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Aims: The current review aims to outline and summarize the latest research on aflatoxin, with research studies describing natural, herbal and chemical compound applications in animal (pig) models and in vitro cellular studies. Aflatoxin, a carcinogenic toxin metabolite, is produced by Aspergillus flavus in humid environments, posing a threat to human health and crop production. The current treatment involves the prevention of exposure to aflatoxin and counteracting its harmful toxic effects, enabling survival and research studies on an antidote for aflatoxin. Objectives: To summarize current research prospects and to outline the influence of aflatoxin on animal forage in farm production, food and crop processing. The research application of remedies to treat aflatoxin is undergoing development to pinpoint biochemical pathways responsible for aflatoxin effects transmission and actions of treatment. Significance: To underline the environmental stress of aflatoxin on meat and dairy products; to describe clinical syndromes associated with aflatoxicosis on human health that are counteracted with proposed treatment and preventive interventions. To understand how to improve the health of farm animals with feed conditions. [ABSTRACT FROM AUTHOR]

The aim: In this study was to determine if sigmoid colorectal cancer (SCC) and colorectal cancer (CRC) in women (W) and men (M) is accompanied by zearalenone (ZEN) mycotoxicosis and changes in selected steroid levels. Materials and Methods: This cohort study was conducted on female and male patients selected from a population based on the presence of SCC or CRC, which was accompanied by the presence or absence (control group) of ZEN in their blood. The control group consisted of 17 patients with symptoms of SCC and CRC, where ZEN and its metabolites were not detected in the peripheral blood. The experimental groups comprised a total of 16 patients with SCC and CRC, where ZEN, but not its metabolites, was detected in their peripheral blood samples. Results: In groups SCC and CRC, the ZEN levels were very high, in the range from 214 to 289 ng/mL of blood. Considerable variations were observed in the concentrations of steroid hormones. Estradiol (E2) levels ranged from 166.25 (group C) to 325 pg/mL (group CRC) in women and from 98 (group C) to 95.5 pg/mL (group CRC) in men. Progesterone (P4) levels ranged from 12.09 (group C) to 13.64 ng/mL (group SCC) in women and from 6.98 (group CRC) to 12.01 ng/mL (group C) in men. Conclusions: These results indicate that post-menopausal women and similarly aged elderly men have a high and individualized demand for estrogen that is relatively effectively met by ZEN, which triggers qualitative changes in estrogen receptors. The shortage of ZEN metabolites (values under the sensitivity of the method) confirmed the high estrogen demand in the studied subjects. The presence or absence of ZEN could have influenced the therapeutic outcomes in the analyzed patients. [ABSTRACT FROM AUTHOR]

This study was conducted to determine if a low monotonic dose of zearalenone (ZEN) affects the immunohistochemical expression (IE) of oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ) in the intestines of sexually immature gilts. Group C (control group; n = 18) gilts were given a placebo. Group E (experimental group; n = 18) gilts were dosed orally with 40 μg ZEN /kg body weight (BW), each day before morning feeding. Samples of intestinal tissue were collected post-mortem six times. The samples were stained to analyse the IE of ERα and Erβ in the scanned slides. The strongest response was observed in ERα in the duodenum (90.387—average % of cells with ERα expression) and in ERβ in the descending colon (84.329—average % of cells with ERβ expression); the opposite response was recorded in the caecum (2.484—average % of cells with ERα expression) and the ascending colon (2.448—average % of cells with ERα expression); on the first two dates of exposure, the digestive tract had to adapt to ZEN in feed. The results of this study, supported by a mechanistic interpretation of previous research findings, suggest that ZEN performs numerous functions in the digestive tract. [ABSTRACT FROM AUTHOR]

