Abstract
Selenoneine is the major selenium compound in fish muscles, and fish appears to be an important source of selenium in the fish-eating population. Selenoneine has strong antioxidant activity and a detoxifying function against methylmercury (MeHg) toxicity. Dietary intake, bioaccumulation, and metabolism of selenoneine have not been characterized in humans. A nutritional survey was conducted in remote islands of the Kagoshima Prefecture in Japan. To evaluate the potential risks and benefits of fish consumption for health, we measured concentrations of selenoneine, total selenium, MeHg, inorganic mercury, and polyunsaturated fatty acid (LC-PUFA) in the blood of a fish-eating human population. The erythrocyte, leukocyte, and platelet residues following removal of serum (cellular fraction) contained 0.510 μg Se/g, 0.212 μg selenoneine Se/g, and 0.262 μg Se-containing proteins Se/g, whereas the serum contained 0.174 μg total Se/g. Selenoneine was highly concentrated in the cellular fraction in a manner that was dependent on subjects' frequency of fish consumption. Concentrations of selenoneine were closely correlated with concentrations of MeHg in the cellular fraction. Selenoneine is the major chemical form of selenium in the blood cells of this fish-eating human population and may be an important biomarker for selenium redox status.
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Introduction
Ocean fish, such as tuna, mackerel, and swordfish, possess a novel selenium-containing imidazole compound, selenoneine, which is the predominant form of organic selenium in tuna [1–3]. This compound has a unique selenoketone structure and is a powerful antioxidant [1–3]. The concentration of selenium in the red blood cells (RBCs) was correlated with the intake of selenium from animal foods and seafood, whereas the concentration of selenium in the serum or plasma was correlated with the intake of selenium from plant foods [4, 5]. Thus, a significant amount of selenoneine is thought to be incorporated through the consumption of seafood. Several studies have examined the bioavailability of selenium from fish and other food sources [6–13].
Fish consumption is also associated with the intake of methylmercury (MeHg) [14–21], which may cause adverse health effects. Concentrations of nutrients, including long chain polyunsaturated fatty acids (LC-PUFA) and specific chemical contaminants, such as MeHg and dioxins, have been characterized in a range of fish species [22, 23]. In addition, the health and nutritional benefits of fish consumption have been compared to the health risks associated with contaminants present in fish [22, 23]. Because selenium reacts with and detoxifies MeHg, its distribution in seafood and the detoxifying functions of dietary selenium from seafood should be characterized. The contents of selenoneine and total selenium in fish are correlated with the content of total mercury [3]. The Se/Hg molar ratio in fish was estimated to be 3:1 and it varied among species, ranging from 1 to 217 [3]. Such ratios may be important for estimating the MeHg risks associated with fish consumption. Animal trials of feeding with both MeHg [0.5 or 50 μmol/kg in diet] and sodium selenite showed that the toxicity of MeHg decreased with selenium intake for Se/Hg molar ratios of >0.2 [17, 18]. Selenoneine accelerated the excretion and demethylation of MeHg through the formation of secretory extracellular lysosomal vesicles via the specific organic cation/carnitine transporter-1 (OCTN1) [21]. Thus, the molar Se/Hg range of 1 to 217 found in the muscle of fish is considered to represent the normal physiological state in terms of MeHg bioaccumulation and metabolism [3]. Therefore, animal studies and human trials should examine various Se/Hg molar ratios and use them to compare the physiological and nutritional effects of fish consumption.
Here, we report the determination of selenoneine concentrations in human blood. Significant amounts of selenoneine accumulated in the cellular fraction, but not in the serum, of the fish-eating Japanese population were studied here. Concentrations of selenoneine and total selenium in the cellular fraction might be used as an important biomarker for fish consumption and selenium antioxidant functions.
