Saxitoxins induce cytotoxicity, genotoxicity and oxidative stress in teleost neurons in vitro

Silva, Cesar Aparecido da; Morais, Elizabeth Cunha Penna de; Costa, Michele D.M.; Ribas, João Luiz Coelho; Guiloski, Izonete Cristina; Ramsdorf, Wanessa Algarte; Zanata, Sı́lvio M.; Cestari, Marta M.; Ribeiro, Ciro Alberto de Oliveira; Magalhães, Valéria Freitas de; Trudeau, Vance L.; Assis, Helena C. Silva de

doi:10.1016/j.toxicon.2014.04.016

Cited by 34 publications

(22 citation statements)

References 38 publications

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“…Cytotoxicity, genotoxicity and oxidative stress of a mixture of 97% saxitoxin, 3% neosaxitoxin andgonyautoxin was assessed in vitro with primary culture of neurons isolated from tropical freshwater fish species Hoplias malabaricus by da Silva et al (2014), using a concentration of 3.0 mg/L. STXs increased specific activity of glutathione peroxidase and lipoperoxidation levels and gave positive results in the comet assay.…”

Section: Genotoxicitymentioning

confidence: 99%

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Testai

Buratti

Funari

et al. 2016

EFS3

104

125

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This report presents the extensive literature search conducted on 1) the occurrence of different cyanotoxins in food matrices; 2) the analytical methods for their detection; 3) their toxicological profile; 3) the environmental factors affecting toxicity of cyanobacterial population and 4) the combined effects of mixtures of cyanotoxins and other chemicals. It also includes a review of guidelines values or health-alert levels for cyanotoxins in food (or drinking water) adopted world-wide. The methodological aspects and the queries used in the extensive literature search, the collection and screening of retrieved papers and the inventory are briefly described in the report; all details are available in 3 supplementary appendices to this report. The analysis of collected papers indicated that most of them are focused on a single microcystin (MC) variant (MC-LR) out of the almost 100 MC known. Many studies on occurrence are affected by limited quality, due to analytical drawbacks in the detection methods and were not considered in the exposure assessment. Toxicity studies useful for the derivation of health based reference values are few, being many of them carried out using i.p. injection, which is poorly representative of actual human exposure. In addition, those toxicological studies carried out with poorly characterised cyanobacterial extracts or focused on single parameters, using a single dose, devoted to elucidation of mechanism of action, reporting qualitative description of effects were not used for data extraction. The relevant exposure scenarios are also described, although being the available data on exposure very limited, no definite conclusion on the health risks for the exposed population could be drawn. However, the possibility of risky exposure is evidenced for fish and shell-fish consumers and for blue-green algae supplements (BGAS) as well in relation to MC contamination. Finally, many data gaps were identified. © European Food Safety Authority, 2016Key words: Cyanobacteria, cyanotoxins, occurrence, toxicity, exposure, risk assessment, data gaps. Question number: EFSA-Q-2015-00141Correspondence:sc.secretariat@efsa.europa.eu Cyanotoxins in foodThe present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors.www.efsa.europa.eu/publications 2 EFSA Supporting publication 2016:EN-998NDisclaimer: The present document has been produced and adopted by the bodies identified above as author(s). This task has b...

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Section: Genotoxicitymentioning

confidence: 99%

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Testai

Buratti

Funari

et al. 2016

EFS3

104

125

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“…[29][30][31][32][33] In addition, cell cultures have been successfully employed as an alternative to the use of whole animal models. [34,35] In this study, we show that primary cultures of M. roosevelti hepatic cells provide a good model for the evaluation of changes in respiratory activity caused by 2,4-D and MCPA. This model may also be useful in other toxicity assessments.…”

Section: Resultsmentioning

confidence: 69%

Toxicity assessment of 2,4-D and MCPA herbicides in primary culture of fish hepatic cells

