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Based on current structural and statistical calculations, thousands of microcystins (MCs) can exist; yet, to date, only 246 MCs were identified and only 12 commercial MC standards are available. Standard mass spectrometry workflows for known and unknown MCs need to be developed and validated for basic and applied harmful algal bloom research to advance. Our investigation focuses on samples taken in the spring of 2018 from an impoundment fed by Oser and Bischoff Reservoirs, Indiana, United States of America (USA). The dominant cyanobacterium found during sampling was Planktothrix agardhii. The goal of our study was to identify and quantify the MCs in the impoundment sample using chemical derivatization and mass spectrometry. Modifying these techniques to use online concentration liquid chromatography tandem mass spectrometry (LC–MS/MS), two untargeted MCs have been identified, [d-Asp3, Dhb7]-MC-LR and [Dhb7]-MC-YR. [Dhb7]-MC-YR is not yet reported in the literature to date, and this was the first reported incidence of Dhb MCs in the United States. Furthermore, it was discovered that the commercially available [d-Asp3]-MC-RR standard was [d-Asp3, Dhb7]-MC-RR. This study highlights a workflow utilizing online concentration LC–MS/MS, high-resolution MS (HRMS), and chemical derivatization to identify isobaric MCs.
Johnna A. Birbeck; Nicholas J. Peraino; Grace M. O’Neill; Julia Coady; Judy A. Westrick. Dhb Microcystins Discovered in USA Using an Online Concentration LC–MS/MS Platform. Toxins 2019, 11, 653 .
AMA StyleJohnna A. Birbeck, Nicholas J. Peraino, Grace M. O’Neill, Julia Coady, Judy A. Westrick. Dhb Microcystins Discovered in USA Using an Online Concentration LC–MS/MS Platform. Toxins. 2019; 11 (11):653.
Chicago/Turabian StyleJohnna A. Birbeck; Nicholas J. Peraino; Grace M. O’Neill; Julia Coady; Judy A. Westrick. 2019. "Dhb Microcystins Discovered in USA Using an Online Concentration LC–MS/MS Platform." Toxins 11, no. 11: 653.
Microcystins are potent hepatotoxins that have become a global health concern in recent years. Their actions in at-risk populations with pre-existing liver disease is unknown. We tested the hypothesis that the No Observed Adverse Effect Level (NOAEL) of Microcystin-LR (MC-LR) established in healthy mice would cause exacerbation of hepatic injury in a murine model (Leprdb/J) of Non-alcoholic Fatty Liver Disease (NAFLD). Ten-week-old male Leprdb/J mice were gavaged with 50 μg/kg, 100 μg/kg MC-LR or vehicle every 48 h for 4 weeks (n = 15–17 mice/group). Early mortality was observed in both the 50 μg/kg (1/17, 6%), and 100 μg/kg (3/17, 18%) MC-LR exposed mice. MC-LR exposure resulted in significant increases in circulating alkaline phosphatase levels, and histopathological markers of hepatic injury as well as significant upregulation of genes associated with hepatotoxicity, necrosis, nongenotoxic hepatocarcinogenicity and oxidative stress response. In addition, we observed exposure dependent changes in protein phosphorylation sites in pathways involved in inflammation, immune function, and response to oxidative stress. These results demonstrate that exposure to MC-LR at levels that are below the NOAEL established in healthy animals results in significant exacerbation of hepatic injury that is accompanied by genetic and phosphoproteomic dysregulation in key signaling pathways in the livers of NAFLD mice.
Apurva Lad; Robin C. Su; Joshua D. Breidenbach; Paul M. Stemmer; Nicholas J. Carruthers; Nayeli K. Sanchez; Fatimah K. Khalaf; Shungang Zhang; Andrew L. Kleinhenz; Prabhatchandra Dube; Chrysan J. Mohammed; Judy A. Westrick; Erin L. Crawford; Dilrukshika Palagama; David Baliu-Rodriguez; Dragan Isailovic; Bruce Levison; Nikolai Modyanov; Amira F. Gohara; Deepak Malhotra; Steven T. Haller; David J. Kennedy. Chronic Low Dose Oral Exposure to Microcystin-LR Exacerbates Hepatic Injury in a Murine Model of Non-Alcoholic Fatty Liver Disease. Toxins 2019, 11, 486 .
