Importance of Molar Ratios in Selenium-Dependent Protection Against Methylmercury Toxicity

Abstract

The influence of dietary selenium (Se) on mercury (Hg) toxicity was studied in weanling male Long Evans rats. Rats were fed AIN-93G-based low-Se torula yeast diets or diets augmented with sodium selenite to attain adequate- or rich-Se levels (0.1, 1.0 or 15 micromol/kg, respectively) These diets were prepared with no added methylmercury (MeHg) or with moderate- or high-MeHg (0.2, 10 or 60 micromol/kg, respectively). Health and weights were monitored weekly. By the end of the 9-week study, MeHg toxicity had impaired growth of rats fed high-MeHg, low-Se diets by approximately 24% (p < 0.05) compared to the controls. Growth of rats fed high-MeHg, adequate-Se diets was impaired by approximately 8% (p < 0.05) relative to their control group, but rats fed high-MeHg, rich-Se diets did not show any growth impairment. Low-MeHg exposure did not affect rat growth at any dietary Se level. Concentrations of Hg in hair and blood reflected dietary MeHg exposure, but Hg toxicity was more directly related to the Hg to Se ratios. Results support the hypothesis that Hg-dependent sequestration of Se is a primary mechanism of Hg toxicity. Therefore, Hg to Se molar ratios provide a more reliable and comprehensive criteria for evaluating risks associated with MeHg exposure.

The Chemical Nature of Mercury in Human Brain Following Poisoning or Environmental Exposure

“…Our results may have some bearing on the "selenium depletion hypothesis" (24), which proposes that mercury compounds scavenge selenium in neurological tissues, causing a local deficiency of essential selenium-dependent enzymes (23,24). This seems plausible because of the potentially limiting transport of selenium to the brain (33).…”

“…b Values were linked together to be consistent with a zincblende-like structure. c Value was fixed at the corresponding value of the Hg-Se bond in case 1. pubs.acs.org/acschemicalneuroscience Article Indeed, it has been proposed that demethylation combined with mercury's affinity for selenium is responsible for its neurotoxic effects (24). The Hg-C bond of methylmercury species has remarkable kinetic stability, with almost no cleavage in strong acids at room temperature.…”

Dietary and tissue selenium in relation to methylmercury toxicity

“…Therefore, intracellular methylmercury tends to diminish the amount of selenium that is biologically available for normal selenoenzyme synthesis, especially as Hg:Se molar ratios approach or exceed a 1:1 stoichiometry. Protective effects of dietary selenium against mercury toxicity (Ganther et al, 1972;Prohaska and Ganther, 1977;Watanabe et al, 1999a,b;Ralston et al, 2007;Yang et al, 2008), and in prevention of mercury-dependent inhibition of selenoenzyme activities (Prohaska and Ganther, 1977;Watanabe et al, 1999b), appear to occur because additional dietary selenium is able to offset the selenium sequestered by mercury and thereby maintain normal antioxidant activities of brain selenoenzymes.…”

Collate the literature on toxicity data on mercury in experimental animals and humans (Part I – Data on organic mercury)

“…However, the LOAEL for reduced body weight gain, severe toxicity and increased mortality was only 0.4 mg/kg b.w. per day in subchronic and chronic rat studies by Ralston et al (2007;. Such effects have not been reported in a comparable study of Day et al (2005, see above), which used the same rat strain and an identical dose.…”