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The high input feeding system is efficient in goats but not popular in Pakistan due to low feed conversion ratio, buck like aroma and high cost. Castration is commonly practiced mitigating the undesirable buck-like aroma. However, it results in deterioration of carcass quality. The use of growth ear implants in some parts of world are common with added benefit of being non-steroidal but function like steroids. There is scanty information available on the use of growth implants along castration especially in Pakistan. The objective of the current study was to find the effect of growth implants on the meat quality of castrated goats at various age under a high input feeding system. A total of 36 kids of Beetal goat (18 animals with 12.36±2 kg BW and ~3-month age and 18 bucks with 19.52±2 kg BW and 6 months age) were selected randomly and divided into 3 groups. A total of 12 animals remained intact, while 24 animals (12 each) were castrated at the age of 90 and 180 days respectively. These groups were subdivided into 3 subgroups (4 animals each) as control, implanted with (12 mg zeranol and 12 mg trenbolone acetate) allotted to treatments using two factors factorial (3×3) with three levels of castration and growth implants each under CRD, fattened for last 70 days of trial. At the end of the trial, 18 animals (2 from each run) were selected randomly and slaughtered to judge meat quality. Average daily gain (ADG) and average daily feed intake (ADFI) were significantly (P<0.01) affected by zeranol implantation and castration at 180 and 90 days respectively. A significant difference (P<0.01) was also observed in feed conversion ratio (FCR) in castrated and entire animals implanted with zeranol. Back fat thickness and yield grade reduced significantly (P<0.01) in zeranol-implanted animals. The eye muscle area of animals treated with zeranol and castrated at 180 days was significantly higher (P<0.01) than other groups. It is concluded that meat overall acceptance, color, and texture also differ significantly (P<0.01) by growth implants coupled with castration and reduced buck-like aroma of meat. Growth implants also improved the lean muscle percentage as compared to the control group. [ABSTRACT FROM AUTHOR]

Endocrine‐disrupting chemicals pose a growing threat to human health through their increasing presence in the environment and their potential interactions with the mammalian endocrine systems. Due to their structural similarity to hormones like estrogen, these chemicals can interfere with endocrine signaling, leading to many deleterious effects. Exposure to estrogenic endocrine‐disrupting compounds (EDC) is a suggested risk factor for the development of breast cancer, one of the most frequently diagnosed cancers in women. However, the mechanisms through which EDCs contribute to breast cancer development remain elusive. To rapidly proliferate, cancer cells undertake distinct metabolic programs to utilize existing nutrients in the tumor microenvironment and synthesize macromolecules de novo. EDCs are known to dysregulate cell signaling pathways related to cellular metabolism, which may be an important mechanism through which they exert their cancer‐promoting effects. These altered pathways can be studied via metabolomic analysis, a new advancement in ‐omics technologies that can interrogate molecular pathways that favor cancer development and progression. This review will summarize recent discoveries regarding EDCs and the metabolic reprogramming that they may induce to facilitate the development of breast cancer. [ABSTRACT FROM AUTHOR]

The objective of this research was to determine the influence of implanting heavy wether lambs with 12 mg of zeranol (1 pellet Ralgro, Merck Animal Health. Madison, NJ, USA) 59 d before harvest. Average daily gain (ADG), feed efficiency, and carcass merit were evaluated. Polypay and crossbred wethers (n = 32) were equally divided into two treatment groups: non-implanted; (CON) or implanted with 12 mg of zeranol (IMP) in a randomized complete block design. Sixteen pens were used, resulting in eight replicate pens per treatment. Wethers were fed a finishing diet consisting of cracked corn, soybean meal, and soybean hulls ad libitum for 59 d. Lambs had access to clean water at all times from water fountains. Lambs were weighed on d -1, 1, 14, and 59. On d 59, 16 lambs (8 lambs/treatment) were harvested in the South Dakota State University Meat Lab. Hot carcass weight (HCW), dressing percent (DP), rib fat, body wall thickness, loin eye area, boneless closely trimmed retail cut percentages, and yield grades were recorded. Final body weight (BW), cumulative ADG, and gain efficiency were greater (p ≤ 0.01) for implanted lambs by 2.9%, 25.0%, and 35.2%, respectively, while dry matter intake (DMI) was unaffected by implant treatment (p = 0.18); thus, the efficiency of dietary net energy utilization was increased for IMP (p ≤ 0.01). No appreciable differences were noted (p ≥ 0.17) between treatments for any carcass traits measured. These results indicate that zeranol improves growth performance in heavy finishing lambs without detriment to carcass quality, which implies that producers can improve profitability due to increased gains and efficiency. [ABSTRACT FROM AUTHOR]

Zeranol (α-zearalanol, α-ZAL), is a resorcyclic acid lactone (RAL). Its administration to farm animals to improve meat production has been prohibited in the European Union due to the potential risk to human health. However, it has been demonstrated that α-ZAL may be present in livestock animals due to Fusarium fungi that produce fusarium acid lactones contamination in feed. The fungi produce a small amount of zearalenone (ZEN), which is metabolized to zeranol. The potential endogenous origin of α-ZAL makes it difficult to correlate positive samples to a potential illicit treatment with α-ZAL. We present two experimental studies that investigated the origin of natural and synthetic RALs in porcine urine. Urine samples from pigs that were either fed with ZEN-contaminated feed or administered α-ZAL by injection were analyzed by liquid chromatography coupled to tandem mass spectrometry, with the method validated according to Commission Implementing Regulation (EU) 2021/808. The data show that although the concentration of α-ZAL in the ZEN feed-contaminated samples is significantly lower than in the illicit administration samples, α-ZAL can occur in porcine urine via natural metabolism. Additionally, the feasibility of using the ratio of forbidden/fusarium RALs in porcine urine as a reliable biomarker for illicit treatment with α-ZAL administration was evaluated for the first time. This study demonstrated that the obtained ratio in the contaminated ZEN feed study was close to 1, while in the illegally administered α-ZAL samples the ratio is always higher than 1 (up to 135). Therefore, this study proves that the ratio criteria (already used when a forbidden RAL is detected in bovine urine) may also be used for porcine urine. [ABSTRACT FROM AUTHOR]

