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Dr. Ana M Cameán
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
Risk Assessment

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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: 16 March 2021 in Food and Chemical Toxicology
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Cylindrospermopsin (CYN) is a toxin with a world-wide increasing occurrence. It can induce toxic effects both in humans and the environment, and toxicity studies are needed to complete its toxicological profile. In this sense, in vivo oral toxicity studies with pure CYN are scarce. The aim of this work was to perform a repeated dose 28-day oral study in rats following the OECD guideline 407 to provide information on health hazard likely to arise from this kind of exposure. Male and female Sprague-Dawley rats were dosed with 18.75, 37.5 and 75 μg CYN/kg b.w./day. After the study period, no clinical signs or mortality and no significant differences in final body weight, body weight gain and total feed intake in both sexes were observed. Only in females some biochemical parameters (triglycerides (TRIG) levels and aspartate aminotransferase (AST) activity) as well as changes in the weight of organs (absolute liver weight values, relative kidney/body weight ratios or relative liver weight/brain weight ratios) were altered, but without toxicological relevance. Histopathological analysis revealed a very mild affectation of liver and kidney in rats. These results suggest the need to perform longer oral toxicity studies to define the potential consequences of long term CYN exposure.

ACS Style

Leticia Díez-Quijada; Rosario Moyano; Verónica Molina-Hernández; Ana M. Cameán; Ángeles Jos. Evaluation of toxic effects induced by repeated exposure to Cylindrospermopsin in rats using a 28-day feeding study. Food and Chemical Toxicology 2021, 151, 112108 .

AMA Style

Leticia Díez-Quijada, Rosario Moyano, Verónica Molina-Hernández, Ana M. Cameán, Ángeles Jos. Evaluation of toxic effects induced by repeated exposure to Cylindrospermopsin in rats using a 28-day feeding study. Food and Chemical Toxicology. 2021; 151 ():112108.

Chicago/Turabian Style

Leticia Díez-Quijada; Rosario Moyano; Verónica Molina-Hernández; Ana M. Cameán; Ángeles Jos. 2021. "Evaluation of toxic effects induced by repeated exposure to Cylindrospermopsin in rats using a 28-day feeding study." Food and Chemical Toxicology 151, no. : 112108.

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: 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: 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.

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.

Conference abstract
Published: 12 September 2018 in Toxicology Letters
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M.G. Hinojosa; D. Gutierrez-Praena; A.I. Prieto; L. Espinar-López; A.M. Cameán; A. Jos. In vitro study of the cytotoxic effects of microcystin-LR, cylindrospermopsin and their mixture in the neuronal SH-SY5Y cell line. Toxicology Letters 2018, 295, S141 .

AMA Style

M.G. Hinojosa, D. Gutierrez-Praena, A.I. Prieto, L. Espinar-López, A.M. Cameán, A. Jos. In vitro study of the cytotoxic effects of microcystin-LR, cylindrospermopsin and their mixture in the neuronal SH-SY5Y cell line. Toxicology Letters. 2018; 295 ():S141.

Chicago/Turabian Style

M.G. Hinojosa; D. Gutierrez-Praena; A.I. Prieto; L. Espinar-López; A.M. Cameán; A. Jos. 2018. "In vitro study of the cytotoxic effects of microcystin-LR, cylindrospermopsin and their mixture in the neuronal SH-SY5Y cell line." Toxicology Letters 295, no. : S141.

Conference abstract
Published: 12 September 2018 in Toxicology Letters
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ACS Style

L. Diez-Quijada Jiménez; M. Puerto; A.I. Prieto; A. Jos; A.M. Cameán. In vitro genotoxicity assessment of cylindrospermopsin-microcystin-lr mixtures by the micronucleus and comet assays. Toxicology Letters 2018, 295, S152 .

AMA Style

L. Diez-Quijada Jiménez, M. Puerto, A.I. Prieto, A. Jos, A.M. Cameán. In vitro genotoxicity assessment of cylindrospermopsin-microcystin-lr mixtures by the micronucleus and comet assays. Toxicology Letters. 2018; 295 ():S152.

Chicago/Turabian Style

L. Diez-Quijada Jiménez; M. Puerto; A.I. Prieto; A. Jos; A.M. Cameán. 2018. "In vitro genotoxicity assessment of cylindrospermopsin-microcystin-lr mixtures by the micronucleus and comet assays." Toxicology Letters 295, no. : S152.

Journal article
Published: 06 July 2018 in Food and Chemical Toxicology
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Research on the human exposure to Cylindrospermopsin (CYN) via consumption of contaminated food is of great interest for risk assessment purposes. The aim of this work is to evaluate for the first time the CYN bioaccessibility in contaminated vegetables (uncooked lettuce and spinach, and boiled spinach) after an in vitro digestion model, including the salivar, gastric and duodenal phases and, colonic fermentation under lactic acid bacteria. The results obtained showed that the digestion processes are able to diminish CYN levels, mainly in the colonic phase, especially in combination with the boiling treatment, decreasing CYN levels in a significant way. Moreover, the potential decomposition products in a pure CYN solution and in CYN-contaminated vegetables were evaluated using UHPLC-MS/MS Orbitrap. Under the conditions assayed, only two diastereoisomers of the same fragment with m/z 292.09617 have been detected in all the analysed samples, with the exception of digested vegetables. Therefore, in terms of risk assessment, the digestion seems to play an important role in reducing the final bioaccesibility of CYN, and the consumption of cooked vegetables (spinach) would be safer in comparison to raw vegetables.

