Aquaporins alteration revealed kidney damages in cerebral ischemia/reperfusion rats.

Background: Restoration of blood supply is a desired goal for the treatment of acute ischemic stroke. However, the restoration often leads to cerebral ischemia-reperfusion injury (CIR/I), which greatly increases the risk of non-neural organ damage. In particular, the acute kidney injury might be one of the most common complications. Aims: The study aimed to understand the damage occurred and the potential molecular mechanisms. Methods: The study was explored on the CIR/I rats generated by performing middle cerebral artery occlusion/reperfusion (MCAO/Reperfusion). The rats were evaluated with injury on the brains, followed by the non-neural organs including kidneys, livers, colons and stomachs. They were examined further with histopathological changes, and gene expression alterations by using RT-qPCR of ten aquaporins (Aqps) subtypes including Aqp1～Aqp9 and Aqp11. Furthermore, the Aqps expression profiles were constructed for each organ and analyzed by performing Principle Component Analysis. In addition, immunohistochemistry was explored to look at the protein expression of Aqp1, Aqp2, Aqp3 and Aqp4 in the rat kidneys. Results: There was a prominent down-regulation profile in the MCAO/Reperfusion rat kidneys. The protein expression of Aqp1, Aqp2, Aqp3 and Aqp4 was decreased in the kidneys of the MCAO/Reperfusion rats. We suggested that the kidney was in the highest risk to be damaged following the CIR/I. Down-regulation of Aqp2, Aqp3 and Aqp4 was involved in the acute kidney injury induced by the CIR/I.

Effects of aflatoxin and fumonisin on gene expression of growth factors and inflammation-related genes in a human hepatocyte cell line.

Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely distributed in maize and maized-based products, often occurring together. The implications of co-exposure to aflatoxin and fumonsin for human health are numerous, but a particular concern is the potential of FB1 to modulate AFB1 hepatotoxicity. This study evaluated the toxicity of these mycotoxins, alone or combined, in a human non-tumorigenic liver cell line, HHL-16 cells, and assessed the effects of AFB1 and FB1 on expression of genes involved in immune and growth factor pathways. The results demonstrated that in HHL-16 cells, both AFB1 and FB1 had dose-dependent and time-dependent toxicity, and the combination of them showed a synergistic toxicity in the cells. Moreover, AFB1 caused upregulation of IL6, CCL20, and BMP2, and downregulation of NDP. In combination of AFB1 with FB1, gene expression levels of IL6 and BMP2 were significantly higher compared to individual FB1 treatment, and had a tendency to be higher than individual AFB1 treatment. This study shows that FB1 may increase the hepatoxicity of AFB1 through increasing the inflammatory response and disrupting cell growth pathways.

Assessment of the Adverse Health Effects of Aflatoxin Exposure from Unpackaged Peanut Oil in Guangdong, China.

Aflatoxins are liver carcinogens and are common contaminants in unpackaged peanut (UPP) oil. However, the health risks associated with consuming aflatoxins in UPP oil remain unclear. In this study, aflatoxin contamination in 143 UPP oil samples from Guangdong Province were assessed via liquid chromatography-tandem mass spectrometry (LC-MS). We also recruited 168 human subjects, who consumed this oil, to measure their liver functions and lipid metabolism status. Aflatoxin B1 (AFB1) was detected in 79.72% of the UPP oil samples, with levels ranging from 0.02 to 174.13 µg/kg. The average daily human intake of AFB1 from UPP oil was 3.14 ng/kg·bw/day; therefore, the incidence of liver cancer, caused by intake of 1 ng/kg·bw/day AFB1, was estimated to be 5.32 cases out of every 100,000 persons per year. Meanwhile, Hepatitis B virus (HBV) infection and AFB1 exposure exerted a synergistic effect to cause liver dysfunction. In addition, the triglycerides (TG) abnormal rate was statistically significant when using AFB1 to estimate daily intake (EDI) quartile spacing grouping (p = 0.011). In conclusion, high aflatoxin exposure may exacerbate the harmful effects of HBV infection on liver function. Contamination of UPP oil with aflatoxins in Guangdong urgently requires more attention, and public health management of the consumer population is urgently required.