Materials and Methods
Subjects
A nutritional interview survey with medical checkup was conducted among rural residents living on remote islands in the Southwestern Islands in Kagoshima Prefecture, Japan, in 2009. A total of 217 persons from four islands participated in this study. Of the 217 persons, 50 were excluded because of missing forms or insufficient blood samples for chemical analysis. A total of 167 persons were covered in this study, comprising 75 males and 92 females, all over 20 years of age. Their mean ages were 63.2 years in both sexes. Information was collected regarding the frequency of consumption of seafood per week and the amounts of fish meat per meal. The study was approved by the Ethics Committee of the Kagoshima University Graduate School of Medical and Dental Sciences, and informed written consent was obtained from participants.
Fish Intake
A food-frequency questionnaire was used to assess the average intake of fish meals including shrimp, crab, squid, octopus, and clam during the previous week. Participants were asked to indicate their usual rate of consumption choosing from six frequency categories. The categories range from “never or less than once/week” to “more than nine times per week”. The servings are specified in terms of units or common portions (e.g., one slice of fish fillet). An average portion size was assigned to each questionnaire item. The subjects were divided into six categories consuming fish meal: less than once per week = f-time 0, once per week = f-time 1, two or three times per week (less than once per 2 days) = f-time 2, three or four times per week (once per 2 days) = f-time 3, everyday (five to eight times per week) = f-time 4, every time (more than nine times per week) = f-time 5, and categories of the amount of fish meat: 25 g per meal = f-mass 1, 50 g per meal = f-mass 2, 75–100 g per meal = f-mass 3, 150 g per meal = f-mass 4, 200 g or more per meal = f-mass 5.
Chemical Analysis of the Blood Samples
Blood samples were obtained from the subjects, and the cellular fraction and serum of a collected blood sample were separated with blood serum separation tubes by centrifugation at 2,000×g for 10 min. The cellular fraction and serum specimens were stored at −80 °C until use. Concentrations of MeHg and LC-PUFA in the blood were previously shown to be correlated with fish consumption [22–25]. Hence, we also analyzed whether the concentrations of selenium and selenoneine in the cellular fraction were correlated with the levels of MeHg and LC-PUFA.
Each sample (0.1 g) was placed in glass test tube and digested at 200–220 °C in 1 mL of a 1:2 mixture of nitric acid and perchloric acid and subjected to a fluorometric assay using 2,3-diaminonaphthalene, as described previously [3, 26]. Detection limit was 0.006 μg/g. For selenium speciation analysis, selenium compounds were detected through online liquid chromatography–inductively coupled plasma mass spectrometry (LC-ICP-MS) using an ELAN DRC II mass spectrometer (PerkinElmer, Waltham, MA) [1, 3]. The cellular fraction (20 mg) was placed in a 1.5-mL microcentrifuge tube and homogenized in 10 volumes of ultrapure water using a Pellet Mixer Pestle (Treff, Degersheim, Switzerland). After centrifugation at 10,000×g for 5 min, the supernatant of cellular fraction was used for the analysis. Each sample (20 μL) of the cellular fraction supernatant and serum was analyzed using an Ultrahydrogel 120 gel permeation chromatography column (7.8 × 250 mm; Nihon Waters, Tokyo, Japan) equilibrated with 0.1 M ammonium acetate buffer containing 0.1 % (w/v) Igepal CA-630 (Sigma-Aldrich Japan, Tokyo, Japan), as described previously [1, 3]. During separation, selenoneine were eluted with retention times of 10.1 min, and Se-containing proteins including glutathione peroxidase (GPx), selenoprotein P, and other Se-containing proteins were eluted in the void volume of the GPC column at 5.4 min. The concentration of selenium was determined using bovine GPx1 (Sigma-Aldrich) as a standard of Se-containing proteins and bluefin tuna blood selenoneine. Detection limit was 0.002 μg/g.
