Zearalenone: Insights into New Mechanisms in Human Health
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Like in the case of other mycotoxins, Sus scrofa is a preferred animal model for ZEA toxicological evaluation. Sus scrofa is a mammal whose organs bear a lot of similarities to those of humans, when it comes to shape and size. Another great advantage of pigs is that they reach sexual maturity at 4–6 months of age, when compared to other nonhuman primates that need several years to reach sexual maturity. Also, a sow will give birth to multiple piglets at once, whereas primates give birth to only a single baby. This can reduce the genetic variability and productivity of the line [15]. The pig enzymes located in the liver, gastrointestinal tracts, and kidney resemble those of humans to a greater degree than in other animal models [16]. Pigs are some of the animals that consume mycotoxin-contaminated cereals in large quantities, and it is known that they convert the less harmful zearalenone substance into α-zearalenol. For instance, in a study conducted in 2005, pigs were given injections with ZEA, and after 11 days their bile, urine, and liver were examined, and only α-zearalenol was found [17].
Fusarium
Dongyou Liu in Laboratory Models for Foodborne Infections, 2017
It is assumed that ZEA has a role in sexual reproduction of the producing fungi [17], and it also affects the growth, development, and photosynthetic apparatus of the contaminated plant [18]. The nonsteroidal, estrogen-like structure also allows the toxin and its metabolites (α-zearalenol and β-zearalenol) to compete with mammalian endogenous estrogens for specific binding sites on their receptors. This estrogenic activity of ZEA causes hyperestrogenism and fertility disorders in farm animals after consumption of a high dose of affected crops (e.g., >0.25 mg/kg ZEA in maize) [14,19]. Pigs—particularly the prepubertal females—are the most sensitive to the higher concentrations of ZEA, whereas ruminants and poultry are reported as less sensitive [14]. Piglets can be affected as well, as ZEA can be excreted into sows’ milk [19]. ZEA also represents a potential risk to human health. It is assumed that ZEA exposure is associated with precocious pubertal development in girls [15,20], and it was also mentioned as a possible causative agent of cervical cancer [21]. Besides its endocrine-disrupting effects on animals and humans, ZEA has been reported to be hepatotoxic, hematotoxic, immunotoxic, and genotoxic [12].
Environmental toxicants on Leydig cell function
C. Yan Cheng in Spermatogenesis, 2018
Many fungi produce toxins. Zearalenone is one of them. Zearalenone is a mycotoxin produced by some Fusarium and Gibberella species. Studies have pointed to the possible toxicity of zearalenone in Leydig cells. Zearalenone inhibited LH-stimulated testosterone production in mouse Leydig cells.265 However, it did not affect the expression and the binding activity of LHCGR.265 It also downregulated Cyp11a1, Cyp17a, and Hsd17b3 mRNA levels, possibly via suppressing Nur77 (a transcription factor) expression in mouse Leydig cells.265 Zearalenone inhibited cell growth and increased autophagy in rat Leydig cells.266 It was found that zearalenone induced Leydig cell apoptosis via an endoplasmic reticulum stress-dependent signaling pathway.267 Proteomics analysis showed that zearalenone increased energy production through promoting fatty acid uptake and beta-oxidation and increased excessive oxidative stress, thus possibly leading to lower steroidogenic enzyme expression levels.268 Prevention of ROS did not seem to restore steroidogenesis in MA-10 Leydig cells,269 suggesting that its ROS-inducing effect does not contribute to the inhibition of steroidogenesis. α-Zearalenol (0.01–100 μM), a zearalenone metabolite, also suppressed hCG-induced testosterone production and downregulated Star, Cyp11a1, and Hsd3b1 in mouse Leydig cells,270 indicating a similar mechanism to that of zearalenone.
Toxic and irritant effects induced by zearalenone: prevention by taurine
Published in Toxin Reviews, 2021
Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by the Fusarium species (Bertero et al. 2018). ZEN is a significant contaminant of many agricultural products thus is a major economic and health problem (Kuiper-Goodman et al. 1987, Zinedine et al. 2007). Several systematic review and meta-analytic approaches reported that 32% of mixed cereal products in Europe were contaminated by ZEN and these products were cornflakes (55%), bread (41%), breakfast cereals (37%), biscuit (22%), pasta (17%), respectively (Mousavi Khaneghah et al. 2018, Al-Jaal et al. 2019). Previous studies declared that the concentration of ZEN in human food could be found at a high level, up to 289 μg/g (Yuwai et al. 1994, Ghedira-Chekir et al. 1999). Therefore, ZEN and its metabolites (α-zearalenol and β-zearalenol) is a potential danger to human and animal health.