AMA StyleApurva Lad, Robin C. Su, Joshua D. Breidenbach, Paul M. Stemmer, Nicholas J. Carruthers, Nayeli K. Sanchez, Fatimah K. Khalaf, Shungang Zhang, Andrew L. Kleinhenz, Prabhatchandra Dube, Chrysan J. Mohammed, Judy A. Westrick, Erin L. Crawford, Dilrukshika Palagama, David Baliu-Rodriguez, Dragan Isailovic, Bruce Levison, Nikolai Modyanov, Amira F. Gohara, Deepak Malhotra, Steven T. Haller, David J. Kennedy. Chronic Low Dose Oral Exposure to Microcystin-LR Exacerbates Hepatic Injury in a Murine Model of Non-Alcoholic Fatty Liver Disease. Toxins. 2019; 11 (9):486.
Chicago/Turabian StyleApurva Lad; Robin C. Su; Joshua D. Breidenbach; Paul M. Stemmer; Nicholas J. Carruthers; Nayeli K. Sanchez; Fatimah K. Khalaf; Shungang Zhang; Andrew L. Kleinhenz; Prabhatchandra Dube; Chrysan J. Mohammed; Judy A. Westrick; Erin L. Crawford; Dilrukshika Palagama; David Baliu-Rodriguez; Dragan Isailovic; Bruce Levison; Nikolai Modyanov; Amira F. Gohara; Deepak Malhotra; Steven T. Haller; David J. Kennedy. 2019. "Chronic Low Dose Oral Exposure to Microcystin-LR Exacerbates Hepatic Injury in a Murine Model of Non-Alcoholic Fatty Liver Disease." Toxins 11, no. 9: 486.
Fast and reliable workflows are needed to quantitate microcystins (MCs), a ubiquitous class of hepatotoxic cyanotoxins, so that the impact of human and environmental exposure is assessed quickly and minimized. Our goal was to develop a high-throughput online concentration liquid chromatography tandem mass spectrometry (LC/MS/MS) workflow to quantitate the 12 commercially available MCs and nodularin in surface and drinking waters. The method run time was 8.5 min with detection limits in the low ng/L range and minimum reporting levels between 5 and 10 ng/L. This workflow was benchmarked by determining the prevalence of MCs and comparing the Adda-ELISA quantitation to our new workflow from 122 samples representing 31 waterbodies throughout Michigan. The frequency of MC occurrence was MC-LA > LR > RR > D-Asp3-LR > YR > HilR > WR > D-Asp3-RR > HtyR > LY = LW = LF, while MC-RR had the highest concentrations. MCs were detected in 33 samples and 13 of these samples had more than 20% of their total MC concentration from MCs not present in US Environmental Protection Agency (US EPA) Method 544. Furthermore, seasonal deviations between the LC/MS/MS and Adda-ELISA data suggest Adda-ELISA cross-reacts with MC degradation products. This workflow provides less than 24-h turnaround for quantification and also identified key differences between LC/MS/MS and ELISA quantitation that should be investigated further.
Johnna A. Birbeck; Judy A. Westrick; Grace M. O’Neill; Brian Spies; David C. Szlag. Comparative Analysis of Microcystin Prevalence in Michigan Lakes by Online Concentration LC/MS/MS and ELISA. Toxins 2019, 11, 13 .
AMA StyleJohnna A. Birbeck, Judy A. Westrick, Grace M. O’Neill, Brian Spies, David C. Szlag. Comparative Analysis of Microcystin Prevalence in Michigan Lakes by Online Concentration LC/MS/MS and ELISA. Toxins. 2019; 11 (1):13.