Concentrations of total mercury in the cellular fraction and serum specimens were determined using flameless atomic absorption spectrometry at 253.7 nm using an HG-310 mercury analyzer (Hiranuma, Tokyo, Japan) according to the manufacturer's instructions, following digestion of the sample material (0.1–0.5 g) with 2 mL of a 1:2:1 mixture of nitric acid/perchloric acid/sulfuric acid and dilution in water to 25–125 mL [3]. MeHg and inorganic mercury in the cellular fraction was determined using LC-ICP-MS with a C18 reverse phase column (Atlantis dC18, 3.6 × 100 mm; Waters Japan, Tokyo) following hydrochloric acid extraction, as described previously [27]. Detection limit was 0.0005 μg/g.
Methyl-esterified fatty acids in the serum were analyzed using gas liquid chromatography on Shinchrom E71 (Shimadzu Co. Ltd., Kyoto) of glass column (3 mm diameter × 3 m long).
[22]. Concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other fatty acids in the serum were determined using heptadecanoate (C17:0) as an internal standard. The concentration of EPA plus DHA in the serum was used in the analysis as an index of LC-PUFA.
Statistical Analysis
Analysis of variance (ANOVA) and correlation analysis were conducted using GraphPad Prism™ 5.03 (GraphPad Software Inc., La Jolla, CA). Multiple regression analysis was done using StatView (ver. 5, SAS Institute, Cary, NC). Statistical significance level was defined as p < 0.05.
Results
To characterize the selenium compounds in the RBCs, we determined organic selenium in the cellular fraction by a speciation analysis method based on monitoring 82Se using LC-ICP-MS with a GPC column (Fig. 1). The contents of selenoneine, Se-containing proteins (including GPx, selenoprotein P, and others), and other unidentified selenium compounds in the cellular fraction were also determined; selenite, selenocysteine, and selenomethionine were not detected in the tissues examined (Table 1). Figure 1 shows how the selenoneine in the cellular fraction was eluted at 10.1 min after the bed volume of the column. The highest concentration of selenoneine was 2.38 μg Se selenoneine/g in the cellular fraction (Fig. 1a). In this subject, total selenium in the cellular fraction was 2.40 μg Se/g (Fig. 1a). In the serum of this subject, selenoneine was below the limit of detection, and selenium was at 0.255 μg total Se/g. In contrast, in another subject, the lowest detected selenium concentrations in the cellular fraction were 0.006 μg selenoneine Se/g and 0.207 μg total Se/g, respectively, and the selenium concentration in the serum was 0.160 μg total Se/g (Fig. 1b). Overall, the cellular fraction contained 0.510 ± 0.389 μg total Se/g, 0.212 ± 0.356 μg selenoneine Se/g, and 0.262 ± 0.093 μg Se-containing proteins Se/g, whereas the serum contained 0.174 ± 0.038 μg total Se/g.
Because we considered the range of concentrations of selenoneine and total selenium observed in the cellular fraction to be due to fish consumption, we compared the concentrations of total selenium, Se-containing proteins, and selenoneine in the cellular fraction and the levels of selenium in the serum with the reported frequency (Fig. 2) and the amount of fish meat per meal (Fig. 3) of fish consumption. For all subjects, the mean concentrations of total selenium in the cellular fraction (p-trend 0.001), selenoneine in the cellular fraction (p-trend 0.005), Se-containing proteins in the cellular fraction (p-trend 0.004), MeHg in the cellular fraction (p-trend 0.008), and mercury in the serum (p-trend 0.009) increased with the frequency of fish consumption (Fig. 2). Subjects who reported consuming fish more than almost every day serving per week had significantly higher concentrations of selenoneine and total selenium in their cellular fraction than those who reported consuming fish under every other day. In addition, concentrations of MeHg in the cellular fraction of subjects who reported consuming more than one or more on the 2 days serving per week were higher than those of subjects who consumed fish under every other day serving of fish. Concentrations of inorganic Hg in the cellular fraction and total selenium and mercury in the serum were not significantly related to the frequency of fish consumption.