Simple Summary: African catfish is one of the most perspective fish species in modern aquaculture. However, the main cost involved in its production is focused chiefly on the cost of feeds. The main reason for this is the behavior of this species (predatory fish) and the high rate of cannibalism in intensive culture. That is why it is essential to assess functional bioactive additives to be used in commercial feed with a positive effect on the growth and survival rates of this commercially valued fish species. In the present study, African catfish juveniles were fed diets enriched with honeybee pollen (BP) and were tested for growth, survival, intestinal microbiota, and tissue histomorphology. It has been shown that BP addition positively affected all the analyzed parameters. This research study spotlights the benefits of BP as a prebiotic supplement for improving the functionality of feeds prepared for African catfish. This study aimed to determine the dietary effects of honeybee pollen (BP) on growth parameters, intestinal microbiota, hepatic histoarchitecture, and intestinal histomorphometry of African catfish Clarias gariepinus juveniles. The feeding experiment was carried out in a recirculating aquaculture system under controlled conditions for 21 days to achieve more than a 10-fold increase in weight in fish from the control group. Fish were fed well-balanced commercial feed without any supplements and served as a reference group (group C) and other diets enriched with varying BP levels as 1% (BP1), 2% (BP2), and 3% (BP3). Results showed a significant (p < 0.05) effect of the dietary BP not only on the growth parameters (such as final body weight: 5.0 g to 6.6–7.5 g, weight gain: 0.23 g/d to 0.31–0.35 g/d, body length: 84.7 mm to 93.8–95.9 mm, and specific growth rate: 11.7%/d to 13.1–13.7%/d, group C vs. experimental groups, respectively) but also on the development of beneficially important gut microbiota, such as lactic acid-producing bacteria. In BP-enriched groups, an average of 45% higher body weight gain was observed compared to those reared in the control group. The histological analysis showed that dietary BP may have a positive effect on the development of the intestinal tract and may enhance the absorption of nutrients with the potential ability to maintain a normal hepatic histoarchitecture of the treated African catfish. The results obtained suggest the optimum level of BP additive to feed for African catfish should be 1%. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate whether low doses of zearalenone (ZEN) affect the carry-over of ZEN and its metabolites to intestinal tissues and the expression of CYP1A1 and GSTπ1 in the large intestine. Prepubertal gilts (with a BW of up to 14.5 kg) were exposed in group ZEN to daily ZEN5 doses of 5 μg/kg BW (n = 15); in group ZEN10, 10 μg/kg BW (n = 15); in group ZEN15, 15 μg/kg BW (n = 15); or were administered a placebo (group C, n = 15) throughout the experiment. After euthanasia, tissues were sampled on exposure days 7, 21, and 42 (D1, D2, and D3, respectively). The results confirmed that the administered ZEN doses (LOAEL, NOAEL, and MABEL) were appropriate to reliably assess the carry-over of ZEN. Based on the observations made during 42 days of exposure to pure ZEN, it can be hypothesized that all mycotoxins (ZEN, α-zearalenol, and β-zearalenol) contribute to a balance between intestinal cells and the expression of selected genes encoding enzymes that participate in biotransformation processes in the large intestine; modulate feminization processes in prepubertal gilts; and elicit flexible, adaptive responses of the macroorganism to mycotoxin exposure at the analyzed doses. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is one of the most prevalent mycotoxins in Europe. Pigs are an animal species that is most susceptible to this mycotoxin. Deoxynivalenol causes significant losses in pig production by lowering feed intake, decreasing daily weight gains, disrupting immune responses, and increasing susceptibility to diseases. The aim of this experiment was to determine the influence of feed contaminated with DON at concentrations insignificantly higher than recommended by the European Commission (900 μg/kg). The experimental feed contained 1008 μg DON/kg. The experiment was performed on eight weaners from the same litter. The animals were randomly divided into two groups: an experimental group (M, n = 4) fed contaminated feed and a control group (C, n = 4) administered feed free of mycotoxins. The experiment lasted for six weeks, and peripheral blood samples were collected from the animals for analyses of selected morphological parameters and changes in the percentages of CD4+8-, CD4-8+, and CD4+8+ lymphocytes and antigen-presenting cells (APC) with CD14+172+ (monocytes), CD172ahigh4-14- (conventional dendritic cells, cDC), and CD172adim4+14- (plasmacytoid dendritic cells, pDC) phenotypes. The morphological parameters of porcine blood samples were determined by flow cytometry with non-fluorescent particle-size calibration standards, and no differences were observed between groups M and C. An immunophenotyping analysis of lymphocytes and dendritic cells (DC) revealed an increase in the percentage of CD4+8-, CD172ahigh4-14-, and CD172adim4+14- cells, and a decrease in the number of CD4-8+ cells in group M. The results of this experiment suggest that prolonged exposure to low doses of DON can change the proportions of immunocompetent cells (a shift towards humoral immunity), without affecting their overall counts. [ABSTRACT FROM AUTHOR]

This study demonstrates that low doses (somewhat above the No Observed Adverse Effect Level, NOAEL) of the mycoestrogen zearalenone (ZEN) and its metabolites display multispecificity towards various biological targets in gilts. The observed responses in gilts were surprising. The presence of ZEN and zearalenols (ZELs) did not evoke a response in the porcine gastrointestinal tract, which was attributed to dietary tolerance. Lymphocyte proliferation was intensified in jejunal mesenteric lymph nodes, and lymphocyte counts increased in the jejunal epithelium with time of exposure. In the distal digestive tract, fecal bacterial counts decreased, the activity of fecal bacterial enzymes and lactic acid bacteria increased, and cecal water was characterized by higher genotoxicity. The accompanying hyperestrogenism led to changes in mRNA activity of selected enzymes (cytochrome P450, hydroxysteroid dehydrogenases, nitric oxide synthases) and receptors (estrogen and progesterone receptors), and it stimulated post-translational modifications which play an important role in non-genomic mechanisms of signal transmission. Hyperestrogenism influences the regulation of the host's steroid hormones (estron, estradiol and progesteron), it affects the virulence of bacterial genes encoding bacterial hydroxysteroid dehydrogenases (HSDs), and it participates in detoxification processes by slowing down intestinal activity, provoking energy deficits and promoting antiporter activity at the level of enterocytes. In most cases, hyperestrogenism fulfils all of the above roles. The results of this study indicate that low doses of ZEN alleviate inflammatory processes in the digestive system, in particular in the proximal and distal intestinal tract, and increase body weight gains in gilts. [ABSTRACT FROM AUTHOR]

Zearalenone and deoxynivalenol are secondary metabolites of fungi of the genus Fusarium. The presence of mycotoxins in cereals and the resulting contamination of feeds and foods pose health risks for animals and humans. The dangers associated with high doses of mycotoxins have been extensively researched but very little is known about NOAEL (No Observed Adverse Effect Level) doses or exposure to a combination of mycotoxins (mixed mycotoxicoses). The aim of this study was to determine the effects of six-week exposure to NOAEL doses of individual and combined mycotoxins on the subpopulations of CD4+8-, CD4-8+ and CD4+8+ lymphocytes in the peripheral blood of pigs. The experiment was performed on 72 gilts with average body weight of 25 kg, divided into three experimental groups (E1, E2 and E3, administered zearalenone (ZEN), deoxynivalenol (DON) and ZEN + DON, respectively, on a daily basis) and a control group (C) receiving placebo. Changes in lymphocyte subpopulations were evaluated by flow cytometry at weekly intervals (experimental days 7, 14, 21, 28, 35 and 42). A linear increase in the percentage of CD4+8+ lymphocytes was highly correlated with time (r = 0.682) in group C. The correlations and linear increase in the above subpopulation were disrupted in the remaining groups. In group E3, a statistically significant (p < 0.05) decrease in CD4+8+ counts was observed in week 5, which could point to a transient depletion of regulatory mechanisms of immune responses. The noted results also suggest that in mixed mycotoxicosis, ZEN and DON exerted stronger immunomodulatory effects. [ABSTRACT FROM AUTHOR]

