Toxicological evaluation of the neurotoxic properties of cylindrospermopsin and its potential interactions with cyanotoxins and chemical pollutants present in food

Abstract

Cyanobacteria are prokaryotic microorganism present in many aquatic and terrestrial environmental samples worldwide able to produce some toxic compounds known as cyanotoxins. Among them, microcystins, in special microcystin-LR (MC-LR) and CYN are some of the most common ones. Both are produced by several species of cyanobacteria. Cylindrospermopsin (CYN) is a cyanotoxin produced by several species of cyanobacteria. Their incidence is increasing in the last decades due to anthropogenic activities and climate change. These hepatotoxin and cytotoxin, respectively, are able to cause intoxication cases in the food chain from fish to humans, as they can also be bioaccumulated. The main mechanisms of action for MC-LR are the the inhibition of protein phosphatases, oxidative stress generation and effects on DNA repair, among others. Furthermore, MC-LR has demonstrated to exert neurotoxicity by irreversible inhibition of Serine/Threonine protein phosphatases 1 and 2A (PP1 and PP2A), Tau hyperphosphorylation, oxidative stress and modifications in neurotransmitters such as ACh, DA and GABA. Concerning the mechanisms of action for CYN, the most important ones are the protein-synthesis inhibition, oxidative stress generation and apoptosis. Furthermore, its metabolite has demonstrated also to be able to cause genotoxicity. Despite being the liver and the kidneys its main targets, the nervous system has recently been studied as a possible target as well. The studies performed in this regard point out a possible effect on the production of oxidative stress and alterations in the acetylcholinesterase activity both in vitro and in vivo. However, the studies in this aspect are scarce.