The amount of fish meat per meal is also closely related to the selenium and MeHg concentration in the blood. The mean concentrations of total selenium in the cellular fraction (p-trend 0.001), selenoneine in the cellular fraction (p-trend 0.005), Se-containing proteins in the cellular fraction (p-trend 0.004), MeHg in the cellular fraction (p-trend 0.008), and mercury in the serum (p-trend 0.009) increased with the categories of amount of fish meat per meal (Fig. 3). Concentrations of inorganic Hg in the cellular fraction and total selenium and mercury in the serum were not significantly related to the amount of fish meat per meal.
We also analyzed the levels of MeHg and LC-PUFA. In the 167 subjects tested, concentrations of MeHg ranged from 0.022 to 0.469 μg total Hg/g (mean ± SD = 0.087 ± 0.076 μg/g). Concentrations of EPA plus DHA ranged from 24 to 585 mg/kg (mean ± SD = 141 ± 83 mg/kg). The content of inorganic Hg ranged from 0.0001 to 0.0549 μg total Hg/g (mean ± SD = 0.013 ± 0.008 μg total Hg/g). Concentrations of total mercury in the serum ranged from 0.000015 to 0.0203 μg/g (mean ± SD = 0.0042 ± 0.005 μg/g).
Concentrations of selenoneine in the cellular fraction were significantly correlated with concentrations of total selenium (r = 0.91, p < 0.0001; Fig. 4a) and MeHg (r = 0.58, p < 0.0001; Fig. 4b) in the cellular fraction and total selenium (r = 0.46, p < 0.0001; Fig. 4c) and LC-PUFA (r = 0.45, p < 0.0001; Fig. 4d) in the serum. In contrast, concentrations of selenoneine in the cellular fraction did not correlate significantly with concentrations of inorganic mercury or Se-containing proteins in the cellular fraction or levels of total mercury in the serum. The selenium–MeHg molar ratio in the cellular fraction ranged from 3.5:1 to 81.1:1 in all cases examined (mean = 41.9:1) (Fig. 5).
Discussion
The present study demonstrates that selenoneine is the major selenium compound in the RBCs of a fish-eating population in Japan. When we compared the concentrations of selenoneine and total selenium in the cellular fraction and the concentration of selenium in the serum with the frequency of fish consumption among the 167 people living in these remote islands, we found that levels of the selenoneine in the cellular fraction were closely related to the frequency of fish consumption. In the serum, we detected Se-containing proteins and a selenosugar-like low molecular weight compound, but not selenoneine, and concentrations of selenium in the serum were not correlated with the frequency of fish consumption. Therefore, selenoneine in the cellular fraction is identified as an important biomarker of the intake of selenium from fish consumption in this Japanese fish-eating population.
There have been several reports on concentrations of selenium in the blood of Japanese subjects. Imai et al. reported that concentrations of selenium in the RBCs and serum of middle-aged Japanese subjects were 0.244 and 0.111 μg Se/g for males and 0.235 and 0.107 μg Se/g for females, respectively [5]. Fish consumption, age, and alcohol intake are related to levels of selenium in the blood. Suzuki et al. reported that concentrations of selenium in the RBCs and serum of Japanese female college students were 0.31 and 0.13 μg Se/g [4]. Alfthan et al. reported that supplementation of selenium-rich yeast increased the concentration of selenium in the plasma from 0.112 to 0.170 μg/g and the concentration of selenium in the RBCs from 0.189 to 0.356 μg/g after 11 weeks [12]. Excessive concentrations of selenium in the RBCs, from 0.36 to 1.32 μg/g, have been reported in residents of a high-selenium region of Venezuela with chronic selenosis [6]. The current findings for these remote islands in Kagoshima show total selenium levels of 0.510 μg/g in the cellular fraction and 0.174 μg/g in the serum, representing the highest exposure to selenium among previous reports on chronic selenosis in the USA, China, Colombia, and Venezuela. In the case of selenosis, selenite or selenomethionine were incorporated [6]. However, the current results indicate that the chemical form of selenium was selenoneine derived from fish consumption, which is distinct from the other reported cases of selenosis [6].
