Purinergic and Energy Metabolism Disruption in Oxidative Stress-Mediated Immunotoxicity Induced by Aflatoxin B1 and Fumonisin B1

Mary, Verónica S.; Velez, Pilar A.; Quiroz, Sol; Díaz Iriso, Sofía A.; Amilibia, Candelaria; Rubinstein, Héctor R.; Theumer, Martín G.

doi:10.3390/jof12070520

Open AccessArticle

Purinergic and Energy Metabolism Disruption in Oxidative Stress-Mediated Immunotoxicity Induced by Aflatoxin B₁ and Fumonisin B₁

by

Verónica S. Mary

^1,2,*

,

Pilar A. Velez

¹,

Sol Quiroz

^1,2,

Sofía A. Díaz Iriso

¹,

Candelaria Amilibia

¹,

Héctor R. Rubinstein

¹ and

Martín G. Theumer

^1,2,*

¹

Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Córdoba X5000HUA, Argentina

²

Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI, UNC-CONICET), Córdoba X5000HUA, Argentina

^*

Authors to whom correspondence should be addressed.

J. Fungi 2026, 12(7), 520; https://doi.org/10.3390/jof12070520

Submission received: 22 May 2026 / Revised: 9 July 2026 / Accepted: 10 July 2026 / Published: 15 July 2026

(This article belongs to the Special Issue Mycotoxin Contamination and Toxicology: Food Safety and Preventive Strategies)

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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.

Keywords: adenosine; ATP; aflatoxin B₁; energy status; fumonisin B₁; immunotoxicity; purinergic metabolism; natural killer cells; oxidative stress; Th1 responses

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MDPI and ACS Style

Mary, V.S.; Velez, P.A.; Quiroz, S.; Díaz Iriso, S.A.; Amilibia, C.; Rubinstein, H.R.; Theumer, M.G. Purinergic and Energy Metabolism Disruption in Oxidative Stress-Mediated Immunotoxicity Induced by Aflatoxin B₁ and Fumonisin B₁. J. Fungi 2026, 12, 520. https://doi.org/10.3390/jof12070520

AMA Style

Mary VS, Velez PA, Quiroz S, Díaz Iriso SA, Amilibia C, Rubinstein HR, Theumer MG. Purinergic and Energy Metabolism Disruption in Oxidative Stress-Mediated Immunotoxicity Induced by Aflatoxin B₁ and Fumonisin B₁. Journal of Fungi. 2026; 12(7):520. https://doi.org/10.3390/jof12070520

Chicago/Turabian Style

Mary, Verónica S., Pilar A. Velez, Sol Quiroz, Sofía A. Díaz Iriso, Candelaria Amilibia, Héctor R. Rubinstein, and Martín G. Theumer. 2026. "Purinergic and Energy Metabolism Disruption in Oxidative Stress-Mediated Immunotoxicity Induced by Aflatoxin B₁ and Fumonisin B₁" Journal of Fungi 12, no. 7: 520. https://doi.org/10.3390/jof12070520

APA Style

Mary, V. S., Velez, P. A., Quiroz, S., Díaz Iriso, S. A., Amilibia, C., Rubinstein, H. R., & Theumer, M. G. (2026). Purinergic and Energy Metabolism Disruption in Oxidative Stress-Mediated Immunotoxicity Induced by Aflatoxin B₁ and Fumonisin B₁. Journal of Fungi, 12(7), 520. https://doi.org/10.3390/jof12070520

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Purinergic and Energy Metabolism Disruption in Oxidative Stress-Mediated Immunotoxicity Induced by Aflatoxin B₁ and Fumonisin B₁

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