The growing interest in toxic substances combined with advancements in biological sciences has shed a new light on the problem of mycotoxins contaminating feeds and foods. An interdisciplinary approach was developed by identifying dose-response relationships in key research concepts, including the low dose theory of estrogen-like compounds, hormesis, NOAEL dose, compensatory response and/or food tolerance, and effects of exposure to undesirable substances. The above considerations increased the researchers' interest in risk evaluation, namely: (i) clinical symptoms associated with long-term, daily exposure to low doses of a toxic compound; and (ii) dysfunctions at cellular or tissue level that do not produce clinical symptoms. Research advancements facilitate the extrapolation of results and promote the use of novel tools for evaluating the risk of exposure, for example exposure to zearalenone in pre-pubertal female dogs. The arguments presented in this paper suggest that low doses of zearalenone in commercial feeds stimulate metabolic processes and increase weight gains. Those processes are accompanied by lower proliferation rates in the ovaries, neoangiogenesis and vasodilation in the ovaries and the uterus, changes in the steroid hormone profile, and changes in the activity of hydroxysteroid dehydrogenases. All of the above changes result from exogenous hyperestrogenizm. [ABSTRACT FROM AUTHOR]

Immature gilts were administered per os with zearalenone (ZEN) at 40 μg/kg BW (group Z, n = 9), deoxynivalenol (DON) at 12 μg/kg BW (group D, n = 9), a mixture of ZEN and DON (group M, n = 9) or a placebo (group C, n = 9) over a period of six weeks. The pigs were sacrificed after one, three, or six weeks of the treatment (12 pigs per each time-point). Histological investigations revealed an increase in the mucosal thickness and the crypt depth as well as a decrease in the ratio of the villus height to the crypt depth in groups D and M after six weeks of exposure to the mycotoxins. The number of goblet cells in the villus epithelium was elevated in groups Z and M after one week and in group D after three weeks. The administration of ZEN increased the lymphocyte number in the villus epithelium after 1 week and the plasma cell quantity in the lamina propria after one, three, and six weeks of the experiment. DON treatment resulted in an increase in the lymphocyte number in the villus epithelium and the lamina propria after six weeks, and in the plasma cell quantity in the lamina propria after one, three, and six weeks of exposure. In group M, lymphocyte counts in the epithelium and the lamina propria increased significantly after six weeks. Neither mycotoxin induced significant adverse changes in the ultrastructure of the mucosal epithelium and the lamina propria or in the intestinal barrier permeability. Our results indicate that immune cells are the principal target of low doses of ZEN and DON. [ABSTRACT FROM AUTHOR]

Zearalenone and its metabolites, α-zearalenol and β-zearalenol, demonstrate estradiol-like activity and disrupt physiological functions in animals. This article evaluates the carryover of zearalenone and its selected metabolites from the digesta to intestinal walls (along the entire intestines) in pre-pubertal gilts exposed to low doses of zearalenone over long periods of time. The term "carryover" describes the transfer of mycotoxins from feed to edible tissues, and it was used to assess the risk of mycotoxin exposure for consumers. The experimental gilts with body weight of up to 25 kg were per os administered zearalenone at a daily dose of 40 µg/kg BW (Group E, n = 18) or placebo (Group C, n = 21) over a period of 42 days. In the first weeks of exposure, the highest values of the carryover factor were noted in the duodenum and the jejunum. In animals receiving pure zearalenone, the presence of metabolites was not determined in intestinal tissues. In the last three weeks of the experiment, very high values of the carryover factor were observed in the duodenum and the descending colon. The results of the study indicate that in animals exposed to subclinical doses of zearalenone, the carryover factor could be determined by the distribution and expression of estrogen receptor beta. [ABSTRACT FROM AUTHOR]

The objective of the study was to determine the effect of exposure of pigs to the Fusarium mycotoxins zearalenone (ZEN) and deoxynivalenol (DON), administered together and separately, on the colon microbiota. An experiment was conducted for 42 days on gilts, randomly assigned to four groups and administered either ZEN, DON, ZEN+DON, or a placebo. The number of aerobic mesophilic bacteria, yeasts, molds, anaerobic Clostridium perfringens, fecal streptococci, Enterobacteriaceae, Escherichia coli, and lactic acid bacteria (LAB) were determined in the contents of the ascending colon. The influence of mycotoxins on the functional diversity of the colonic microbiota was assessed using EcoPlate tests (Biolog). Analysis revealed the predominance of LAB in all groups of pigs. Zearalenone, administered separately and together with DON, was found to have an adverse effect on mesophilic aerobic bacteria, but only after long exposure to this mycotoxin. During the six weeks of the experiment, the concentration of C. perfringens, E. coli, and other bacteria in the family Enterobacteriaceae was most considerably reduced in the experimental groups exposed to zearalenone, both separately and together with DON. Mycotoxins also affected the functional biodiversity of microorganisms. Both Shannon's diversity index and the number of catabolized substrates in Biolog plate (the R index) were much higher in the group subjected to mixed mycotoxicosis. [ABSTRACT FROM AUTHOR]

