Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study investigated whether mammalian brain and immune cells can be a target of certain
cyanotoxins, at doses approximating those in the guideline levels for
drinking water, either alone or in mixtures. We examined the effects on cellular viability, apoptosis and
inflammation signalling of several toxins on murine macrophage-like RAW264.7, microglial BV-2 and
neuroblastoma N2a cell lines. We tested
cylindrospermopsin (CYN),
microcystin-LR (MC-LR), and
anatoxin-a (ATX-a), individually as well as their mixture. In addition, we studied the
neurotoxins β-N-methylamino-
l-alanine (BMAA) and its isomer
2,4-diaminobutyric acid (DAB), as well as the mixture of both. Cellular viability was determined by the MTT assay. Apoptosis induction was assessed by measuring the activation of
caspases 3/7. Cell death and
inflammation are the hallmarks of
neurodegenerative diseases. Thus, our final step was to quantify the expression of a major proinflammatory
cytokine TNF-α by ELISA. Our results show that CYN, MC-LR and ATX-a, but not BMAA and DAB, at low doses, especially when present in a mixture at threefold less concentrations than individual compounds are 3-15 times more potent at inducing apoptosis and
inflammation. Our results suggest that common
cyanotoxins at low doses have a potential to induce
inflammation and apoptosis in immune and brain cells. Further research of the neuroinflammatory effects of these compounds in vivo is needed to improve safety limit levels for
cyanotoxins in
drinking water and food.