Role of Environmental Weathering and Gastrointestinal Digestion on the Bioavailability and Toxicity of Microplastic and Cadmium Mixtures - A Platform for Undergraduate Interdisciplinary Training

环境风化和胃肠消化对微塑料和镉混合物的生物利用度和毒性的作用——本科生跨学科培训平台

• 批准号: 10580388
• 负责人: Jorge Gonzalez Estrella
• 金额: $ 44.45万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-20 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580388
• 关键词: Accidents; Address; Adverse effects; Affect; Affinity; Attention; Binding; Biological Availability; Caco-2 Cells; Cadmium; Cells; Cellular biology; Chemicals; Chemistry; Collaborations; Communities; Consumption; Data; Digestion; Dose; Ecosystem; Endocytosis; Endosomes; Environment; Environmental Engineering technology; Environmental Pollutants; Exposure to; Fishes; Food Contamination; Fresh Water; Gastrointestinal Process; Goals; Graduate Degree; Health; Health Hazards; Heavy Metals; Homeostasis; Human; Ingestion; Interdisciplinary Study; Intestines; Knowledge; Link; Liquid substance; Lysosomes; Metabolism; Metals; Methodology; Mineral Waters; Modification; Morphology; Oklahoma; Organism; Physiological; Physiology; Plastics; Process; Reporting; Research; Research Personnel; Risk; Role; Route; Scientist; Specific qualifier value; Spectrum Analysis; Students; Surface; System; Testing; Toxic effect; Toxicology; Trace metal; Training; UV Radiation Exposure; Water; Weather; World Health Organization; acute toxicity; aged; aquatic organism; aqueous; bioaccumulation; career; cellular imaging; design; environmental chemical; environmental chemistry; environmental toxicology; gastrointestinal; gastrointestinal imaging; graduate student; innovation; intestinal epithelium; metal metabolism; meter; novel; pollutant; skills; student training; theories; tool; ultraviolet; undergraduate student; uptake

Project Summary Microplastics (MPs) represent an emerging human health hazard as either a direct environmental contaminant or as a component of other mixed pollutants. Microplastics in the environment are exposed to ultraviolet radiation (UV) that change their chemical, morphological composition, and reactivity. Microplastics frequently interact with other heavy metals (e.g., cadmium (Cd)) in contaminated aquatic systems. Fish are continuously exposed to UV-degraded MPs directly by accidental ingestion or indirectly by ingesting pray contaminated with MPs. Humans are mainly exposed to MPs via ingestion of contaminated food and water. The fate of MPs during digestion is largely unknown. The key barrier to advancing our understanding of the health risk of MPs is a lack of information linking MPs’ environmental chemical transformations with bioaccumulation of MPs, and specific health impacts. Our overall goal is to involve undergraduate researchers in an interdisciplinary environmental engineering and toxicology project that targets key knowledge gaps of MP transformation, reactivity, bioavailability, and toxicity to develop a strong set of skills in undergraduate students that encourages to pursue a graduate degree and career in STEM. The overarching objective is to use quantifiable approaches and innovative tools to better understand the role of environmental weathering and gastrointestinal digestion on the bioavailability and toxicity of MPs and MPs and cadmium mixtures. We hypothesize that ultraviolet weathering of MPs increases sorption of legacy pollutants (i.e., Cd) and gastrointestinal processes affect their bioavailability and toxicity at the intestinal epithelium. Moreover, considering that MPs are taken up via endocytosis we propose that MPs can interfere with endosome and lysosome function, specifically affecting essential trace metal metabolism. To test this hypothesis, we propose the following interconnected aims: Specific Aim 1: Evaluate the transformation and reactivity of ultraviolet-aged micro- and nanoplastics in freshwater, commercial mineral water, and gastrointestinal (GI) fluids (i.e., during digestion); Specific Aim 2: Evaluate the bioavailability and acute toxicity of MPs and MPs/Cd mixtures in intestinal cells form fish RTgutGC cells, and human Caco-2 cells. The goal of aim 2 is to investigate the link between MPs type (size and composition) and chemical modifications (aim 1) to bioavailability and acute toxicity of MPs alone or in combination with Cd. Specific Aim 3: Evaluate the physiological impact of MPs on intestinal cells: using data from aim 1 we will select MPs with higher reactivity and sorption capability and using data from aim 2 we will select subtoxic but detectable doses of MPs and MPs/Cd mixtures and evaluate their impact on essential trace metal homeostasis and metabolism. Our results will contribute to bridge the knowledge gap between chemical transformations of MPs in the environment and implications on fish and human health. Our project will serve as a platform for integrating undergraduate students into multidisciplinary research and will allow them to acquire multiple skills spanning from environmental chemistry to cell biology and toxicology.

项目摘要 微塑料（MPS）代表新兴的人类健康危害作为直接的环境污染物 或作为其他混合污染物的组成部分。环境中的微塑料暴露于紫外线 辐射（紫外线）改变其化学，形态组成和反应性。微塑料经常 与受污染的水生系统中的其他重金属（例如镉（CD））相互作用。鱼是连续的 直接通过意外摄入或间接摄取祈祷污染而直接暴露于紫外线的国会议员 国会议员。人类主要通过摄入受污染的食物和水暴露于国会议员。国会议员的命运 在消化过程中基本上未知。促进我们对国会议员健康风险的理解的关键障碍 缺乏将MPS环境化学转化与MP的生物积累联系起来的信息， 特定的健康影响。我们的总体目标是让本科研究人员参与跨学科 针对MP转化的关键知识差距的环境工程和毒理学项目， 反应性，生物利用度和毒性，以在本科生中发展出强大的技能 鼓励攻读STEM的研究生学位和职业。总体目标是使用可量化的 方法和创新工具，以更好地了解环境风化和胃肠道的作用 MPS和MPS和镉混合物的生物利用度和毒性的消化。我们假设这一点 MPS的紫外线风化增加了遗产污染物（即CD）和胃肠道过程的焊接 影响其在肠上皮的生物利用度和毒性。而且，考虑到议员被接纳 通过内吞作用，我们提出MP可以干扰内体和溶酶体功能，特别影响 必不可少的金属代谢。为了检验这一假设，我们提出了以下相互联系的目的： 特定目的1：评估紫外细胞微塑料和纳米塑料的转化和反应性 淡水，商业矿泉水和胃肠道（GI）流体（即消化过程中）；具体目标2： 评估MPS和MPS/CD混合物在肠细胞中的生物利用度和急性毒性形成鱼类 RTGUTGC细胞和人CACO-2细胞。 AIM 2的目标是研究MPS类型之间的链接（大小 和组成）和化学修饰（目标1）单独或在 与CD结合。特定目标3：评估MPS对肠细胞的物理影响：使用数据 从AIM 1中，我们将选择具有更高反应性和焊接能力的MPS，并使用AIM 2的数据，我们将 选择可检测到的MPS和MPS/CD混合物的无毒但可检测到的剂量，并评估其对基本痕迹的影响 金属稳态和代谢。我们的结果将有助于弥合化学之间的知识差距 国会议员在环境中的转变及其对鱼类和人类健康的影响。我们的项目将作为 一个将本科生整合到多学科研究中的平台，并将允许他们获取 从环境化学到细胞生物学和毒理学的多种技能。