Background: Zearalenone (ZEN) is a mycotoxin contaminating grains and processed foods. ZEN alters nuclear estrogen receptor α/β signaling earning its designation as a mycoestrogen. Experimental evidence demonstrates that mycoestrogen exposure during pregnancy is associated with altered maternal sex steroid hormones, changes in placental size, and decreases in fetal weight and length. While mycoestrogens have been detected in human biospecimens worldwide, exposure assessment of ZEN in US populations, particularly during pregnancy, is lacking., Objective: To characterize urinary and placental concentrations of ZEN and its metabolites in healthy US pregnant people and examine demographic, perinatal, and dietary predictors of exposure., Methods: Urine samples were collected in each trimester from pregnant participants in the UPSIDE study and placenta samples were collected at delivery (Rochester, NY, n = 317). We used high performance liquid chromatography and high-resolution tandem mass spectrometry to measure total urinary (ng/ml) and placental mycoestrogens (ng/g). Using linear regression and linear mixed effect models, we examined associations between mycoestrogen concentrations and demographic, perinatal, and dietary factors (Healthy Eating Index [HEI], ultra-processed food [UPF] consumption)., Results: Mycoestrogens were detected in 97% of urines (median 0.323 ng/ml) and 84% of placentas (median 0.012 ng/g). Stability of urinary mycoestrogens across pregnancy was low (ICC: 0.16-0.22) and did not correlate with placental levels. In adjusted models, parity (multiparous) and pre-pregnancy BMI (higher) predicted higher urinary concentrations. Birth season (fall) corresponded with higher placental mycoestrogens. Dietary analyses indicated that higher HEI (healthier diets) predicted lower exposure (e.g., Σmycoestrogens %∆ -2.03; 95%CI -3.23, -0.81) and higher percent calories from UPF predicted higher exposure (e.g., Σmycoestrogens %∆ 1.26; 95%CI 0.29, 2.24)., Impact: The mycotoxin, zearalenone (ZEN), has been linked to adverse health and reproductive impacts in animal models and livestock. Despite evidence of widespread human exposure, relatively little is known about predictors of exposure. In a pregnant population, we observed that maternal ZEN concentrations varied by maternal pre-pregnancy BMI and parity. Consumption of ultra-processed foods, added sugars, and refined grains were linked to higher ZEN concentrations while healthier diets were associated with lower levels. Our research suggests disparities in exposure that are likely due to diet. Further research is needed to understand the impacts of ZEN on maternal and offspring health., (© 2024. The Author(s).)

While mammographic breast density is associated with breast cancer risk in humans, there is no comparable surrogate risk measure in mouse and rat mammary glands following various environmental exposures. In the current study, mammary glands from mice and rats subjected to reproductive factors and exposures to environmental chemicals that have been shown to influence mammary gland development and/or susceptibility to mammary tumors were evaluated for histologic density by manual and automated digital methods. Digital histological density detected changes due to hormonal stimuli/reproductive factors (parity), dietary fat, and exposure to environmental chemicals, such as benzophenone-3 and a combination of perfluorooctanoic acid and zeranol. Thus, digital analysis of mammary gland density offers a high throughput method that can provide a highly reproducible means of comparing a measure of histological density across independent experiments, experimental systems, and laboratories. This methodology holds promise for the detection of environmental impacts on mammary gland structure in mice and rats that may be comparable to human breast density, thus potentially allowing comparisons between rodent models and human breast cancer studies. • Digital histologic density detected environmental impacts in rodent mammary glands. • Alteration of stromal, epithelial, and adipose compartments were detected. • Exposures to hormones, dietary fat, and environmental chemicals elicited impacts. • Digital histologic methods allow comparison across rodent models. • Digital histologic methods hold promise for comparisons between rodents and humans. [ABSTRACT FROM AUTHOR]

Synthetic growth stimulants are widely used to get high productivity of animals. These preparations can accumulate in the meat and their residual quantities will adversely affect the health of consumers. The purpose of the work was to monitor the content of zeranol, growth stimulant of ruminants in beef which goes to meat processing enterprises of the Western region of Ukraine and to determine the effect of heat treatment on its quantity. It was found out that 29.8% of beef samples taken at meat processing enterprises contained a stimulant for the growth of ruminant zeranol. It was found that during the storage of beef samples frozen at a temperature of -18 °C with different content of zeranol there is a decrease in its number. The most intense process of destruction of zeranol occurred during the first month of storage, during this period of time the amount of zeranol is reduced by an average of 20%, regardless of the initial content. Within two months of storage of frozen beef, the content of zeranol decreases by 28.2 ±0.17%, and at the end of the sixth month its quantity decreases to 33.2 ±0.58%. It was also found that the dynamics of zeranol reducing in beef samples with large quantities (22.5 μg.kg-1) and small (2.3 μg.kg-1) were the same. It was set up that during 30 min of meat cooking there was a decrease in the content of zeranol 24.7 ±0.23% and 32.0 ±0.35% for 60 min, compared to its content in fresh meat. At the same time, when stored in the frozen state and subsequent cooking, the reduction of zeranol content in meat was 39.3 ±0.3%. Therefore, it is proposed to revise and amendments into the regulatory documents of Ukraine regarding the control and supervision of the presence of hormone (zeranol) residues in meat and meat products in order to prevent their sale and consumption by humans.

