دورية أكاديمية
أعرض في EDS

Mixture designs to investigate adverse effects upon co-exposure to environmental cyanotoxins.

التفاصيل البيبلوغرافية
العنوان: Mixture designs to investigate adverse effects upon co-exposure to environmental cyanotoxins.
المؤلفون: Martin RM; Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States., Stallrich J; Department of Statistics, North Carolina State University, Raleigh, NC, United States., Bereman MS; Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States. Electronic address: michaelbereman@ncsu.edu.
المصدر: Toxicology [Toxicology] 2019 Jun 01; Vol. 421, pp. 74-83. Date of Electronic Publication: 2019 Apr 25.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Ireland NLM ID: 0361055 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3185 (Electronic) Linking ISSN: 0300483X NLM ISO Abbreviation: Toxicology Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier
Original Publication: Amsterdam. Elsevier/North-Holland.
مواضيع طبية MeSH: Cyanobacteria*, Bacterial Toxins/*toxicity, Animals ; Cell Line ; Cell Survival/drug effects ; Drug Interactions ; Mice ; No-Observed-Adverse-Effect Level ; Proteome/drug effects ; Risk Assessment/methods ; Toxicity Tests/methods
مستخلص: The goal of this study was to implement powerful mixture design techniques, commonly used in process optimization, to investigate enhanced adverse effects upon co-exposure to environmental cyanotoxins. Exposure to cyanobacteria, which are found ubiquitously in environmental water reservoirs, have been linked to several neurodegenerative diseases. Despite the known co-occurrence of various cyanotoxins, the majority of studies investigating this link have focused on the investigation of a single cyanotoxin, a noncanonical amino acid called β-methylamino-L-alanine (BMAA), which poorly recapitulates an actual environmental exposure. Interactions amongst cyanotoxic compounds is an area of great concern and remains poorly understood. To this end, we describe the use of a simplex axial mixture design to screen for interactive adverse effects of cyanotoxic mixtures. Using a combination of basic toxicity assays coupled with contemporary proteomic techniques, our results show the existence of a significant (p ≤ 0.01) interaction between BMAA and its isomers aminoethyl glycine (AEG) and 2,4-diaminobutyric acid (2,4DAB). Cyanotoxic mixtures significantly decreased cell viability by an average of 19% and increased caspases 3/7 activities by an average of 110% when compared to individual cyanotoxins (p ≤ 0.05). Cyanotoxic mixtures perturbed various biological pathways associated with neurodegeneration, including inhibition of protective autophagy and activation of mitochondrial dysfunction (z-score >|2|). Additionally, exposure to mixtures perturbed important upstream regulators involved in cellular dysfunction, morbidity, and development. Taken together, our results highlight: (1) the need to study combinations of cyanotoxins when investigating the link between cyanobacteria and neurodegenerative pathologies and (2) the application of design of experiment (DoE) as an efficient methodology to study mixtures of relevant environmental toxins.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Cyanotoxins; Environmental exposure; Interaction; Mixture design; Proteomics
المشرفين على المادة: 0 (Bacterial Toxins)
0 (Proteome)
تواريخ الأحداث: Date Created: 20190429 Date Completed: 20200403 Latest Revision: 20240330
رمز التحديث: 20240330
DOI: 10.1016/j.tox.2019.04.013
PMID: 31029734
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-3185
DOI:10.1016/j.tox.2019.04.013