Alterations in acetylcholinesterase activity and oxidative stress parameters induced by pure cylindrospermopsin in brain of orally exposed rats and determination of potential metabolites

Cylindrospermopsin (CYN) is a secondary metabolite produced by cyanobacteria. In view of its toxic effects, CYN is frequently classified as a cytotoxin, although it has been associated with neurotoxicological effects. Despite this, few studies have explored the impact of CYN on the nervous system and none of them have been conducted in mammals. Therefore, the objective of the present work was to evaluate the effect of different doses of pure CYN (7.5-75.0 µg/kg body weight) on the brain of rats after gavage exposure for 48 h. For this purpose, the activity of acetylcholinesterase (AChE) enzyme and different biomarkers of oxidative stress were assessed. A significant inhibition of AChE activity was observed at all doses tested. Additionally, the results showed a dose-dependent increase in lipid peroxidation (LPO) levels, as well as alterations in superoxide dismutase (SOD) and catalase (CAT) activities. These changes could be produced by CYN metabolites detected in brain samples by ultra-high-performance liquid chromatography coupled to a tandem mass spectrometry system (UHPLC-MS/MS). These findings suggest that metabolites of pure CYN could cause alterations in the brain of rats after oral exposure and highlight the need for further studies focusing on CYN's neurotoxicity and its potential role in neurodegenerative diseases.