Recent findings from human trials have raised concern that high long-term selenium supplementation may be associated with type 2 diabetes or insulin resistance [28, 29]. Type 2 diabetes is associated with oxidative stress attributable to the production of excess levels of reactive oxygen species in hyperglycemia [30–32]. Selenium supplementation induces selenoproteins, such as GPx1 and selenoprotein P [31, 32]. High activity of GPx1 can interfere with insulin signaling by removing hydrogen peroxide that acts as a second messenger [30–32]. Selenoprotein P is also implicated in insulin resistance [33]. Selenoprotein P impaired insulin signaling in the liver and skeletal muscle in mouse and induced glucose intolerance [33]. In contrast, mice deficient in selenoprotein P showed improved glucose tolerance and enhanced insulin signaling [33]. Selenium yeast is predominantly selenomethionine, a form that is not abundant in ocean fish [34]. Since long-term selenium supplementation with selenium yeast is linked to the development of type 2 diabetes, further research is required to characterize whether higher selenium intake by fish and seafood consumption may be associated with type 2 diabetes risk. According to a recent large-scale, population-based cohort study in Japan, fish consumption was associated with a lower risk of type 2 diabetes in men but not in women [35]. Fish intake was not associated with an increased risk of type 2 diabetes in either men or women [35]. Therefore, selenoneine intake by fish consumption might not associate with the increased risk of type 2 diabetes that found in long-term selenium supplementation with selenium yeast.
Selenoneine is incorporated into animal cells through the OCTN1 transporter [21]. RBCs express the OCTN1 transporter and accumulate selenoneine. The RBCs of marine animals, such as bluefin tuna [15] and dolphins (Yamashita et al., unpublished), contain high levels of selenoneine (>1 μg Se/g). Anan also reported selenoneine in the liver of turtle [36]. Klein et al. reported a selenoneine-derivative Se-methylselenoneine in human urine [37]. Mammalian OCTN1 is thought to be involved in the secretion of cations in renal proximal tubules and the small intestine [38]. Mutations and variations of the OCTN1 gene and selenium status are linked to Crohn's disease [39–41]. Further investigation will require surveying a relationship between the susceptibility to Crohn's disease in patients with OCTN1 variations and the dietary selenium intake from seafood.
Previously, contents of selenium in the serum and levels of total selenium in hair and toenail samples were measured as a biomarker of selenium in a human population [42–46]. Plasma selenoprotein P and GPx levels were used as biomarkers for selenium supplementation [42]. However, the current study clearly demonstrates that the level of selenoneine in the RBCs should be determined as a biomarker for selenium intake and redox status by fish consumption.
Furthermore, levels of selenoneine in the cellular fraction are closely related to levels of MeHg in the cellular fraction and levels of LC-PUFA in the serum. Previously, mercury levels in the cellular fraction showed a significant positive correlation with selenium levels, suggesting that Se potentially can work to moderate the toxicity of MeHg [47]. Blood MeHg and LC-PUFA are also confirmed to be correlated with fish consumption [22–25]. The selenium–MeHg molar ratio in the cellular fraction ranged from 3.5:1 to 81.1:1 (mean = 41.9:1), suggesting that excess amounts of selenium against MeHg contents might be present in the cellular fraction and reduce MeHg toxicity (Fig. 5). High mercury exposure risks by fish consumption may depend on dietary selenium intakes and selenium status, as pointed out by Raymond et al. [18]. To estimate the MeHg risks associated with fish consumption, animal trials of feeding with both MeHg and selenoneine for selenium–MeHg molar ratios of >3.5:1 in the cellular fractions will be conducted. Selenoneine mediated MeHg demethylation and excretion in human cultured cells and zebrafish embryos [21]. Further study is required to obtain evidences that inorganic mercury might be produced by exosomal secretion mechanisms mediated by selenoneine and OCTN1 in humans.