This experiment was conducted to evaluate the effects zeranol implant on meat quality of Awassi lambs and cross-bred Khalkhali and Abadeh goat kids. Ten ram lambs (33.7 ± 0.5 kg and 4-month-old) and ten male goat kids (18.8 ± 0.7 kg and 4-month-old) were randomly assigned into two treatments (5 each treatment); C (control, 0 mg zeranol) and Z (24 mg zeranol implant) for each species. After 43 days experimental period. The animals were slaughtered, left for 24 hr post-mortem period and Biceps femoris muscle of each species were separated for measuring the proximal composition, TBARS values, cooking loss, drip loss and free fatty acids concentrations. Zeranol implants had significant (P<0.05) effect on dry matter, but did not have any effect on all other meat characteristics. However, dry mater was significantly higher for zeranol-implanted group as compared with control one. Moreover, significant effect of animal species was found for cooking loss, being highest in goat meat than ram lamb meat. Similarly, significant effect of animal species was noticed on TBARS values being highest in ram lamb meat. An obvious increase (P<0.005) in drip loss and TBARS values were observed for meat of both zeranol-implanted and non-implanted groups with storage period. It can be concluded that zeranol implant did not have any effect on meat quality for both ram lambs and male goat kids’ meat. [ABSTRACT FROM AUTHOR]

• The mycoestrogen zeranol promoted preadipocyte differentiation in a TRP-dependent pathway. • Zeranol antagonized the calcium influx activity of TRP-V1 and -C6. • The TRP antagonism could be a possible obesogenic pathway. Recent findings have revealed that exposure to environmental contaminants may result in obesity and pose a health threat to the general public. As the activity of transient receptor potential channels (TRPs) plays a permissive role in adipogenesis, the interactions between TRPs and some food pollutants, i.e. bisphenol A, di (2-ethylhexyl) phthalate, zearalenone, and zeranol at 10 μM were investigated in the present study. TRP-V1,-V3, -C4 and -C6 are reported to be differentially expressed in the adipocyte differentiation, and immunoblotting was performed to quantify changes in these TRPs affected by the pollutants. Our result indicated that the mycoestrogen zeranol or α-zearalanol suppressed the expression of the V1 and C6 isoforms. Subsequently, confocal microscopy was used to measure the calcium inflow repressed by zeranol from 0.1 μM to 10 μM. Oil Red O staining was used to determine the differentiation of 3T3 L1 preadipocytes. Zeranol could suppress the expression of TRP-V1 and -C6 protein and inhibit the associated flow of calcium into the cytosol of 3T3 L1 cells. Its IC 50 value for inhibiting calcium inflow stimulated by 40 μM capsaicin or 10 μM GSK1702934A was estimated to be around 6 μM. Reduced TRP-V1 or -C6 activity might result in promoting adipogenesis. In conclusion, this study demonstrated that zeranol could potentiate fat cell differentiation through antagonizing TRP-V1 and –C6 activities. [ABSTRACT FROM AUTHOR]

The aim of this study was the detection of ethinyl estradiol and resorcylic acid lactones (zeranol and taleranol) in poultry meat samples as unauthorized substances included in the Italian national residue plan. The samples were purified by a solid phase extraction using a C18 column combined with alumina, and the analytes were detected by two specific enzyme‐linked immunosorbent assay (ELISA) kits. As they were collected in the frame of official control activities, the method was also validated according to the Commission Decision 2002/657/EC requirements for screening methods with qualitative purpose. Specificity and detection capability were the performance criteria considered for the validation study, and the latter parameter showed a value of 0.5 μg/kg for both the investigated compounds. Such result was well comparable with the data reported by using chromatographic techniques as confirmation methods, and therefore, the ELISA kits tested in this study could be used for the screening of large numbers of samples. [ABSTRACT FROM AUTHOR]

Zeranol is one of non-steroidal hormonal growth promoters (HGP) that is still permitted to be used in some countries such as Australia, the United States, and others to increase weight gain. However, this non-steroidal HGP is not permitted in Indonesia. The use of zeranol to increase the growth of livestock can cause the occurrence of residue in livestock tissues and organs, having a great dangerous potential for human health. This study aimed to investigate the presence of zeranol residues in 105 samples of bovine meat collected from Jakarta, Surabaya, and Malang cities and analyzed by high-performance liquid chromatography (HPLC). The samples were added with the deproteinizing extractant of 0.2% metaphosphoric acid and acetonitrile (6:4, v/v), and purified using SAX SPE cartridge. Zeranol was then analyzed by HPLC using Shimp-pack VP-ODS (4.6x250 mm) column with a mixture of acetonitrile-water (40:60, v/v) as the mobile phase and detected on photo diode array detector at 262 nm. The recoveries of the method of 3 different concentrations (2, 5, and 10 ng/g) of zeranol were 73.96% to 103.48%. The detection limit and quantification limits were 0.54 ng/g and 1.80 ng/g, respectively. Zeranol residues were detected in 12 (11.43%) out of 105 samples at the concentration of 1.67 to 33.29 ng/g and 7 among them exceeding 2.0 ng/g. The results obtained in this study indicated that zeranol was still being used to increase cattle-meat production. Therefore, strict control must be implemented at all stages, from production to consumption, regarding the application of this HGP in livestock.

