Mineshi Sakamoto

Balancing the benefits of n-3 polyunsaturated fatty acids and the risks of methylmercury exposure from fish consumption

Fish and shellfish are widely available foods that provide important nutrients, particularly n-3 polyunsaturated fatty acids (n-3 PUFAs), to many populations globally. These nutrients, especially docosahexaenoic acid, confer benefits to brain and visual system development in infants and reduce risks of certain forms of heart disease in adults. However, fish and shellfish can also be a major source of methylmercury (MeHg), a known neurotoxicant that is particularly harmful to fetal brain development. This review documents the latest knowledge on the risks and benefits of seafood consumption for perinatal development of infants. It is possible to choose fish species that are both high in n-3 PUFAs and low in MeHg. A framework for providing dietary advice for women of childbearing age on how to maximize the dietary intake of n-3 PUFAs while minimizing MeHg exposures is suggested.

Intrauterine methylmercury intoxication: Consequence of the inherent brain lesions and cognitive dysfunction in maturity

We studied the effects of intrauterine neurotoxicity by methylmercury (MeHg) on the postnatal developing and adult stages of rats. We used offspring delivered from dams that had been given 1 mg/kg/day methylmercury chloride for 5 pregestational days and throughout pregnancy. Histopathological examination of the brains of a proportion of the offspring on postnatal days 1 (P1) and P3 revealed degenerative neurons in the brain stem and the limbic system, including the hippocampus and the amygdala. At P7 and P14, degenerative neurons were indiscernible, but reactive astrocytosis remained in the brain stem. At P70 and P180, the brains seemed to have developed well. However, in behavioral analyses performed at 6 months of age, MeHg-exposed rats showed a significant learning disability in the passive avoidance response compared with controls, but no differences in water maze performance. Furthermore, morphometric analysis of the amygdala and hippocampus revealed significantly fewer neurons in both areas in the MeHg-exposed rats. Thus, chronic intrauterine exposure to low-dose MeHg induces a decrease in neuron population in the limbic system, and the offspring have impaired higher brain function.

Relationships between trace element concentrations in chorionic tissue of placenta and umbilical cord tissue: potential use as indicators for prenatal exposure.

The role of the placenta was assessed by comparing the profiles of methylmercury (MeHg), inorganic mercury (I-Hg), lead (Pb), cadmium (Cd), selenium (Se), zinc (Zn), and copper (Cu) in freeze-dried chorionic tissue of the placenta and umbilical cord tissue. The significance of the placenta and cord tissue as predictors of prenatal exposure to these trace elements in pregnant women and newborns was also examined by comparing the element profiles among placenta and cord tissue, and maternal and cord blood red blood cells (RBCs). The samples were collected from 48 mother-child pairs at birth in the general population of Japanese. The concentrations of all elements, except for MeHg, were significantly higher in placenta than in cord tissue. In particular, the Cd showed the highest placenta vs. cord tissue ratio (59:1), followed by I-Hg (2.4:1), indicating that the placental barrier works most strongly against Cd among the examined toxic elements. Contrary to the other elements, the MeHg concentration in cord tissue was significantly higher (1.6 times) than that in placenta, indicating its exceptionally high placental transfer. The MeHg in placenta showed significant correlations with total mercury (T-Hg) in maternal and cord RBCs (rs=0.80 and 0.91, respectively). The MeHg in cord tissue also showed significant correlations with T-Hg in maternal and cord RBCs (rs=0.75 and 0.85, respectively). Therefore, both placenta and cord tissue are useful for predicting maternal and fetal exposure to MeHg. The Se concentration in placenta showed significant but moderate correlations with that in maternal and cord RBCs (rs=0.38 and 0.57, respectively). The Pb, Zn, and Cu concentrations in placenta and cord tissue showed no significant correlations with those in maternal and cord RBCs. As an exception, the Cd concentration in placenta showed a moderate but significant correlation (rs=0.41) with that in maternal RBCs, suggesting that the placenta is useful for predicting maternal exposure to Cd during gestation.