Chicago/Turabian StyleJohnna A. Birbeck; Judy A. Westrick; Grace M. O’Neill; Brian Spies; David C. Szlag. 2019. "Comparative Analysis of Microcystin Prevalence in Michigan Lakes by Online Concentration LC/MS/MS and ELISA." Toxins 11, no. 1: 13.
Cyanobacteria and cyanotoxins became an emerging issue for the drinking water industry in 1998 by appearing in the first US Environmental Protection Agency drinking water Contaminant Candidate List (CCL 1). Before CCL, cyanotoxin contaminants did not fit into the two prevailing paradigms: synthetic chemicals and pathogens. Cyanotoxins added a new paradigm: natural chemical toxins. Driven by anthropogenic influences, nutrient loading, and climate change, cyanobacterial blooms are increasing in frequency and distribution. To efficiently produce potable water from a source impacted by a toxic cyanobacterial bloom, drinking water practitioners need to take a multidisciplinary approach. Bloom dynamics (biology), surrogate and analytical methods (chemistry), inactivation/removal of intra‐ and extracellular toxins and multibarrier treatment (engineering), and risk management (public health) must all be part of a comprehensive management strategy. This article provides a holistic primer for water professionals on cyanotoxin treatment and management using pertinent literature, technical sources, case studies, and experience.
Judy A. Westrick; David Szlag. A Cyanotoxin Primer for Drinking Water Professionals. Journal AWWA 2018, 110, E1 -E16.
AMA StyleJudy A. Westrick, David Szlag. A Cyanotoxin Primer for Drinking Water Professionals. Journal AWWA. 2018; 110 (8):E1-E16.
Chicago/Turabian StyleJudy A. Westrick; David Szlag. 2018. "A Cyanotoxin Primer for Drinking Water Professionals." Journal AWWA 110, no. 8: E1-E16.
An environmental protection agency EPA expert workshop prioritized three cyanotoxins, microcystins, anatoxin-a, and cylindrospermopsin (MAC), as being important in freshwaters of the United States. This study evaluated the prevalence of potentially toxin producing cyanobacteria cell numbers relative to the presence and quantity of the MAC toxins in the context of this framework. Total and potential toxin producing cyanobacteria cell counts were conducted on weekly raw and finished water samples from utilities located in five US states. An Enzyme-Linked Immunosorbant Assay (ELISA) was used to screen the raw and finished water samples for microcystins. High-pressure liquid chromatography with a photodiode array detector (HPLC/PDA) verified microcystin concentrations and quantified anatoxin-a and cylindrospermopsin concentrations. Four of the five utilities experienced cyanobacterial blooms in their raw water. Raw water samples from three utilities showed detectable levels of microcystins and a fourth utility had detectable levels of both microcystin and cylindrospermopsin. No utilities had detectable concentrations of anatoxin-a. These conventional plants effectively removed the cyanobacterial cells and all finished water samples showed MAC levels below the detection limit by ELISA and HPLC/PDA.
David C. Szlag; James L. Sinclair; Benjamin J Southwell; Judy A. Westrick. Cyanobacteria and Cyanotoxins Occurrence and Removal from Five High-Risk Conventional Treatment Drinking Water Plants. Toxins 2015, 7, 2198 -2220.
AMA StyleDavid C. Szlag, James L. Sinclair, Benjamin J Southwell, Judy A. Westrick. Cyanobacteria and Cyanotoxins Occurrence and Removal from Five High-Risk Conventional Treatment Drinking Water Plants. Toxins. 2015; 7 (6):2198-2220.
Chicago/Turabian StyleDavid C. Szlag; James L. Sinclair; Benjamin J Southwell; Judy A. Westrick. 2015. "Cyanobacteria and Cyanotoxins Occurrence and Removal from Five High-Risk Conventional Treatment Drinking Water Plants." Toxins 7, no. 6: 2198-2220.