Zeranol is one of non-steroidal hormonal growth promoters (HGP) that is still permitted to be used in some countries such as Australia, the United States, and others to increase weight gain. However, this non-steroidal HGP is not permitted in Indonesia. The use of zeranol to increase the growth of livestock can cause the occurrence of residue in livestock tissues and organs, having a great dangerous potential for human health. This study aimed to investigate the presence of zeranol residues in 105 samples of bovine meat collected from Jakarta, Surabaya, and Malang cities and analyzed by high-performance liquid chromatography (HPLC). The samples were added with the deproteinizing extractant of 0.2% metaphosphoric acid and acetonitrile (6:4, v/v), and purified using SAX SPE cartridge. Zeranol was then analyzed by HPLC using Shimp-pack VP-ODS (4.6x250 mm) column with a mixture of acetonitrile-water (40:60, v/v) as the mobile phase and detected on photo diode ar- ray detector at 262 nm. The recoveries of the method of 3 different concentrations (2, 5, and 10 ng/g) of zeranol were 73.96% to 103.48%. The detection limit and quantification limits were 0.54 ng/g and 1.80 ng/g, respectively. Zeranol residues were detected in 12 (11.43%) out of 105 samples at the concentration of 1.67 to 33.29 ng/g and 7 among them exceeding 2.0 ng/g. The results obtained in this study indicated that zeranol was still being used to increase cattle-meat production. Therefore, strict control must be implemented at all stages, from production to consumption, regarding the application of this HGP in livestock. [ABSTRACT FROM AUTHOR]

The current experiment was designed to investigate the effect of zeranol implantation on lambs and goats’ kids raised under commercial conditions. Ten male Awassi lambs (AL) (4-5 months old) with an average body weight of 33.7 ± 0.5 kg and 10 male black goat kids (GK) (3-4 months old) with an average body weight of 18.8 ± 0.7 kg were used in the experiment. The experiment was conducted in Berebuhar village close to Duhok city in May the 15th, 2019The animals from each group were randomly divided into two subgroups, the first group was the control group and the other group was implanted with 24 mg zeranol. The animals were grown for 43 days and then slaughtered. Growth rate, average daily gain and carcass characteristics were measured. Data were analysed as factorial 2 × 2. The results showed that implantation both animal groups with zeranol significantly reduced testicular weight by approximately 55 % and 71 % for goat kids and Awassi lambs respectively. Moreover, the results showed that zeranol implantation found to reduce total body fat from 892 to 816g in goat kids and from 3395 to 2856 g in Awassi lambs. It can be concluded that zeranol implantation has an effect on total body fat and fat tissue distribution. [ABSTRACT FROM AUTHOR]

In this study, it was aimed to investigate the levels of zeranol residue in the meat, liver and kidney samples of cattle slaughtered in slaughterhouses in Kayseri by Enzyme-Linked Immune Sorbent Assay (ELISA) method. For this purpose, three different first class slaughterhouses where cattle were slaughtered in Kayseri province were visited three times in October-December 2018 at 1-month periodic intervals. At each visit, 20 liver, 20 kidney and 20 meat samples belonging to the animals randomly selected from each slaughterhouse were taken and a total of 180 sample materials were used. In this study, zeranol residues were detected in 23 kidney (38.3%), 20 liver (33.3%) and 17 (28.3%) meat samples from the analyzed bovine tissue samples. The residual amount in beef kidney, liver and meat samples were detected between 50.23 - 1120.61 ppt, 38.94-1057.96 ppt and 32.29 - 1195.8 ppt, respectively. The zeranol residue in the analyzed samples was below the legal limit specified in Kodeks Alimentarius. In conclusion, although the amount of zeranol residues in the analyzed samples are low, it was concluded that consuming meat containing these residues may pose a risk to public healththerefore, this chemical should be monitored periodically as a food safety measure. [ABSTRACT FROM AUTHOR]

Synthetic growth stimulants are widely used to get high productivity of animals. These preparations can accumulate in the meat and their residual quantities will adversely affect the health of consumers. The purpose of the work was to monitor the content of zeranol, growth stimulant of ruminants in beef which goes to meat processing enterprises of the Western region of Ukraine and to determine the effect of heat treatment on its quantity. It was found out that 29.8% of beef samples taken at meat processing enterprises contained a stimulant for the growth of ruminant zeranol. It was found that during the storage of beef samples frozen at a temperature of -18 °C with different content of zeranol there is a decrease in its number. The most intense process of destruction of zeranol occurred during the first month of storage, during this period of time the amount of zeranol is reduced by an average of 20%, regardless of the initial content. Within two months of storage of frozen beef, the content of zeranol decreases by 28.2 ±0.17%, and at the end of the sixth month its quantity decreases to 33.2 ±0.58%. It was also found that the dynamics of zeranol reducing in beef samples with large quantities (22.5 µg.kg-1) and small (2.3 µg.kg-1) were the same. It was set up that during 30 min of meat cooking there was a decrease in the content of zeranol 24.7 ±0.23% and 32.0 ±0.35% for 60 min, compared to its content in fresh meat. At the same time, when stored in the frozen state and subsequent cooking, the reduction of zeranol content in meat was 39.3 ±0.3%. Therefore, it is proposed to revise and amendments into the regulatory documents of Ukraine regarding the control and supervision of the presence of hormone (zeranol) residues in meat and meat products in order to prevent their sale and consumption by humans. [ABSTRACT FROM AUTHOR]