Highly resistant and sensitive colorimetric immunochromatographic assay for sibutramine (SBT) illegally adulterated into diet food based on PDA/AuNP labelling.

A gold nanoparticle (AuNP) based immunochromatographic assay strip is a valuable tool for monitoring chemicals in foods. However, the sensitive ICA strip for SBT is rarely reported due to the fact that monoclonal antibodies (mAbs) against SBT with high affinity are commercially unavailable. Herein, a monoclonal antibody against SBT was prepared through a designed hapten with a carboxyl end-capped space arm. The obtained mAb showed high affinity for SBT and N-desmethylsibutramine, a metabolite of SBT. Furthermore, a series of core-shell NPs, polydopamine (PDA) coated AuNPs (PDA/AuNPs) with controlled shell thickness and packing density were synthesized. The obtained PDA/AuNP-mAb conjugate demonstrated high tolerance to salt and good stability in a wide pH range, which is beneficial for improving the matrix interference common in ICA. As a result, PDA/AuNP-based ICA could quantify SBT in the range of 3.39-69.60 ng mL-1 with a limit of detection (LOD) of 0.98 ng mL-1. This novel ICA improved the sensitivity of the traditional AuNP-based ICA by nearly 12 times. Method validation was conducted with spiked samples of slimming food and human serum and compared with HPLC-MS/MS. Consistent results indicated that high sensitivity, accuracy, and reliability of the PDA/AuNP-based ICA approach were achieved. To the best of our knowledge, this study reported the most sensitive immunoassay for SBT thus far.

An aggregation-induced emission immunoassay for broad detection of polychlorinated biphenyls in chicken and crab.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) with multiple variants, which may be harmful to human health by absorption and bioaccumulation. To ensure food safety, it is necessary to develop multi-residue immunoassays for broad recognition of PCBs. In this study, by mimicking the generic core structure of PCBs, three haptens have been designed and synthesized for monoclonal antibody (mAb) generation. A carboxylic acid derivative of PCB80 was a hapten that induced a mAb with broad recognition of PCBs. The results of ELISA further identified that the mAb could recognize 11 different kinds of PCBs; half-maximal inhibition concentrations (IC50) ranged from 33.12 to 476.42 ng/mL. Subsequently, using aggregation-induced emission luminogen (AIEgen) nanobeads as the tracer for the output signal, the IC50 value of the various PCBs was improved to 6.38-252.1 ng/mL. The limit of detection (LOD) varied from 0.32 to 42.15 ng/mL. Recoveries of 76.90-95.74% and intra-assay coefficients of variation of 8.5-14.4% were obtained with spiked chicken and crab meat samples. Matrix interference was eliminated by dilution, and no false-positive and false-negative results were observed. The developed assay provides a simple, broad-spectrum, and sensitive tool for detecting PCBs, with high-throughput possibilities for large-scale screening of PCBs in food.

Super-Sensitive LC-MS Analyses of Exposure Biomarkers for Multiple Mycotoxins in a Rural Pakistan Population.

High levels of mycotoxin contamination have been reported in various food commodities in Pakistan, however, there has been no exposure assessment study using multiple mycotoxins' biomarkers. This study aimed to simultaneously assess the exposure to the five major mycotoxins: aflatoxin B1 (AFB1), deoxynivalenol (DON), fumonisin B1 (FB1), ochratoxin A (OTA) and zearalenone (ZEN) in a Pakistani population using an integrated approach of human biomonitoring. Human urine samples (n = 292) were analyzed by a super-sensitive liquid-chromatography tandem mass spectrometry (LC-MS/MS) method. Rice and wheat were also collected and analyzed for mycotoxins by the LC-MS/MS method. Food consumption data were collected using a 24 h recall method. A high prevalence of urinary AFM1 (66%, mean ± SD 20.8 ± 41.3 pg/mL) and OTA (99%, 134.7 ± 312.0 pg/mL) were found, whilst urinary DON, FB1 and ZEN levels were low. The probable daily intake (PDI) derived from the urinary biomarkers revealed that 89% of the participants had exposure to OTA exceeding the established tolerable daily intake (TDI = 17 ng/kg bw/day). The average PDI of AFB1 for the studied population was 43 ng/kg bw/day, with rice as the main source of AFB1 exposure. In summary, exposure to AFB1 and OTA are of health concern and require further management.

