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Prof. Dr. Angeles Jos
University of Seville, Department of Food Science, Toxicology and Legal Medicine, Faculty of Pharmacy, Seville 41012, Spain

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0 Food Safety
0 Risk Assessment
0 Toxicology
0 cyanotoxins
0 microcystins

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Cylindrospermopsin
microcystins
cyanotoxins
Food Safety
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Review
Published: 19 August 2021 in Microorganisms
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Since 2013, Xylella fastidiosa Wells et al. has been reported to infect several hosts and to be present in different areas of Europe. The main damage has been inflicted on the olive orchards of southern Apulia (Italy), where a severe disease associated with X. fastidiosa subspecies pauca strain De Donno has led to the death of millions of trees. This dramatic and continuously evolving situation has led to European and national (Italian and Spanish) measures being implemented to reduce the spread of the pathogen and the associated olive quick decline syndrome (OQDS). Research has been also carried out to find solutions to better and directly fight the bacterium and its main insect vector, Philaenus spumarius L. In the course of this frantic effort, several treatments based on chemical or biological substances have been tested, in addition to plant breeding techniques and integrated pest management approaches. This review aims to summarize the attempts made so far and describe the prospects for better management of this serious threat, which poses alarming questions for the future of olive cultivation in the Mediterranean basin and beyond.

ACS Style

Massimiliano Morelli; José Manuel García-Madero; Ángeles Jos; Pasquale Saldarelli; Crescenza Dongiovanni; Magdalena Kovacova; Maria Saponari; Alberto Baños Arjona; Evelyn Hackl; Stephen Webb; Stéphane Compant. Xylella fastidiosa in Olive: A Review of Control Attempts and Current Management. Microorganisms 2021, 9, 1771 .

AMA Style

Massimiliano Morelli, José Manuel García-Madero, Ángeles Jos, Pasquale Saldarelli, Crescenza Dongiovanni, Magdalena Kovacova, Maria Saponari, Alberto Baños Arjona, Evelyn Hackl, Stephen Webb, Stéphane Compant. Xylella fastidiosa in Olive: A Review of Control Attempts and Current Management. Microorganisms. 2021; 9 (8):1771.

Chicago/Turabian Style

Massimiliano Morelli; José Manuel García-Madero; Ángeles Jos; Pasquale Saldarelli; Crescenza Dongiovanni; Magdalena Kovacova; Maria Saponari; Alberto Baños Arjona; Evelyn Hackl; Stephen Webb; Stéphane Compant. 2021. "Xylella fastidiosa in Olive: A Review of Control Attempts and Current Management." Microorganisms 9, no. 8: 1771.

Journal article
Published: 06 August 2021 in Current Drug Delivery
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Background: In this work the cytotoxicity and gastric and gastrointestinal resistance of a high-load synthetic expandable mica, Na-mica-4, is studied for the first time. The hydrophilic character of this clay mineral can be modified by ion exchange reaction between Na+ inorganic cations housed in the interlayer space, and surfactant molecules, resulting in the formation of an organophilic material. This adsorption capability of organic compounds makes them very useful for a wide range of applications, such as their use as drug carriers. Previous studies have shown the high adsorption capacity of organofunctionalized Na-mica-4 of different types of drugs. Objetive: To carry out initial trials aimed at testing the cytotoxicity of a synthetic organofunctional expandable mica and evaluating its resistance to gastric and gastrointestinal digestion. Methods: A highly charged sodium mica (Na-mica-4) was synthesized and organofunctional by cationic exchange with an alkilamine, primary amine of 18 carbon atoms (C18-mica-4). Both were characterized by X-ray diffraction, field transmission electron microscopy, surface-specific analysis, differential scanning calorimetry, and thermal gravimetric analysis. In addition, screening cytotoxicity trials were conducted on the human intestinal cell line Caco-2 with C18-mica-4 (0-125 µg/ml). Results: Only one of the endpoints evaluated (the reduction of tetrazolium MTS salt by dehydrogenase enzymes) showed a significant decrease in cellular viability after 48h at the highest concentration tested. C18-mica-4 shows structural resistance to both, gastric and gastrointestinal, digestion. Conclusion: A successful development of a functionalized mica has been made with a promising potential application as a carrier to the drug.

ACS Style

M. Mar Orta; Sara Maisanaba; Santiago Medina-Carrasco; Angeles Jos. Potential Application of A Synthetic Organo-funtionalized High Load Expandable Mica as A Drug Carrier for Controlled Release. Current Drug Delivery 2021, 18, 645 -653.

AMA Style

M. Mar Orta, Sara Maisanaba, Santiago Medina-Carrasco, Angeles Jos. Potential Application of A Synthetic Organo-funtionalized High Load Expandable Mica as A Drug Carrier for Controlled Release. Current Drug Delivery. 2021; 18 (5):645-653.

Chicago/Turabian Style

M. Mar Orta; Sara Maisanaba; Santiago Medina-Carrasco; Angeles Jos. 2021. "Potential Application of A Synthetic Organo-funtionalized High Load Expandable Mica as A Drug Carrier for Controlled Release." Current Drug Delivery 18, no. 5: 645-653.

Journal article
Published: 01 May 2021 in Foods
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Propyl-propanethiosulfinate (PTS) is a component of Allium essential oils. This organosulfur molecule can be used as a feed additive to decrease the appearance of bacterial resistances caused by the residues of antibiotics. In previous in vitro genotoxicity studies, contradictory results were reported for PTS. In this work, the in vivo genotoxicity of PTS in male and female rats was assessed for the first time, following OECD (Organisation for Economic Co-operation and Development) guidelines. After oral administration (doses: 5.5, 17.4, and 55.0 mg/kg PTS body weight), a combination of the micronucleus (MN) assay (OECD 474) in bone marrow and the standard and enzyme-modified comet assay (OECD 489) was performed. After necropsy, histopathological studies were also carried out. The results did not show the in vivo genotoxicity of PTS at any doses assayed, revealed by the absence of increased MN, and DNA strand breaks or oxidative DNA damage in the standard and enzyme-modified comet assays. The histopathological study revealed that only the highest dose tested (55.0 mg/kg) in the liver and all dose groups in the stomach presented minimal pathological lesions in the organs studied. Consequently, the present work confirms that PTS is not genotoxic at the doses assayed, and it is a promising natural alternative to synthetic preservatives and antibiotics in animal feed.