Deoxynivalenol is also known as vomitoxin due to its impact on livestock through interference with animal growth and acceptance of feed. At the molecular level, deoxynivalenol disrupts normal cell function by inhibiting protein synthesis via binding to the ribosome and by activating critical cellular kinases involved in signal transduction related to proliferation, differentiation and apoptosis. Because of concerns related to deoxynivalenol, the United States FDA has instituted advisory levels of 5 μg/g for grain products for most animal feeds and 10 μg/g for grain products for cattle feed. The aim of the study was to determine the effect of low doses of deoxynivalenol applied per os on the presence of this mycotoxin in selected tissues of the alimentary canal of gilts. The study was performed on 39 animals divided into two groups (control, C; n = 21 and experimental, E; n = 18), of 20 kg body weight at the beginning of the experiment. Gilts received the toxin in doses of 12 μg/kg b.w./day (experimental group) or placebo (control group) over a period of 42 days. Three animals from two experimental groups were sacrificed on days 1, 7, 14, 21, 28, 35 and 42, excluding day 1 when only three control group animals were scarified. Tissues samples were prepared for high performance liquid chromatography (HPLC) analyses with the application of solid phase extraction (SPE). The results show that deoxynivalenol doses used in our study, even when applied for a short period, resulted in its presence in gastrointestinal tissues. The highest concentrations of deoxynivalenol reported in small intestine samples ranged from 7.2 (in the duodenum) to 18.6 ng/g (in the ileum) and in large intestine samples from 1.8 (in transverse the colon) to 23.0 ng/g (in the caecum). In liver tissues, the deoxynivalenol contents ranged from 6.7 to 8.8 ng/g. [ABSTRACT FROM AUTHOR]

The aim of the study was to verify the hypothesis that intoxication with low doses of mycotoxins leads to changes in the mRNA expression levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes in tissues of the gastrointestinal tract and the liver. The experiment involved four groups of immature gilts (with body weight of up to 25 kg) which were orally administered zearalenone in a daily dose of 40 μg/kg BW (group Z, n = 18), deoxynivalenol at 12 μg/kg BW (group D, n = 18), zearalenone and deoxynivalenol (group M, n = 18) or placebo (group C, n = 21) over a period of 42 days. The lowest mRNA expression levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes were noted in the sixth week of the study, in particular in group M. Our results suggest that the presence of low mycotoxin doses in feed slows down the mRNA expression of both nitric oxide synthase isomers, which probably lowers the concentrations of nitric oxide, a common precursor of inflammation. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether low doses of zearalenone (ZEN) influence the carry-over of ZEN and its metabolites to the bone marrow microenvironment and, consequently, haematological parameters. Pre-pubertal gilts (with a body weight of up to 14.5 kg) were exposed to daily ZEN doses of 5 μg/kg BW (group ZEN5, n = 15), 10 μg/kg BW (group ZEN10, n = 15), 15 μg/kg BW (group ZEN15, n = 15), or were administered a placebo (group C, n = 15) throughout the entire experiment. Bone marrow was sampled on three dates (exposure dates 7, 21, and 42—after slaughter) and blood for haematological analyses was sampled on 10 dates. Significant differences in the analysed haematological parameters (WBC White Blood Cells, MONO—Monocytes, NEUT—Neutrophils, LYMPH—Lymphocytes, LUC—Large Unstained Cells, RBC—Red Blood Cells, HGB—Haemoglobin, HCT—Haematocrit, MCH—Mean Corpuscular Volume, MCHC—Mean Corpuscular Haemoglobin Concentrations, PLT—Platelet Count and MPV—Mean Platelet Volume) were observed between groups. The results of the experiment suggest that exposure to low ZEN doses triggered compensatory and adaptive mechanisms, stimulated the local immune system, promoted eryptosis, intensified mycotoxin biotransformation processes in the liver, and produced negative correlations between mycotoxin concentrations and selected haematological parameters. [ABSTRACT FROM AUTHOR]

This study applied multi-mycotoxin liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) methods to determine the biomarkers of exposure in urine and serum samples from a dose-response study with pigs. The 24 studied pigs were divided into three groups: a control and two experimental ones (with different levels of feed contamination). They were exposed to feed prepared from cereals contaminated with deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA) and citrinin (CIT) for 14 days. After that, both experimental groups received the same feed as the control group for the next 14 days to determine the kinetics of the disappearance of mycotoxin biomarkers. Urine samples were collected daily in the morning and blood samples—eight-times during the experiment. The study reported herein was the first prolonged exposure experiment for multiple mycotoxins like OTA and CIT in pigs. The urinary and serum levels of all biomarkers correlated well with the respective toxin intake; thereby demonstrating that they are suitable biomarkers of exposure in pigs. Urine is a good candidate to monitor DON, ZEN, OTA, CIT exposure while serum may be used to monitor DON, OTA and CIT. Additionally, OTA has even been quantified in both matrices in the experimental groups two weeks after changing the contaminated feed back to the control, this result differed from those produced by the other mycotoxins which were only quantified during the first two weeks. Therefore both matrices are suitable candidates to monitor prolonged OTA exposure in pigs. [ABSTRACT FROM AUTHOR]