La utilización de anabólicos durante la etapa de recría en temeros Holando Argentino machos es motivo del presente trabajo. Para determinar los posibles beneficios de esta práctica llevada a cabo por productores tamberos sobre el desarrollo de los animales, se utilizaron 60 temeros machos castrados, los cuales fueron divididos en tres grupos: Grupo Control, que no recibió ningún tratamiento, Grupo Proferm, tratado con una dosis de 36 mg de Proferm y el Grupo FEV, con 5 ml de F.E.V. al comienzo de la recría. La ganancia de peso promedio total obtenida a los 200 días fue utilizada para evaluar el desarrollo de los animales. Se determinó que los animales tratados con Proferm obtuvieron una ganancia de peso adicional a los 200 días pos-tratamiento

Para determinar si los implantes neonatales (IN) de zeranol producen alteracioneste sticulares al igual que las hormonas estrogénicas se utilizaron 20 terneros machos Aberdeen Angus divididos en dos grupos de igual número. El Grupo Implantado (GI) recibió un IN de 24 mg de zeranol mientras que el Grupo Testigo (GT) no recibió ningún tratamiento. Los animales fueron pesados al nacimiento y a los 8 meses de edad, momento en que fueron castrados. Se comparó la ganancia de peso corporal entre el GI y el GT y se estimó la diferencia del desarrollo testicular entre ambos grupos a través del peso de los testículos. Se encontró una disminución del desarrollo testicular (p0,001) y un aumento de la ganancia de peso corporal (p0,10) en el GI respecto al GT. Se concluye que el IN de zeranol produce sobre los testículos y la ganancia de peso corporal un efecto similar a la aplicaciónn eonatald e las hormonal gonadalese strogénicas

Contamination of the world’s food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has also been detected at lower levels in meat, milk, and spices. ZEN’s synthetic derivative, zeranol, is used as a growth promoter in United States (US) and Canadian beef production. Experimental research suggests that ZEN and zeranol disrupt the endocrine and reproductive systems, leading to infertility, polycystic ovarian syndrome-like phenotypes, pregnancy loss, and low birth weight. With widespread human dietary exposure and growing experimental evidence of endocrine-disrupting properties, a comprehensive review of the impact of ZEN, zeranol, and their metabolites on the female reproductive system is warranted. The objective of this systematic review was to summarize the in vitro, in vivo, and epidemiological literature and evaluate the potential impact of ZEN, zeranol, and their metabolites (commonly referred to as mycoestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registration CRD42020166469) of the literature (2000–2020) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data sources were primary literature published in English obtained from searching PubMed, Web of Science, and Scopus. The ToxR tool was applied to assess risk of bias. In vitro and in vivo studies (n = 104) were identified and, overall, evidence consistently supported adverse effects of mycoestrogens on physiological processes, organs, and tissues associated with female reproduction. In non-pregnant animals, mycoestrogens alter follicular profiles in the ovary, disrupt estrus cycling, and increase myometrium thickness. Furthermore, during pregnancy, mycoestrogen exposure contributes to placental hemorrhage, stillbirth, and impaired fetal growth. No epidemiological studies fitting the inclusion criteria were identified.

Zeranol is one of non-steroidal hormonal growth promoters (HGP) that is still permitted to be used in some countries such as Australia, the United States, and others to increase weight gain. However, this non-steroidal HGP is not permitted in Indonesia. The use of zeranol to increase the growth of livestock can cause the occurrence of residue in livestock tissues and organs, having a great dangerous potential for human health. This study aimed to investigate the presence of zeranol residues in 105 samples of bovine meat collected from Jakarta, Surabaya, and Malang cities and analyzed by high-performance liquid chromatography (HPLC). The samples were added with the deproteinizing extractant of 0.2% metaphosphoric acid and acetonitrile (6:4, v/v), and purified using SAX SPE cartridge. Zeranol was then analyzed by HPLC using Shimp-pack VP-ODS (4.6x250 mm) column with a mixture of acetonitrile-water (40:60, v/v) as the mobile phase and detected on photo diode array detector at 262 nm. The recoveries of the method of 3 different concentrations (2, 5, and 10 ng/g) of zeranol were 73.96% to 103.48%. The detection limit and quantification limits were 0.54 ng/g and 1.80 ng/g, respectively. Zeranol residues were detected in 12 (11.43%) out of 105 samples at the concentration of 1.67 to 33.29 ng/g and 7 among them exceeding 2.0 ng/g. The results obtained in this study indicated that zeranol was still being used to increase cattle-meat production. Therefore, strict control must be implemented at all stages, from production to consumption, regarding the application of this HGP in livestock. [ABSTRACT FROM AUTHOR]

Incidence of stroke increases in postmenopausal women with dangerous consequences. In this study we used zeranol to protect ovariectomized (OVX) rats against cerebral I/R damage and our target is to identify the mechanism of its protection, in addition to investigating whether this mechanism inhibits inflammation (by preventing glial cell activation) and apoptosis. First 18 ovariectomized rats were allocated into 3 groups: I/R group, zeranol+ I/R group and U0126, MEK1/2 inhibitor + zeranol+ I/R group. After 24 h reperfusion, protein expression of total extracellular signal-regulated protein kinase (t-ERK1/2), phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2), Bcl-2, and Bax were quantified. Second 36 female rats were allocated into 3 groups: sham group, I/R group (after ovariectomy by 7 weeks, rats exposed to cerebral I/R) and zeranol group (after ovariectomy by 2 weeks, rats received zeranol for 5 weeks). After 24 h of reperfusion, the following parameters were measured; total nitrate/nitrite, interleukin-10, myeloperoxidase, caspase-3, and finally immunohistochemistry analysis of glial fibrillary acidic protein, cyclooxygenase-2 in cortex and hippocampus (CA1) regions were performed. U-0126 administration reversed the neuroprotective effect induced by zeranol through decreasing ratio of p-ERK1/2:ERK1/2 and Bcl-2/Bax in brain tissue. Activation of ERK signaling pathway by zeranol caused reduction in brain apoptosis and inflammation. Zeranol showed protective effect in OVX rats that were exposed to cerebral I/R by activation of ERK signaling pathway which was blocked by U0126. This protective effect in turns led to decrease inflammation and apoptosis. Representative diagram presenting the mechanistic pathway of zeranol against I/R injury in OVX rats. ER: estrogen receptor; MEK1/2: mitogen activated protein kinase; p-ERK: phosphorylated extracellular signal regulated protein kinase 1/2; iNOS: inducible nitric oxide sunthase; IL-10: interleukin-10; GFAP: glial fibrillary acidic protein; COX-2: cyclooxygenase-2; MPO: myeloperoxidase; Bax: Bcl-2 associated x protein; Bcl-2: B-cell lymphoma 2. Unlabelled Image [ABSTRACT FROM AUTHOR]