ACS Style

Antonio Cascajosa-Lira; María Puerto; Ana Prieto; Silvia Pichardo; Leticia Díez-Quijada Jiménez; Alberto Baños; Enrique Guillamón; Rosario Moyano; Verónica Molina-Hernández; Ángeles Jos; Ana Cameán. Genotoxicity Evaluation of Propyl-Propane-Thiosulfinate (PTS) from Allium genus Essential Oils by a Combination of Micronucleus and Comet Assays in Rats. Foods 2021, 10, 989 .

AMA Style

Antonio Cascajosa-Lira, María Puerto, Ana Prieto, Silvia Pichardo, Leticia Díez-Quijada Jiménez, Alberto Baños, Enrique Guillamón, Rosario Moyano, Verónica Molina-Hernández, Ángeles Jos, Ana Cameán. Genotoxicity Evaluation of Propyl-Propane-Thiosulfinate (PTS) from Allium genus Essential Oils by a Combination of Micronucleus and Comet Assays in Rats. Foods. 2021; 10 (5):989.

Chicago/Turabian Style

Antonio Cascajosa-Lira; María Puerto; Ana Prieto; Silvia Pichardo; Leticia Díez-Quijada Jiménez; Alberto Baños; Enrique Guillamón; Rosario Moyano; Verónica Molina-Hernández; Ángeles Jos; Ana Cameán. 2021. "Genotoxicity Evaluation of Propyl-Propane-Thiosulfinate (PTS) from Allium genus Essential Oils by a Combination of Micronucleus and Comet Assays in Rats." Foods 10, no. 5: 989.

Journal article
Published: 08 December 2020 in Toxins
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Simultaneous occurrence of cylindrospermopsin (CYN) and microcystin-LR (MCLR) has been reported in the aquatic environment and thus human exposure to such mixtures is possible. As data on the combined effects of CYN/MCLR are scarce, we aimed to investigate the adverse effects related to genotoxic activities induced by CYN (0.125, 0.25 and 0.5 µg/mL) and MCLR (1 µg/mL) as single compounds and their combinations in HepG2 cells after 24 and 72 h exposure. CYN and CYN/MCLR induced DNA double-strand breaks after 72 h exposure, while cell cycle analysis revealed that CYN and CYN/MCLR arrested HepG2 cells in G0/G1 phase. Moreover, CYN and the combination with MCLR upregulated CYP1A1 and target genes involved in DNA-damage response (CDKN1A, GADD45A). Altogether, the results showed that after 72 h exposure genotoxic activity of CYN/MCLR mixture was comparable to the one of pure CYN. On the contrary, MCLR (1 µg/mL) had no effect on the viability of cells and had no influence on cell division. It did not induce DNA damage and did not deregulate studied genes after prolonged exposure. The outcomes of the study confirm the importance of investigating the combined effects of several toxins as the effects can differ from those induced by single compounds.

ACS Style

Leticia Díez-Quijada; Klara Hercog; Martina Štampar; Metka Filipič; Ana M. Cameán; Ángeles Jos; Bojana Žegura. Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line. Toxins 2020, 12, 778 .

AMA Style

Leticia Díez-Quijada, Klara Hercog, Martina Štampar, Metka Filipič, Ana M. Cameán, Ángeles Jos, Bojana Žegura. Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line. Toxins. 2020; 12 (12):778.

Chicago/Turabian Style

Leticia Díez-Quijada; Klara Hercog; Martina Štampar; Metka Filipič; Ana M. Cameán; Ángeles Jos; Bojana Žegura. 2020. "Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line." Toxins 12, no. 12: 778.

Editorial
Published: 13 October 2020 in Toxins
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Climate change and human activities are more and more affecting the dynamics of phytoplankton communities

ACS Style

Angeles Jos; Ana M. Cameán. Freshwater Algal Toxins: Monitoring and Toxicity Profile. Toxins 2020, 12, 653 .

AMA Style

Angeles Jos, Ana M. Cameán. Freshwater Algal Toxins: Monitoring and Toxicity Profile. Toxins. 2020; 12 (10):653.

Chicago/Turabian Style

Angeles Jos; Ana M. Cameán. 2020. "Freshwater Algal Toxins: Monitoring and Toxicity Profile." Toxins 12, no. 10: 653.

Journal article
Published: 29 July 2020 in Food and Chemical Toxicology
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Propyl-propane-thiosulfonate (PTSO) is one of the main organosulfur compounds present in Allium essentials oil. Different applications in the food sector have been proposed for PTSO, such as food and feed additive and as active packaging. However, the authorization of its use depends on its toxicity profile. Thus, as a part of its safety assessment, in this work a repeated dose 90-day oral toxicity study has been conducted for the first time in rats following the OECD guideline 408. PTSO was administered to groups of 10 male and 10 female rats at dose levels of 0, 14, 28, and 55 mg/kg/day. No clinical signs or mortality and no changes in body weight, food consumption and feed conversion efficiency were detected through the study. Moreover, no treatment-related changes in hematological and biochemical parameters were observed, for either sex or dose groups. The histopathology study performed revealed no differences in organ weights, and no morphological and histopathological changes were observed. Based on these results, the no-observed-adverse-effect level (NOAEL) of PTSO was judged to be ≥ 55 mg/kg/day for both sexes.

ACS Style

Antonio Cascajosa Lira; Ana Isabel Prieto; Alberto Baños; Enrique Guillamón; Rosario Moyano; Angeles Jos; Ana M. Cameán. Safety assessment of propyl-propane-thiosulfonate (PTSO): 90-days oral subchronic toxicity study in rats. Food and Chemical Toxicology 2020, 144, 111612 .