Vascular toxicity induced by xenobiotics is associated with dysfunctions or damage to endothelial cells, changes in vascular permeability or dysregulation of the vascular redox state. The aim of this study was to determine whether per os administration of zearalenone (ZEN) influences selected hemostatic parameters in prepubertal gilts. This study was performed on female gilts divided into a control group which received placebo and an experimental group which received ZEN at a dose of 5.0 µg·kg−1 b.w. × day−1. On days 14, 28 and 42, blood samples were collected from the animals for analyses of hematological, coagulation and fibrinolysis parameters, nitric oxide, von Willebrand factor antigen content and catalase activity. The results demonstrated that the treatment of gilts with ZEN at a dose below no observable adverse effect level did not affect the primary hemostasis and the blood coagulation cascade. However, ZEN could have temporarily affected the selected indicators of endothelial cell function (increase of von Willebrand factor, decrease of nitric oxide levels) and the oxidative status plasma (decrease of catalase activity) of the exposed gilts. In summary, these results suggest that the adaptive response to ZEN-exposure can induce a transient imbalance in the vascular system by acting on vascular endothelial cells. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEN) and its metabolites, alpha-zearalenol (α-ZEL) and beta-zearalenol (β-ZEL), are ubiquitous in plant materials used as feed components in dairy cattle diets. The aim of this study was to confirm the occurrence of ZEN and its selected metabolites in blood samples collected from different sites in the hepatic portal system (posthepatic–external jugular vein EJV; prehepatic–abdominal subcutaneous vein ASV and median caudal vein MCV) of dairy cows diagnosed with mastitis, ovarian cysts and pyometra. The presence of mycotoxins in the blood plasma was determined with the use of combined separation methods involving immunoaffinity columns, a liquid chromatography system and a mass spectrometry system. The parent compound was detected in all samples collected from diseased cows, whereas α-ZEL and β-ZEL were not identified in any samples, or their concentrations were below the limit of detection (LOD). Zearalenone levels were highest in cows with pyometra, where the percentage share of average ZEN concentrations reached 44%. Blood sampling sites were arranged in the following ascending order based on ZEN concentrations: EJV (10.53 pg/mL, 44.07% of the samples collected from this site), ASV (14.20 pg/mL, 49.59% of the samples) and MCV (26.67 pg/mL, 67.35% of the samples). The results of the study indicate that blood samples for toxicological analyses should be collected from the MCV (prehepatic vessel) of clinically healthy cows and/or cows with subclinical ZEN mycotoxicosis. This sampling site increases the probability of correct diagnosis of subclinical ZEN mycotoxicosis. [ABSTRACT FROM AUTHOR]

The carry-over of zearalenone (ZEN) to the myocardium and its effects on coronary vascular reactivity in vivo have not been addressed in the literature to date. Therefore, the objective of this study was to verify the hypothesis that low ZEN doses (MABEL, NOAEL and LOAEL) administered per os to prepubertal gilts for 21 days affect the accumulation of ZEN, α-ZEL and β-ZEL in the myocardium and the reactivity of the porcine coronary arteries to vasoconstrictors: acetylcholine, potassium chloride and vasodilator sodium nitroprusside. The contractile response to acetylcholine in the presence of a cyclooxygenase (COX) inhibitor, indomethacin and / or an endothelial nitric oxide synthase (e-NOS) inhibitor, L-NAME was also studied. The results of this study indicate that the carry-over of ZEN and its metabolites to the myocardium is a highly individualized process that occurs even at very low mycotoxin concentrations. The concentrations of the accumulated ZEN metabolites are inversely proportional to each other due to biotransformation processes. The levels of vasoconstrictors, acetylcholine and potassium chloride, were examined in the left anterior descending branch of the porcine coronary artery after oral administration of ZEN. The LOAEL dose clearly decreased vasoconstriction in response to both potassium chloride and acetylcholine (P < 0.05 for all values) and increased vasodilation in the presence of sodium nitroprusside (P = 0.021). The NOAEL dose significantly increased vasoconstriction caused by acetylcholine (P < 0.04), whereas the MABEL dose did not cause significant changes in the vascular response. Unlike higher doses of ZEN, 5 μg/kg had no negative influence on the vascular system. [ABSTRACT FROM AUTHOR]

Plant materials can be contaminated with Fusarium mycotoxins and their derivatives, whose toxic effects on humans and animals may remain subclinical. Zearalenone (ZEN), a low-molecular-weight compound, is produced by molds in crop plants as a secondary metabolite. The objective of this study will be to analyze the in vivo correlations between very low monotonic doses of ZEN (5, 10, and 15 μg ZEN/kg body weight—BW for 42 days) and the carryover of this mycotoxin and its selected metabolites from the intestinal contents to the intestinal walls, the mRNA expression of estrogen receptor alfa (ERα) and estrogen receptor beta (ERβ) genes, and the mRNA expression of genes modulating selected colon enzymes (CYP1A1 and GSTP1) in the intestinal mucosa of pre-pubertal gilts. An in vivo experiment will be performed on 60 clinically healthy animals with initial BW of 14.5 ± 2 kg. The gilts will be randomly divided into a control group (group C, n = 15) and three experimental groups (group ZEN5, group ZEN10, and group ZEN15; n = 15). Group ZEN5 will be administered per os 5 μg ZEN/kg BW (MABEL), group ZEN10—10 μg ZEN/kg BW (NOAEL), and group ZEN15—15 µg ZEN/kg BW (low LOAEL). In each group, five animals will be euthanized on analytical dates 1 (exposure day 7), 2 (exposure day 21), and 3 (exposure day 42). Samples for in vitro analyses will be collected from an intestinal segment resected from the following regions: the third (horizontal) part of the duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, and descending colon. The experimental material will be collected under special conditions, and it will be transported to specialist laboratories where samples will be obtained for further analyses. [ABSTRACT FROM AUTHOR]

