title: Anti-apoptotic effects of novel phenolic antioxidant isolated from the Pacific oyster (Crassostrea gigas) on cultured human hepatocytes under oxidative stress.
abstract: The antioxidant, and hepatoprotective properties of 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a natural phenolic antioxidant isolated from the Pacific oyster, were defined using cultured human hepatocyte-derived cells (C3A). DHMBA showed no cytotoxicity at 62.5-500μM, as well as chlorogenic acid (CGA), vitamin C, and vitamin E. However, butylated hydroxytoluene, eicosapentaenoic acid, docosahexaenoic acid and catechin reduced cell viability. In the presence of the prooxidant 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), DHMBA at 125-500μM improved cell viability, whereas CGA had no effect. DNA ladder formation and flow-cytometric studies indicated that DHMBA inhibited AAPH-induced apoptosis and necrosis. CGA was ineffective. Thus, DHMBA is a novel, potent antioxidant, effectively protecting cultured hepatocytes from apoptosis and necrosis caused by oxidative stress. Additionally, the concentration of DHMBA was determined by mass spectrometry to be 24.4μmol/kg wet oyster meat, and three polyphenols (gentisic acid, daidzein, and matairesinol) were newly identified in the oyster extracts.
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Fuda
authors.affiliation: Watanabe Oyster Laboratory Co. Ltd., 490-3, Shimoongata-cho, Hachioji, Tokyo 190-0154, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Hui
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Sae
authors.initials: S
authors.lastname: Joko
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okabe
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Jin
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Watanabe Oyster Laboratory Co. Ltd., 490-3, Shimoongata-cho, Hachioji, Tokyo 190-0154, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Miki
authors.affiliation: Watanabe Oyster Laboratory Co. Ltd., 490-3, Shimoongata-cho, Hachioji, Tokyo 190-0154, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan. Electronic address: chibahit@med.hokudai.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Chiba
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D049896:Crassostrea / Q000737:chemistry / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D010636:Phenols
keywords: Apoptosis; Butylated hydroxytoluene; Chlorogenic acid; DHMBA; Liver; Polyphenol; Polyunsaturated fatty acid; Vitamin