Synthesis and quantitation of microcystins and anabaenopeptins in the Great Lakes region to establish human exposure risks via ingestion and inhalation

五大湖地区微囊藻毒素和鱼腥肽的合成和定量，以确定人类通过摄入和吸入接触的风险

• 批准号: 10660161
• 负责人: Andrew P Ault
• 金额: $ 160.96万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-10 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660161
• 关键词: Address; Aerosols; Agriculture; Air; Amino Acids; Area; Asthma; Attention; Behavior; Biological Assay; Biological Process; Biology; Cells; Cellular Assay; Certification; Chemical Structure; Chemicals; Chemistry; Chromatography; Communities; Cyanobacterium; Cyanotoxin; Dangerousness; Data; Dose; Ecology; Environment; Environmental Risk Factor; Environmental Wind; Enzyme-Linked Immunosorbent Assay; Event; Exposure to; Farm; Fishes; Frequencies; Fresh Water; Gastrointestinal Diseases; Gastrointestinal tract structure; Gene Expression; Goals; Great Lakes Region; Growth; Health; Human; Human Cell Line; Hypersensitivity; In Vitro; Ingestion; Inhalation; Inhalation Exposure; Investigation; Kidney Diseases; Lead; Letters; Liver diseases; Lung; Malignant Neoplasms; Mass Spectrum Analysis; Methods; Microcystis; Monitor; National Institute of Environmental Health Sciences; Nose; Nutrient; Pathway interactions; Peptides; Pharmacologic Substance; Pharmacology; Prevalence; Public Health; Recreation; Reference Standards; Reporting; Reproducibility; Research; Research Personnel; Resources; Respiratory System; Risk; Risk Assessment; Role; Route; Sampling; Seafood; Sewage; Source; Speed; Tissues; Toxic effect; Toxicology; Toxin; Variant; Water; Work; aerosolized; analytical method; anthropogenesis; antimicrobial; climate change; contaminated drinking water; contaminated seafood; cyanoginosin LR; design; drinking water; empowerment; exposed human population; exposure pathway; exposure route; gut microbiome; harmful algal blooms; hydrology; immunotoxicity; marine; microcystin; nervous system disorder; programs; public drinking; reconstitution; secondary metabolite; skin disorder

PROJECT ABSTRACT Climate change, agriculture practices, hydrology alterations, and sewage sheds are contributing to an increase in the frequency and intensity of cyanobacteria harmful algal blooms (cHABs) that produce bioactive and toxic secondary peptide metabolites. As a result, public health and drinking water advisories, recreational water closures, and coastal seafood contamination have increased. Cyanobacteria peptide toxins are known causes or suspect in liver, neurological, dermal, gastrointestinal and kidney disease. Although hundreds of potential toxic and beneficial bioactive peptides have been reported, only a handful of reference materials are commercially available. cHAB peptide research, monitoring, and mitigation has been bottlenecked by lack of certified and bulk reference materials. Analytically pure (certified) synthetic standards cyanotoxin and reliable analytical workflows are critically needed to protect public health. Our long-term goal is to create a stable and reliable supply of CHAB cyanopeptide reference materials to enable investigation of cyanopeptides’ occurrence and human health impacts. Our objectives in this proposal are to establish efficient synthetic routes and bioactivity profiles for anabaenopeptins (ABPs) and microcystins (MCs), to create mass spectrometry workflows for their identification and quantification, and to establish the impact of ingestion and inhalation pathways as exposure routes. In particular, we will assess cyanotoxins’ impact on cells from the respiratory tract and on reconstituted GI microbiomes. The ABPs and MCs are observed in the Great Lakes region’s freshwater bodies in high concentrations and are known to have hundred(s) of congeners with varying degrees of toxicity and bioactivity. Many of these lakes/rivers contain congeners with tentative or unassigned identifications. Our congener selection is designed to increase the reliability and reproducibility of targeted and untargeted mass spectrometry workflows. Understanding the cyanotoxin exposure routes and health risk is dependent on chemical structure and its interplay with the environment. Our proposed aerosol studies will assist in determining the risk associated with inhalation. There is a critical need for cyanopeptides/congeners to be synthesized, characterized, and systematically studied to quantify their associated exposure risks in cHAB water and aerosols. Our proposed work combines the expertise of several areas of chemistry and pharmacology and is important because it advances empowers ongoing fundamental cHAB research in the areas of ecology, toxicology, biology, and fate and transport, and provides reliable cyanotoxin quantification through certified standards for water resource managers and public health decision makers.

项目摘要 气候变化、农业实践、水文变化和污水棚正在导致这一增长 产生生物活性和有毒物质的蓝藻有害藻华 (chHAB) 的频率和强度 因此，公共卫生和饮用水咨询、娱乐用水。 关闭和沿海海鲜污染增加是已知的原因。 或怀疑有数百种潜在的肝脏、神经、皮肤、胃肠道和肾脏疾病。 有毒和有益的生物活性肽已被报道，但只有少数参考资料 商业化的 cHAB 肽研究、监测和缓解一直因缺乏技术而受到阻碍。 经认证的批量参考材料。分析纯（经认证）的合成标准品蓝毒素和 保护公众健康迫切需要可靠的分析工作流程。 稳定可靠地供应 CHAB 氰肽标准物质，以实现氰肽的研究 我们在本提案中的目标是建立有效的合成路线。 以及鱼腥肽 (ABP) 和微囊藻毒素 (MC) 的生物活性谱，以创建质谱分析 识别和量化的工作流程，并确定摄入和吸入的影响 特别是，我们将评估蓝藻毒素对呼吸道细胞的影响。 以及在五大湖地区淡水中观察到的重组胃肠道微生物组。 体内浓度很高，并且已知有数百种具有不同程度毒性的同系物 这些湖泊/河流中的许多含有我们的暂定或未指定的同源物。 同系物选择旨在提高目标和非目标质量的可靠性和再现性 了解蓝藻毒素暴露途径和健康风险取决于 我们提出的气溶胶研究将有助于确定化学结构及其与环境的相互作用。 与吸入相关的风险迫切需要合成氰肽/同源物， 进行了表征和系统研究，以量化其在 CHAB 水和 我们提出的工作结合了化学和药理学多个领域的专业知识，并且是 重要的是因为它的进步增强了生态学领域正在进行的基础 CHAB 研究， 毒理学、生物学、命运和运输，并通过认证提供可靠的蓝藻毒素定量 水资源管理者和公共卫生决策者的标准。