Yumiko Yamashita

Identification of a Novel Selenium-containing Compound, Selenoneine, as the Predominant Chemical Form of Organic Selenium in the Blood of Bluefin Tuna

A novel selenium-containing compound having a selenium atom in the imidazole ring, 2-selenyl-Nα,Nα,Nα-trimethyl-l-histidine, 3-(2-hydroseleno-1H-imidazol-5-yl)-2-(trimethylammonio)propanoate, was identified from the blood and other tissues of the bluefin tuna, Thunnus orientalis. The selenium-containing compound was purified from the tuna blood in several chromatographic steps. High resolution mass spectrometry and nuclear magnetic resonance spectroscopy showed that the exact mass of the [M+H]+ ion of the compound was 533.0562 and the molecular formula was C18H29N6O4Se2. Its gross structure was assigned as the oxidized dimeric form of an ergothioneine selenium analog in which the sulfur of ergothioneine is replaced by selenium. Therefore, we named this novel selenium-containing compound “selenoneine.” By speciation analysis of organic selenium compounds using liquid chromatography inductively coupled plasma mass spectrometry, selenoneine was found widely distributed in various tissues of the tuna, with the highest concentration in blood; mackerel blood contained similar levels. Selenoneine was measurable at 2–4 orders of magnitude lower concentration in a limited set of tissues from squid, tilapia, pig, and chicken. Quantitatively, selenoneine is the predominant form of organic selenium in tuna tissues.

Discovery of the strong antioxidant selenoneine in tuna and selenium redox metabolism

A novel selenium-containing compound, selenoneine, has been isolated as the major form of organic selenium in the blood and tissues of tuna. Selenoneine harbors a selenium atom in the imidazole ring, 2-selenyl-N(α), N(α), N(α)-trimethyl-L-histidine, and is a selenium analog of ergothioneine. This selenium compound has strong antioxidant capacity and binds to heme proteins, such as hemoglobin and myoglobin, to protect them from iron auto-oxidation, and it reacts with radicals and methylmercury (MeHg). The organic cations/carnitine transporter OCTN1 transports selenoneine and MeHg, regulates Se-enhanced antioxidant activity, and decreases MeHg toxicity. Thus, the dietary intake of selenoneine, by consuming fish, might decrease the formation of reactive oxygen radicals that could oxidize nucleotides in DNA, and thereby inhibit carcinogenesis, chronic diseases, and aging.

Distinct regional profiles of trace element content in muscle of Japanese eel Anguilla japonica from Japan, Taiwan, and China

Trace element distribution patterns were examined in Japanese eel from five Asian regions for the purpose of identifying the elements and patterns that could be used to determine provenance. Distinctive patterns were found in eels from the Japanese prefectures of Miyazaki, Kagawa, and Shizuoka, and from Taiwan and China. The levels of six trace elements, selenium, mercury, copper, manganese, zinc, and arsenic, in muscle tissue varied among eels of different origins, and factorial analysis of the elemental patterns showed that Factor 1 was attributable to selenium and mercury levels and Factor 2 to zinc and copper levels. Multivariate analysis showed that the patterns of elemental composition in fish muscle were mainly differentiated by these two factors.

Selenium Content in Seafood in Japan

Selenium is an essential micronutrient for humans, and seafood is one of the major selenium sources, as well as red meat, grains, eggs, chicken, liver and garlic. A substantial proportion of the total amount of selenium is present as selenium containing imidazole compound, selenoneine, in the muscles of ocean fish. In order to characterize the selenium content in seafood, the total selenium levels were measured in the edible portions of commercially important fish and shellfish species. Among the tested edible portions, alfonsino muscle had the highest selenium levels (concentration of 1.27 mg/kg tissue). High levels of selenium (1.20–1.07 mg/kg) were also found in the salted ovary products of mullet and Pacific herring. In other fish muscles, the selenium levels ranged between 0.12 and 0.77 mg/kg tissue. The selenium levels were closely correlated with the mercury levels in the white and red muscles in alfonsino. The selenium content in spleen, blood, hepatopancreas, heart, red muscle, white muscle, brain, ovary and testis ranged between 1.10 and 24.8 mg/kg tissue in alfonsino.

Differences in vitamin K concentration in Japanese eel Anguilla japonica from different cultured areas