AMA Style

Antonio Cascajosa Lira, Ana Isabel Prieto, Alberto Baños, Enrique Guillamón, Rosario Moyano, Angeles Jos, Ana M. Cameán. Safety assessment of propyl-propane-thiosulfonate (PTSO): 90-days oral subchronic toxicity study in rats. Food and Chemical Toxicology. 2020; 144 ():111612.

Chicago/Turabian Style

Antonio Cascajosa Lira; Ana Isabel Prieto; Alberto Baños; Enrique Guillamón; Rosario Moyano; Angeles Jos; Ana M. Cameán. 2020. "Safety assessment of propyl-propane-thiosulfonate (PTSO): 90-days oral subchronic toxicity study in rats." Food and Chemical Toxicology 144, no. : 111612.

Journal article
Published: 26 May 2020 in Toxins
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Cylindrospermopsin (CYN) and microcystins (MC) are cyanotoxins that can occur simultaneously in contaminated water and food. CYN/MC-LR mixtures previously investigated in vitro showed an induction of micronucleus (MN) formation only in the presence of the metabolic fraction S9. When this is the case, the European Food Safety Authority recommends a follow up to in vivo testing. Thus, rats were orally exposed to 7.5 + 75, 23.7 + 237, and 75 + 750 μg CYN/MC-LR/kg body weight (b.w.). The MN test in bone marrow was performed, and the standard and modified comet assays were carried out to measure DNA strand breaks or oxidative DNA damage in stomach, liver, and blood cells. The results revealed an increase in MN formation in bone marrow, at all the assayed doses. However, no DNA strand breaks nor oxidative DNA damage were induced, as shown in the comet assays. The histopathological study indicated alterations only in the highest dose group. Liver was the target organ showing fatty degeneration and necrotic hepatocytes in centrilobular areas, as well as a light mononuclear inflammatory periportal infiltrate. Additionally, the stomach had flaking epithelium and mild necrosis of epithelial cells. Therefore, the combined exposure to cyanotoxins may induce genotoxic and histopathological damage in vivo.

ACS Style

Leticia Díez-Quijada; Concepción Medrano-Padial; María Llana-Ruiz-Cabello; Giorgiana M. Cătunescu; Rosario Moyano; Maria A. Risalde; Ana M. Cameán; Ángeles Jos. Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats. Toxins 2020, 12, 348 .

AMA Style

Leticia Díez-Quijada, Concepción Medrano-Padial, María Llana-Ruiz-Cabello, Giorgiana M. Cătunescu, Rosario Moyano, Maria A. Risalde, Ana M. Cameán, Ángeles Jos. Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats. Toxins. 2020; 12 (6):348.

Chicago/Turabian Style

Leticia Díez-Quijada; Concepción Medrano-Padial; María Llana-Ruiz-Cabello; Giorgiana M. Cătunescu; Rosario Moyano; Maria A. Risalde; Ana M. Cameán; Ángeles Jos. 2020. "Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats." Toxins 12, no. 6: 348.

Journal article
Published: 20 March 2020 in Toxins
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Toxic cyanobacterial blooms are a major contaminant in inland aquatic ecosystems. Furthermore, toxic blooms are carried downstream by rivers and waterways to estuarine and coastal ecosystems. Concerning marine and estuarine animal species, very little is known about how these species are affected by the exposure to freshwater cyanobacteria and cyanotoxins. So far, most of the knowledge has been gathered from freshwater bivalve molluscs. This work aimed to infer the sensitivity of the marine mussel Mytilus galloprovincialis to single as well as mixed toxic cyanobacterial cultures and the underlying molecular responses mediated by toxic cyanobacteria. For this purpose, a mussel exposure experiment was outlined with two toxic cyanobacteria species, Microcystis aeruginosa and Chrysosporum ovalisporum at 1 × 105 cells/mL, resembling a natural cyanobacteria bloom. The estimated amount of toxins produced by M. aeruginosa and C. ovalisporum were respectively 0.023 pg/cell of microcystin-LR (MC-LR) and 7.854 pg/cell of cylindrospermopsin (CYN). After 15 days of exposure to single and mixed cyanobacteria, a depuration phase followed, during which mussels were fed only non-toxic microalga Parachlorella kessleri. The results showed that the marine mussel is able to filter toxic cyanobacteria at a rate equal or higher than the non-toxic microalga P. kessleri. Filtration rates observed after 15 days of feeding toxic microalgae were 1773.04 mL/ind.h (for M. aeruginosa), 2151.83 mL/ind.h (for C. ovalisporum), 1673.29 mL/ind.h (for the mixture of the 2 cyanobacteria) and 2539.25 mL/ind.h (for the non-toxic P. kessleri). Filtering toxic microalgae in combination resulted in the accumulation of 14.17 ng/g dw MC-LR and 92.08 ng/g dw CYN. Other physiological and biochemical endpoints (dry weight, byssus production, total protein and glycogen) measured in this work did not change significantly in the groups exposed to toxic cyanobacteria with regard to control group, suggesting that mussels were not affected with the toxic microalgae. Nevertheless, proteomics revealed changes in metabolism of mussels related to diet, specially evident in those fed on combined cyanobacteria. Changes in metabolic pathways related with protein folding and stabilization, cytoskeleton structure, and gene transcription/translation were observed after exposure and feeding toxic cyanobacteria. These changes occur in vital metabolic processes and may contribute to protect mussels from toxic effects of the toxins MC-LR and CYN.

ACS Style

Flavio Oliveira; Leticia Diez-Quijada; Maria V. Turkina; João Morais; Aldo Barreiro Felpeto; Joana Azevedo; Angeles Jos; Ana M. Camean; Vitor Vasconcelos; José Carlos Martins; Alexandre Campos. Physiological and Metabolic Responses of Marine Mussels Exposed to Toxic Cyanobacteria Microcystis aeruginosa and Chrysosporum ovalisporum. Toxins 2020, 12, 196 .

