Metabolic Conversion of Zearalenone to .ALPHA.-Zearalenol by Goat Tissues

Abstract

ABSTRACT. Zearalenone (ZEA), an estrogenic mycotoxin produced by several Fusarium species, is converted into a more active metabolite, -zearalenol (-ZOL), and a less active metabolite, -zearalenol (-ZOL), by liver subcellular fractions, but evidence of this reaction in other tissues is limited. In order to clarify the role of various tissues in ZEA metabolism in ruminant, we investigated the in vitro metabolic conversion of ZEA by various tissues of adult male and female goats. The results indicate that in the liver, -ZOL was a major metabolite in cytosolic fractions, whereas -ZOL was a predominant metabolite in microsome fractions. Such a feature of ZEA metabolism was confirmed by the K m and V max values from an enzyme kinetics experiment. Post-mitochondrial fractions of the liver converted ZEA predominantly to -ZOL, indicating that the goat liver may function as an activation organ rather than as an inactivation organ, for ZEA metabolism in goats. In most other tissues including rumen tissue, the activity converting ZEA to -ZOL was higher than that to -ZOL. The amount of -ZOL formed by gastrointestinal tissues was 1/8-1/3 of that by the liver tissue in terms of the amount per mg protein, but the contribution of all gastrointestinal tissues to production of -ZOL was estimated to be comparable to that of the liver because of the large mass of gastrointestinal tissues in ruminants. Overall the results show the importance of not only the liver tissue, but also other tissues, especially gastrointestinal ones, in the formation of a potent estrogenic metabolite, -ZOL.

Invited review: Diagnosis of zearalenone (ZEN) exposure of farm animals and transfer of its residues into edible tissues (carry over)

“…3a-HSD and 3b-HSD were inhibited by ZEN and ZAL in human hyperplastic prostate suggesting a possible interference with the male reproductive system (Thouvenot and Morfin, 1980). ZEN incubations of caprine hepatic cell preparations revealed that a-ZEL was predominantly formed by the cytosolic and postmitochondrial fractions while b-ZEL was the main product of the microsomal fraction (Dong et al, 2010b). Corresponding cell preparations of rumen and intestinal tissues were also shown to metabolize ZEN, predominantly to a-ZEL.…”

“…Related to protein, the amount of metabolites formed by extrahepatic tissues was approximately 1/8-1/3 of that produced by hepatic preparations. However, the authors suggested that the contribution of extrahepatic tissues is equal to that of the liver, because of the larger absolute mass of the former (Dong et al, 2010b). Although the literature compilation covered a period of more than 30 years characterized by a continuing development of analytical methods with steadily decreasing limits of detection/ quantification (LOD/LOQ), the principal metabolite pattern remains comparable.…”

Risks for animal health related to the presence of zearalenone and its modified forms in feed

“…• Exposure to modified forms The incubation of either lamb liver microsomal or cytosolic fractions with a-ZAL (Zeranol) resulted in the NAD + -mediated formation of ZAN and of small amounts of b-ZAL; the latter was almost entirely due to the NADH-dependent reduction of ZAN (Pompa et al, 1988) Goats • Exposure to ZEN After incubating caprine hepatic cell preparations with ZEN, a-ZEL was proved to be predominantly formed by the cytosolic and postmitochondrial fractions while b-ZEL turned out to be the main product of the microsomal fraction (Dong et al, 2010a). Corresponding cell preparations of rumen and intestinal tissues were also reported to biotransform ZEN mostly to a-ZEL.…”

Endocrine Disruptors Induced Distinct Expression of Thyroid and Estrogen Receptors in Rat versus Mouse Primary Cerebellar Cell Cultures

“…In some of the internal organs (mostly liver, kidneys, testes, prostate, ovaries, intestines, and the hypothalamus), a specific enzyme group called 3αand 3β-hydroxysteroid dehydrogenase (HSD) break ZEN down into metabolites (α-and β-zearalenol, zearalanon, αand β-zearalenon). Some of the metabolites possess an even stronger estrogen-like effect than the original molecule (for example, the estrogen-like effect of α-zearalenol is 3-100 times higher than ZEN) [76,77]. After entering the circulation, ZEN and its metabolites target the ERs all over the body.…”