Resorcylic Acid Lactones, including zeranol, anabolics listed in the group A4 of Directive 96/23/EC, are banned in Europe for use in animals since 1985. Zeranol, after administration to animals, is metabolized to taleranol and zearalanone. It can also naturally occur in the urine due to conversion of zearalenone that may be present in animal feed. In 2010–2017, in Poland, 7746 animal samples were tested for zeranol residues within the official monitoring program. In 13, zeranol was detected after screening. Re-examinations confirmed resorcylic acid lactones in six samples. The recommendations state that only the presence of zeranol and/or taleranol gives the basis for non-compliance. Confirmation should cover the entire profile of six resorcylic acid lactones. In case of detection, the relationship ratio should be verified. Following the proposed criteria, it could be concluded that zeranol detected in urine samples in Poland originated from contamination of feed with mycotoxin, not from illegal use. [ABSTRACT FROM AUTHOR]

Abstract Aims Cerebral ischemia reperfusion (I/R) is a neurovascular disease leading to cerebral damage. It was found that postmenopausal women are liable to more dangerous effects than men at same age in stroke. The objective of this study is to investigate the neuroprotective effect of zeranol against cerebral ischemia reperfusion in ovariectomized rats. Main methods 36 female wistar rats divided in to 3 groups: sham group, I/R group (where I/R was induced 7 weeks after ovariectomy), zeranol group (0.5 mg/kg every 3 days for 5 weeks before I/R). Cerebral ischemia reperfusion (I/R) was performed by bilateral common carotid artery occlusion then de-ligated to restore blood flow. After 24 h of reperfusion, rats performed cylinder test to evaluate behavioral dysfunction followed by decapitation. Brain tissues were collected for biochemical measures such as oxidative stress marker malondialdehyde, antioxidant markers reduced glutathione, inflammatory markers (interleukin-1 beta, tumor necrosis factor alpha, and inducible nitric oxide synthase), matrix metalloproteinase-9, adenosine triphosphate, brain derived neurotrophic factor, glucose transporter-3, phosphorylated c-AMP response element binding protein and finally nissl staining for histopathological examination. Key findings The zeranol administered group showed a reversal of neuronal damage caused by ischemia evidenced by the decrease in MDA, IL-1β, TNF-α, and MMP-9 levels, increase GSH, and ATP levels, decrease expression of iNOS in both regions cortex and hippocampus, increase protein level of p-CREB, GLUT-3 and BDNF, increase number of intact neuron cells in both regions and attenuated histological changes in both cortex and hippocampus regions. Significance Zeranol has neuroprotective potential against cerebral ischemia reperfusion in ovariectomized rats. [ABSTRACT FROM AUTHOR]

Abstract To investigate the effects of feed contamination with zearalenone (ZEN) at the current European Commission (EC) guidance value (2 mg⋅kg−1 feed) on the growth and health of rainbow trout, we performed a long-term feeding trial under aquaculture conditions. It started with the external feeding of the fish larvae, and continued for 96 weeks, at which point the fish had reached market size. To assess the growth of fish and their feeding efficiency throughout this period, the fish were regularly weighed and measured, and their feed consumption was monitored. Additionally, to investigate potential health effects, after 72 weeks of the exposure to ZEN, the fishes' blood was analyzed for major hematological and biochemical indices, and their head kidney, spleen, and liver were examined for morphological, histopathological, cytological, and molecular changes. Finally, to gain insight into the metabolism and distribution of ZEN in fish, the content of free and glucuronidated forms of ZEN and its major metabolites was measured in the intestine, liver, and muscles of the exposed fish. The feed-borne exposure of rainbow trout to ZEN at a dose of 2 mg⋅kg−1 feed resulted in higher feeding efficiency and growth rate, most probably due to the anabolic properties of the ZEN metabolite. Importantly for the consumers of fish, despite absorption and metabolism of ZEN in the digestive system of the fish that had been exposed for 72 weeks, the residuals of ZEN were not transferred to the fishes' muscles, which rules out a potential risk to human health related to the consumption of fish meat. However, the increased growth of fish fed with the contaminated feed may come at some cost, as the exposure to ZEN was associated with modulation of key components of the adaptive and innate immune systems. Moreover, the trunk kidney of ZEN-fed fish showed massive inflammation that was likely caused by pathogen infection. These findings raise concerns about fish health under the current recommended EC guidance values. Highlights • The study shows effects of ZEN on growth and health of trout after long-term exposure. • Feed contaminated with ZEN promoted growth performance of the exposed fish, but ... • The exposure affected the immune system of fish, which may have affected their health. • ZEN was not found in the fishes' meat, which rules out health risk to consumers. [ABSTRACT FROM AUTHOR]

Zeranol is one of the synthetic growth hormone produced from mycotoxin that could affect humanhealth. The objective of this study was to determine zeranol residue in beef meat imported from Australiaand New Zealand using Enzyme-Linked Immunosorbent Assay (ELISA). The results showed that zeranolresidue was detected in 5 of 59 meat samples (8,5 %) of Australia and 1 of 59 meat samples (1,7 %) of NewZealand, with mean concentration of 0,644±0,157 ppb and 0.680±0.00 ppb, respectively. There were nosignificant differences in the concentration of zeranol residue between the meat from both countries(p>0,005). In addition the concentration of zeranol residue was below the National Standardization Agencyof Indonesia Maximum Residue Limit (MRL) which is 2 ppb.

