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

doi:10.1016/j.heliyon.2019.e02079

Metabolism of 3-[5'-deoxy-5'-(dimethylarsinoyl)-β-ribofuranosyloxy]-2-hydroxypropylene glycol in an artificial digestive system

Heliyon. 2019 Jul 19;5(7):e02079. doi: 10.1016/j.heliyon.2019.e02079. eCollection 2019 Jul.

Authors

Akihisa Hata¹, Momoko Hasegawa², Takenori Yamauchi³, Yuki Otomo², Motofumi Miura⁴, Kenzo Yamanaka⁵, Yuko Yamano³, Noboru Fujitani⁶, Ginji Endo⁷

Affiliations

¹ Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoino-oka, Imabari, Ehime, 794-8555, Japan.
² 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.
³ Department of Hygiene and Preventive Medicine, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
⁴ Laboratory of Molecular Chemistry, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
⁵ Laboratory of Environmental Toxicology and Carcinogenesis, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
⁶ Biomedical Science Examination and Research Center, Okayama University of Science, 1-3 Ikoino-oka, Imabari, Ehime, 794-8555, Japan.
⁷ Osaka Occupational Health Service Center, Japan Industrial Safety and Health Association, 2-3-8 Tosabori, Nishi-ku, Osaka, 550-0001, Japan.

Abstract

Seaweeds contain large amounts of organoarsenic compounds, mostly arsenosugars (AsSug) and arsenolipids (AsLipid). AsSug is mainly metabolized into dimethylarsinic acid (DMA ^V ) 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 DMA ^V 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 DMA ^V in the liver and subsequently excreted through urine.

Keywords: Arsenic; Arsenosugar; Environmental Health; Environmental Toxicology; Food Analysis; Food Science; Intestinal bacteria; Public Health; Seafood; Thiolation; Toxicology.