Selenomethionine Protects against Neuronal Degeneration by Methylmercury in the Developing Rat Cerebrum

Although many experimental studies have shown that selenium protects against methylmercury (MeHg) toxicity at different end points, the direct interactive effects of selenium and MeHg on neurons in the brain remain unknown. Our goal is to confirm the protective effects of selenium against neuronal degeneration induced by MeHg in the developing postnatal rat brain using a postnatal rat model that is suitable for extrapolating the effects of MeHg to the fetal brain of humans. As an exposure source of selenium, we used selenomethionine (SeMet), a food-originated selenium. Wistar rats of postnatal days 14 were orally administered with vehicle (control), MeHg (8 mg Hg/kg/day), SeMet (2 mg Se/kg/day), or MeHg plus SeMet coexposure for 10 consecutive days. Neuronal degeneration and reactive astrocytosis were observed in the cerebral cortex of the MeHg-group but the symptoms were prevented by coexposure to SeMet. These findings serve as a proof that dietary selenium can directly protect neurons against MeHg toxicity in the mammalian brain, especially in the developing cerebrum.

Mercury exposure in female artisanal small-scale gold miners (ASGM) in Mongolia: An analysis of human biomonitoring (HBM) data from 2008

BACKGROUND Many poor in developing countries have turned to artisanal small-scale gold mining (ASGM) in an attempt to improve their situation. However, the mercury used to extract gold from ore is discharged in vaporized form into the environment, where it poses a hazard for human health. METHODS As part of an environmental epidemiological study in Mongolia-to evaluate the burden of environmental mercury contamination-urine, blood and hair samples were collected from residents of areas with or without mercury contamination. A total of 200 blood, urine and hair samples were analyzed for mercury and divided into three subgroups according to mercury content: (1) occupational exposure (high/medium); (2) environmental exposure (low); and (3) no exposure. Internal mercury distributions of the subgroups were compared using the Kruskal-Wallis and Mann-Whitney U-test. The Chi-square test and likelihood ratio proportion were used to compare the findings with threshold limits. RESULTS The highest values and greatest differences were seen in the urine samples (p<0.001, Kruskal-Wallis). The occupational group showing the highest exposure with a median mercury level of 4.36μg/l (control group: 0.10μg/l, p<0.001), 7.18μg/g creatinine and 12 results above the threshold limit HBM I (Human Biomonitoring I). Even participants from the low-exposure subgroup showed elevated mercury levels (median 2.88μg/l urine and 2.98μg/g creatinine, p<0.001), with 10 individuals above the HBM I threshold limits. DISCUSSION The body burden resulting from the use of mercury in artisanal gold mining is high not only in the miners themselves, an increased mercury hazard was also found for inhabitants of mining areas who were not actively involved in mining. Public health support measures are urgently needed to alleviate the situation.

Distinct pattern of neuronal degeneration in the fetal rat brain induced by consecutive transplacental administration of methylmercury

The transplacental neurotoxicity of methylmercury (MeHg) on the fetal rat brain was studied. Adult female rats were administered 1, 2 or 3 mg/kg/day methylmercury chloride (MMC) orally for either 5 or 12 days, and were then mated. They were subsequently administered MMC in the same manner until the end of gestation. On embryonic day 22, a proportion of the fetal brains were histologically examined. Neuronal degeneration of varying degree was detected consistently in the brain stem, cingulate cortex, thalamus and cerebral basal area, including the hypothalamus. The distribution pattern of neuronal damage was different from those in rats treated with MeHg in the postnatal or adult stages. This finding suggests that pathomechanisms in MeHg intoxication operate distinctively in the fetal brain. The offspring derived from dams treated with 1 mg/kg/day MMC for 5 pregestational days and throughout pregnancy survived with inherent brain lesions. This experimental model could be a useful tool for research on the neurotoxicity of MeHg in the human fetal brain.

