Integrated Approach to Cyclopiazonic Acid Cytotoxicity Using In Vitro (2D and 3D Models) and In Silico Methods

Area of Science:

• Neuroscience
• Toxicology
• Mycotoxicology

Background:

• Cyclopiazonic acid (CPA) is a neurotoxic mycotoxin produced by Aspergillus and Penicillium species.
• CPA is commonly found in contaminated fruits, cereals, and nuts, posing a potential health risk.

Purpose of the Study:

• To compare the cytotoxicity of CPA in human neuroblastoma SH-SY5Y cells using 2D monolayers and 3D spheroids.
• To evaluate the toxicokinetics of CPA using in silico models.
• To assess the impact of CPA on spheroid morphology and organization.

Main Methods:

• Cytotoxicity was assessed using the MTT assay across different CPA exposure times (24, 48, 72 hours).
• In silico models (SwissADME, admetSAR) were employed for ADMEt profiling.
• Morphological changes in SH-SY5Y spheroids were observed following CPA exposure.

Main Results:

• CPA exhibited dose- and time-dependent cytotoxicity, with lower IC50 values in 2D monolayers compared to 3D spheroids.
• Exposure to CPA induced morphological alterations and disaggregation in SH-SY5Y spheroids.
• In silico analysis predicted high gastrointestinal absorption and blood-brain barrier penetration for CPA.

Conclusions:

• 3D spheroid models provide a more robust assessment of CPA cytotoxicity than traditional 2D monolayers.
• In silico toxicokinetic profiling enhances the understanding of CPA's potential systemic effects.
• This integrated approach offers a comprehensive strategy for mycotoxin risk assessment.