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Zearalenone (ZEN) and its derivatives a- and b-zearalenol (a- and b-ZEL), zearalenone (ZAN), and a- and b-zearalanol (a- and b-ZAL) are mycotoxins produced by
Fusarium species, such as Fusarium graminearum and Fusarium culmorum. They
are common molds found in temperate and warm countries, and a frequent contaminant of cereal crops, foods, and feeds worldwide posing risks to human and animal
health. These nonsteroidal estrogenic mycotoxins bind competitively to estrogen
receptors, and estrogenic effects and infertility caused by ZEN and its metabolites
have been demonstrated in pigs, sheep, and experimental animals. In rats, both ZEN
and its metabolites are transferred through the placenta. Although human exposure
to ZEN has been demonstrated via dietary intake, little is known about the health
effects except a few studies in cancer patients and prepubertal girls. In mammals,
ZEN is metabolized to two hydroxyl isomers, a-ZEL and b-ZEL by 3a- and
3b-hydroxysteroid dehydrogenase enzymes (HSD). ZEN also undergoes minor
metabolism to catechol structures. Zearalenone and its metabolites are conjugated
with UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs). During
gestation human placenta produces a considerable amount of estrogens which are
essential for development of the fetus and progress of the pregnancy. Based on
mycotoxins estrogenic activity human placental metabolism of ZEN and ZAN was
investigated in vitro by using chorion carcinoma JEG-3 cells, human term placental
subcellular fractions, and recombinant CYP19A1 enzyme (Huuskonen et al. 2015).
ZEN is an estrogenic mycotoxin mainly produced by several Fusarium species.
ZEN-producing fungi mainly occur in wet, temperate weather and high-moisture
storage environments. Exposure to ZEN has been associated with estrogenic effects,
mainly reflected in precocious puberty in girls. In addition, ZEN may cause toxicity
by producing reactive oxygen species (ROS). Among the cereals, maize seems to
present higher infection rates by ZEN; however, wheat, soybean, and rice have been
frequently found to be contaminated with ZEN. Rice, barley, and corn from Korea
have been reported to be contaminated with ZEA with co-occurrence of OTA,
AFB1, FB1, and DON. In Nigeria, ZEN incidence in 196 analyzed moldy rice samples was 50%, with concentrations ranging from 0 to 1169 mg/kg. Milk samples
were investigated in China, and the ZEN metabolite a-zearalenol, which is three
times more estrogenic than ZEN, was found at levels up to 73.5 ng/kg (Luo
et al. 2018).
Glucuronides are the most important class of phase II xenobiotic metabolites and
as a general rule have chemical and biological properties which are significantly
different from the parent compound and therefore play an important role in detoxification, being particularly important for hormonal inactivation and excretion. The
presence of a glucuronide moiety leads to an increased molecular mass and greater
polarity. This can greatly affect a compound’s ability to enter the cell and cause
toxicity due to the decreased ability to diffuse across the lipids of the membrane.
However, a number of glucuronides are known to be pharmacologically active, in
that they retain and have enhanced or different pharmacological activities compared
to the parent compound. There are two sites prone to glucuronidation present in
ZEN and three in ZOL; this is due to the presence of either two or three hydroxyl
groups at C-7, C-14, or C-16. The aromatic glucuronides carrying the glucuronic
N. M. Abdelmotilib et al.
Zearalenone (ZEN) and its derivatives a- and b-zearalenol (a- and b-ZEL), zearalenone (ZAN), and a- and b-zearalanol (a- and b-ZAL) are mycotoxins produced by
Fusarium species, such as Fusarium graminearum and Fusarium culmorum. They
are common molds found in temperate and warm countries, and a frequent contaminant of cereal crops, foods, and feeds worldwide posing risks to human and animal
health. These nonsteroidal estrogenic mycotoxins bind competitively to estrogen
receptors, and estrogenic effects and infertility caused by ZEN and its metabolites
have been demonstrated in pigs, sheep, and experimental animals. In rats, both ZEN
and its metabolites are transferred through the placenta. Although human exposure
to ZEN has been demonstrated via dietary intake, little is known about the health
effects except a few studies in cancer patients and prepubertal girls. In mammals,
ZEN is metabolized to two hydroxyl isomers, a-ZEL and b-ZEL by 3a- and
3b-hydroxysteroid dehydrogenase enzymes (HSD). ZEN also undergoes minor
metabolism to catechol structures. Zearalenone and its metabolites are conjugated
with UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs). During
gestation human placenta produces a considerable amount of estrogens which are
essential for development of the fetus and progress of the pregnancy. Based on
mycotoxins estrogenic activity human placental metabolism of ZEN and ZAN was
investigated in vitro by using chorion carcinoma JEG-3 cells, human term placental
subcellular fractions, and recombinant CYP19A1 enzyme (Huuskonen et al. 2015).
ZEN is an estrogenic mycotoxin mainly produced by several Fusarium species.
ZEN-producing fungi mainly occur in wet, temperate weather and high-moisture
storage environments. Exposure to ZEN has been associated with estrogenic effects,
mainly reflected in precocious puberty in girls. In addition, ZEN may cause toxicity
by producing reactive oxygen species (ROS). Among the cereals, maize seems to
present higher infection rates by ZEN; however, wheat, soybean, and rice have been
frequently found to be contaminated with ZEN. Rice, barley, and corn from Korea
have been reported to be contaminated with ZEA with co-occurrence of OTA,
AFB1, FB1, and DON. In Nigeria, ZEN incidence in 196 analyzed moldy rice samples was 50%, with concentrations ranging from 0 to 1169 mg/kg. Milk samples
were investigated in China, and the ZEN metabolite a-zearalenol, which is three
times more estrogenic than ZEN, was found at levels up to 73.5 ng/kg (Luo
et al. 2018).
Glucuronides are the most important class of phase II xenobiotic metabolites and
as a general rule have chemical and biological properties which are significantly
different from the parent compound and therefore play an important role in detoxification, being particularly important for hormonal inactivation and excretion. The
presence of a glucuronide moiety leads to an increased molecular mass and greater
polarity. This can greatly affect a compound’s ability to enter the cell and cause
toxicity due to the decreased ability to diffuse across the lipids of the membrane.
However, a number of glucuronides are known to be pharmacologically active, in
that they retain and have enhanced or different pharmacological activities compared
to the parent compound. There are two sites prone to glucuronidation present in
ZEN and three in ZOL; this is due to the presence of either two or three hydroxyl
groups at C-7, C-14, or C-16. The aromatic glucuronides carrying the glucuronic
N. M. Abdelmotilib et al.