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首页> 外文学位 >Interactions of Dietary Antioxidants and Methylmercury on Health Outcomes and Toxicodynamics: Evidence from Developmental Rat Model Studies and Human Epidemiology.
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Interactions of Dietary Antioxidants and Methylmercury on Health Outcomes and Toxicodynamics: Evidence from Developmental Rat Model Studies and Human Epidemiology.

机译：饮食抗氧化剂和甲基汞对健康结局和毒理动力学的相互作用：来自发育大鼠模型研究和人类流行病学的证据。

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摘要

The contamination of seafood with methylmercury (MeHg) is a global health issue, as MeHg is a well known neurotoxin. Since dietary nutrients may interact with MeHg toxicity, and oxidative stress is one of the primary mechanisms underlying MeHg neurotoxicity, we characterized dietary antioxidant-MeHg interactions. Firstly, we used an ethnobotanical study to confirm the antioxidant activity of Northern Labrador Tea, Rhododendron tomentosum ssp. subarcticum (Tea), for the Canadian Inuit, a population with elevated MeHg exposure. Secondly, we determined the ability of Tea to ameliorate MeHg-induced toxicity in a rat perinatal exposure study. MeHg exposure (2 mg/KgBW/d) was associated with perturbed development and behaviour, elevated brain N-methyl-D-aspartate receptors, and serum lipid peroxidation. Surprisingly, Tea co-exposure (100 mg/KgBW/d) modulated MeHg's effects on brain NMDA-R levels and lipid peroxidation, but also increased mercury serum concentrations. Thirdly, using a toxicogenomics approach we determined that MeHg exposure caused the down-regulation of Nr4a2 and its protein product Nurr1. These novel MeHg targets are implicated in developmental learning functions and were corrected with MeHg + Tea co-exposure. Lastly, we conducted a risk assessment survey and cross-sectional dietary epidemiology study in Costa Rica to further investigate dietary nutrient-MeHg interactions. Costa Rica is a Central American country with multiple sources of Hg and a high per capital fish consumption. Here, 5 of the 14 populations we studied exceeded the recommended MeHg provisional tolerable daily intake (pTDI) of 0.2 microg/KgBW/d. In Heredia the pTDI was exceeded by 34% of woman participants, primarily associated with canned tuna consumption. Interestingly, we detected that Hg body burden was significantly reduced by the consumption of antioxidant-rich dietary items. Considering our collective results, we hypothesized that MeHg toxicokinetics may be altered by dietary nutrients at the site of intestinal absorption from the disruption of gut flora, or at the site of cellular demethylation in tissues from the improvement of cellular redox state. The interaction of dietary nutrients on MeHg outcomes has a large impact on risk assessment and may provide a public health approach for managing the risk associated with MeHg exposure without reducing local fish consumption.
机译：甲基汞（MeHg）对海鲜的污染是全球性的健康问题，因为甲基汞是众所周知的神经毒素。由于膳食营养素可能与MeHg毒性相互作用，而氧化应激是MeHg神经毒性的主要机制之一，因此我们表征了膳食抗氧化剂与MeHg的相互作用。首先，我们通过一项民族植物学研究来确认北拉布拉多茶，杜鹃杜鹃（Shodo杜鹃）的抗氧化活性。 subarcticum（茶），对于加拿大因纽特人来说，是MeHg暴露水平升高的人群。其次，我们在大鼠围产期暴露研究中确定了茶改善MeHg诱导的毒性的能力。 MeHg暴露（2 mg / KgBW / d）与发育和行为紊乱，脑N-甲基-D-天冬氨酸受体升高以及血脂过氧化有关。出人意料的是，茶的共同暴露（100 mg / KgBW / d）调节了MeHg对大脑NMDA-R水平和脂质过氧化的影响，但同时也增加了汞血清浓度。第三，使用毒理基因组学方法，我们确定MeHg暴露引起Nr4a2及其蛋白产物Nurr1的下调。这些新颖的MeHg靶标与发育学习功能有关，并已通过MeHg + Tea共同暴露进行了校正。最后，我们在哥斯达黎加进行了风险评估调查和横断面饮食流行病学研究，以进一步调查饮食中营养物与MeHg的相互作用。哥斯达黎加是中美洲国家，其汞来源多种多样，人均鱼类消费量很高。在这里，我们研究的14个人群中有5个超出了建议的MeHg临时耐受每日摄入量（pTDI），即0.2 microg / KgBW / d。在埃雷迪亚，有34％的女性参与者超过了pTDI，这主要与金枪鱼罐头的消费有关。有趣的是，我们发现食用富含抗氧化剂的饮食可以显着降低汞的负担。考虑到我们的集体研究结果，我们假设MeHg的毒代动力学可能会因肠道菌群破坏而引起的肠道吸收部位或组织中细胞氧化还原状态改善引起的细胞脱甲基部位的饮食营养改变。膳食营养素对甲基汞结果的相互作用对风险评估有很大影响，并可能提供一种公共卫生方法来管理与甲基汞暴露相关的风险，而又不减少当地鱼类的消费。

著录项

  • 作者

    Black, Paleah L.;

  • 作者单位

    University of Ottawa (Canada).;

  • 授予单位 University of Ottawa (Canada).;
  • 学科 Health Sciences Toxicology.;Health Sciences Epidemiology.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 245 p.
  • 总页数 245
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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