AMA Style

Flavio Oliveira, Leticia Diez-Quijada, Maria V. Turkina, João Morais, Aldo Barreiro Felpeto, Joana Azevedo, Angeles Jos, Ana M. Camean, Vitor Vasconcelos, José Carlos Martins, Alexandre Campos. Physiological and Metabolic Responses of Marine Mussels Exposed to Toxic Cyanobacteria Microcystis aeruginosa and Chrysosporum ovalisporum. Toxins. 2020; 12 (3):196.

Chicago/Turabian Style

Flavio Oliveira; Leticia Diez-Quijada; Maria V. Turkina; João Morais; Aldo Barreiro Felpeto; Joana Azevedo; Angeles Jos; Ana M. Camean; Vitor Vasconcelos; José Carlos Martins; Alexandre Campos. 2020. "Physiological and Metabolic Responses of Marine Mussels Exposed to Toxic Cyanobacteria Microcystis aeruginosa and Chrysosporum ovalisporum." Toxins 12, no. 3: 196.

Journal article
Published: 21 February 2020 in Environmental Research
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The aim of this study was to optimize the extraction conditions of Microcystin-LR (MC-LR), Microcystin-RR (MC-RR), Microcystin-YR (MC-YR) and Cylindrospermopsin (CYN) simultaneously from mussels by using response surface methodology (RSM) and to validate the method by a dual solid phase extraction (SPE) system combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The optimal parameters were: 90% MeOH (% v/v) for the extraction, a solvent/sample ratio of 75 and 15% MeOH in the extract before loading onto SPE. Mussels were spiked at 10; 37.5 and 75 ng g−1 fresh weight (f.w) of the 4 toxins, showing linear ranges of 0.5–75 ng g−1 f.w; low values for the limits of detection (0.01–0.39 ng g−1 f.w.) and quantification (0.23–0.40 ng g−1 f.w.); acceptable recoveries (70.37–114.03%) and relative standard deviation (%RSDIP) values (2.61–13.73%). The method was successfully applied to edible mussels exposed to cyanobacterial extracts under laboratory conditions, and it could allow the monitoring of these cyanotoxins in environmental mussel samples.

ACS Style

Leticia Díez-Quijada Jiménez; Remedios Guzmán-Guillén; Giorgiana M. Cătunescu; Alexandre Campos; Vitor Vasconcelos; Ángeles Jos; Ana M. Cameán. A new method for the simultaneous determination of cyanotoxins (Microcystins and Cylindrospermopsin) in mussels using SPE-UPLC-MS/MS. Environmental Research 2020, 185, 109284 .

AMA Style

Leticia Díez-Quijada Jiménez, Remedios Guzmán-Guillén, Giorgiana M. Cătunescu, Alexandre Campos, Vitor Vasconcelos, Ángeles Jos, Ana M. Cameán. A new method for the simultaneous determination of cyanotoxins (Microcystins and Cylindrospermopsin) in mussels using SPE-UPLC-MS/MS. Environmental Research. 2020; 185 ():109284.

Chicago/Turabian Style

Leticia Díez-Quijada Jiménez; Remedios Guzmán-Guillén; Giorgiana M. Cătunescu; Alexandre Campos; Vitor Vasconcelos; Ángeles Jos; Ana M. Cameán. 2020. "A new method for the simultaneous determination of cyanotoxins (Microcystins and Cylindrospermopsin) in mussels using SPE-UPLC-MS/MS." Environmental Research 185, no. : 109284.

Journal article
Published: 25 November 2019 in Chemosphere
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The presence of the toxin cylindrospermopsin is increasingly frequent in samples from different ecosystems and it is a serious problem both at environmental level and for animal and human health. To be able to prevent CYN exposure risk, it is important to have suitable analytical methods, but also quick and economical ones. Analytical pyrolysis coupled to GC/MS (Py-GC/MS) represents an important alternative for the rapid detection, characterization or “fingerprinting” of different materials. However, it has been less studied with cyanotoxins up to date. The present work aims to investigate: 1) the suitability of Py-GC/MS for detection of CYN and its decomposition products in raw and cooked fish samples before consumption and 2) the influence of the different cooking methods on the presence of different CYN degradation products detected by Py-GC/MS. For first time, these results present that Py-GC/MS could be a rapid and economical alternative for the detection and monitoring of CYN and its degradation products (DP. m/z 290.1, 169.1 and 336.2) in raw or cooked fish. Moreover, the changes induced in CYN and DP by cooking could be amenable and detected by Py-GC/MS.

ACS Style

Ana I. Prieto; Remedios Guzmán-Guillén; Ángeles Jos; Ana M. Cameán; José Ma de la Rosa; José A. González-Pérez. Detection of cylindrospermopsin and its decomposition products in raw and cooked fish (Oreochromis niloticus) by analytical pyrolysis (Py-GC/MS). Chemosphere 2019, 244, 125469 .

AMA Style

Ana I. Prieto, Remedios Guzmán-Guillén, Ángeles Jos, Ana M. Cameán, José Ma de la Rosa, José A. González-Pérez. Detection of cylindrospermopsin and its decomposition products in raw and cooked fish (Oreochromis niloticus) by analytical pyrolysis (Py-GC/MS). Chemosphere. 2019; 244 ():125469.

Chicago/Turabian Style

Ana I. Prieto; Remedios Guzmán-Guillén; Ángeles Jos; Ana M. Cameán; José Ma de la Rosa; José A. González-Pérez. 2019. "Detection of cylindrospermopsin and its decomposition products in raw and cooked fish (Oreochromis niloticus) by analytical pyrolysis (Py-GC/MS)." Chemosphere 244, no. : 125469.

Journal article
Published: 28 October 2019 in Toxins
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Cyanobacteria and cyanotoxins constitute a serious environmental and human health problem. Moreover, concerns are raised with the use of contaminated water in agriculture and vegetable production as this can lead to food contamination and human exposure to toxins as well as impairment in crop development and productivity. The objective of this work was to assess the susceptibility of two green vegetables, spinach and lettuce, to the cyanotoxins microcystin (MC) and cylindrospermopsin (CYN), individually and in mixture. The study consisted of growing both vegetables in hydroponics, under controlled conditions, for 21 days in nutrient medium doped with MC or CYN at 10 μg/L and 50 μg/L, or CYN/MC mixture at 5 + 5 μg/L and 25 + 25 μg/L. Extracts from M. aeruginosa and C. ovalisporum were used as sources of toxins. The study revealed growth inhibition of the aerial part (Leaves) in both species when treated with 50µg/L of MC, CYN and CYN/MC mixture. MC showed to be more harmful to plant growth than CYN. Moreover spinach leaves growth was inhibited by both 5 + 5 and 25 + 25 µg/L CYN/MC mixtures, whereas lettuce leaves growth was inhibited only by 25 + 25 µg/L CYN/MC mixture. Overall, growth data evidence increased sensitivity of spinach to cyanotoxins in comparison to lettuce. On the other hand, plants exposed to CYN/MC mixture showed differential accumulation of CYN and MC. In addition, CYN, but not MC, was translocated from the roots to the leaves. CYN and MC affected the levels of minerals particularly in plant roots. The elements most affected were Ca, K and Mg. However, in leaves K was the mineral that was affected by exposure to cyanotoxins.

ACS Style

Maria Llana-Ruiz-Cabello; Angeles Jos; Ana Cameán; Flavio Oliveira; Aldo Barreiro; Joana Machado; Joana Azevedo; Edgar Pinto; Agostinho Almeida; Alexandre Campos; Vitor Vasconcelos; Marisa Freitas. Analysis of the Use of Cylindrospermopsin and/or Microcystin-Contaminated Water in the Growth, Mineral Content, and Contamination of Spinacia oleracea and Lactuca sativa. Toxins 2019, 11, 624 .

AMA Style

Maria Llana-Ruiz-Cabello, Angeles Jos, Ana Cameán, Flavio Oliveira, Aldo Barreiro, Joana Machado, Joana Azevedo, Edgar Pinto, Agostinho Almeida, Alexandre Campos, Vitor Vasconcelos, Marisa Freitas. Analysis of the Use of Cylindrospermopsin and/or Microcystin-Contaminated Water in the Growth, Mineral Content, and Contamination of Spinacia oleracea and Lactuca sativa. Toxins. 2019; 11 (11):624.

Chicago/Turabian Style

Maria Llana-Ruiz-Cabello; Angeles Jos; Ana Cameán; Flavio Oliveira; Aldo Barreiro; Joana Machado; Joana Azevedo; Edgar Pinto; Agostinho Almeida; Alexandre Campos; Vitor Vasconcelos; Marisa Freitas. 2019. "Analysis of the Use of Cylindrospermopsin and/or Microcystin-Contaminated Water in the Growth, Mineral Content, and Contamination of Spinacia oleracea and Lactuca sativa." Toxins 11, no. 11: 624.

Journal article
Published: 03 July 2019 in Food and Chemical Toxicology
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Cylindrospermopsin (CYN) is a potent cyanotoxin recognized as an emerging human threat due to its cytotoxicity and potential carcinogenicity. Although the genotoxicity of CYN has been extensively studied in vitro, limited data are available on its in vivo genotoxicity. The aim of this study was to evaluate the in vivo genotoxicity of pure CYN (7.5–75 μg/kg body weight) after oral exposure of rats through a combined assay of the micronucleus test (MN) in bone marrow, and the standard and modified comet assay in stomach, liver and blood. Also, histopathological changes in stomach and liver were evaluated. Positive results in the MN test were observed in bone marrow in the exposed rats at all the tested concentrations. However, the comet assay revealed that CYN did not induce DNA strand breaks nor oxidative DNA damage in any of the tissues investigated. Finally, histopathological changes were observed in stomach and liver (7.5–75 μg/kg) in intoxicated rats. These results could indicate that CYN is able to induce irritation in stomach before its biotransformation in rats orally exposed, and genotoxicity in bone marrow.

ACS Style

Leticia Díez-Quijada; Maria Llana-Ruiz-Cabello; Giorgiana M. Cătunescu; María Puerto; Rosario Moyano; Angeles Jos; Ana M. Cameán. In vivo genotoxicity evaluation of cylindrospermopsin in rats using a combined micronucleus and comet assay. Food and Chemical Toxicology 2019, 132, 110664 .

AMA Style

Leticia Díez-Quijada, Maria Llana-Ruiz-Cabello, Giorgiana M. Cătunescu, María Puerto, Rosario Moyano, Angeles Jos, Ana M. Cameán. In vivo genotoxicity evaluation of cylindrospermopsin in rats using a combined micronucleus and comet assay. Food and Chemical Toxicology. 2019; 132 ():110664.

Chicago/Turabian Style

Leticia Díez-Quijada; Maria Llana-Ruiz-Cabello; Giorgiana M. Cătunescu; María Puerto; Rosario Moyano; Angeles Jos; Ana M. Cameán. 2019. "In vivo genotoxicity evaluation of cylindrospermopsin in rats using a combined micronucleus and comet assay." Food and Chemical Toxicology 132, no. : 110664.

Journal article
Published: 04 June 2019 in Toxins
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The co-occurrence of various cyanobacterial toxins can potentially induce toxic effects different than those observed for single cyanotoxins, as interaction phenomena cannot be discarded. Moreover, mixtures are a more probable exposure scenario. However, toxicological information on the topic is still scarce. Taking into account the important role of mutagenicity and genotoxicity in the risk evaluation framework, the objective of this study was to assess the mutagenic and genotoxic potential of mixtures of two of the most relevant cyanotoxins, Microcystin-LR (MC-LR) and Cylindrospermopsin (CYN), using the battery of in vitro tests recommended by the European Food Safety Authority (EFSA) for food contaminants. Mixtures of 1:10 CYN/MC-LR (CYN concentration in the range 0.04–2.5 µg/mL) were used to perform the bacterial reverse-mutation assay (Ames test) in Salmonella typhimurium, the mammalian cell micronucleus (MN) test and the mouse lymphoma thymidine-kinase assay (MLA) on L5178YTk± cells, while Caco-2 cells were used for the standard and enzyme-modified comet assays. The exposure periods ranged between 4 and 72 h depending on the assay. The genotoxicity of the mixture was observed only in the MN test with S9 metabolic fraction, similar to the results previously reported for CYN individually. These results indicate that cyanobacterial mixtures require a specific (geno)toxicity evaluation as their effects cannot be extrapolated from those of the individual cyanotoxins.

ACS Style

Leticia Díez-Quijada; Ana I. Prieto; María Puerto; Ángeles Jos; Ana M. Cameán. In Vitro Mutagenic and Genotoxic Assessment of a Mixture of the Cyanotoxins Microcystin-LR and Cylindrospermopsin. Toxins 2019, 11, 318 .

AMA Style

Leticia Díez-Quijada, Ana I. Prieto, María Puerto, Ángeles Jos, Ana M. Cameán. In Vitro Mutagenic and Genotoxic Assessment of a Mixture of the Cyanotoxins Microcystin-LR and Cylindrospermopsin. Toxins. 2019; 11 (6):318.

Chicago/Turabian Style

Leticia Díez-Quijada; Ana I. Prieto; María Puerto; Ángeles Jos; Ana M. Cameán. 2019. "In Vitro Mutagenic and Genotoxic Assessment of a Mixture of the Cyanotoxins Microcystin-LR and Cylindrospermopsin." Toxins 11, no. 6: 318.

Review
Published: 28 December 2018 in Food and Chemical Toxicology
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The occurrence of cyanobacterial toxins is being increasingly reported. This is a reason for concern as they can induce toxic effects both in humans and in the environment. Among them, microcystins (MCs) are the best described and most diverse group of cyanobacterial toxins, and MC-LR and MC-RR are the congeners most widely investigated. However, the number of MC variants has also increased in recent years. Some of these minority variants have been shown to have a different toxicokinetic and toxicodynamic profile, but research focused on them is still limited. Moreover, in some water bodies these minority variants can be the predominant toxins. Nonetheless, MC-LR is the only one used for risk evaluation purposes at present. In order to contribute to more realistic risk assessments in the future, the aim of this review was to compile the available information in the scientific literature regarding the occurrence and concentration of minority MCs in water and food samples, and their toxic effects. The data retrieved demonstrate the congener-specific toxicity of MCs, as well as many data gaps in relation to analytical or mechanistic aspects, among others. Therefore, further research is needed to improve the toxicological characterization of these toxins and the exposure scenarios.

ACS Style

Leticia Díez-Quijada; Ana I. Prieto; Remedios Guzmán-Guillén; Angeles Jos; Ana M. Cameán. Occurrence and toxicity of microcystin congeners other than MC-LR and MC-RR: A review. Food and Chemical Toxicology 2018, 125, 106 -132.

AMA Style

Leticia Díez-Quijada, Ana I. Prieto, Remedios Guzmán-Guillén, Angeles Jos, Ana M. Cameán. Occurrence and toxicity of microcystin congeners other than MC-LR and MC-RR: A review. Food and Chemical Toxicology. 2018; 125 ():106-132.

Chicago/Turabian Style

Leticia Díez-Quijada; Ana I. Prieto; Remedios Guzmán-Guillén; Angeles Jos; Ana M. Cameán. 2018. "Occurrence and toxicity of microcystin congeners other than MC-LR and MC-RR: A review." Food and Chemical Toxicology 125, no. : 106-132.

Research article
Published: 20 November 2018 in Environmental Toxicology
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Cylindrospermopsin (CYN) and Microcystin-LR (MC-LR) are toxins produced by different cyanobacterial species, which are found mainly in freshwater reservoirs. Both of them can induce, separately, toxic effects in humans and wildlife. However, little is known about the toxic effects of the combined exposure, which could likely happen, taking into account the concomitant occurrence of the producers. As both cyanotoxins are well known to induce hepatic damage, the human hepatocellular HepG2 cell line was selected for the present study. Thus, the cytotoxicity of both pure cyanotoxins alone (0–5 μg/mL CYN and 0–120 μg/mL MC-LR) and in combination for 24 and 48 h was assayed, as long as the cytotoxicity of extracts from CYN-producing and nonproducing cyanobacterial species. The potential interaction of the combination was evaluated by the isobologram or Chou–Talalay's method, which provides a combination index as a quantitative measure of the two cyanotoxins interaction's degree. Moreover, a morphological study of the individual pure toxins and their combinations was also performed. Results showed that CYN was the most toxic pure cyanotoxin, being the mean effective concentrations obtained ≈4 and 90 μg/mL for CYN and MC-LR, respectively after 24 h. However, the simultaneous exposure showed an antagonistic effect. Morphologically, autophagy, at low concentrations, and apoptosis, at high concentrations were observed, with affectation of the rough endoplasmic reticulum and mitochondria. These effects were more pronounced with the combination. Therefore, it is important to assess the toxicological profile of cyanotoxins combinations in order to perform more realistic risk evaluations.

ACS Style

Daniel Gutiérrez-Praena; Remedios Guzmán-Guillén; Silvia Pichardo; Francisco Javier Moreno; Vitor Vasconcelos; Ángeles Jos; Ana María Cameán. Cytotoxic and morphological effects of microcystin-LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2. Environmental Toxicology 2018, 34, 240 -251.

AMA Style

Daniel Gutiérrez-Praena, Remedios Guzmán-Guillén, Silvia Pichardo, Francisco Javier Moreno, Vitor Vasconcelos, Ángeles Jos, Ana María Cameán. Cytotoxic and morphological effects of microcystin-LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2. Environmental Toxicology. 2018; 34 (3):240-251.

