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

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.

Fig. 1

Speciation analysis of organic selenium in the human blood by LC-ICP-MS. Water-soluble selenium compounds were analyzed in the cellular fraction and in the serum. a A sample that contains a high concentration of total selenium. b A sample that contains a low concentration of total selenium. c Standards. An asterisk indicates that Se-containing proteins including GPx were eluted close to the void volume of the column. An arrow indicates the elution of selenoneine. d, Standard curve for selenium detection by LC-ICP-MS. Total counts of ⁸²Se per min in a peak area were accounted for bovine GPx1 (closed circle) and purified selenoneine (open square)

Fig. 2

Mean selenium and mercury concentrations of groups categorized by frequency of fish consumption. Concentrations of total selenium, selenoneine, and Se-containing proteins (Se protein) in the cellular fraction, total selenium in the serum, MeHg and inorganic mercury in the cellular fraction, and total mercury in the serum were compared to the frequency of fish consumption. 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. a–g, significant differences between the mean values (ANOVA)

Fig. 3

Mean selenium and mercury concentrations of groups categorized by volume of fish consumption. Concentrations of total selenium, selenoneine, and Se-containing proteins (Se protein) in the cellular fraction, total selenium in the serum, MeHg and inorganic mercury in the cellular fraction, and total mercury in the serum were compared to the volume of fish consumption. The subjects were divided into five categories of the amount of fish meat per meal: 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. a–f, significant differences between the mean values (ANOVA)

Fig. 4

Relationships between concentrations of selenoneine and total selenium in the cellular fraction (a), total selenium in the serum (b), MeHg in the cellular fraction (c), or LC-PUFA (EPA + DHA) (d)

Fig. 5

Relationship between MeHg concentration and Se/MeHg molar ratio in cellular fraction