Mycotoxins trigger systemic responses that profoundly affect animal health and performance (Helmut, 2015; Mavrommatis et al., 2021). One of the primary metabolic consequences of these contaminants is the biological imbalance between the production of reactive oxygen species (ROS) and the animal’s endogenous antioxidant capacity, the oxidative stress.
This delicate balance between antioxidants and pro-oxidants in the body in general and specifically in the cell is responsible for regulation of various metabolic pathways leading to maintenance of immunocompetence, growth and development and protection against stress conditions associated with commercial production (Surai and Dvorska, 2001).
Mechanisms of Mycotoxin-Induced Oxidative Stress
Mycotoxins negatively impact cellular homeostasis by disrupting the balance between pro-oxidants and antioxidants through an interconnected network of biochemical processes (Surai and Dvorska, 2004). Among their primary mechanisms of action are the induction of intestinal malabsorption syndrome, which compromises the uptake of essential antioxidants such as vitamins A, E, and carotenoids, the depletion of tissue reduced glutathione (GSH), and the impairment of the endogenous enzymatic system (Surai and Dvorska, 2004). Concurrently, the excessive generation of ROS attacks the polyunsaturated fatty acids of cell membranes, increasing lipid peroxidation, altering cellular fluidity, and triggering genotoxic damage alongside apoptotic signaling cascades (Surai and Dvorska, 2004).
In the case of aflatoxins, oxidative stress is initially triggered by interference with the uptake and transport of carotenoids as well as micelle formation in the intestinal mucosa, reducing the availability of pigments and fat-soluble vitamins (Tyczkowski and Hamilton, 1987; Schaeffer et al., 1988; Surai and Dvorska, 2004). At the cellular level, they cause the depletion of reduced glutathione (GSH) in hepatocytes and drastically reduce the activity of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione-S-transferase, and glutathione reductase, leading to a massive generation of ROS, accumulation of thiobarbituric acid reactive substances (TBARS), and an increase in conjugated dienes (Rastogi et al., 2001; Surai and Dvorska, 2004).
For their part, trichothecenes such as deoxynivalenol (DON), T-2 toxin, and nivalenol generate oxidative stress by disrupting intestinal micelle formation, severely decreasing the concentration of antioxidants such as α-tocopherol, carotenoids, ascorbate, and vitamin A in plasma and tissues (Coffin and Combs, 1981; Dvorska and Surai, 2001; Surai and Dvorska, 2004). In addition to causing massive hepatic GSH depletion and inhibiting SOD, catalase, and GSH-Px enzymes, they trigger a ribotoxic stress response that activates JNK and p38 MAPK kinases, elevates intracellular calcium levels, and promotes cytosolic accumulation of cytochrome C with subsequent activation of caspases-3 and 9 (Shifrin and Anderson, 1999; Surai and Dvorska, 2004).
Ochratoxin A (OTA) promotes a pro-oxidant state by inducing hypocarotenoidemia via malabsorption, depleting hepatic GSH, and reducing tissue α-tocopherol (Huff and Hamilton, 1975; Hoehler and Marquardt, 1996; Atroshi et al., 2000; Surai and Dvorska, 2004). This mycotoxin directly stimulates the formation of free radicals such as the hydroxyl radical, which accelerates lipid peroxidation as measured by TBARS and ethane exhalation, while facilitating single-strand DNA cleavage, DNA adduct formation, activation of the JNK pathway, and increased expression of the oxidative stress protein heme oxygenase-1 (Hameed et al., 2017; Gautier et al., 2001; Surai and Dvorska, 2004).
Fumonisins, especially fumonisin B1 (FB1), stimulate lipid peroxidation in cell membranes, microsomes, and phosphatidylcholine bilayers while reducing GSH levels (Sahu et al., 1998; Yin et al., 1998; Surai and Dvorska, 2004). Their hallmark mechanism lies in the inhibition of the enzyme ceramide synthase, which alters sphingolipid metabolism by elevating the sphinganine:sphingosine ratio (Sa/So); this shift alters membrane composition and fluidity, induces calmodulin expression, generates oxidative DNA modifications such as 8-OH-dG formation, and activates the apoptotic pathway coordinated by TNFα and caspase-3 (Dragan et al., 2001; Kim et al., 2001; Surai and Dvorska, 2004).
Finally, zearalenone acts as a potent activator of lipid peroxidation in mitochondrial and microsomal fractions, increasing TBARS levels (Surai and Dvorska, 2004). In particular, zearalenone disrupts mitochondrial ROS homeostasis and induces cell cycle arrest at the G2/M phase, promoting DNA fragmentation and the formation of apoptotic bodies (Abid-Essefi et al., 2003; Surai and Dvorska, 2004).
Health Repercussions of Oxidative Stress in Livestock
Through all the mechanisms described, mycotoxins disrupt cellular homeostasis and severely compromise the animal’s redox balance. This oxidative stress compromises immunity, welfare, and, ultimately, farm profitability, as it marks the beginning of functional degradation (Oke et al., 2024). Oxidative stress leads to:
- Cellular integrity alteration: Free radicals attack cell membranes, particularly affecting the hepatocytes and enterocytes of the gastrointestinal tract.
- Intestinal barrier disruption: Oxidative damage weakens tight junctions, causing leaky gut syndrome and facilitating the entry of other pathogens and toxins into the bloodstream.
- Organ dysfunction: Key organs such as the liver and kidneys suffer inflammatory lesions that waste metabolic energy away from production (meat, eggs, or milk) and toward cellular repair processes.
The impact of oxidative stress is directly reflected in production parameters (An et al., 2024; Chen et al., 2021; Longobardi et al., 2022):
- Impairment in feed conversion ratio: Lower nutrient absorption due to damage to the intestinal epithelium.
- Immunosuppression: The immune system weakens, increasing vulnerability to health challenges and reducing the efficacy of vaccination programs.
- Mortality: Chronic lesions in vital organs lead to a loss of longevity and an increase in mortality rates.
Conclusion
Mycotoxins disrupt cellular homeostasis by depleting antioxidant reserves, inhibiting enzymatic defenses, and triggering massive oxidative stress that destroys lipid membranes and damages cellular DNA. This functional degradation severely compromises the intestinal epithelium and key organs such as the liver and kidneys, forcing the animal to divert metabolic energy from production toward cellular repair; consequently, the immune system weakens, the feed conversion ratio deteriorates, meat, milk, or egg yields decline, and farm mortality rates rise significantly.