Estrogenic activity of zearalenone, α-zearalenol and β-zearalenol assessed using the E-screen assay in MCF-7 cells
Published in Toxicology Mechanisms and Methods, 2018
Elena Tatay, Silvia Espín, Antonio-Juan García-Fernández, María-José Ruiz
Mycotoxins are biologically active metabolites produced by fungal species that are toxic to humans and other animals. They represent a serious problem since mycotoxin contamination of agricultural products can occur worldwide and cause several health disorders. Zearalenone (ZEA) is a resorcylic acid lactone derivate produced by Fusarium fungi. ZEA and its derivatives (α-zearalenol [α-ZOL]; β-zearalenol [β-ZOL]) have structural analogy to estrogen, and their structures are flexible enough to bind to mammalian ERs (Parveen et al. 2009). Thus, they are able to mimic the activity of naturally occurring estrogens (Gajecka 2012). The estrogenic activity of ZEA and its metabolites has been determined both in vivo and in vitro (Le Guevel and Pakdel 2001; Minervini et al. 2005; Caloni et al. 2009; Parveen et al. 2009; Frizzell et al. 2011; Busk et al. 2012; Prouillac et al. 2012; Cortinovis et al. 2013). It is known that these mycotoxins, also called mycoestrogens, induce their toxicity by competitive binding to the ER and modifying steroid metabolism and producing morphological and functional changes in the reproductive system (Salem et al. 2017). It has been shown that ZEA decreases fertility due to reproductive tract disorders and abnormal fetal development, reduces the size and weight of the adrenal and pituitary glands in animals, and alters the ovulation cycle (Parveen et al. 2009; Cortinovis et al. 2013; EFSA Panel on Contaminants in the Food Chain (CONTAM) 2016). Due to the anabolic activity of ZEA, it is used as a hormonal growth-promoter in food animals in the United States and Canada, whereas any use of ZEA as a growth promoter is forbidden in the EU (Le Guevel and Pakdel 2001).
Biomonitoring of mycotoxin exposure using urinary biomarker approaches: a review
Published in Toxin Reviews, 2021
Larissa Tuanny Franco, Amin Mousavi Khaneghah, Sarah Hwa In Lee, Carlos Augusto Fernandes Oliveira
After oral intake of contaminated foods, ZEN is rapidly absorbed and then metabolized in the intestines or liver. There, the toxin undergoes hydroxylation with the production of several metabolites that are usually conjugated with glucuronic acid, thus facilitating their excretion in urine (Borchers et al.2010). In pigs, the calculated plasma half-life was 87 h after the intravenous or oral routes (Riley and Voss 2011). However, there is very little information on the absorption rate and metabolic fate/bioavailability (European Food Safety Authority 2016). ZEN is primarily degraded in the liver after considerable enterohepatic recirculation into α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL), which undergo additional reduction into α-zearalanol (α-ZAL) and β-zearalanol (β-ZAL) (Kiessling and Pettersson 1978; Olsen et al.1981). The α-ZAL is metabolized into its isomer β-ZAL and, to a lesser extent, into zearalenone (ZAN). These compounds are, then, partially conjugated with sulfonic or glucuronic acid and excreted in the urine (Kuiper-Goodman et al.1987; Bernhoft et al.2001; Zinedine et al.2007). The intestinal mucosa is also active in reducing ZEA to α-ZEL as well as conjugating with glucuronic acid (Biehl et al.1993). In humans, urinary excretion of ZEN is approximately 10% of the administered dose, with ZEN glucuronides and α-ZEL as the main metabolites, along with minor amounts of β-ZEL (Fleck et al.2016). Urinary biomarkers in piglets show excretion 36.8% of dietary ZEN in 24 h (Gambacorta et al.2013). Half-life is approximately 3 days after ZEN administration (Ueno et al.1977; Olsen et al.1985; Bernhoft et al.2001).
Related Knowledge Centers
- Epimer
- Estrogen
- Fusarium
- Gastrointestinal Tract
- Metabolite
- Zearalenone
- Liver
- NONsteroidal
- Resorcylic Acid Lactone
- Β-Zearalenol