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Synthesis, quantification and in vivo assessment of arsenolipids prevalent in seafoods

海鲜中常见砷脂的合成、定量和体内评估

基本信息

批准号：
10289276
负责人：
Jeremy Davidson Bailoo
金额：
$ 7.47万
依托单位：
TEXAS TECH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-21 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10289276
关键词：
Accounting Acute Address Affect Arsenic Attention Behavioral Biological Bladder Brain Characteristics Chemical Structure Chronic Cognitive Collaborations Consequentialism Consumption Coupled Data Development Diabetes Mellitus Diet Disease Evaluation Exposure to Fatty Acids Fatty Alcohols Feces Food Future Goals Health Health Benefit High Pressure Liquid Chromatography Human Hydrocarbons In Vitro Inductively Coupled Plasma Mass Spectrometry Ingestion Knowledge Laboratories Lead Light Link Liver Metabolism Methods Modeling Mus Neurologic Deficit Organ Outcome Population Proteins Public Health Reference Standards Regulation Research Risk Risk Assessment Role Route Seafood Source System Texas Thinness Tissues Toxic Environmental Substances Toxic effect Toxicokinetics Toxicology Universities Urine Work bioaccumulation cardiovascular disorder risk cohort cytotoxic cytotoxicity drinking water health economics improved in vitro Model in vivo insight malignant neurologic neoplasms mouse model neurotoxic novel marker public health relevance tool

项目摘要

PROJECT SUMMARY / ABSTRACT Arsenic (As) is an environmental toxin that is causally associated with increased risk of cardiovascular disease, diabetes, neurological deficits and cancers in humans. The primary route of As exposure in humans is via diet: food and drinking water. While the toxicological risks of exposure to As from drinking water have been well studied, little is known about the toxicological risk of exposure to As from food sources. Addressing this data gap is critical considering that 93% of As exposure occurs via the ingestion of food—with seafood consumption accounting for 83.7% of that exposure. Moreover, increasing evidence suggests that chronic exposure to As, as would be expected from the consumption of seafood, can affect cognitive-behavioral development—an understudied, yet significant, health- and economic- consequence. Given the associated health benefits with the consumption of seafood as a lean source of protein, and consequential predicted increase in consumption, delineating the elimination, bioaccumulation and behavioral consequences of the ingestion of As species common to seafood is of paramount importance. In seafoods, a large fraction of As occurs as arsenolipids, a class of compounds which includes arseno-fatty acids (As-FA), arseno-hydrocarbons (As-HC) and arseno-fatty alcohols (TMA-FOH). It is commonly assumed that organically-bound As species, such as As- FAs, As-HCs, and TMA-FOHs, have no toxicological consequence. This assumption is refuted by two converging lines of evidence. First, inorganic As is often metabolized to organic As species which are toxic. Second, As-FAs and As-HCs have been determined in vitro to be cytotoxic and potentially neurotoxic. TMA-FOHs have received scant attention, despite having a similar chemical structure and thus potentially similar toxicological characteristics. To address these critical knowledge gaps, we will develop methods for the synthesis and quantification of TMA-FOHs in biological matrices, such as organs, urine and feces. We will also characterize the elimination profile of mice acutely exposed to representative As-FA, As-HC and TMA-FOH compounds at varying concentrations. This evaluation will provide significant new knowledge about the potential for toxicity of three common arsenolipids in seafood. To further disentangle this potential, we will also extend this evaluation to mice exposed chronically to these As species. We will evaluate storage of these species in organs as well as the health-related behavioral consequences of such exposure. Completion of this study will provide significant new knowledge about the role of organic As species, in general, and arsenolipids, in particular, in human health and disease, with potential consequences for the development of public health regulations.

项目摘要/摘要