In vitro and in silico assessment of cytotoxicity and chromosome instability induced by saxitoxin in human derived neural cell line

Abstract

In freshwater, saxitoxins (STX) are produced by different cyanobacteria genera, including Raphidiopsis. Data regarding cytogenotoxicity effects of STX on human cells are scarse, this merit further studies of its toxicology. This study assessed the cytotoxicity and the chromosome instability of STX on SHSY-5Y human cell line. The CBMN assay allows the detection of chromosome breaks and abnormal chromosomal segregation. Additionally, in silico systems biology approach, used to search for known and predicted interaction networks, was applied to study the interactions between STX and SHSY-5Y cellular components. The results of the CBMN assay demonstrated that STX concentrations of 2.5 -10 µg/L induced cytostasis and chromosome instability in a dose-response relationship. Apoptosis was detected after exposure of SHSY-5Y cultured cells to STX concentration of 10 µg/L. The results of the systems biology analysis revealed the interaction of STX with proteins related with acetylcoline pathway, cell cycle regulation and apoptosis. Furthermore, combining the in vitro and in silico approachs, it was possible to suggest a mechanism of action of STX in SHSY-5Y cells.Overall, the data demonstrated the cytotoxicity and mutagenicity of environmentally relevant concentrations of STX. These results should be considered when setting up guidelines for monitoring STX in water supply.

Sublethal neurotoxicity of saxitoxin in early zebrafish development: Impact on sensorimotor function and neurotransmission systems

“…The present results also show the zebrafish cholinergic dynamics following STX exposure, as we observed an upsurge in ache mRNA levels at both 144-h of exposure with 10 and 100 μg/L STX, while 1 μg/L only at 168-h of exposure. This trend aligns with literature denoting an imbalanced ache and chat dynamic, leading to augmented ACh neurotransmitter concentrations, presenting potential genotoxic effects [ 39 ]. Further evidence also underscores that extended STX exposure augments malondialdehyde levels in larvae and induce a lipid peroxidation.…”