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Kevin V Thomas - One of the best experts on this subject based on the ideXlab platform.
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improved method for the determination of Zinc Pyrithione in environmental water samples incorporating on line extraction and preconcentration coupled with liquid chromatography atmospheric pressure chemical ionisation mass spectrometry
Journal of Chromatography A, 2006Co-Authors: Jonathan Bones, Kevin V Thomas, Brett PaullAbstract:Abstract A method has been developed for the determination of Zinc Pyrithione (ZnPT) in environmental water samples using monolithic reversed-phase silica columns for rapid on-line large volume solid phase extraction in tandem with on-line matrix removal using sacrificial strong anion exchange (SAX) columns. This is coupled with reversed-phase liquid chromatography with atmospheric pressure chemical ionisation mass spectrometric detection. Limits of detection in spiked river water samples, using a 200 mL preconcentration volume, were determined as 18 ng L −1 , with a limit of quantitation of 62 ng L −1 . The percentage recovery from spiked river water was found to be 72 ± 9 ( n = 3 extractions), whilst overall method precision, following 10 repeat complete analyses was found to be 27% RSD at 1 μg L −1 . Linearity was determined over the concentration range of 0.25–10 μg L −1 and the calculated regression coefficient was R 2 = 0.9802. The method was used to investigate the environmental fate of Zinc Pyrithione in waters and its partition coefficient between sediment and water phases.
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determination of the antifouling agent Zinc Pyrithione in water samples by copper chelate formation and high performance liquid chromatography atmospheric pressure chemical ionisation mass spectrometry
Journal of Chromatography A, 1999Co-Authors: Kevin V ThomasAbstract:Zinc Pyrithione has recently been incorporated into antifouling paints as a booster biocide, which is slowly released into the water as the paint ages. In order to determine concentrations of Zinc Pyrithione (ZPT) in aqueous samples, a liquid chromatographic method has been developed. Since ZPT interacts with certain reversed-phase packing materials or stainless steel components of the HPLC system, the method uses transchelation of the ZPT into the stable copper(II) complex before analysis by liquid chromatography coupled to atmospheric pressure chemical ionisation mass spectrometry. ZPT was extracted as copper Pyrithione using dichloromethane with adequate recovery (77%±17%, n=6) from 2-l water samples. The limit of detection was calculated to be 20 ng/l, using selected ion monitoring. The analysis of samples collected from various UK marinas showed no detectable concentrations to be present, whilst a laboratory-based study confirmed that this is probably due to the rapid photodegradation of ZPT in seawater.
Marina Mauri - One of the best experts on this subject based on the ideXlab platform.
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novel antifouling agent Zinc Pyrithione stress induction and genotoxicity to the marine mussel mytilus galloprovincialis
Aquatic Toxicology, 2011Co-Authors: Marco Marcheselli, Paola Azzoni, Marina MauriAbstract:Abstract The anti-fouling biocide Zinc Pyrithione (ZnPT) was recently demonstrated to be more persistent than expected in the coastal environment, and to have a potential for bioaccumulation. We investigated the occurrence of adverse effects in the marine mussel Mytilus galloprovincialis when exposed to non-lethal concentrations of the contaminant (0.2 and 0.4 μM ZnPT), through the use of a battery of biomarkers from the molecular to the individual level. In particular, the expression of HSP27, HSP60, HSP70 and the presence of genotoxic damage were investigated in the gills and digestive gland of mussels by means of Western blot and TUNEL procedures, respectively. In addition, a stress on stress response test was performed in order to highlight a possible general stress conditions in the exposed bivalves. A concentration of 0.2 μM ZnPT was found sufficient to trigger a marked stress response in gills and digestive gland, and a concentration-dependent HSP expression was highlighted. Moreover, at the tested concentrations, ZnPT was found able to induce genotoxic effects, as demonstrated by an amplified DNA fragmentation (up to +37% of TUNEL positive cells in comparison to the control group) and by an increased frequency of apoptotic cells (up to +5%) in the tissues of the exposed mussels. In addition, the stress on stress response test demonstrated a heavily decreased tolerance to anoxic conditions in mussels exposed to the higher tested concentration of the biocide (LT50 = 5.4 days) compared to the control individuals (LT50 = 10.7 days). Multivariate analyses highlighted a strong correspondence between the observed biological effects in M. galloprovincialis, HSP over-expression and DNA damage in the gills and digestive gland, and the bioaccumulation levels of the biocide. Data presented here indicate the need for further investigations on the ZnPT effects on the key species of marine coastal communities, with the aim of obtaining the necessary information for a sound risk assessment of the impact of this new antifoulant on marine ecosystems.