Environmentally sensitive hotspots in the methylome of the early human embryo.

In humans, DNA methylation marks inherited from gametes are largely erased following fertilisation, prior to construction of the embryonic methylome. Exploiting a natural experiment of seasonal variation including changes in diet and nutritional status in rural Gambia, we analysed three datasets covering two independent child cohorts and identified 259 CpGs showing consistent associations between season of conception (SoC) and DNA methylation. SoC effects were most apparent in early infancy, with evidence of attenuation by mid-childhood. SoC-associated CpGs were enriched for metastable epialleles, parent-of-origin-specific methylation and germline differentially methylated regions, supporting a periconceptional environmental influence. Many SoC-associated CpGs overlapped enhancers or sites of active transcription in H1 embryonic stem cells and fetal tissues. Half were influenced but not determined by measured genetic variants that were independent of SoC. Environmental 'hotspots' providing a record of environmental influence at periconception constitute a valuable resource for investigating epigenetic mechanisms linking early exposures to lifelong health and disease.

Organ Specific Differences in Alteration of Aquaporin Expression in Rats Treated with Sennoside A, Senna Anthraquinones and Rhubarb Anthraquinones.

Senna and rhubarb are often used as routine laxatives, but there are differences in mechanism of action and potential side effects. Here, we studied metabolites of senna anthraquinones (SAQ), rhubarb anthraquinones (RAQ) and their chemical marker, sennoside A (SA), in a rat diarrhea model. In in vitro biotransformation experiments, SAQ, RAQ and SA were incubated with rat fecal flora solution and the metabolites produced were analyzed using HPLC. In in vivo studies, the same compounds were investigated for purgation induction, with measurement of histopathology and Aqps gene expression in six organs. The results indicated that SAQ and RAQ had similar principal constituents but could be degraded into different metabolites. A similar profile of Aqps down-regulation for all compounds was seen in the colon, suggesting a similar mechanism of action for purgation. However, in the kidneys and livers of the diarrhea-rats, down-regulation of Aqps was found in the RAQ-rats whereas up-regulation of Aqps was seen in the SAQ-rats. Furthermore, the RAQ-rats showed lower Aqp2 protein expression in the kidneys, whilst the SA-rats and SAQ-rats had higher Aqp2 protein expression in the kidneys. This may have implications for side effects of SAQ or RAQ in patients with chronic kidney or liver diseases.

Aflatoxin Exposure during Early Life Is Associated with Differential DNA Methylation in Two-Year-Old Gambian Children.

Background: DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin B1 from the maternal diet, as measured using biomarkers in the mothers' blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia. Methods: Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population (n = 244), in relation to the child's dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months. Results: Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways. Conclusions: This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.

Estimating the risk of aflatoxin-induced liver cancer in Tanzania based on biomarker data.

Evidence about the magnitude of the aflatoxin menace can help policy makers appreciate the importance of the problem and strengthen policies to support aflatoxin mitigation measures. In this study, we estimated aflatoxin-induced liver cancer risk in 2016 for Tanzania and used the information to estimate the health burden due to the aflatoxin exposure in the country. The burden of aflatoxin-induced liver cancer was assessed based on available aflatoxin biomarker data from a previous epidemiology study, hepatitis B virus infection prevalence and population size of Tanzania in 2016. The health burden due to aflatoxin-induced liver cancer was estimated using disability adjusted life years (DALYs). The aflatoxin exposures ranged from 15.0-10,926.0 ng/kg bw/day (median, 105.5 ng/kg bw/day). We estimated that in 2016 there were about 1,480 (2.95 per 100,000 persons) new cases of aflatoxin-induced liver cancer in Tanzania and assumed all of them would die within a year. These morbidity and mortality rates led to a total loss of about 56,247.63 DALYs. These results show, quantitatively, the cases of liver cancer and related deaths that could be avoided, and the healthy life years that could be saved, annually, by strengthening measures to control aflatoxin contamination in Tanzania.

