Saxitoxin potentiates human neuronal cell death induced by Zika virus while sparing neural progenitors and astrocytes.

The Zika virus (ZIKV) epidemic declared in Brazil between 2015 and 2016 was associated with an increased prevalence of severe congenital malformations, including microcephaly. The distribution of microcephaly cases was not uniform across the country, with a disproportionately higher incidence in the Northeast region (NE). Our previous work demonstrated that saxitoxin (STX), a toxin present in the drinking water reservoirs of the NE, exacerbated the damaging effects of ZIKV on the developing brain. We hypothesized that the impact of STX might vary among different neural cell types. While ZIKV infection caused severe damages on astrocytes and neural stem cells (NSCs), the addition of STX did not exacerbate these effects. We observed that neurons subjected to STX exposure were more prone to apoptosis and displayed higher ZIKV infection rate. These findings suggest that STX exacerbates the harmful effects of ZIKV on neurons, thereby providing a plausible explanation for the heightened severity of ZIKV-induced congenital malformations observed in Brazil's NE. This study highlights the importance of understanding the interactive effects of environmental toxins and infectious pathogens on neural development, with potential implications for public health policies.

Guanidinium Toxins and Their Interactions with Voltage-Gated Sodium Ion Channels.

Guanidinium toxins, such as saxitoxin (STX), tetrodotoxin (TTX) and their analogs, are naturally occurring alkaloids with divergent evolutionary origins and biogeographical distribution, but which share the common chemical feature of guanidinium moieties. These guanidinium groups confer high biological activity with high affinity and ion flux blockage capacity for voltage-gated sodium channels (NaV). Members of the STX group, known collectively as paralytic shellfish toxins (PSTs), are produced among three genera of marine dinoflagellates and about a dozen genera of primarily freshwater or brackish water cyanobacteria. In contrast, toxins of the TTX group occur mainly in macrozoa, particularly among puffer fish, several species of marine invertebrates and a few terrestrial amphibians. In the case of TTX and analogs, most evidence suggests that symbiotic bacteria are the origin of the toxins, although endogenous biosynthesis independent from bacteria has not been excluded. The evolutionary origin of the biosynthetic genes for STX and analogs in dinoflagellates and cyanobacteria remains elusive. These highly potent molecules have been the subject of intensive research since the latter half of the past century; first to study the mode of action of their toxigenicity, and later as tools to characterize the role and structure of NaV channels, and finally as therapeutics. Their pharmacological activities have provided encouragement for their use as therapeutants for ion channel-related pathologies, such as pain control. The functional role in aquatic and terrestrial ecosystems for both groups of toxins is unproven, although plausible mechanisms of ion channel regulation and chemical defense are often invoked. Molecular approaches and the development of improved detection methods will yield deeper understanding of their physiological and ecological roles. This knowledge will facilitate their further biotechnological exploitation and point the way towards development of pharmaceuticals and therapeutic applications.

Saxitoxins and okadaic acid group: accumulation and distribution in invertebrate marine vectors from Southern Chile.

Harmful algae blooms (HABs) are the main source of marine toxins in the aquatic environment surrounding the austral fjords in Chile. Huichas Island (Aysén) has an history of HABs spanning more than 30 years, but there is limited investigation of the bioaccumulation of marine toxins in the bivalves and gastropods from the Region of Aysén. In this study, bivalves (Mytilus chilenses, Choromytilus chorus, Aulacomya ater, Gari solida, Tagelus dombeii and Venus antiqua) and carnivorous gastropods (Argobuccinum ranelliformes and Concholepas concholepas) were collected from 28 sites. Researchers analysed the accumulation of STX-group toxins using a LC with a derivatisation post column (LC-PCOX), while lipophilic toxins (OA-group, azapiracids, pectenotoxins and yessotoxins) were analysed using LC-MS/MS with electrospray ionisation (+/-) in visceral (hepatopancreas) and non-visceral tissues (mantle, adductor muscle, gills and foot). Levels of STX-group and OA-group toxins varied among individuals from the same site. Among all tissue samples, the highest concentrations of STX-group toxins were noted in the hepatopancreas in V. antiqua (95 ± 0.1 µg STX-eq 100 g(-1)), T. dombeii (148 ± 1.4 µg STX-eq 100 g(-1)) and G. solida (3232 ± 5.2 µg STX-eq 100 g(-1); p < 0.05); in the adductor muscle in M. chilensis (2495 ± 6.4 µg STX-eq 100 g(-1); p < 0.05) and in the foot in C. concholepas (81 ± 0.7 µg STX-eq 100 g(-1)) and T. dombeii (114 ± 1.2 µg STX-eq 100 g(-1)). The highest variability of toxins was detected in G. solida, where high levels of carbamate derivatives were identified (GTXs, neoSTX and STX). In addition to the detected hydrophilic toxins, OA-group toxins were detected (OA and DTX-1) with an average ratio of ≈1:1. The highest levels of OA-group toxins were in the foot of C. concholepas, with levels of 400.3 ± 3.6 µg OA eq kg(-1) (p < 0.05) and with a toxic profile composed of 90% OA. A wide range of OA-group toxins was detected in M. chilensis with a toxicity < 80 µg OA eq kg(-1), but with 74% of those toxins detected in the adductor muscle. In all evaluated species, there was no detection of lipophilic toxins associated with biotransformation in molluscs and carnivorous gastropods. In addition, the STX-group and OA-group toxin concentrations in shellfish was not associated with the presence of HAB. The ranking of toxin concentration in the tissues of most species was: digestive glands > mantle > adductor muscle for the STX-group toxins and foot > digestive gland for the OA-group toxins. These results gave a better understanding of the variability and compartmentalisation of STX-group and OA-group toxins in different bivalve and gastropod species from the south of Chile, and the analyses determined that tissues could play an important role in the biotransformation of STX-group toxins and the retention of OA-group toxins.