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novel antifouling agent Zinc Pyrithione determination acute toxicity and bioaccumulation in marine mussels mytilus galloprovincialis
Environmental Toxicology and Chemistry, 2010Co-Authors: Marco Marcheselli, Cecilia Rustichelli, Marina MauriAbstract:Antifouling biocide Zinc Pyrithione (ZnPT) and its biological fate have received little attention because this compound was assumed not to be persistent in marine ecosystems. An analytical procedure was developed that has proved to be efficient and very sensitive in extracting ZnPT and its main secondary products, Zn and ionized Pyrithione (PT−), from both seawater and biological samples, namely in the gills and digestive gland of the bioindicator species Mytilus galloprovincialis. Short-term experiments were carried out to investigate ZnPT toxicity and bioaccumulation. The effects on survival and tissue bioaccumulation of ZnPT and its secondary products were studied on adult mussels from a natural population, collected in the harbor area of Porto Santo Stefano (Italy) and exposed to sublethal doses of the biocide for up to 7 d. Zinc Pyrithione was shown to be persistent in the experimental seawater in the short term. A basal level of ZnPT and ionized PT− was detected in the mussels, indicating that ZnPT availability in the sampling site is already high enough to induce a detectable accumulation in individuals of the native population. Zinc Pyrithione rapidly accumulated in the tissues of the exposed mussels, proportionately to both exposure concentration and time, identifying the gills and digestive gland as important targets in the biological pathway of the contaminants. Even though the 7-d median lethal concentration (LC50) = 8.27 µM established here appears high with respect to reported ZnPT environmental concentrations, the results indicate that this biocide could represent a threat for marine organisms in coastal environments and that further investigations on its biological effects at sublethal doses are needed. Environ. Toxicol. Chem. 2010;29:2583–2592. © 2010 SETAC
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novel antifouling agent Zinc Pyrithione short and long term effects on survival and reproduction of the marine polychaete dinophilus gyrociliatus
Aquatic Toxicology, 2010Co-Authors: Marco Marcheselli, Francesco Conzo, Marina Mauri, Roberto SimoniniAbstract:Abstract The recent ban on TBT in boat antifouling paints has resulted in a large employment of the biocide Zinc Pyrithione (ZnPT) as substitute. Despite concerns of its environmental toxicity at ultra-trace concentrations, ZnPT has received little attention, as it was assumed to photo-degrade easily. However, recent evidence has suggested that ZnPT degrades only partially, and persists in the marine environment, especially where the influence of light is limited, such as in harbours. Short-term acute toxicity tests and life table response experiments (LTREs) were performed to evaluate the effects of ZnPT on the polychaete Dinophilus gyrociliatus at both individual and population level. The 96h-LC50 values for ZnPT on D. gyrociliatus were 7.8 and 11.5 nM under dark and 12 h light/12 h dark conditions, respectively. In LTREs, laboratory cultured cohorts of D. gyrociliatus were exposed to sublethal concentrations of ZnPT (0.5 and 1 nM) and compared to a control cohort. The survival among individuals exposed to the highest concentration decreased already during the 2nd week of life with respect to the control. The effects of the biocide on fecundity were even more evident: ZnPT caused a considerable reduction in both the exposed groups. The demographic approach applied here succeeded in identifying ZnPT effects both on the biological cycle and on the growth potential of polychaete D. gyrociliatus. The net growth rate (R0) appeared to be the demographic parameter most sensitive to ZnPT, as the biocide exposure was associated with a sharp decline of R0 in both the 0.5 and the 1 nM groups (−41% and −63%, respectively) in comparison to the control cohort. The population growth rate λ (often used as an index of population fitness) and the life expectancy e0 were also significantly reduced, while ZnPT exposure did not affect the generation time T. These results highlight the potential ecological threat posed by the biocide ZnPT, even at the very low tested concentrations, which are already detectable in some European marinas.
Hongbiao Huang - One of the best experts on this subject based on the ideXlab platform.
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repurposing an antidandruff agent to treating cancer Zinc Pyrithione inhibits tumor growth via targeting proteasome associated deubiquitinases
Oncotarget, 2017Co-Authors: Chong Zhao, Xin Chen, Changshan Yang, Dan Zang, Xiaoying Lan, Siyan Liao, Peiquan Zhang, Ningning Liu, Yuning Liao, Hongbiao HuangAbstract:The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activity are currently in clinical use for treatment of multiple myeloma and other cancers, and the deubiquitinase activity associated with the proteasome is also a valid target for anticancer agents. Recent studies suggested that Zinc Pyrithione, an FDA-approved antidandruff agent, may have antitumor activity, but the detailed molecular mechanisms remain unclear. Here we report that Zinc Pyrithione (ZnPT) targets the proteasome-associated DUBs (USP14 and UCHL5) and inhibits their activities, resulting in a rapid accumulation of protein-ubiquitin conjugates, but without inhibiting the proteolytic activities of 20S proteasomes. Furthermore, ZnPT exhibits cytotoxic effects against various cancer cell lines in vitro, selectively kills bone marrow cells from leukemia patients ex vivo, and efficiently inhibits the growth of lung adenocarcinoma cancer cell xenografts in nude mice. This study has identified Zinc Pyrithione, an FDA-approved pharmacological agent with potential antitumor properties as a proteasomal DUB inhibitor.
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repurposing an antidandruff agent to treating cancer Zinc Pyrithione inhibits tumor growth via targeting proteasome associated deubiquitinases
Oncotarget, 2017Co-Authors: Chong Zhao, Xin Chen, Changshan Yang, Dan Zang, Xiaoying Lan, Siyan Liao, Peiquan Zhang, Ningning Liu, Yuning Liao, Hongbiao HuangAbstract:// Chong Zhao 1, 2, * , Xin Chen 1, * , Changshan Yang 1, * , Dan Zang 1 , Xiaoying Lan 1 , Siyan Liao 1 , Peiquan Zhang 1 , Jinjie Wu 1 , Xiaofen Li 1 , Ningning Liu 1, 3 , Yuning Liao 1 , Hongbiao Huang 1 , Xianping Shi 1 , Lili Jiang 1 , Xiuhua Liu 4 , Q. Ping Dou 5 , Xuejun Wang 1, 6 , Jinbao Liu 1 1 State Key Laboratory of Respiratory Disease, Protein Modification and Degradation Laboratory, Department of Pathophysiology, Guangzhou Medical University, Guangdong 510182, China 2 Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China 3 Guangzhou Research Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510260, China 4 Institute of Environmental and Analytical Sciences, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004, China 5 The Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, and Departments of Oncology, Pharmacology and Pathology, School of Medicine, Wayne State University, Detroit, Michigan 48201-2013, USA 6 Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, South Dakota 57069, USA * These authors have contributed equally to this work Correspondence to: Jinbao Liu, email: jliu@gzhmu.edu.cn Xuejun Wang, email: xuejun.wang@usd.edu Keywords: Zinc Pyrithione, proteasome, deubiquitinases, DNA damage, tumor Received: November 08, 2016 Accepted: December 27, 2016 Published: January 10, 2017 ABSTRACT The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activity are currently in clinical use for treatment of multiple myeloma and other cancers, and the deubiquitinase activity associated with the proteasome is also a valid target for anticancer agents. Recent studies suggested that Zinc Pyrithione, an FDA-approved antidandruff agent, may have antitumor activity, but the detailed molecular mechanisms remain unclear. Here we report that Zinc Pyrithione (ZnPT) targets the proteasome-associated DUBs (USP14 and UCHL5) and inhibits their activities, resulting in a rapid accumulation of protein-ubiquitin conjugates, but without inhibiting the proteolytic activities of 20S proteasomes. Furthermore, ZnPT exhibits cytotoxic effects against various cancer cell lines in vitro , selectively kills bone marrow cells from leukemia patients ex vivo , and efficiently inhibits the growth of lung adenocarcinoma cancer cell xenografts in nude mice. This study has identified Zinc Pyrithione, an FDA-approved pharmacological agent with potential antitumor properties as a proteasomal DUB inhibitor.
Marco Marcheselli - One of the best experts on this subject based on the ideXlab platform.
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novel antifouling agent Zinc Pyrithione stress induction and genotoxicity to the marine mussel mytilus galloprovincialis
Aquatic Toxicology, 2011Co-Authors: Marco Marcheselli, Paola Azzoni, Marina MauriAbstract:Abstract The anti-fouling biocide Zinc Pyrithione (ZnPT) was recently demonstrated to be more persistent than expected in the coastal environment, and to have a potential for bioaccumulation. We investigated the occurrence of adverse effects in the marine mussel Mytilus galloprovincialis when exposed to non-lethal concentrations of the contaminant (0.2 and 0.4 μM ZnPT), through the use of a battery of biomarkers from the molecular to the individual level. In particular, the expression of HSP27, HSP60, HSP70 and the presence of genotoxic damage were investigated in the gills and digestive gland of mussels by means of Western blot and TUNEL procedures, respectively. In addition, a stress on stress response test was performed in order to highlight a possible general stress conditions in the exposed bivalves. A concentration of 0.2 μM ZnPT was found sufficient to trigger a marked stress response in gills and digestive gland, and a concentration-dependent HSP expression was highlighted. Moreover, at the tested concentrations, ZnPT was found able to induce genotoxic effects, as demonstrated by an amplified DNA fragmentation (up to +37% of TUNEL positive cells in comparison to the control group) and by an increased frequency of apoptotic cells (up to +5%) in the tissues of the exposed mussels. In addition, the stress on stress response test demonstrated a heavily decreased tolerance to anoxic conditions in mussels exposed to the higher tested concentration of the biocide (LT50 = 5.4 days) compared to the control individuals (LT50 = 10.7 days). Multivariate analyses highlighted a strong correspondence between the observed biological effects in M. galloprovincialis, HSP over-expression and DNA damage in the gills and digestive gland, and the bioaccumulation levels of the biocide. Data presented here indicate the need for further investigations on the ZnPT effects on the key species of marine coastal communities, with the aim of obtaining the necessary information for a sound risk assessment of the impact of this new antifoulant on marine ecosystems.
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novel antifouling agent Zinc Pyrithione determination acute toxicity and bioaccumulation in marine mussels mytilus galloprovincialis
Environmental Toxicology and Chemistry, 2010Co-Authors: Marco Marcheselli, Cecilia Rustichelli, Marina MauriAbstract:Antifouling biocide Zinc Pyrithione (ZnPT) and its biological fate have received little attention because this compound was assumed not to be persistent in marine ecosystems. An analytical procedure was developed that has proved to be efficient and very sensitive in extracting ZnPT and its main secondary products, Zn and ionized Pyrithione (PT−), from both seawater and biological samples, namely in the gills and digestive gland of the bioindicator species Mytilus galloprovincialis. Short-term experiments were carried out to investigate ZnPT toxicity and bioaccumulation. The effects on survival and tissue bioaccumulation of ZnPT and its secondary products were studied on adult mussels from a natural population, collected in the harbor area of Porto Santo Stefano (Italy) and exposed to sublethal doses of the biocide for up to 7 d. Zinc Pyrithione was shown to be persistent in the experimental seawater in the short term. A basal level of ZnPT and ionized PT− was detected in the mussels, indicating that ZnPT availability in the sampling site is already high enough to induce a detectable accumulation in individuals of the native population. Zinc Pyrithione rapidly accumulated in the tissues of the exposed mussels, proportionately to both exposure concentration and time, identifying the gills and digestive gland as important targets in the biological pathway of the contaminants. Even though the 7-d median lethal concentration (LC50) = 8.27 µM established here appears high with respect to reported ZnPT environmental concentrations, the results indicate that this biocide could represent a threat for marine organisms in coastal environments and that further investigations on its biological effects at sublethal doses are needed. Environ. Toxicol. Chem. 2010;29:2583–2592. © 2010 SETAC
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novel antifouling agent Zinc Pyrithione short and long term effects on survival and reproduction of the marine polychaete dinophilus gyrociliatus
Aquatic Toxicology, 2010Co-Authors: Marco Marcheselli, Francesco Conzo, Marina Mauri, Roberto SimoniniAbstract:Abstract The recent ban on TBT in boat antifouling paints has resulted in a large employment of the biocide Zinc Pyrithione (ZnPT) as substitute. Despite concerns of its environmental toxicity at ultra-trace concentrations, ZnPT has received little attention, as it was assumed to photo-degrade easily. However, recent evidence has suggested that ZnPT degrades only partially, and persists in the marine environment, especially where the influence of light is limited, such as in harbours. Short-term acute toxicity tests and life table response experiments (LTREs) were performed to evaluate the effects of ZnPT on the polychaete Dinophilus gyrociliatus at both individual and population level. The 96h-LC50 values for ZnPT on D. gyrociliatus were 7.8 and 11.5 nM under dark and 12 h light/12 h dark conditions, respectively. In LTREs, laboratory cultured cohorts of D. gyrociliatus were exposed to sublethal concentrations of ZnPT (0.5 and 1 nM) and compared to a control cohort. The survival among individuals exposed to the highest concentration decreased already during the 2nd week of life with respect to the control. The effects of the biocide on fecundity were even more evident: ZnPT caused a considerable reduction in both the exposed groups. The demographic approach applied here succeeded in identifying ZnPT effects both on the biological cycle and on the growth potential of polychaete D. gyrociliatus. The net growth rate (R0) appeared to be the demographic parameter most sensitive to ZnPT, as the biocide exposure was associated with a sharp decline of R0 in both the 0.5 and the 1 nM groups (−41% and −63%, respectively) in comparison to the control cohort. The population growth rate λ (often used as an index of population fitness) and the life expectancy e0 were also significantly reduced, while ZnPT exposure did not affect the generation time T. These results highlight the potential ecological threat posed by the biocide ZnPT, even at the very low tested concentrations, which are already detectable in some European marinas.
T A Albanis - One of the best experts on this subject based on the ideXlab platform.
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aqueous phototransformation of Zinc Pyrithione degradation kinetics and byproduct identification by liquid chromatography atmospheric pressure chemical ionisation mass spectrometry
Journal of Chromatography A, 2007Co-Authors: Vasilios A Sakkas, K Shibata, Y Yamaguchi, S Sugasawa, T A AlbanisAbstract:The photochemical behavior of the antifouling agent Zinc Pyrithione (ZnPT) was studied in aqueous media of different composition under simulated solar irradiation using a xenon light source. The influence of important constituents of natural water (dissolved organic matter and nitrate) was also examined using a multivariate kinetic model. It was found that photodegradation proceeds via a pseudo first-order reaction. Kinetic experiments were monitored by LC-MS and photolytic half-lives ranging between 9.2 and 15.1 min have been observed. The increasing concentration of dissolved organic matter (DOM) accelerates the photolysis reaction, while the effect of nitrate ions was also positive since it increased the degradation rate, but to a lesser extent. Irradiation of the aqueous ZnPT solutions gave rise to several transformation products that were isolated by means of solid-phase extraction using poly(styrene-divinylbenzene) extraction disks. These byproducts were identified using liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry. Besides 2-pyridinesulfonic-acid, other degradation products formed included pyridine-N-oxide, 2-mercaptopyridine, 2,2'-dithiobis(pyridine-N-oxide), 2,2-dipyridyl disulfide and the pyridine/Pyrithione mixed disulfide, 2,2'-dithiobispyridine mono-N-oxide (PPMD).