Vitamin K was discovered by Dann as an essential cofactor in blood coagulation, and its importance in bone health has recently been documented in mammals. Vitamin K is well known to have several derivatives, such as phylloquinone (PK), mennaquinone (MK) and menadione (MD). PK, also called vitamin K1, is produced by plants. MK, also called vitamin K2, is produced by bacteria and exists as a homologous series, termed the MK-n series, that differs in the length of the side chain made by the repeated isoprene units (n). MD, also called vitamin K3, has no side chain and is an artificial product. The water-soluble salt of MD, menadione sodium bisulfite, is commonly added to commercial diets for domestic animals, including fish. Long-chain MK such as MK-7 and MK-9 are the major forms of vitamin K utilized in mammals. In fish, however, the utilizable form of vitamin K differs with feeding habits. Planktons and diatoms contain much PK, and the body tissue of pelagic fish and ayu Plecoglossus altivelis, which feed on these organisms, show a considerable accumulation of PK. In contrast, the body tissue of demersal fish contains mostly long-chain MK, because benthos, the main component of their diet, are rich in long-chain MK. Cultured fish, which feed on commercial diets, are rich in MK-4, because MD is metabolized to MK-4 after intake. The Japanese eel Anguilla japonica is a major fish throughout Japan, because a large amount of the cultured variety is consumed. It is cultured in many areas of Japan, as well as in Taiwan and China. Recently, the traceability of produce has become an important issue because quality must be considered as a meeting of the consumers’ wishes and needs, and the intrinsic and extrinsic quality attributes of fish. Today’s consumers want to be able to carefully select among fish cultured anywhere or wild fish. Consumers are concerned about how the fish are produced, and which types of feed ingredients are used. However, it is difficult to determine the place of origin simply by the appearance of the fish. In this study, therefore, the types of vitamin K in Japanese eel cultured in various areas were measured in order to detect differences by area of culture. There are two types of culture conditions, a controlled indoor pond and a non-controlled outdoor pond. In this study, the authors analyzed Japanese eel cultured in Aichi and Miyazaki Prefectures as examples of controlled indoor culture, and Japanese eel cultured in an outdoor pond in Taiwan as an example of noncontrolled outdoor culture. Specimens of Japanese eel were purchased at a commercial store in Yokohama (Kanagawa Prefecture) on 15 occasions, on a weekly basis from June 29 to October 26 2004; the fish had been cultured at Aichi, Miyazaki and Taiwan. The average body weight and length of the fish were: 52.2 g and 250.9 mm (Aichi), 53.5 g and 259.7 mm (Miyazaki), and 55.8 g and 284.1 mm (Taiwan). The fish were alive after transportation. After purchase, the fish were killed, and their liver and muscle were excised and frozen at -30°C until measurement. Ten fish were each pooled for measurement of vitamin K concentration in the muscle (Fig. 1) and liver (Fig. 3). However, for the first measurement made *Corresponding author: Tel: 81-45-788-7645. Fax: 81-45-788-5001. Email: udagawa@affrc.go.jp Received 18 May 2006. Accepted 22 January 2007. FISHERIES SCIENCE 2008; 74: 690–692

Selenoneine in Marine Organisms

A novel selenium-containing compound, selenoneine, 2-selenyl- N α Open image in new window, N α Open image in new window, N α Open image in new window-trimethyl-l-histidine, has been identified as the predominant form of organic selenium in the blood and tissues of tuna. This selenium compound has a selenium atom in the imidazole ring, and is a selenium analog of a thiol compound, ergothioneine. Selenoneine has radical scavenging activity and exerts an antioxidant effect by binding to hemoglobin and myoglobin, protecting them from iron auto-oxidation. In addition, selenoneine has detoxifying activity against methylmercury (MeHg). Selenoneine has been found to be a specific substrate for the organic cation/carnitine transporter OCTN1 (solute carrier family 22 Open image in new window member 4 Open image in new window, SLC22A4), and mediated the excretion and demethylation of MeHg by exosomal small vesicle formation. The dietary intake of selenoneine through fish consumption is an important selenium source in the human diet. Since selenoneine and its related selenoproteins have strong antioxidant activities, disease protective functions, such as anticarcinogenesis and aging effects, may be expected.

Dietary Supplementation of Selenoneine-Containing Tuna Dark Muscle Extract Effectively Reduces Pathology of Experimental Colorectal Cancers in Mice

Selenoneine is an ergothioneine analog with greater antioxidant activity and is the major form of organic selenium in the blood, muscles, and other tissues of tuna. The aim of this study was to determine whether a selenoneine-rich diet exerts antioxidant activities that can prevent carcinogenesis in two types of colorectal cancer model in mice. We administrated selenoneine-containing tuna dark muscle extract (STDME) to mice for one week and used azoxymethane (AOM) and dextran sodium sulfate (DSS) for inducing colorectal carcinogenesis. Next, we examined the incidence of macroscopic polyps and performed functional analysis of immune cells from the spleen. In the AOM/DSS-induced colitis-associated cancer (CAC) model, the oral administration of STDME significantly decreased tumor incidence and inhibited the accumulation of myeloid-derived suppressor cells (MDSCs) while also inhibiting the downregulation of interferon-γ (IFN-γ) production during carcinogenesis. These results suggest that dietary STDME may be an effective agent for reducing colorectal tumor progression.

Methylmercury and Selenium in Seafood

化学と生物 Vol. 50, No. 11, 2012 807 マグロ類やカジキ類,ハクジラ類などの海洋の高次捕食者に は,食物連鎖によって生物濃縮されたメチル水銀が,筋肉に 含まれることから,魚食からのメチル水銀の摂取による毒性 を明らかにする必要がある.水俣病のように,メチル水銀の 中毒事例から予想すると,低濃度のメチル水銀の長期曝露に よって,脳神経系や心臓・血管系の分化・発達異常が生じる 可能性がありうるが,実際には魚食によって微量なメチル水 銀を摂取し続けても,メチル水銀中毒は生じない.その理由 は,魚から高度不飽和脂肪酸やセレンなどを多量に摂取する ので,これらの成分がメチル水銀の蓄積や毒性発現の機序に 作用して,毒性を軽減することがわかってきた.魚食由来の メチル水銀の健康リスクは過大に評価されているのではない か.なぜ,魚食ではメチル水銀の毒性が打ち消されるのか. 水産物のメチル水銀とセレンによる解毒に関する最近の知見 を紹介する.