Chicago/Turabian Style

Daniel Gutiérrez-Praena; Remedios Guzmán-Guillén; Silvia Pichardo; Francisco Javier Moreno; Vitor Vasconcelos; Ángeles Jos; Ana María Cameán. 2018. "Cytotoxic and morphological effects of microcystin-LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2." Environmental Toxicology 34, no. 3: 240-251.

Journal article
Published: 08 October 2018 in Toxins
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Cyanotoxins are a large group of noxious metabolites with different chemical structure and mechanisms of action, with a worldwide distribution, producing effects in animals, humans, and crop plants. When cyanotoxin-contaminated waters are used for the irrigation of edible vegetables, humans can be in contact with these toxins through the food chain. In this work, a method for the simultaneous detection of Microcystin-LR (MC-LR), Microcystin-RR (MC-RR), Microcystin-YR (MC-YR), and Cylindrospermopsin (CYN) in lettuce has been optimized and validated, using a dual solid phase extraction (SPE) system for toxin extraction and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for analysis. Results showed linear ranges (5–50 ng g−1 f.w.), low values for limit of detection (LOD) (0.06–0.42 ng g−1 f.w.), and limit of quantification (LOQ) (0.16–0.91 ng g−1 f.w.), acceptable recoveries (41–93%), and %RSDIP values for the four toxins. The method proved to be robust for the three variables tested. Finally, it was successfully applied to detect these cyanotoxins in edible vegetables exposed to cyanobacterial extracts under laboratory conditions, and it could be useful for monitoring these toxins in edible vegetables for better exposure estimation in terms of risk assessment.

ACS Style

Leticia Díez-Quijada; Remedios Guzmán-Guillén; Ana Prieto Ortega; María Llana-Ruíz-Cabello; Alexandre Campos; Vítor Vasconcelos; Ángeles Jos; Ana Cameán. New Method for Simultaneous Determination of Microcystins and Cylindrospermopsin in Vegetable Matrices by SPE-UPLC-MS/MS. Toxins 2018, 10, 406 .

AMA Style

Leticia Díez-Quijada, Remedios Guzmán-Guillén, Ana Prieto Ortega, María Llana-Ruíz-Cabello, Alexandre Campos, Vítor Vasconcelos, Ángeles Jos, Ana Cameán. New Method for Simultaneous Determination of Microcystins and Cylindrospermopsin in Vegetable Matrices by SPE-UPLC-MS/MS. Toxins. 2018; 10 (10):406.

Chicago/Turabian Style

Leticia Díez-Quijada; Remedios Guzmán-Guillén; Ana Prieto Ortega; María Llana-Ruíz-Cabello; Alexandre Campos; Vítor Vasconcelos; Ángeles Jos; Ana Cameán. 2018. "New Method for Simultaneous Determination of Microcystins and Cylindrospermopsin in Vegetable Matrices by SPE-UPLC-MS/MS." Toxins 10, no. 10: 406.

Journal article
Published: 18 September 2018 in Food and Chemical Toxicology
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Cylindrospermopsin (CYN) is a cyanobacterial toxin with an increasing world-wide occurrence. The main route of human exposure is through the ingestion of contaminated food and water. The European Food Safety Authority has identified the need to further characterize the toxicological profile of cyanotoxins and in this regard the genotoxicity is a key toxicological effect. The data available in the scientific literature show contradictory results. Thus, the aim of this study was to investigate the mutagenic and genotoxic effects of pure CYN using a battery of different in vitro assays including: the bacterial reverse-mutation assay in Salmonella typhimurium (Ames test) (0–10 μg/mL), the mammalian cell micronucleus (MN) test (0–1.35 μg/mL and 0–2 μg/mL in absence or presence of S9 fraction, respectively) and the mouse lymphoma thymidine-kinase assay (MLA)(0–0.675 μg/mL) on L5178YTk ± cells, and the standard and enzyme-modified comet assays (0–2.5 μg/mL) on Caco-2 cells. Positive results were obtained only when the metabolic fraction S9 was employed in the MN test, suggesting pro-genotoxic properties of CYN. Also, DNA damage was not mediated by oxidative stress as CYN did not induced changes in the modified comet assay. These data could contribute to a better risk assessment of this cyanotoxin.

ACS Style

María Puerto; Ana I. Prieto; Sara Maisanaba; Daniel Gutiérrez-Praena; Pilar Mellado-García; Ángeles Jos; Ana M. Cameán. Mutagenic and genotoxic potential of pure Cylindrospermopsin by a battery of in vitro tests. Food and Chemical Toxicology 2018, 121, 413 -422.

AMA Style

María Puerto, Ana I. Prieto, Sara Maisanaba, Daniel Gutiérrez-Praena, Pilar Mellado-García, Ángeles Jos, Ana M. Cameán. Mutagenic and genotoxic potential of pure Cylindrospermopsin by a battery of in vitro tests. Food and Chemical Toxicology. 2018; 121 ():413-422.

Chicago/Turabian Style

María Puerto; Ana I. Prieto; Sara Maisanaba; Daniel Gutiérrez-Praena; Pilar Mellado-García; Ángeles Jos; Ana M. Cameán. 2018. "Mutagenic and genotoxic potential of pure Cylindrospermopsin by a battery of in vitro tests." Food and Chemical Toxicology 121, no. : 413-422.

