title: Inhibition of the thioredoxin system in the brain and liver of zebra-seabreams exposed to waterborne methylmercury.
abstract: Mercury compounds were recently found to interact in vitro with the thioredoxin system, inhibiting both Thioredoxin (Trx) and Thioredoxin reductase (TrxR). In order to evaluate if Trx and TrxR are affected in vivo by methylmercury (MeHg), we exposed juvenile zebra-seabreams to different concentrations of this toxicant in water for 28days followed by a 14-day depuration period. Methylmercury accumulated to a larger extent in the kidney and liver of fishes, but decreased significantly during the depuration. During the exposure, MeHg percentage in the liver reached levels above 90% of total mercury (HgT) decreasing to 60% of HgT by the end of the depuration period. In the kidney, MeHg accounted for 50-70% of HgT. In the brain and muscle, mercury accumulated throughout the exposure with all mercury being MeHg. The total mercury kept increasing in these organs during the depuration period. However, in the brain, this increase in HgT was accompanied by a decrease in the MeHg percentage (~10%). In the liver, both Trx and TrxR activities were significantly reduced (TrxR--40%; Trx--70%) by the end of the exposure, but recovered to control levels (100%) during the depuration. In the brain, both enzymes where inhibited during the depuration period (TrxR--75%; Trx--70%) when some production of inorganic mercury was detected. Activity of glutathione reductase showed increased levels when TrxR activity was low, suggesting complementarity between both systems. These results indicate that in vivo the thioredoxin system is a toxicological target for MeHg with TrxR being particularly affected.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon. Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Vasco
authors.initials: V
authors.lastname: Branco
authors.forename: João
authors.initials: J
authors.lastname: Canário
authors.forename: Arne
authors.initials: A
authors.lastname: Holmgren
authors.forename: Cristina
authors.initials: C
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D021541:Sea Bream / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013879:Thioredoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
chemical_list: D008767:Methylmercury Compounds; D014874:Water Pollutants, Chemical; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase