{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:17:07Z","timestamp":1791494227758,"version":"4.3.4"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":2489,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Methylmercury (MeHg) exhibits neurotoxicity through accumulation in the brain. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) plays an important role in reducing the cellular accumulation of MeHg.<\/jats:p>\n                  <jats:p>Objectives: We investigated the protective effect of isothiocyanates, which are known to activate Nrf2, on the accumulation of mercury after exposure to MeHg in vitro and in vivo.<\/jats:p>\n                  <jats:p>Methods: We used primary mouse hepatocytes in in vitro experiments and mice as an in vivo model. We used Western blotting, luciferase assays, atomic absorption spectrometry assays, and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assays, and we identified toxicity in mice based on hind-limb flaccidity and mortality.<\/jats:p>\n                  <jats:p>Results: The isothiocyanates 6-methylsulfinylhexyl isothiocyanate (6-HITC) and sulforaphane (SFN) activated Nrf2 and up-regulated downstream proteins associated with MeHg excretion, such as glutamate-cysteine ligase, glutathione S-transferase, and multidrug resistance\u2013associated protein, in primary mouse hepatocytes. Under these conditions, intracellular glutathione levels increased in wild-type but not Nrf2-deficient primary mouse hepatocytes. Pretreatment with 6-HITC and SFN before MeHg exposure suppressed cellular accumulation of mercury and cytotoxicity in wild-type but not Nrf2-deficient primary mouse hepatocytes. In comparison, in vivo administration of MeHg to Nrf2-deficient mice resulted in increased sensitivity to mercury concomitant with an increase in mercury accumulation in the brain and liver. Injection of SFN before administration of MeHg resulted in a decrease in mercury accumulation in the brain and liver of wild-type, but not Nrf2-deficient, mice.<\/jats:p>\n                  <jats:p>Conclusions: Through activation of Nrf2, 6-HITC and SFN can suppress mercury accumulation and intoxication caused by MeHg intake.<\/jats:p>","DOI":"10.1289\/ehp.1003123","type":"journal-article","created":{"date-parts":[[2011,3,7]],"date-time":"2011-03-07T15:16:16Z","timestamp":1299510976000},"page":"1117-1122","source":"Crossref","is-referenced-by-count":97,"title":["Isothiocyanates Reduce Mercury Accumulation via an Nrf2-Dependent Mechanism during Exposure of Mice to Methylmercury"],"prefix":"10.1021","volume":"119","author":[{"given":"Takashi","family":"Toyama","sequence":"first","affiliation":[{"name":"Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan"},{"name":"Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Shinkai","sequence":"additional","affiliation":[{"name":"Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yasutake","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Biochemistry Section, National Institute for Minamata Disease, Minamata, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Uchida","sequence":"additional","affiliation":[{"name":"Graduate School of Bioagricultural Sciences, Nagoya University, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Kumagai","sequence":"additional","affiliation":[{"name":"Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2011,3,7]]},"reference":[{"key":"2026080509063078100_micit1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1126\/science.181.4096.230","article-title":"Methylmercury poisoning in Iraq.","volume":"181","author":"Bakir","year":"1973","journal-title":"Science"},{"issue":"suppl 5","key":"2026080509063078100_micit2","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1289\/ehp.02110s5689","article-title":"Transport of toxic metals by molecular mimicry.","volume":"110","author":"Ballatori","year":"2002","journal-title":"Environ Health 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