Diabetic gastroenteropathy is a common complication, which develops in patients with long-term diabetes. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known for its cytoprotective properties and plays an important role in neuronal development, neuromodulation and neuroprotection. The present study was designed to elucidate, for the first time, the impact of prolonged hyperglycaemia conditions on a population of PACAP-like immunoreactive neurons in selected parts of the porcine gastrointestinal tract. The experiment was conducted on 10 juvenile female pigs assigned to two experimental groups: The DM group (pigs with streptozocin-induced diabetes) and the C group (control pigs). Diabetes conditions were induced by a single intravenous injection of streptozocin. Six weeks after the induction of diabetes, all animals were euthanised and further collected, and fixed fragments of the stomach, duodenum, jejunum, ileum and descending colon were processed using the routine double-labelling immunofluorescence technique. Streptozotocin-induced hyperglycaemia caused a significant increase in the population of PACAP-containing enteric neurons in the porcine stomach, small intestines and descending colon. The recorded changes may result from the direct toxic effect of hyperglycaemia on the ENS neurons, oxidative stress or inflammatory conditions accompanying hyperglycaemia and suggest that PACAP is involved in regulatory processes of the GIT function in the course of diabetes. [ABSTRACT FROM AUTHOR]

Plant materials used in the production of pig feed are frequently contaminated with mycotoxins. T-2 toxin is a secondary metabolite of selected Fusarium species, and it can exert a harmful influence on living organisms. Most mycotoxins enter the body via the gastrointestinal tract, and they can modulate the gut-associated lymphoid tissue (GALT) function. However, little is known about the influence of low T-2 toxin doses on GALT. Therefore, the aim of this study was to evaluate the effect of T-2 toxin administered at 50% of the lowest-observed-adverse-effect level (LOAEL) on the percentage of CD2+ T cells, CD4+ T helper cells, CD8+ cytotoxic T cells, CD4+CD8+ double-positive T cells, TCRγδ+ cells, CD5+CD8- B1 cells, and CD21+ B2 cells, and the secretion of proinflammatory (IFN-γ, IL-1β, IL-2, IL-12/23p40, IL-17A), anti-inflammatory, and regulatory (IL-4, IL-10, TGF-β) cytokines in the porcine ileal wall. The results of the study revealed that T-2 toxin disrupts the development of tolerance to food antigens by enhancing the secretion of proinflammatory and regulatory cytokines and decreasing the production of anti-inflammatory TGF-β. T-2 toxin triggered the cellular response, which was manifested by an increase in the percentage of CD8+ T cells and a decrease in the percentage of B2 and Tγδ lymphocytes. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the effect of zearalenone (ZEN), administered per os to gilts at doses equivalent to 50%, 100%, and 150% of no-observed-adverse-effect level (NOAEL) values for 14, 28, and 42 days during weaning, on changes in the parameters of the oxidoreductive balance, cytokine secretion, and basal metabolism in ileal Payer's patches. Immunoenzymatic ELISA tests and biochemical methods were used to measure the concentrations of interleukin 1α, interleukin 1β, interleukin 12/23p40, interleukin 2, interferon γ, interleukin 4, interleukin 6, interleukin 8, tumor necrosis factor α, interleukin 10, transforming growth factor β, malondialdehyde, sulfhydryl groups, fructose, glucose, and proline, as well as the activity of peroxidase, superoxide dismutase and catalase. The study demonstrated that ZEN doses corresponding to 50%, 100%, and 150% of NOAEL values, i.e., 5 µg, 10 µg, and 15 µg ZEN/kg BW, respectively, have proinflammatory properties, exacerbate oxidative stress responses, and disrupt basal metabolism in ileal Payer's patches in gilts. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the effect of long-term (48 days), per os administration of specific zearalenone (ZEN) doses (20 and 40 μg ZEN/kg BW in experimental groups EI and EII, which were equivalent to 200% and 400% of the upper range limit of the no-observed-adverse-effect-level (NOAEL), respectively) on the bioavailability of ZEN and the rate of changes in estradiol and testosterone concentrations in the peripheral blood of pre-pubertal gilts. ZEN and α-ZEL levels were similar until day 28. After day 28, α-ZEL concentrations increased significantly in group EI, whereas a significant rise in ZEN levels was noted in group EII. The presence of estradiol in peripheral blood plasma was not observed until day 20 of the experiment. Spontaneous secretion of estradiol was minimal, and it was determined at very low levels of up to 10 pg/mL in EI and EII groups. Testosterone concentrations ranged from 4 to 9 ng/mL in all groups. A decrease in the concentrations of both analyzed hormones was reported in the last stage of the experiment. The results of the experiment indicate that: (i) The bioavailability of ZEN in peripheral blood has low diagnostic value, (ii) exposure to low doses of ZEN induces minor changes in the concentrations of the analyzed hormones, which could lead to situational supraphysiological hormone levels and changes in endogenous hormonal balance. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEN) is a mycotoxin that not only binds to estrogen receptors, but also interacts with steroidogenic enzymes and acts as an endocrine disruptor. The aim of this study was to verify the hypothesis that low doses, minimal anticipated biological effect level (MABEL), no-observed-adverse-effect level (NOAEL) and lowest-adverse-effect level (LOAEL), of ZEN administered orally for 42 days can induce changes in the peripheral blood concentrations of selected steroid hormones (estradiol, progesterone and testosterone) in pre-pubertal gilts. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 animals were orally administered ZEN at 5 μg ZEN/kg BW, group ZEN10 — at 10 μg ZEN/kg BW, group ZEN15 — at 15 μg ZEN/kg BW, whereas group C received a placebo. Five gilts from every group were euthanized on analytical dates 1, 2 and 3 (days 7, 14 and 42 of the experiment). Qualitative and quantitative changes in the biotransformation of low ZEN doses were observed. These processes were least pronounced in group ZEN5 (MABEL dose) where ZEN metabolites were not detected on the first analytical date, and where β-ZEL was the predominant metabolite on successive dates. The above was accompanied by an increase in the concentration of estradiol (E2) which, together with "free ZEN", probably suppressed progesterone (P4) and testosterone (T) levels. [ABSTRACT FROM AUTHOR]