Salvo

Malucelli

Silva

et al. 2015

Journal of Environmental Science and Health, Part B

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In this study, we used primary cultures of fish hepatic cells as a tool for evaluating the effects of environmental contamination. Primary hepatic cell cultures derived from the subtropical fish Metynnis roosevelti were exposed to different concentrations (0.275, 2.75 and 27.5 μg L(-1)) of the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA). Cellular respiratory activity was evaluated by polarography using three substrates: 0.5 M glucose, 0.5 M succinate and 0.5 M α-ketoglutarate. Significant changes were observed in cellular oxygen consumption with 0.5 M α-ketoglutarate. Even at low concentrations, 2,4-D and MCPA were potent uncouplers of oxidative phosphorylation. Primary cultures of M. roosevelti liver cells may provide a useful tool for the evaluation of environmental contaminant effects. A review of regulations regarding permitted concentrations of these herbicides is needed.

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“…However, additional tests for apoptosis detection need to be carried out to elucidate STX-induced apoptosis. Da Silva et al (2014) found that STX induced apoptosis through a mechanism involving effector caspases such as caspase 6 or 7 or initiated caspase cascades such as caspase 9. However, further in vitro studies need to be conducted to clarify the apoptotic pathway that might be involved following STX exposure.…”

Section: Dna Fragmentationmentioning

confidence: 99%

“…The Neuro 2A (N2A) bioassay of the neuroblastoma mouse cell line was described by Jellett et al (1995) as a method to detect STX, and this cell line proved to be suitable for use with in vitro cytotoxicity assays (Perreault et al 2011). Various investigators with in vitro studies demonstrated the cytotoxic effects of STX Perreault et al 2011;Da Silva et al 2014). Perreault et al (2011) suggested that STX produced indirect genotoxic effects in N2A cells at concentrations ranging from 0.5 to 64 nM through induction of DNA methylation.…”

mentioning

confidence: 99%

“…found that STX at a concentration of 1.5 nM induced oxidative stress as evidenced by lipid peroxidation (LPO) in N2A cell line. Cytotoxicity based upon cell viability utilizing the MTT assay, genotoxicity as evidenced from comet assay, and oxidative stress based upon LPO levels using the xylenol orange assay were reported by Da Silva et al (2014) following exposure of neuronal cells of Hoplias malabaricus to STX at concentrations of 3 µg/L (STXeq).…”

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confidence: 99%

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Evaluation of Cytotoxicity and Cell Death Induced In Vitro by Saxitoxin in Mammalian Cells

Melegari

Pinto

Moukha

et al. 2015

Journal of Toxicology and Environmental Health, Part A

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Since the cyanotoxin saxitoxin (STX) is a neurotoxin and induces ecological changes in aquatic environments, a potential risk to public and environmental health exists. However, data on STX-mediated cytotoxic and genotoxic effects are still scare. In order to gain a better understanding of the effects of this toxin, the cytotoxic and genotoxic potential of STX was examined in two mammalian cell lines. Neuro 2A (N2A), a neuroblastoma mouse cell line, and Vero cell line, derived from Vero green monkey kidney cells, were exposed to several concentrations of STX ranging from 0.5 to 64 nM to determine cell viability, induction of apoptosis (DNA fragmentation assay), and formation of micronuclei (MN) (cytokinesis-block micronucleus assay; CBMN) following 24 h of incubation. The half maximal effective concentration (EC50) values for STX calculated in cell viability tests were 1.01 nM for N2A and 0.82 nM for Vero cells. With increasing STX concentration there was evidence of DNA fragmentation indicating apoptosis induction in Vero cells with a 50% increase in DNA fragmentation compared to control at the highest STX concentration tested (3 nM). The results demonstrated no significant changes in the frequency of micronucleated binucleated cells in N2A and Vero cells exposed to STX, indicating the absence of genotoxicity under these test conditions. There was no apparent cellular necrosis as evidenced by a lack of formation of multinucleated cells. In conclusion, data reported herein demonstrate that STX produced death of both cell types tested through an apoptotic process.

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Saxitoxins induce cytotoxicity, genotoxicity and oxidative stress in teleost neurons in vitro

Cited by 34 publications

References 38 publications

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Toxicity assessment of 2,4-D and MCPA herbicides in primary culture of fish hepatic cells

Evaluation of Cytotoxicity and Cell Death Induced In Vitro by Saxitoxin in Mammalian Cells

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