El noreste argentino es, por sus características geográficas y ambientales, una región con fuerte potencial para la actividad ganadera. Los rodeos vacunos de esta zona tienen como base alimenticia pastizales y pasturas mejoradas, las que suelen suplementarse con granos, fuentes proteicas y reservas en forma de rollos o silaje. Estos alimentos son sustratos ricos para que especies de hongos produzcan micotoxinas como zearalenona (ZEA). El consumo de ZEA por los animales hace que se excreten diferentes metabolitos en orina entre los que se encuentra el zeranol. Por su parte, la presencia de zeranol en orina es utilizada como indicador del uso indebido de promotores de crecimiento que se hallan prohibidos en el país. El objetivo de este trabajo fue analizar los metabolitos relacionados con la ZEA excretados en la orina de novillos según los siguientes tratamientos: alimentación con un concentrado de ZEA, exposición a la aplicación de zeranol inyectable y acción simultánea de alimentación con un concentrado de ZEA más exposición a la aplicación de zeranol inyectable. Se presentan los perfiles de metabolitos excretados en orina y su evolución en el tiempo.

Zearalenone (ZEN) and its derivatives are prevalent contaminants in cereal crops. This study investigated a novel thermostable ZEN lactonase (ZENM) from Monosporascus sp. GIB2. ZENM demonstrated its highest activity at 60 °C, maintaining over 90% relative activity from 50 to 60 °C. Notably, efficient hydrolysis of ZEN and its two derivatives was achieved using ZENM, with specific activities of 333 U/mg for ZEN, 316 U/mg for α-zearalenol (α-ZOL), and 300 U/mg for α-zearalanol (α-ZAL). The activity of ZENM toward α-ZOL is noteworthy as most ZEN lactonases rarely achieve such a high degradation rate of α-ZOL. Based on the sequence-structure analysis, five residues (L123, G163, E171, S199, and S202) conserved in other ZEN lactonases were substituted in ZENM. Of interest was the G163S mutant in the cap domain that displayed enhanced activity toward α-ZOL compared to the wild-type enzyme. Notably, the mutant G163S exhibited higher catalytic activity toward α-ZOL ( k cat / K m 0.223 min -1 μM -1 ) than ZEN ( k cat / K m 0.191 min -1 μM -1 ), preferring α-ZOL as its optimum substrate. In conclusion, a thermostable ZEN lactonase has been reported, and the alteration of residue G163 in the cap domain has been shown to modify the substrate specificity of ZEN lactonase.

To investigate the influence of zeranol administration by implantation and castration on fatty acids composition, 20 weaned kids (3-4 month old) with an average live weight of 17.3±0.23 kg were divided randomly into two equal main groups, the first was left intact as a control and the 2nd group was castrated. Each main group was then blocked randomly into two sub groups, the 1st was left as control and the 2nd implanted with Ralgro (12mg zeranol). Kids were fed a concentrate adlib and slaughtered after 70 days of fattening. After chilling for 24 hours, a homogenous samples of meat from L.dorsi muscle was blended for analysis of fatty acid composition. Results revealed that mono unsaturated fatty acid have the highest contribution towards fatty acid of goat meat, followed by saturated fatty acids and poly unsaturated fatty acids. Among individual fatty acids C18:1 contributed highest followed by C16:0, C18:0 and C18:3 Neither implanting kids with zeranol nor castration alter significantly the fatty acid profile or PUSF to SFA ratio or the proportion of C18+C18:1/C16. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system mainly by interacting with nuclear hormone receptors (NRs). Humans are generally exposed to low doses of pollutants, and current researches aim at deciphering the mechanisms accounting for the health impact of EDCs at environmental concentrations. Our correlative analysis of structural, interaction and cell-based data has revealed a variety of, sometimes unexpected, binding modes, reflecting a wide range of EDC affinities and specificities. Here, we present a few representative examples to illustrate various means by which EDCs achieve high-affinity binding to NRs. These examples include the binding of the mycoestrogen α-zearalanol to estrogen receptors, the covalent interaction of organotins with the retinoid X- and peroxisome proliferator-activated receptors, and the cooperative binding of two chemicals to the pregnane X receptor. We also discuss some hypotheses that could further explain low-concentration effects of EDCs with weaker affinity towards NRs. [ABSTRACT FROM AUTHOR]

European Union prohibited the use of anabolic agents in food producing animals since 1988. An efficient control of abuses is guaranteed not only by highly performing analytical methods, but also by knowledge of metabolic pathways, kinetics of elimination and tissue distribution. To obtain data concerning metabolites production and accumulation in bile, two typical growth promoting treatments are carried out in cattle. In the first study, sixteen beef cattle were implanted with trenbolone acetate and estradiol. In the second one, three animals were implanted with zeranol and three were fed a diet containing zearalenone. Methods based on liquid chromatography–tandem mass spectrometry (LC-MS/MS) were developed and validated to quantify the analytes of interest. The results evidenced that the biliary concentrations of the marker residues were always higher than those determined at the same time in urine and liver which are the matrices generally collected within the official monitoring programmes. [ABSTRACT FROM AUTHOR]