Zearalenone is a frequent contaminant of cereals and their by-products in regions with a temperate climate. This toxic molecule is produced naturally by Fusarium fungi in crops. The aim of this study was to determine the influence of low zearalenone doses (LOAEL, NOAEL and MABEL) on the intestinal microbiome of gilts on different days of exposure (days 7, 21 and 42). Intestinal contents were sampled from the duodenal cap, the third part of the duodenum, jejunum, caecum and the descending colon. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 animals were orally administered ZEN at 5 μg /kg BW, group ZEN10—10 μg ZEN/kg BW and group ZEN15—15 µg ZEN/kg BW. Five gilts from every group were euthanized on analytical dates 1, 2 and 3. Differences in the log values of microbial counts, mainly Escherichia coli and Enterococcus faecalis, were observed between the proximal and distal segments of the intestinal tract on different analytical dates as well as in the entire intestinal tract. Zearalenone affected the colony counts of intestinal microbiota rather than microbiome diversity, and its effect was greatest in groups ZEN10 and ZEN15. Microbial colony counts were similar in groups ZEN5 and C. In the analysed mycobiome, ZEN exerted a stimulatory effect on the log values of yeast and mould counts in all intestinal segments, in particular in the colon, and the greatest increase was noted on the first analytical date. [ABSTRACT FROM AUTHOR]

Several observations from experiments in rodents and human patients suggest that diabetes affects pineal gland function, including melatonin secretion; however, the accumulated data are not consistent. The aim of the present study was to determine the effects of streptozotocin-induced diabetes on the pineal gland in the domestic pig, a species widely used as a model in various biomedical studies. The study was performed on 10 juvenile pigs, which were divided into two groups: control and diabetic. Diabetes was evoked by administration of streptozotocin (150 mg/kg of body weight). After six weeks, the animals were euthanized between 12.00 and 14.00, and the pineal glands were removed and divided into two equal parts, which were used for biochemical analyses and for preparation of explants for the superfusion culture. The pineal contents (per 100 μg protein) of serotonin, 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid, 5-methoxytryptophol, and 5-methoxytryptamine were significantly lower in diabetic pigs than in control pigs. In contrast, the level of N-acetylserotonin was significantly higher in diabetic animals. No significant differences were found in the level of melatonin between control and experimental pigs. The amounts of 3,4-dihydroxyphenylalanine, dopamine, norepinephrine, and 3,4-dihydroxyphenylacetic acid were significantly lower in the pineal glands of diabetic animals. The level of vanillylmandelic acid was higher in diabetic pigs. No differences were observed in the level of basal and NE-stimulated release of N-acetylserotonin or melatonin between the pineal explants prepared from control and experimental animals. In vitro treatment with insulin was ineffective. In conclusion, streptozotocin-induced diabetes affects both indole metabolism and adrenergic neurotransmission in the pig pineal gland. [ABSTRACT FROM AUTHOR]

Zearalenone is a toxic low-molecular-weight molecule that is naturally produced by moulds on crops as a secondary metabolite. The aim of this study was to determine the genotoxicity of caecal water collected successively from the caecal contents of gilts exposed to low doses (LOAEL, NOAEL, and MABEL) of zearalenone. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 were orally administered ZEN at 5 μg/kg BW, group ZEN10—10 μg ZEN/kg BW and group ZEN15—15 µg ZEN/kg BW. Five gilts from every group were euthanized on analytical dates 1, 2, and 3. Caecal water samples for in vitro analysis were collected from the ileocaecal region. The genotoxicity of caecal water was noted, particularly after date 1 in groups ZEN10 and ZEN15 with a decreasing trend. Electrophoresis revealed the presence of numerous comets without tails in groups C and ZEN5 and fewer comets with clearly expressed tails in groups ZEN10 and ZEN15. The distribution of LLC-PK1 cells ranged from 15% to 20% in groups C and ZEN5, and from 30% to 60% in groups ZEN10 and ZEN15. The analysis of caecal water genotoxicity during exposure to very low doses of ZEN revealed the presence of a counter response and a compensatory effect in gilts. [ABSTRACT FROM AUTHOR]

The contamination of feed with mycotoxins results in reduced growth, feed refusal, immunosuppression, and health problems. Deoxynivalenol (DON) and zearalenone (ZEN) are among the most important mycotoxins. The aim of the study was to examine the effects of low doses of these mycotoxins on the histological structure and ultrastructure of the large intestine in the pig. The study was performed on 36 immature gilts of mixed breed (White Polish Big × Polish White Earhanging), which were divided into four groups administrated per os with ZEN at 40 µg/kg BW, DON at 12 µg/kg BW, a mixture of ZEN (40 µg/kg BW) and DON (12 µg/kg BW) or a placebo. The pigs were killed by intravenous overdose of pentobarbital after one, three, and six weeks of treatment. The cecum, ascending and descending colon samples were prepared for light and electron microscopy. Administration of toxins did not influence the architecture of the mucosa and submucosa in the large intestine. ZEN and ZEN + DON significantly decreased the number of goblet cells in the cecum and descending colon. The mycotoxins changed the number of lymphocytes and plasma cells in the large intestine, which usually increased in number. However, this effect differed between the intestine segments and toxins. Mycotoxins induced some changes in the ultrastructure of the mucosal epithelium. They did not affect the expression of proliferative cell nuclear antigen and the intestinal barrier permeability. The obtained results indicate that mycotoxins especially ZEN may influence the defense mechanisms of the large intestine. [ABSTRACT FROM AUTHOR]