Methylmercury exposure and neurological outcomes in Taiji residents accustomed to consuming whale meat

Methylmercury (MeHg) is a major environmental neurotoxicant that causes damage to the central nervous system. In Japan, industrial emission of MeHg has resulted in MeHg intoxication in Minamata and Niigata, the so-called Minamata disease. Humans are exposed to MeHg derived from natural sources, primarily fish and fish predators. Therefore, MeHg continues to be an environmental risk to human health, particularly in susceptible populations that frequently consume substantial amounts of fish or fish predators such as whale. This study aimed to investigate the health effects of MeHg exposure in adults. The subjects were 194 residents (117 males, 77 females; age 20-85 years) who resided in the coastal town of Taiji, the birthplace of traditional whaling in Japan. We analyzed hair for mercury content and performed detailed neurological examinations and dietary surveys. Audiometry, magnetic resonance imaging, and electromyography were performed to diagnose neurological defects. Whole blood mercury and selenium (Se) levels were measured in 23 subjects. The geometric mean of the hair mercury levels was 14.9 μg/g. Twelve subjects revealed hair mercury levels >50 μg/g (NOAEL) set by WHO. Hair mercury levels significantly correlated with daily whale meat intake. These results suggested that residents in Taiji were highly exposed to MeHg by ingesting MeHg-contaminated whale meat. Multivariate regression analysis demonstrated no significant correlations between hair mercury levels and neurological outcomes, whereas some of the findings significantly correlated with age. A significantly positive correlation between whole blood mercury and Se levels was observed and the whole blood mercury/Se molar ratios of all subjects were <1. These findings suggested that sufficient Se intake might be one of causes of the absence of adverse effects of MeHg exposure in this study.

Retrospective study on temporal and regional variations of methylmercury concentrations in preserved umbilical cords collected from inhabitants of the Minamata area, Japan.

The present study was conducted to investigate the historical time-course changes and regional distribution of methylmercury concentrations in preserved umbilical cords collected from Minamata-area inhabitants born between 1947 and 1989. The data from Miyazaki, Tottori, Akita, Tsushima (Nagasaki), Fukuoka and Tokyo were used as controls. A total of 325 data were analyzed to estimate the temporal and spatial distribution of methylmercury among inhabitants born in the Minamata area. Elevated methylmercury concentrations (>or=1 microg/g) were mainly observed in inhabitants born between 1947 and 1968. That peak coincided with the peak of acetaldehyde production in Minamata. The methylmercury concentrations started to decrease in keeping with the decline of acetaldehyde production, which ceased in 1968, and thereafter the methylmercury levels gradually decreased to the control levels. Elevated methylmercury concentrations were first observed in the districts of Minamata, followed by Izumi, Tsunagi and Ashikita, indicating the time-course-dependent regional distributions of methylmercury pollution.

Mercury and docosahexaenoic acid levels in maternal and cord blood in relation to segmental maternal hair mercury concentrations at parturition.

Fish is a major source of harmful methylmercury (MeHg) and beneficial docosahexaenoic acid (DHA) in the developing brain. In this study, we investigated the correlations among maternal and umbilical cord (cord) MeHg and DHA levels at parturition, and mercury (Hg) concentration in 1-cm incremental segments hair samples which grew during gestation representing monthly MeHg exposure levels throughout the period. Whole blood Hg and plasma DHA levels were measured in blood sample pairs collected from 54 mothers at early gestation and parturition, and in cord blood. Maternal hair samples were collected at parturition, and Hg concentrations were measured in 1-cm incremental segments. Hg level in mothers at parturition was slightly lower than that at early gestation and the level in cord blood were approximately 1.9 times higher than that in mothers at parturition. On the other hand, DHA level in mothers at parturition was approximately 2.3 and 1.6 times higher than those in mothers at early gestation and in cord plasma, respectively. These results indicate that kinetics of these chemicals in mothers during gestation and placental transfer are completely different. However, Hg and DHA levels had significant positive correlation in fetal circulation. The cord blood Hg showed the strongest correlation with maternal hair Hg in the first 1-cm segment from the scalp at parturition (r=0.87), indicating that fetal MeHg level reflects maternal MeHg burden at late gestation. In contrast, maternal and cord plasma DHA concentrations at parturition showed the highest correlation coefficients with Hg in the fifth (r=0.43) and fourth (r=0.38) 1-cm hair segments, suggesting that maternal and fetal DHA levels reflects maternal fish intake during mid-gestation.

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 –1day–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