Metabolism of 3-[5'-deoxy-5'-(dimethylarsinoyl)-β-ribofuranosyloxy]-2-hydroxypropylene glycol in an artificial digestive system
Akihisa Hata,
Momoko Hasegawa,
Takenori Yamauchi,
Yuki Otomo,
Motofumi Miura,
Kenzo Yamanaka,
Yuko Yamano,
Noboru Fujitani,
Ginji Endo
Affiliations
Akihisa Hata
Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoino-oka, Imabari, Ehime, 794-8555, Japan; Corresponding author.
Momoko Hasegawa
Department of Medical Risk Management, Graduate School of Risk and Crisis Management, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba, 288-0025, Japan
Takenori Yamauchi
Department of Hygiene and Preventive Medicine, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
Yuki Otomo
Department of Medical Risk Management, Graduate School of Risk and Crisis Management, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba, 288-0025, Japan
Motofumi Miura
Laboratory of Molecular Chemistry, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan
Kenzo Yamanaka
Laboratory of Environmental Toxicology and Carcinogenesis, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan
Yuko Yamano
Department of Hygiene and Preventive Medicine, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
Noboru Fujitani
Biomedical Science Examination and Research Center, Okayama University of Science, 1-3 Ikoino-oka, Imabari, Ehime, 794-8555, Japan
Ginji Endo
Osaka Occupational Health Service Center, Japan Industrial Safety and Health Association, 2-3-8 Tosabori, Nishi-ku, Osaka, 550-0001, Japan
Seaweeds contain large amounts of organoarsenic compounds, mostly arsenosugars (AsSug) and arsenolipids (AsLipid). AsSug is mainly metabolized into dimethylarsinic acid (DMAV) in humans. However, this metabolic process is not well understood. We investigated the metabolism of an AsSug, 3-[5'-deoxy-5'-(dimethylarsinoyl)-β-ribofuranosyloxy]-2-hydroxypropylene glycol (AsSug328), in the gastrointestinal tract using an in vitro artificial gastrointestinal digestion system. AsSug328 was incubated with gastric juice for 4 h, with bile-pancreatic juice for 0.5 h, and finally with enteric bacteria solution for 24 h. The conversion of arsenic compounds after artificial digestion was analyzed by HPLC-ICP-MS and HPLC-ESI-Q-TOF-MS. Our results show that artificial gastrointestinal digestion converted AsSug328 into thio-AsSug328. However, no formation of DMAV was detected. Under the artificial digestion system, the 5-deoxyribofuranose structure of AsSug was maintained. Therefore, AsSug should be absorbed in the intestinal tract after its sugar moiety is partially decomposed. They are then possibly metabolized to DMAV in the liver and subsequently excreted through urine.