The Aim: In this study was to determine if sigmoid colorectal cancer (SCC) and colorectal cancer (CRC) in women (W) and men (M) is accompanied by zearalenone (ZEN) mycotoxicosis and changes in selected steroid levels., Materials and Methods: This cohort study was conducted on female and male patients selected from a population based on the presence of SCC or CRC, which was accompanied by the presence or absence (control group) of ZEN in their blood. The control group consisted of 17 patients with symptoms of SCC and CRC, where ZEN and its metabolites were not detected in the peripheral blood. The experimental groups comprised a total of 16 patients with SCC and CRC, where ZEN, but not its metabolites, was detected in their peripheral blood samples., Results: In groups SCC and CRC, the ZEN levels were very high, in the range from 214 to 289 ng/mL of blood. Considerable variations were observed in the concentrations of steroid hormones. Estradiol (E 2 ) levels ranged from 166.25 (group C) to 325 pg/mL (group CRC) in women and from 98 (group C) to 95.5 pg/mL (group CRC) in men. Progesterone (P 4 ) levels ranged from 12.09 (group C) to 13.64 ng/mL (group SCC) in women and from 6.98 (group CRC) to 12.01 ng/mL (group C) in men., Conclusions: These results indicate that post-menopausal women and similarly aged elderly men have a high and individualized demand for estrogen that is relatively effectively met by ZEN, which triggers qualitative changes in estrogen receptors. The shortage of ZEN metabolites (values under the sensitivity of the method) confirmed the high estrogen demand in the studied subjects. The presence or absence of ZEN could have influenced the therapeutic outcomes in the analyzed patients.

This study was undertaken to analyze whether prolonged exposure to low-dose zearalenone (ZEN) mycotoxicosis affects the concentrations of ZEN, α-zearalenol (α-ZEL), and β-zearalenol (β-ZEL) in selected reproductive system tissues (ovaries, uterine horn-ovarian and uterine sections, and the middle part of the cervix), the hypothalamus, and pituitary gland, or the concentrations of selected steroid hormones in pre-pubertal gilts. For 42 days, gilts were administered per os different ZEN doses (MABEL dose [5 µg/kg BW], the highest NOAEL dose [10 µg/kg BW], and the lowest LOAEL dose [15 µg/kg BW]). Tissue samples were collected on days seven, twenty-one, and forty-two of exposure to ZEN (exposure days D1, D2, and D3, respectively). Blood for the analyses of estradiol and progesterone concentrations was collected in vivo on six dates at seven-day intervals (on analytical dates D1-D6). The analyses revealed that both ZEN and its metabolites were accumulated in the examined tissues. On successive analytical dates, the rate of mycotoxin accumulation in the studied tissues decreased gradually by 50% and proportionally to the administered ZEN dose. A hierarchical visualization revealed that values of the carry-over factor (CF) were highest on exposure day D2. In most groups and on most exposure days, the highest CF values were found in the middle part of the cervix, followed by the ovaries, both sections of the uterine horn, and the hypothalamus. These results suggest that ZEN, α-ZEL, and β-ZEL were deposited in all analyzed tissues despite exposure to very low ZEN doses. The presence of these undesirable compounds in the examined tissues can inhibit the somatic development of the reproductive system and compromise neuroendocrine coordination of reproductive competence in pre-pubertal gilts.

This study demonstrates that low doses (somewhat above the No Observed Adverse Effect Level, NOAEL) of the mycoestrogen zearalenone (ZEN) and its metabolites display multispecificity towards various biological targets in gilts. The observed responses in gilts were surprising. The presence of ZEN and zearalenols (ZELs) did not evoke a response in the porcine gastrointestinal tract, which was attributed to dietary tolerance. Lymphocyte proliferation was intensified in jejunal mesenteric lymph nodes, and lymphocyte counts increased in the jejunal epithelium with time of exposure. In the distal digestive tract, fecal bacterial counts decreased, the activity of fecal bacterial enzymes and lactic acid bacteria increased, and cecal water was characterized by higher genotoxicity. The accompanying hyperestrogenism led to changes in m RNA activity of selected enzymes (cytochrome P450, hydroxysteroid dehydrogenases, nitric oxide synthases) and receptors (estrogen and progesterone receptors), and it stimulated post-translational modifications which play an important role in non-genomic mechanisms of signal transmission. Hyperestrogenism influences the regulation of the host's steroid hormones (estron, estradiol and progesteron), it affects the virulence of bacterial genes encoding bacterial hydroxysteroid dehydrogenases (HSDs), and it participates in detoxification processes by slowing down intestinal activity, provoking energy deficits and promoting antiporter activity at the level of enterocytes. In most cases, hyperestrogenism fulfils all of the above roles. The results of this study indicate that low doses of ZEN alleviate inflammatory processes in the digestive system, in particular in the proximal and distal intestinal tract, and increase body weight gains in gilts.