Abstract

Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are cereal-contaminating mycotoxins; co-exposure to these compounds is associated with hepatocellular carcinoma, although the underlying immunological mechanisms remain unclear. This study aimed to investigate the impact of AFB1 and FB1, individually and combined, on immune cell function, focusing on Th1-associated cytokines, cytotoxic capacity, oxidative stress involvement, and energy and purinergic metabolism. Rat splenocytes and intrahepatic leukocytes were exposed to AFB1 (20 μM), FB1 (10 μM), or a mixture of both (MIX), in the presence or absence of catalase. Cytokines and phenotypes were assessed by flow cytometry and ELISA, cytotoxicity by co-culture assays, and intra/extracellular adenine nucleotides and purines by HPLC. The MIX significantly impaired Th1-like differentiation and reduced IFNγ and TNFα production, FAS-L expression and cytolytic activity while increasing IL4 production, indicating a shift toward a Th2-like profile. These effects were prevented by catalase, supporting a key role for oxidative stress. Co-exposure disrupted intracellular energy balance, decreasing adenosine triphosphate (ATP) levels, ATP/ADP ratios, and total adenine nucleotide pools. It also enhanced purine degradation, extracellular ATP release and adenosine accumulation, suggesting altered purinergic signaling. Consequently, AFB1-FB1 co-exposure disrupts immune function through interconnected redox and metabolic mechanisms, promoting an immunosuppressive environment that may favor tumor progression.

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