Targeted biomonitoring studies quantifying the concentration of zeranols in biological matrices have focused on liquid chromatography interfaced to mass spectrometry (LC-MS). The MS platform for measurement, quadrupole, time-of-flight (ToF), ion trap, etc., is often chosen based on either sensitivity or selectivity. An instrument performance comparison of the benefits and limitations using matrix-matched standards containing 6 zeranols on 4 MS instruments, 2 low-resolution (linear ion traps), and 2 high-resolution (Orbitrap and ToF) was undertaken to identify the best measurement platform for multiple biomonitoring projects characterizing the endocrine disruptive properties of zeranols. Analytical figures of merit were calculated for each analyte to compare instrument performance across platforms. The calibration curves had correlation coefficients r = 0.989 ± 0.012 for all analytes and LODs and LOQs were ranked for sensitivity: Orbitrap > LTQ > LTQXL > G1 (V mode) > G1 (W mode). The Orbitrap had the smallest measured variation (lowest %CV), while the G1 had the highest. Instrumental selectivity was calculated using full width at half maximum (FWHM) and as expected, the low-resolution instruments had the broadest spectrometric peaks, concealing coeluting peaks under the same mass window as the analyte. Multiple peaks from concomitant ions, unresolved at low resolution (within a unit mass window), were present but did not match the exact mass predicted for the analyte. For example, the high-resolution platforms were able to differentiate between a concomitant peak at 319.1915 from the analyte at 319.1551, included in low-resolution quantitative analyses demonstrating the need to consider coeluting interfering ions in biomonitoring studies. Finally, a validated method using the Orbitrap was applied to human urine samples from a pilot cohort study., (© 2023. The Author(s).)

Recently, magnetic solid-phase extraction has gained interest because it presents various operational advantages over classical solid-phase extraction. Furthermore, magnetic nanoparticles are easy to prepare, and various materials can be used in their synthesis. In the literature, there are only few studies on the determination of mycoestrogens in milk, although their carryover in milk has occurred. In this work, we wanted to develop the first (to the best of our knowledge) magnetic solid-phase extraction protocol for six mycoestrogens from milk, followed by liquid chromatography and tandem mass spectrometry analysis. Magnetic graphitized carbon black was chosen as the adsorbent, as this carbonaceous material, which is very different from the most diffuse graphene and carbon nanotubes, had already shown selectivity towards estrogenic compounds in milk. The graphitized carbon black was decorated with Fe3O4, which was confirmed by the characterization analyses. A milk deproteinization step was avoided, using only a suitable dilution in phosphate buffer as sample pretreatment. The overall process efficiency ranged between 52 and 102%, whereas the matrix effect considered as signal suppression was below 33% for all the analytes even at the lowest spiking level. The obtained method limits of quantification were below those of other published methods that employ classical solid-phase extraction protocols. [ABSTRACT FROM AUTHOR]

Objective(s): The aim of this study was to observe the influence of phytoestrogenɑZearalanol on ovariectomy-induced postmenopausal osteoporosis in rats. Materials and Methods: 40 SD female rats were randomly divided into four groups: Sham group, OVX group (ovariectomized and fed estrogen), ɑ-Zearalanol group (ovariectomized and fed ɑ-Zearalanol) and untreated group (ovariectomized). Three weeks later after surgery, α-Zearalanol and estradiol valerate were administered by oral gavage for 12 weeks to the α-Zearalanol group and the OVX group, respectively. In contrast, the sham and untreated controls were treated with distilled water in a daily basis. After the treatments, uterus histomorphometry, bone mechanical strength, bone histomorphometry, bone mineral density (BMD) of femur, and serum biochemical indicators, such as serum E2, CT and PTH, as well as the levels of TNF and IL-1 were examined. Results: The BMD was overall declined rigorously in the OVX rats, and that could be mitigated through feeding on either estrogen or ɑ-Zearalanol. Estrogen or ɑ-Zearalanol was found to decrease the levels of serum ALP and BGP in OVX rats, while, ɑ-Zearalanol was found to increase the levels of serum E2 and CT, the thickness of the endometrium, and decrease the levels of PTH, TNF and IL-1 in serum in OVX rats. Feeding the OVX rats on ɑ-Zearalanol improved the bone histomorphometric parameters impaired due to estrogen deficiency and enhanced the bone mechanical properties in the ovariectomized rats. Conclusion: ɑ-Zearalanol treated rats reduced the resorption of bone, and showed a preventive and therapeutic effect of ɑ-Zearalanol on postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Transient Receptor Potential Channels (TRPs) are commonly expressed in the reproductive tissues in human. Many female reproductive processes have been associated with these TRPs. The mycotoxin zeranol or α-zearalanol is derived from fungi in the Fusarium family. Limited exposure to zeranol appears to be safe. In North America, farmers are using synthetic zeranol to promote growth in livestock. As the health risks of exposure to residual zeranol have not been determined, this practice is disallowed in the European Community. In the present study the cellular calcium levels were elevated in JEG-3 cells treated with zeranol at or above 10 nM. Subsequent study indicated that expressions of TRP channels were induced. In response to the calcium flow, ERK, P38 and PKCβ were activated and COX-2 expression was increased. Specific TRP inhibitors were employed to establish the connection between the ion channel activity and COX-2 expression, and TRPC-3 appeared to be the triggering mechanism. Since the involvement of COX-2 is implicated in placental development and parturition, exposure to this mycotoxin poses a potential threat to pregnant women. [ABSTRACT FROM AUTHOR]