Evaluation of the genotoxic potential of the natural neurotoxin Tetrodotoxin (TTX) in a battery of in vitro and in vivo genotoxicity assays

Guzmán, Antonio; Henestrosa, Antonio R. Fernández de; Marín, Ana-Paz; Ho, Ahn; Borroto, Jorge I. González; Carasa, Inés; Pritchard, L.

doi:10.1016/j.mrgentox.2007.05.016

Cited by 24 publications

(18 citation statements)

References 22 publications

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“…The data were analyzed using the Student's t-test and ANOVA. Results were considered positive when there was a statistically significant increase (P < 0.05) in the frequency of MNPCEs for at least one dose, which exceeded the negative control range (Krishna and Hayashi, 2000; Guidelines for the Testing of Chemicals (OECD), 1997; Guzmán et al, 2007).…”

Section: Mouse Bone Marrow Micronucleus Testmentioning

confidence: 99%

Evaluation of the genotoxic and cytotoxic effects of crude extracts of Cordia ecalyculata and Echinodorus grandiflorus

Silva

Bastos

Takahashi

2010

Journal of Ethnopharmacology

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Section: Mouse Bone Marrow Micronucleus Testmentioning

confidence: 99%

Evaluation of the genotoxic and cytotoxic effects of crude extracts of Cordia ecalyculata and Echinodorus grandiflorus

Silva

Bastos

Takahashi

2010

Journal of Ethnopharmacology

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“…Flatworms (genus Planocera ), the eggs of horseshoe crabs (genus Limulus ), pufferfish (genus Fugu ), xanthid crabs (genus Xantho ), blue-ringed octopi (genus Hapalochlaena ), and newts (family Salamandridae) are all known to possess TTX (Brodie III and Brodie Jr, 1990; Geffeney et al, 2005; Hanifin, 2010; Lorentz et al, 2016; Miyazawa et al, 1986; Noguchi et al, 1984; Ritson-Williams et al, 2006), which is recognized as an exceptionally deadly poison to many vertebrates (Guzmán et al, 2007). Among the 12 species of newts in the family Salamandridae known to possess TTX (Hanifin, 2010), the highest average dermal concentrations (25 µg cm 2 −1 ) occur in members of the genus Taricha (Wakely et al, 1966).…”

Section: Introductionmentioning

confidence: 99%

Noxious newts and their natural enemies: Experimental effects of tetrodotoxin exposure on trematode parasites and aquatic macroinvertebrates

Calhoun

Bucciarelli

Kats

et al. 2017

Toxicon

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The dermal glands of many amphibian species secrete toxins or other noxious substances as a defense strategy against natural enemies. Newts in particular possess the potent neurotoxin tetrodotoxin (TTX), for which the highest concentrations are found in species within the genus Taricha. Adult Taricha are hypothesized to use TTX as a chemical defense against vertebrate predators such as garter snakes (Thamnophis spp.). However, less is known about how TTX functions to defend aquatic-developing newt larvae against natural enemies, including trematode parasites and aquatic macroinvertebrates. Here we experimentally investigated the effects of exogenous TTX exposure on survivorship of the infectious stages (cercariae) of five species of trematode parasites that infect larval amphibians. Specifically, we used dose-response curves to test the sensitivity of trematode cercariae to progressively increasing concentrations of TTX (0.0 [control], 0.63, 3.13, 6.26, 31.32, and 62.64 nmol L−1) and how this differed among parasite species. We further compared these results to the effects of TTX exposure (0 and 1,000 nmolL−1) over 24 hr on seven macroinvertebrate taxa commonly found in aquatic habitats with newt larvae. TTX significantly reduced the survivorship of trematode cercariae for all species, but the magnitude of such effects varied among species. Ribeiroia ondatrae – which causes mortality and limb malformations in amphibians – was the least sensitive to TTX, whereas the kidney-encysting Echinostoma trivolvis was the most sensitive. Among the macroinvertebrate taxa, only mayflies (Ephemeroptera) showed a significant increase in mortality following exogenous TTX exposure, despite the use of a concentration 16x higher than the maximum used for trematodes. Our results suggest that maternal investment of TTX into larval newts may provide protection against certain trematode infections and highlight the importance of future work assessing the effects of newt toxicity on both parasite infection success and the palatability of larval newts to invertebrate predators.

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“…The genotoxicity of a well-known neurotoxin tetrodotoxin toward brown mouse bone cells was examined by Guzmán et al (2007), who found no evidence of genotoxic potential. In another study, the genotoxic potential of others known cyanotoxins, such as domoic and ocadaic acids, was evaluated in the Caco-2 cells line by Pinto- Silva Carvalho et al (2006), who showed that both toxins were considered mutagenic attributed to induction of MN formation.…”

Section: Cbmn Assaymentioning

confidence: 99%

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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Evaluation of the genotoxic potential of the natural neurotoxin Tetrodotoxin (TTX) in a battery of in vitro and in vivo genotoxicity assays

Cited by 24 publications

References 22 publications

Evaluation of the genotoxic and cytotoxic effects of crude extracts of Cordia ecalyculata and Echinodorus grandiflorus

Evaluation of the genotoxic and cytotoxic effects of crude extracts of Cordia ecalyculata and Echinodorus grandiflorus

Noxious newts and their natural enemies: Experimental effects of tetrodotoxin exposure on trematode parasites and aquatic macroinvertebrates

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

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