Dietary selenium protects against selected signs of aging and methylmercury exposure.

Acute or short-term exposure to high doses of methylmercury (MeHg) causes a well-characterized syndrome that includes sensory and motor deficits. The environmental threat from MeHg, however, comes from chronic, low-level exposure, the consequences of which are poorly understood. Selenium (Se), an essential nutrient, both increases deposition of mercury (Hg) in neurons and mitigates some of MeHg's neurotoxicity in the short term, but it is unclear whether this deposition produces long-term adverse consequences. To investigate these issues, adult Long-Evans rats were fed a diet containing 0.06 or 0.6 ppm of Se as sodium selenite. After 100 days on these diets, the subjects began consuming 0.0, 0.5, 5.0, or 15 ppm of Hg as methylmercuric chloride in their drinking water for 16 months. Somatosensory sensitivity, grip strength, hindlimb cross (clasping reflex), flexion, and voluntary wheel-running in overnight sessions were among the measures examined. MeHg caused a dose- and time-dependent impairment in all measures. No effects appeared in rats consuming 0 or 0.5 ppm of Hg. Somatosensory function, grip strength, and flexion were among the earliest signs of exposure. Selenium significantly delayed or blunted MeHg's effects. Selenium also increased running in unexposed animals as they aged, a novel finding that may have important clinical implications. Nerve pathology studies revealed axonal atrophy or mild degeneration in peripheral nerve fibers, which is consistent with abnormal sensorimotor function in chronic MeHg neurotoxicity. Lidocaine challenge reproduced the somatosensory deficits but not hindlimb cross or flexion. Together, these results quantify the neurotoxicity of long-term MeHg exposure, support the safety and efficacy of Se in ameliorating MeHg's neurotoxicity, and demonstrate the potential benefits of Se during aging.

Dietary and tissue selenium in relation to methylmercury toxicity.

Selenium (Se) supplementation in the nutritionally relevant range counteracts methylmercury (MeHg) toxicity. Since Se tends to be abundant in fish, MeHg exposures alone may not provide an accurate index of risk from fish consumption. Molar ratios of MeHg:Se in the diets and Hg:Se in tissues of exposed individuals may provide a more accurate index. This experiment compared MeHg toxicity in relation to MeHg exposure vs. Hg:Se molar ratios in diets and tissues. Diets were prepared using low-Se torula yeast basal diets supplemented with Na(2)SeO(4) to contain 0.1, 1.0, or 10.0 micromol Se/kg ( approximately 0.01, 0.08, or 0.8 ppm Se), reflecting low-, adequate-, or rich-Se intakes, respectively. Diets contained either low or high (0.5 micromol or 50 micromol MeHg/kg) ( approximately 0.10 or 10 ppm Hg). Sixty weanling male Long Evans rats were distributed into six weight-matched groups (three Se levels x two MeHg levels) that were supplied with water and their respective diets ab libitum for 18 weeks. No Se-dependent differences in growth were noted among rats fed low-MeHg diets, but growth impairments among rats fed high-MeHg were inversely related to dietary Se. After 3 weeks on the diet, growth impairments were evident among rats fed high-MeHg with low- or adequate-Se and after 10 weeks, rats fed low-Se, high-MeHg diets started to lose weight and displayed hind limb crossing. No weight loss or hind limb crossing was noted among animals fed high-MeHg, rich-Se diets. Methylmercury toxicity was not predictable by tissue Hg, but was inversely related to tissue Se (P<0.001) and directly related to Hg:Se ratios (P<0.001). Methylmercury-selenocysteine complexes (proposed name; pseudomethionine) appear likely to impair Se bioavailability, interrupting synthesis of selenium-dependent enzymes (selenoenzymes) that provide antioxidant protection in brain. Therefore, selenoenzymes may be the molecular target of methylmercury toxicity.