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Increased methylmercury toxicity related to obesity in diabetic KK‐Ay mice
Author(s) -
Yamamoto Megumi,
Yanagisawa Rie,
Motomura Eriko,
Nakamura Masaaki,
Sakamoto Mineshi,
Takeya Motohiro,
Eto Komyo
Publication year - 2014
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2954
Subject(s) - methylmercury , endocrinology , toxicity , medicine , spleen , kidney , body weight , diabetes mellitus , chemistry , bioaccumulation , organic chemistry
ABSTRACT 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 –1 day –1 p.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 –1 after 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.