a marker for injured tissues. BW loss and significant pathological changes were not observed in other groups of mice. These results indicate that body fat gain in type 2 diabetes mellitus and low mercury accumulation in adipose tissue increased MeHg concentrations in organs and enhanced toxicity in KK‐Ay mice at the same dose of MeHg per BW. Copyright © 2013 John Wiley & Sons, Ltd.