ACS Style

Sara Maisanaba; Remedios Guzmán-Guillén; Rocío Valderrama; Giuseppe Meca; Guillermina Font; Ángeles Jos; Ana M. Cameán. Bioaccessibility and decomposition of cylindrospermopsin in vegetables matrices after the application of an in vitro digestion model. Food and Chemical Toxicology 2018, 120, 164 -171.

AMA Style

Sara Maisanaba, Remedios Guzmán-Guillén, Rocío Valderrama, Giuseppe Meca, Guillermina Font, Ángeles Jos, Ana M. Cameán. Bioaccessibility and decomposition of cylindrospermopsin in vegetables matrices after the application of an in vitro digestion model. Food and Chemical Toxicology. 2018; 120 ():164-171.

Chicago/Turabian Style

Sara Maisanaba; Remedios Guzmán-Guillén; Rocío Valderrama; Giuseppe Meca; Guillermina Font; Ángeles Jos; Ana M. Cameán. 2018. "Bioaccessibility and decomposition of cylindrospermopsin in vegetables matrices after the application of an in vitro digestion model." Food and Chemical Toxicology 120, no. : 164-171.

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.

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.

Journal article
Published: 01 November 2017 in Journal of Chromatography A
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Compound-specific isotope analysis (CSIA) usually requires preparative steps (pretreatments, extraction, derivatization) to get amenable chromatographic analytes from bulk geological, biological or synthetic materials. Analytical pyrolysis (Py-GC/MS) can help to overcome such sample manipulation. This communication describe the results obtained by hyphenating analytical pyrolysis (Py-GC) with carbon isotope-ratio mass spectrometry (IRMS) for the analysis of a polylactic acid (PLA) a based bio-plastic extruded with variable quantities of a natural plant extract or oregano essential oil. The chemical structural information of pyrolysates was first determined by conventional analytical pyrolysis and the measure of δ(13)C in specific compounds was done by coupling a pyrolysis unit to a gas chromatograph connected to a continuous flow IRMS unit (Py-GC-C-IRMS). Using this Py-CSIA device it was possible to trace natural additives with depleted δ(13)C values produced by C3 photosystem vegetation (cymene: -26.7‰±2.52; terpinene: -27.1‰±0.13 and carvacrol: -27.5‰±1.80 from oregano and two unknown structures: -23.3‰±3.32 and -24.4‰±1.70 and butyl valerate: -24.1‰±3.55 from Allium spp.), within the naturally isotopically enriched bio-plastic backbone derived from corn (C4 vegetation) starch (cyclopentanones: -14.2‰±2.11; lactide enantiomers: -9.2‰±1.56 and larger polymeric units: -17.2‰±1.71). This is the first application of Py-CSIA to characterize a bio-plastic and is shown as a promising tool to study such materials, providing not only a fingerprinting, but also valuable information about the origin of the materials, allowing the traceability of additives and minimizing sample preparation.

ACS Style

M. Llana-Ruíz-Cabello; S. Pichardo; N.T. Jiménez-Morillo; F.J. González-Vila; E. Guillamón; Jose Maria Bermudez; S. Aucejo; A.M. Camean; J.A. González-Pérez. Pyrolysis-gas chromatography–isotope ratio mass spectrometry for monitoring natural additives in polylactic acid active food packages. Journal of Chromatography A 2017, 1525, 145 -151.

AMA Style

M. Llana-Ruíz-Cabello, S. Pichardo, N.T. Jiménez-Morillo, F.J. González-Vila, E. Guillamón, Jose Maria Bermudez, S. Aucejo, A.M. Camean, J.A. González-Pérez. Pyrolysis-gas chromatography–isotope ratio mass spectrometry for monitoring natural additives in polylactic acid active food packages. Journal of Chromatography A. 2017; 1525 ():145-151.

Chicago/Turabian Style

M. Llana-Ruíz-Cabello; S. Pichardo; N.T. Jiménez-Morillo; F.J. González-Vila; E. Guillamón; Jose Maria Bermudez; S. Aucejo; A.M. Camean; J.A. González-Pérez. 2017. "Pyrolysis-gas chromatography–isotope ratio mass spectrometry for monitoring natural additives in polylactic acid active food packages." Journal of Chromatography A 1525, no. : 145-151.

Journal article
Published: 01 July 2017 in Food Control
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Remedios Guzmán-Guillén; Sara Maisanaba; Ana Isabel Prieto Ortega; Ana María Cameán Fernández; Ángeles Jos; Ana M. Cameán. Changes on cylindrospermopsin concentration and characterization of decomposition products in fish muscle ( Oreochromis niloticus ) by boiling and steaming. Food Control 2017, 77, 210 -220.

AMA Style

Remedios Guzmán-Guillén, Sara Maisanaba, Ana Isabel Prieto Ortega, Ana María Cameán Fernández, Ángeles Jos, Ana M. Cameán. Changes on cylindrospermopsin concentration and characterization of decomposition products in fish muscle ( Oreochromis niloticus ) by boiling and steaming. Food Control. 2017; 77 ():210-220.

Chicago/Turabian Style

Remedios Guzmán-Guillén; Sara Maisanaba; Ana Isabel Prieto Ortega; Ana María Cameán Fernández; Ángeles Jos; Ana M. Cameán. 2017. "Changes on cylindrospermopsin concentration and characterization of decomposition products in fish muscle ( Oreochromis niloticus ) by boiling and steaming." Food Control 77, no. : 210-220.