Toxicokinetic Studies in Piglets Reveal Age-Related Differences in Systemic Exposure to Zearalenone, Zearalenone-14-Glucoside, and Zearalenone-14-Sulfate

Abstract

Juveniles are considered as one of the most vulnerable population groups concerning mycotoxins and their modified forms. The weaning stage is a particularly vulnerable period in the life of mammals, reflected in intestinal and immune dysfunction. The current study investigated the toxicokinetic (TK) characteristics of zearalenone (ZEN), zearalenone-14-glucoside (ZEN14G), and zearalenone-14-sulfate (ZEN14S) in weaned (4-week-old) piglets, by means of oral and intravenous administration of equimolar doses, i.e., 331, 500, and 415 μg/kg bodyweight, respectively. Plasma and urine were sampled pre- and post-administration and were quantitatively analyzed for ZEN, ZEN14G, ZEN14S, and in vivo metabolites by liquid chromatography–high-resolution mass spectrometry. Tailor-made TK models were elaborated to process data. A statistical comparison of the results was performed with TK data obtained in a previously reported study in pigs of 8 weeks of age. Additionally, porcine plasma protein binding was determined to support TK findings. The TK results for ZEN, ZEN14G, and ZEN14S, obtained in 4- and 8-week-old pigs, revealed significant age-related differences, based on differences in intestinal permeability, body fat content, gastrointestinal transit time, and biotransformation, with a special emphasis on an increased absorbed fraction of ZEN14G, i.e., 94 vs 61% in 4- compared to 8-week-old pigs. Since the growing pig has been reported to be a suitable pediatric animal model for humans concerning TK processes, these results may contribute to refine the risk assessment concerning modified ZEN forms in juvenile animals and humans.

New Insights into the Deposition of Zearalenone in Minipigs: A Suitable Bioindicator for Internal Exposure

“…These results were consistent with those of previously published studies performed on crossbreed pigs. , However, several studies reported relatively low conjugation rates of ZEN and ZOLs in urine with a wide range of values, ranging from 27 to 94% and 23 to 93% . Many studies revealed that a variety of factors could influence ZEN metabolism, including animal species, breed, gender, age, physiological status, individual difference, and so on. ,, The minipig appears to have a higher rate of phase I and phase II metabolic activities for ZEN compared to the crossbred pigs, resulting in conjugated [ZEN + α-ZOL] in plasma being the potential bioindicator of ZEN exposure in minipigs. It is possibly due to genetic differences between experimental pigs employed in the present study and previous studies.…”

Updated Review of the Toxicity of Selected Fusarium Toxins and Their Modified Forms

“…A different experiment, using a considerably lower toxin dose (15.1 µg/kg BW for ZEN-14G and 12.5 µg/kg BW for ZEN-14S), reported that ZEN-14S was not present in urine following oral administration. In the study, the urine also contained ZEN, which indicated the hydrolysis of ZEN-14S [132,134,135]. Low bioavailability of α-ZOL and α-ZOL-14G was observed in rats, which can be explained by their efficient metabolism within the GI system [28,133].…”

Organic Cation Receptor for Colorimetric Lateral Flow Device: Detection of Zearalenone in Food Samples

“…Among these mycotoxins, fumonisin B, ochratoxin A, zearalenone (ZEN), and aflatoxin B1 are appearing extensively in cereals such as soybean, sorghum, corn, oat, and rice and their by-products, and further as residues and metabolites in animal food. , The occurrence of these mycotoxins in animal feed is one of the main issues in animal husbandry owing to the poisonous effect of these mycotoxins observed in animals. In particular, ZEN can cause serious effects, like dysfunction of the nervous system, cancer, and immunotoxicity. , ZEN cytotoxicity truly influences the proliferation, insusceptibility, endocrine activities, and animal inheritance, and stimulates human sex function. , Albeit, the toxicity of ZEN is moderately low (oral LD 50 value = 2g/kg) after oral intake by animals; it has been associated with cervical malignant growth in humans, early adolescence, and hyperplasic and neoplastic endometrium development. , Thus, the International Agency for Research on Cancer (IARC) has categorized ZEN as a group 3 carcinogen . Furthermore, several nations, for instance, Austria, Bulgaria, France, Hungary, Italy, Mexico, Armenia, Ukraine, and Latvia, have set the cutoff limits for ZEN from 0.02 to 1000 μg/kg in natural and prepared cereals to circumscribe the hazard to the people and animals .…”

“…2,3 ZEN cytotoxicity truly influences the proliferation, insusceptibility, endocrine activities, and animal inheritance, and stimulates human sex function. 4,5 Albeit, the toxicity of ZEN is moderately low (oral LD 50 value = 2g/kg) after oral intake by animals; it has been associated with cervical malignant growth in humans, early adolescence, and hyperplasic and neoplastic endometrium development. 6,7 Thus, the International Agency for Research on Cancer (IARC) has categorized ZEN as a group 3 carcinogen.…”