Journal article
Published: 01 February 2018 in Toxins
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Reports on the occurrence of the cyanobacterial toxin cylindrospermopsin (CYN) have increased worldwide because of CYN toxic effects in humans and animals. If contaminated waters are used for plant irrigation, these could represent a possible CYN exposure route for humans. For the first time, a method employing solid phase extraction and quantification by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) of CYN was optimized in vegetables matrices such as lettuce (Lactuca sativa). The validated method showed a linear range, from 5 to 500 ng CYN g−1 of fresh weight (f.w.), and detection and quantitation limits (LOD and LOQ) of 0.22 and 0.42 ng CYN g−1 f.w., respectively. The mean recoveries ranged between 85 and 104%, and the intermediate precision from 12.7 to 14.7%. The method showed to be robust for the three different variables tested. Moreover, it was successfully applied to quantify CYN in edible lettuce leaves exposed to CYN-contaminated water (10 µg L−1), showing that the tolerable daily intake (TDI) in the case of CYN could be exceeded in elderly high consumers. The validated method showed good results in terms of sensitivity, precision, accuracy, and robustness for CYN determination in leaf vegetables such as lettuce. More studies are needed in order to prevent the risks associated with the consumption of CYN-contaminated vegetables.

ACS Style

Ana I. Prieto; Remedios Guzmán-Guillén; Leticia Díez-Quijada; Alexandre Campos; Vitor Vasconcelos; Ángeles Jos; Ana M. Cameán. Validation of a Method for Cylindrospermopsin Determination in Vegetables: Application to Real Samples Such as Lettuce (Lactuca sativa L.). Toxins 2018, 10, 63 .

AMA Style

Ana I. Prieto, Remedios Guzmán-Guillén, Leticia Díez-Quijada, Alexandre Campos, Vitor Vasconcelos, Ángeles Jos, Ana M. Cameán. Validation of a Method for Cylindrospermopsin Determination in Vegetables: Application to Real Samples Such as Lettuce (Lactuca sativa L.). Toxins. 2018; 10 (2):63.

Chicago/Turabian Style

Ana I. Prieto; Remedios Guzmán-Guillén; Leticia Díez-Quijada; Alexandre Campos; Vitor Vasconcelos; Ángeles Jos; Ana M. Cameán. 2018. "Validation of a Method for Cylindrospermopsin Determination in Vegetables: Application to Real Samples Such as Lettuce (Lactuca sativa L.)." Toxins 10, no. 2: 63.

Journal article
Published: 01 January 2018 in Journal of Hazardous Materials
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The clay montmorillonite (Mt) is among the nanofillers more frequently used for food packaging applications. The organomodification of clays with different modifiers, such as silanes, is an important step in the preparation of improved polymer/clay materials known as nanocomposites. However, the toxicological data about these nanofillers is still scarce. In the present study, an in vitro toxicological evaluation in Caco-2 cells of two silane-modified clays based on Mt, Clay3 and Clay4 (0-250μg/ml), was performed. The cytotoxicity, cell death, genotoxicity and oxidative stress produced by both organoclays were evaluated after 24 and 48h of exposure. Moreover, the migration extracts obtained from nanocomposites of polypropylene (PP) + Clay3 and only PP were also investigated. Only Clay4 induced cytotoxicity, showing a reduction of cell viability to 63% of the control, as well as oxidative stress in a concentration-dependent manner. Regarding the PP-Clay3 migration extract, no cytotoxic effects were observed after exposure to the tested concentrations (0-100%). Moreover, significant differences in the presence of Ca, Mg and Si compared to the PP extract were obtained, although migration levels were in accordance with the food contact materials regulation. These findings indicate that a case-by-case toxicological assessment of organoclays should be performed.

ACS Style

Sara Maisanaba; Remedios Guzmán-Guillén; María Puerto; Daniel Gutiérrez-Praena; Natalia Ortuño; Ángeles Jos. In vitro toxicity evaluation of new silane-modified clays and the migration extract from a derived polymer-clay nanocomposite intended to food packaging applications. Journal of Hazardous Materials 2018, 341, 313 -320.

AMA Style

Sara Maisanaba, Remedios Guzmán-Guillén, María Puerto, Daniel Gutiérrez-Praena, Natalia Ortuño, Ángeles Jos. In vitro toxicity evaluation of new silane-modified clays and the migration extract from a derived polymer-clay nanocomposite intended to food packaging applications. Journal of Hazardous Materials. 2018; 341 ():313-320.

Chicago/Turabian Style

Sara Maisanaba; Remedios Guzmán-Guillén; María Puerto; Daniel Gutiérrez-Praena; Natalia Ortuño; Ángeles Jos. 2018. "In vitro toxicity evaluation of new silane-modified clays and the migration extract from a derived polymer-clay nanocomposite intended to food packaging applications." Journal of Hazardous Materials 341, no. : 313-320.

Review
Published: 16 December 2017 in Toxins
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Cylindrospermopsin (CYN) is a cyanobacterial toxin that is gaining importance, owing to its increasing expansion worldwide and the increased frequency of its blooms. CYN mainly targets the liver, but also involves other organs. Various mechanisms have been associated with its toxicity, such as protein synthesis inhibition, oxidative stress, etc. However, its toxic effects are not yet fully elucidated and additional data for hazard characterization purposes are required. In this regard, in vitro methods can play an important role, owing to their advantages in comparison to in vivo trials. The aim of this work was to compile and evaluate the in vitro data dealing with CYN available in the scientific literature, focusing on its toxicokinetics and its main toxicity mechanisms. This analysis would be useful to identify research needs and data gaps in order to complete knowledge about the toxicity profile of CYN. For example, it has been shown that research on various aspects, such as new emerging toxicity effects, the toxicity of analogs, or the potential interaction of CYN with other cyanotoxins, among others, is still very scarce. New in vitro studies are therefore welcome.

ACS Style

Silvia Pichardo; Ana M. Cameán; Angeles Jos. In Vitro Toxicological Assessment of Cylindrospermopsin: A Review. Toxins 2017, 9, 402 .

AMA Style

Silvia Pichardo, Ana M. Cameán, Angeles Jos. In Vitro Toxicological Assessment of Cylindrospermopsin: A Review. Toxins. 2017; 9 (12):402.

Chicago/Turabian Style

Silvia Pichardo; Ana M. Cameán; Angeles Jos. 2017. "In Vitro Toxicological Assessment of Cylindrospermopsin: A Review." Toxins 9, no. 12: 402.