In conclusion, selenoneine was the major chemical form of selenium in the cellular fraction of this fish-eating human population. Concentrations of selenoneine and total selenium in the cellular fraction might be used as an important biomarker for fish consumption and selenium antioxidant and detoxification functions.
References
Yamashita Y, Yamashita M (2010) Identification of a novel selenium-containing compound, selenoneine, as the predominant chemical form of organic selenium in the blood of bluefin tuna. J Biol Chem 285(24):18134–18138
Yamashita Y, Yabu T, Yamashita M (2010) Discovery of the strong antioxidant selenoneine in tuna and selenium redox metabolism. World J Biol Chem 1(5):144–150
Yamashita Y, Amlund H, Suzuki T, Hara T, Hossain MA, Yabu T, Touhata K, Yamashita M (2011) Selenoneine, total selenium, and total mercury content in the muscle of fishes. Fish Sci 77(4):679–686
Suzuki T, Hongo T, Ohba T, Kobayashi K, Imai H, Ishida H, Suzuki H (1989) The relation of dietary selenium to erythrocyte and plasma selenium concentrations in Japanese college women. Nutr Res 9:839–848
Imai H, Suzuki T, Kashiwazaki H, Takemoto T, Izumi T, Moji K (1990) Dietary habit and selenium concentrations in erythrocyte and serum in a group of middle-aged and elderly Japanese. Nutr Res 10:1205–1214
Gerald F Jr, Combs SB (1986) The role of selenium in nutrition. Academic, New York
Fairweather-Tait SJ, Collings R, Hurst R (2010) Selenium bioavailability: current knowledge and future research requirements. Am J Clin Nutr 91(5):S1484–S1491
Hagmar L, Persson-Moschos M, Akesson B, Schütz A (1998) Plasma levels of selenium, selenoprotein P and glutathione peroxidase and their correlations to fish intake and serum levels of thyrotropin and thyroid hormones: a study on Latvian fish consumers. Eur J Clin Nutr 52(11):796–800
Fox TE, Van den Heuvel EG, Atherton CA, Dainty JR, Lewis DJ, Langford NJ, Crews HM, Luten JB, Lorentzen M, Sieling FW, van Aken-Schneyder P, Hoek M, Kotterman MJ, van Dael P, Fairweather-Tait SJ (2004) Bioavailability of selenium from fish, yeast and selenate: a comparative study in humans using stable isotopes. Eur J Clin Nutr 58(2):343–349
Fox TE, Atherton C, Dainty JR, Lewis DJ, Langford NJ, Baxter MJ, Crews HM, Fairweather-Tait SJ (2005) Absorption of selenium from wheat, garlic, and cod intrinsically labeled with Se-77 and Se-82 stable isotopes. Int J Vitam Nutr Res 75(3):179–186
McAdam PA, Orville LA (1987) Chronic toxicity and retention of dietary selenium fed to rats as D- or L-selenomethionine, selenite, or selenate. Nutr Res 7:601–610
Alfthan G, Aro A, Arvilommi H, Huttunen JK (1991) Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite, and selenate. Am J Clin Nutr 53(1):120–125
Rayman MP, Infante HG, Sargent M (2008) Food-chain selenium and human health: spotlight on speciation. Br J Nutri 100(2):238–253
Ganther HE, Goudie C, Sunde ML, Kopecky MJ, Wagner P (1972) Selenium: relation to decreased toxicity of methylmercury added to diets containing tuna. Science 175(4026):1122–1124
Cuvin-Aralar ML, Furness RW (1991) Mercury and selenium interaction: a review. Ecotoxicol Environ Saf 21(3):348–364
Suzuki T, Imura N, Clarkson TW (1991) Advances in mercury toxicology. Plenum, New York
Ralston NV, Ralston CR, Blackwell JL 3rd, Raymond LJ (2008) Dietary and tissue selenium in relation to methylmercury toxicity. Neurotoxicology 29(5):802–811
