Combined exposure to emerging Fusarium mycotoxins produces concentration-dependent synergistic toxicity in Jurkat T cells

Information from the abstract

Introduction Beauvericin (BEA), enniatin B (ENN B), and moniliformin (MON), mainly produced by Fusarium species, are often described as emerging mycotoxins due to their frequent detection in cereals and cereal‐based products and their current lack of regulatory limits. Despite increasing evidence regarding their individual toxicities–including immunotoxic, genotoxic, reproductive, and cardiotoxic effects–information on their combined toxicity and the underlying mechanisms remains limited. To address this gap, this study aimed to evaluate the cytotoxic effects, reactive oxygen species (ROS) generation, and interaction patterns of BEA, ENN B, and MON in human Jurkat T cells following a 24‐hour exposure under individual, dual, and triple treatment conditions. Methods The experimental approach evaluated cellular responses and toxicological interactions across single and combined exposures. Cytotoxicity was assessed using the MTT assay to determine cell viability, while intracellular ROS levels were measured using a fluorescence‐based assay. To analyze the dual and mixture interaction patterns among the mycotoxins, the study utilized the Chou–Talalay method for quantitative assessment of synergism and antagonism. Results The individual toxicity assessments yielded IC 50 values of 1.81 μM for BEA, 4.47 μM for ENN B, and 40.45 μM for MON, establishing the potency ranking of BEA > ENN B > MON. Across all treatments, cell viability decreased in a concentration-dependent manner, which was consistently accompanied by an elevation in intracellular ROS fluorescence signals. Combination Index (CI) analysis of binary mixtures (BEA + ENN B, BEA + MON, and ENN B + MON) revealed synergistic interactions at low to moderate effect levels (IC 10 –IC 50 ), which shifted toward antagonism at higher effect levels (IC 75 –IC 90 ). In contrast, the ternary mixture of all three mycotoxins (BEA + ENN B + MON) predominantly exhibited sustained synergism across the entire evaluated concentration range (IC 10 –IC 90 ). Discussion Overall, these findings demonstrate that co-exposure to BEA, ENN B, and MON leads to complex interactive toxicities, with the ternary mixture showing persistent synergistic effects based on Combination Index analysis. Although these cellular responses strongly correlate with elevated ROS‐associated fluorescence signals, direct experimental validation is still required to confirm the specific downstream molecular mechanisms involved.

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Related topics: Mycotoxins in Agriculture and Food · Immunotoxicology and immune responses · Toxin Mechanisms and Immunotoxins