Integrated Approach to Cyclopiazonic Acid Cytotoxicity Using (2D and 3D Models) and Methods.

Cyclopiazonic acid (CPA) is an indole-tetramic acid neurotoxin produced by and genera present mainly in fruit, cereals and nuts. This study compares the cytotoxicity produced by CPA after 24, 48 and 72 h of exposure using both monolayers and 3D spheroids in human neuroblastoma SH-SY5Y cells. Furthermore, CPA toxicokinetics was evaluated using models. Cytotoxicity increased dose- and time-dependently, as shown by the MTT assay. The lowest CPA IC values were found in the monolayer study compared to the 3D spheroids at all exposure times (24 h: 864.01 vs. 1132; 48 h: 437 vs. 1069; 72 h: 392 vs. 567 nM). The CPA exposure on SH-SY5Y spheroid organization and morphology was also studied. Morphological changes, including spheroid disaggregation, were observed after mycotoxin exposure. The methods, SwissADME and admetSAR, were used for short and full ADMEt profiles of CPA. The ADMEt predictive profile shows high gastrointestinal absorption and ability to penetrate the blood-brain barrier. Including studies emphasizes the comprehensive approach to understanding mycotoxin toxicity and risk assessment. By combining 3D spheroid models with computational simulations, this study aims to provide a holistic perspective on the effects of CPA, enhancing the accuracy and relevance of our findings.