An Overview of Zearalenone

Zearalenone Toxicity

It is well-known that Zearalenone poses significant health risks, and related research on its toxicity, including exposure, detection, and detoxification methods, has long been a focal point of study.

Zearalenone primarily exhibits hepatotoxicity, reproductive toxicity, immunotoxicity, and intestinal toxicity. Upon oral exposure, Zearalenone is rapidly absorbed into the digestive tract. The intestinal immune barrier and microbiota balance are first disrupted, leading to reduced resistance and inflammatory responses. Zearalenone is metabolized into α-ZOL and β-ZOL, which are absorbed by the intestinal mucosa and enter the bloodstream, being transported to various tissues and organs, thereby interfering with their normal structure and function. Zearalenone derivatives are widely distributed in the body, primarily accumulating in the liver, but can also be detected in the lungs, bile, digestive system, reproductive system, blood, and excreta.

Figure 2. Major toxicities and mechanisms of action of Zearalenone
(Source: Han X, et al. 2022)

Zearalenone carries reproductive toxicity and can cause reproductive disorders in various animals, manifesting as abnormal secretion of reproductive hormones, changes in the morphology and function of reproductive organs, and reduced fertility. In females, conditions such as vaginitis, uterine hypertrophy, infertility, precocious puberty, preterm birth, and miscarriage may occur. In males, symptoms such as testicular atrophy, reduced sperm count, and decreased sperm motility can be observed.

Zearalenone exhibits immunotoxicity, which can damage the immune system, reducing the activity and proliferation of B and T lymphocytes. Zearalenone may affect innate immune functions by inhibiting macrophage production. Additionally, Zearalenone metabolites can significantly reduce immunoglobulin synthesis. In various animals, regardless of the toxin concentration or exposure duration, Zearalenone has been found to reduce serum levels of IgG, IgM, and IgA. Research data on the cellular mechanisms through which Zearalenone triggers different immune responses is still insufficient.

Recently, in addition to the general toxicities, Zearalenone's cytotoxicity and carcinogenicity have also been highlighted. Zearalenone and its derivatives cause disruptions in cell proliferation and apoptosis. α-ZOL and β-ZOL may damage cell membranes, induce mitochondrial damage, and inhibit RNA transcription, DNA replication, and protein synthesis, leading to genomic instability and an increased susceptibility to cancer and genetic diseases. Zearalenone may primarily induce apoptosis through the oxidative stress and endoplasmic reticulum stress (ERS) signaling pathways. Depending on the concentration, zearalenone has distinct effects on cells. Zearalenone causes cell division and inhibits apoptosis at low and medium concentrations, while it causes apoptosis at high quantities. Future studies on cell type specificity, long-term exposure effects, and protective mechanisms can be methodically and thoroughly guided by elucidating the dose-effect relationship and molecular mechanisms of zearalenone at various concentrations. These findings can also be used to optimize risk assessment models and establish safety standards.

The carcinogenicity of Zearalenone in humans is still uncertain. In 2017, the International Agency for Research on Cancer classified Zearalenone as a Group 3 carcinogen, indicating that its cancer-causing potential in humans is not well established. However, recent studies have highlighted the role of apolipoprotein E (ApoE) in the intestine, which is crucial for lipid secretion and metabolism. Zearalenone has been found to significantly reduce ApoE levels, thereby increasing the risk of developing cancers such as intestinal, breast, and colorectal cancer. This suggests that ApoE could be a critical target in understanding the link between Zearalenone exposure and cancer development.

Zearalenone Application and Degradation Methods in Agricultural Production

Besides health risks, Zearalenone causes significant losses in agriculture. It directly results in severe crop yield reductions, decreases output by up to 19%, and indirectly causes economic losses in animal husbandry. Major livestock such as pigs and ruminants are highly sensitive to Zearalenone. Zearalenone contamination not only significantly reduces milk production in cattle and sheep but also causes symptoms in breeding sows, such as uterine and mammary inflammation, infertility, miscarriage, premature birth, vulvovaginitis, vaginal prolapse, retained placenta, and abnormal litter sizes, leading to high perinatal mortality rates and inconsistent piglet development. The global direct economic losses from reproductive disorders in sows due to moldy feed exceed 100 trillion yuan annually. Thus, alleviating and enhancing the reproductive capacity of pigs affected by Zearalenone is a critical issue.

Zearalenone also poses significant challenges to the agricultural and food industries. The main factors influencing Zearalenone concentrations in food include pre-harvest factors (fertilization levels, fungicide use, and harvest methods), post-harvest factors (drying methods, storage conditions), and processing factors (sorting, fermentation, etc.). Specifically, nitrogen fertilization, improper fungicide use, late harvesting, pre-harvest exposure to rainfall, and humid storage conditions increase Zearalenone deposition in grains. Current global climate changes, with rising temperatures and irregular precipitation, are likely to increase the risk of Zearalenone contamination in the coming decades. Additionally, improper industrial wastewater discharge can transfer Zearalenone through water, contaminating agricultural and drinking water sources, thus increasing human exposure directly and indirectly.

On-site prevention in agricultural production is an important strategy to enhance feed and food safety. The priority is the use of soil amendments, such as activated charcoal, which can adsorb Zearalenone and delay spore germination. Certain natural extracts (e.g., essential oils from peppermint, citrus, rosemary, tea tree, and montmorillonite–lemongrass) can inhibit the growth of Fusarium fungi and Zearalenone release. During processing, proper cleaning, dehulling, and fermentation can significantly reduce Zearalenone concentrations, further reduced by physical methods (radiation) and chemical methods (O3, H2O2).

Figure 3 presents various reported strategies and methods for controlling Zearalenone levels in grains and processed foods. (a) Plant hormone-mediated defense mechanisms in maize against Fusarium verticillioides; (b) Developing resistant maize varieties using molecular tools; (c) Altering the soil microenvironment with soil amendments; (d, e, f) Post-harvest methods)

Figure 3. Methods for Controlling Zearalenone Levels in Grains and Processed Foods
(Source: Hudu A. R., et al. 2024)

Although effective, these methods are costly and inevitably affect the flavor/palatability and nutritional value of food/feed, and might even produce secondary pollutants. Safer and more effective control and detoxification methods are needed, with microbial degradation being one promising approach. It is highly specific, efficient, and harmless. Recent studies have shown that certain natural strains like Yeast, Bacillus, and Lactic acid bacteria can achieve different levels of detoxification by adsorbing Zearalenone and preventing its absorption by animals, with degradation rates exceeding 90%. Microbial degradation is suitable for laboratory work but requires further research for commercial-scale application.

Enzymatic degradation, as a more stable, cost-effective, and rapid strategy compared to microbial degradation, has attracted researchers' attention in recent years. The rapid development of genetic engineering has enabled the safe expression of recombinant enzyme genes in microorganisms. Zearalenone lactonase, characterized by high activity and non-toxicity, shows potential for developing innovative enzyme degradation technologies and promising biocatalysts, with significant industrial application potential.

In summary, future research directions include further exploring the exposure of Zearalenone in different animals and humans, particularly its long-term effects during specific physiological periods. Additionally, developing more effective prevention and management strategies is paramount. This includes improving agricultural practices, developing safe and sustainable degradation methods, and innovative detoxification technologies. Additionally, if your laboratory is planning or currently conducting research or testing related to Zearalenone, Creative Diagnostics offers a comprehensive range of Zearalenone detection products for your selection, including a variety of convenient and effective Antigens, Antibodies (monoclonal, monoclonal (RHA^TM), polyclonal), ELISA kits, etc.