Raymond LJ, Ralston NVC, Seale LA (2011) Seafood selenium in relation to assessments of methylmercury exposure risks. In: Hatfield DL, Berry MJ, Gladyshev VN (eds) Selenium: its molecular biology and role in human health. Springer, New York, pp 399–408
FAO (2011) Fisheries and Aquaculture Report No. 978 Report of the Joint FAO/WHO Expert Consultation on the Risks and Benefits of Fish Consumption
Mozaffarian D (2009) Fish, mercury, selenium and cardiovascular risk: current evidence and unanswered questions. Int J Environ Res Public Health 6(6):1894–1916
Yamashita M, Yamashita Y, Suzuki T, Kani K, Mizusawa N, Imamura S, Takemoto T, Hara T, Hossain MA, Yabu T, Touhata K (2013) Selenoneine, a novel selenium-containing compound, mediates detoxification mechanisms against methylmercury accumulation and toxicity in zebrafish embryo. Mar Biotechnol 15(5):559−570
Andoh T, Uda H, Yoshimitsu N, Hatano H, Ueda T, Iwamatsu Y, Akiba S (1997) The sex differences in cord-blood cholesterol and fatty-acid levels among Japanese fetuses. J Epidem 7(4):226–231
Wakisaka I, Ando T, Yanagihashi T (1986) Interrelationships among hair mercury levels, fish-eating habits and fatty acid composition of serum lipid. Jpn J Hyg 41:828–835
Wakisaka I, Ando T, Yanagihashi T, Tominaga K (1986) Fatty acid composition of serum lipids of remote islanders in Kagoshima Prefecture. Jpn J Public Health 33:11
Tsuji M, Ando T, Kitano T, Wakamiya J, Koriyama C, Akiba S (2012) Relationship between RBC mercury levels and serum n3 polyunsaturated fatty acid concentrations among Japanese men and women. J Environ Pub Health 2012; Article ID 849305
Hasunuma R, Ogawa T, Kawanishi Y (1982) Fluorometric determination of selenium in nanogram amounts in biological materials using 2,3-diaminonaphthalene. Anal Biochem 126:242–245
Friberg L, Mottet NK (1989) Accumulation of methylmercury and inorganic mercury in the brain. Biol Trace Elem Res 21:201–206
Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, Cappuccio FP, Ceriello A, Reid ME (2007) Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med 147(4):217–223
Rayman MP, Stranges S (2013) Epidemiology of selenium and type2 diabetes: can we make sense of it? Free Radic Biol Med. doi:10.1016/j.freeradbiomed.2013.04.003
Ezaki O (1990) The insulin-like effects of selenite in rat adipocytes. J Biol Chem 265(2):1124–1128
Steinbrenner H, Speckmann B, Pinto A, Sies H (2011) High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism. J Clin Biochem Nutr 48(1):40–45
Chung SS, Kim M, Youn BS, Lee NS, Park JW, Lee IK, Lee YS, Kim JB, Cho YM, Lee HK, Park KS (2009) Glutathione peroxidase 3 mediates the antioxidant effect of peroxisome proliferator-activated receptor gamma in human skeletal muscle cells. Mol Cell Biol 29(1):20–30
Wang XD, Vatamaniuk MZ, Wang SK, Roneker CA, Simmons RA, Lei XG (2008) Molecular mechanisms for hyperinsulinaemia induced by overproduction of selenium-dependent glutathione peroxidase-1 in mice. Diabetologia 51(8):1515–1524
Schrauzer G (2006) Selenium yeast: composition, quality, analysis, and safety. Pure Appl Chem 78(1):105–109
Nanri A, Mizoue T, Noda M, Takahashi Y, Matsushita Y, Poudel-Tandukar K, Kato M, Oba S, Inoue M, Tsugane S (2011) Japan public health center-based prospective study group. Fish intake and type 2 diabetes in Japanese men and women: the Japan public health center-based prospective study. Am J Clin Nutr 94(3):884–891
