Increased methylmercury toxicity related to obesity in diabetic KK-Ay mice.
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.
Integrated Physiology Section, Department of Basic Medical Science, National Institute for Minamata Disease, Minamata, Kumamoto, Japan.
Megumi
M
Yamamoto
Rie
R
Yanagisawa
Eriko
E
Motomura
Masaaki
M
Nakamura
Mineshi
M
Sakamoto
Motohiro
M
Takeya
Komyo
K
Eto
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000473:pathology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008767:Methylmercury Compounds / Q000097:blood / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
D001786:Blood Glucose; D008767:Methylmercury Compounds
CD204; Diabetes; Methylmercury; Neurotoxicity; Obesity