Evaluating the human neurotoxicity and toxicological interactions impact of co-occurring regulated and emerging mycotoxins

• Published in: Food research international 2024-05, Vol.184, p.114239-114239, Article 114239
• Main Authors: de Sá, Soraia V.M., Sousa Monteiro, Carolina, Fernandes, José O., Pinto, Eugénia, Faria, Miguel A., Cunha, Sara C.
• Format: Article
• Language: English
• Subjects: Aflatoxin B1; Cereals; Combination index; Cytotoxicity; Edible Grain; Human exposure; Humans; Interactions; Mycotoxins - toxicity; Neuroblastoma; SH-SY5Y cells
• ISSN: 0963-9969; 1873-7145
• DOI: 10.1016/j.foodres.2024.114239

Image size: please provide an image with a minimum of 531 × 1328 pixels (h × w) or proportionally more. The image should be readable at a size of 5 × 13 cm using a regular screen resolution of 96 dpi. Preferred file types: TIFF, EPS, PDF or MS Office files. [Display omitted] •ENNB was the most neurotoxic (IC50 = 3.72 µM), followed by OTA (9.10 µM) and STG (9.99 µM).•OTA + STG presented the lowest IC50 of binary mixtures.•The most synergistic mixture was STG + CIT at low exposition levels.•Strong synergism in STG + CIT mixture, 50-fold CIT dose reduction for same effect.•The six mycotoxińs combination presented synergism at most inhibition levels. Mycotoxins can inflict harmful effects on diverse organs, and mounting evidence indicates their potential involvement in human neurodegenerative diseases. Given the common occurrence of these toxins in food, there is an increasing demand for a comprehensive assessment of their combined toxicity to enhance our understanding of their potential hazards. This research investigates mycotoxin exposure from widely consumed cereal-based products, including enniatin B (ENNB), sterigmatocystin (STG), aflatoxin B1 (AFB1), cyclopiazonic acid (CPZ), citrinin (CIT), and ochratoxin A (OTA). Employing the median-effect equation based on Chou and Talalay's mass-action law, we assessed their cytotoxicity in human SH-SY5Y neuronal cells. Notably, ENNB displayed the highest neurotoxicity (IC50 = 3.72 µM), followed by OTA (9.10 µM) and STG (9.99 µM). The combination of OTA + STG exhibited the highest toxicity (IC50 = 3.77 µM), while CPZ + CIT showed the least detrimental effect. Approximately 70 % of tested binary combinations displayed synergistic or additive effects, except for ENNB + STG, ENNB + AFB1, and CPZ + CIT, which showed antagonistic interactions. Intriguingly, the senary combination displayed moderate antagonism at the lowest exposure and moderate synergism at higher doses. OTA exhibited predominantly synergistic interactions, comprising approximately 90 %, a noteworthy finding considering its prevalence in food. Conversely, ENNB interactions tended to be antagonistic. The most remarkable synergy occurred in the STG and CIT combination, enabling a 50-fold reduction in CIT dosage for an equivalent toxic effect. These findings highlight the biological relevance of robust synergistic interactions, emphasizing the need to assess human exposure hazards accurately, particularly considering frequent mycotoxin co-occurrence in env