Anan Y, Ishiwata K, Suzuki N, Tanabe S, Ogra Y (2011) Speciation and identification of low molecular weight selenium compounds in the liver of sea turtles. J Anal At Spectrom 26:80–85
Klein M, Ouerdane L, Bueno M, Pannier F (2011) Identification in human urine and blood of a novel selenium metabolite, Se-methylselenoneine, a potential biomarker of metabolization in mammals of the naturally occurring selenoneine, by HPLC coupled to electrospray hybrid linear ion trap-orbital ion trap MS. Metallomics 3(5):513–520
Kato Y, Kubo Y, Iwata D, Kato S, Sudo T, Sugiura T, Kagaya T, Wakayama T, Hirayama A, Sugimoto M, Sugihara K, Kaneko S, Soga T, Asano M, Tomita M, Matsui T, Wada M, Tsuji A (2010) Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharm Res 27(5):832–840
Taubert D, Grimberg G, Jung N, Rubbert A, Schömig E (2005) Functional role of the 503F variant of the organic cation transporter OCTN1 in Crohn's disease. Gut 54(10):1505–1506
Rannem T, Ladefoged K, Hylander E, Hegnhıj J, Jarnum S (1992) Selenium status in patients with Crohn's disease. Am J Clin Nutr 56(5):933–937
Xuan C, Zhang BB, Yang T, Deng KF, Li M, Tian RJ (2012) Association between OCTN1/2 gene polymorphisms (1672C-T, 207G-C) and susceptibility of Crohn's disease: a meta-analysis. Int J Colorectal Dis 27(5):11–19
Burk RF, Norsworthy BK, Hill KE, Motley AK, Byrne DW (2006) Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial. Cancer Epidemiol Biomarkers Prev 15(4):804–810
Mozaffarian D, Shi P, Morris JS, Spiegelman D, Grandjean P, Siscovick DS, Willett WC, Rimm EB (2011) Mercury exposure and risk of cardiovascular disease in two US cohorts. N Engl J Med 364(12):1116–1125
Longnecker MP, Stampfer MJ, Morris JS et al (1993) A 1-y trial of the effect of high-selenium bread on selenium concentrations in blood and toenails. Am J Clin Nutr 57(3):408–413
Longnecker MP, Stram DO, Taylor PR, Levander OA, Howe M, Veillon C, McAdam PA, Patterson KY, Holden JM, Morris JS, Swanson CA, Willett WC (1996) Use of selenium concentration in whole blood, serum, toenails, or urine as a surrogate measure of selenium intake. Epidemiology 7(4):384–390
Koriyama C, Campos FI, Yamamoto M, Serra M, Carrasquilla G, Carrascal E, Akiba S (2008) Toenail selenium level and gastric cancer risk in Cali, Colombia. J Toxicl Sci 33(2):227–235
Sakamoto M, Murata K, Kubota M, Nakai K, Satoh H (2010) Mercury and heavy metal profiles of maternal and umbilical cord RBCs in Japanese population. Ecotoxicol Environ Saf 73(1):1–6
Acknowledgments
We thank T. Suzuki and T. Hara for selenium and mercury analysis. This work was supported in part by grants from the Japan Society for the Promotion of Science, the Fisheries Research Agency, and the Ministry of Agriculture, Forestry and Fisheries of Japan.
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Yamashita, M., Yamashita, Y., Ando, T. et al. Identification and Determination of Selenoneine, 2-Selenyl-N α , N α , N α -Trimethyl-l-Histidine, as the Major Organic Selenium in Blood Cells in a Fish-Eating Population on Remote Japanese Islands. Biol Trace Elem Res 156, 36–44 (2013). https://doi.org/10.1007/s12011-013-9846-x
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DOI: https://doi.org/10.1007/s12011-013-9846-x