Estimating the health burden of aflatoxin attributable stunting among children in low income countries of Africa.

Numerous population-based studies have documented high prevalence of aflatoxin associated childhood stunting in low income countries. We provide an estimate of the disease burden of aflatoxin related stunting using data from the four African countries. For this empirical analysis, we obtained blood aflatoxin albumin adduct biomarker based exposure data as measured using ELISA technique and anthropometric measurement data from surveys done over a 12-year period from 2001 to 2012 in four low income countries in Africa. We used these data to calculate population attributable risk (PAR), life time disease burden for children under five by comparing two groups of stunted children using both prevalence and incidence-based approaches. We combined prevalence estimates with a disability weight, measuring childhood stunting and co-occurrence of stunting-underweight to produce years lived with disability. Using a previously reported mortality, years of life lost were estimated. We used probabilistic analysis to model these associations to estimate the disability-adjusted life-years (DALYs), and compared these with those given by the Institute for Health Metrics and Evaluation's Global Burden of Disease (GBD) 2016 study. The PAR increased from 3 to 36% for aflatoxin-related stunting and 14-50% for co-occurrence of stunting and underweight. Using prevalence-based approach, children with aflatoxin related stunting resulted in 48,965.20 (95% uncertainty interval (UI): 45,868.75-52,207.53) DALYs per 100,000 individuals. Children with co-occurrence of stunting and underweight due to exposure to aflatoxin resulted in 40,703.41 (95% UI: 38,041.57-43,517.89) DALYs per 100,000 individuals. Uncertainty analysis revealed that reducing aflatoxin exposure in high exposure areas upto non-detectable levels could save the stunting DALYs up to 50%. The burden of childhood all causes stunting is greater in countries with higher aflatoxin exposure such as Benin. In high exposure areas, these results might help guide research protocols and prioritisation efforts and focus aflatoxin exposure reduction. HEFCE Global Challenge Research Fund Aflatoxin project.

Recent trends in detecting, controlling, and detoxifying of patulin mycotoxin using biotechnology methods.

Patulin (PAT) is a mycotoxin that can contaminate many foods and especially fruits and fruit-based products. Therefore, accurate and effective testing is necessary to enable producers to comply with regulations and promote food safety. Traditional approaches involving the use of chemical compounds or physical treatments in food have provided practical methods that have been used to date. However, growing concerns about environmental and health problems associated with these approaches call for new alternatives. In contrast, recent advances in biotechnology have revolutionized the understanding of living organisms and brought more effective biological tools. This review, therefore, focuses on the study of biotechnology approaches for the detection, control, and mitigation of PAT in food. Future aspects of biotechnology development to overcome the food safety problem posed by PAT were also examined. We find that biotechnology advances offer novel, more effective, and environmental friendly approaches for the control and elimination of PAT in food compared to traditional methods. Biosensors represent the future of PAT detection and use biological tools such as aptamer, enzyme, and antibody. PAT prevention strategies include microbial biocontrol, the use of antifungal biomolecules, and the use of microorganisms in combination with antifungal molecules. PAT detoxification aims at the breakdown and removal of PAT in food by using enzymes, microorganisms, and various adsorbent biopolymers. Finally, biotechnology advances will be dependent on the understanding of fundamental biology of living organisms regarding PAT synthesis and resistance mechanisms.

Biomonitoring of Aflatoxin B1 and Deoxynivalenol in a Rural Pakistan Population Using Ultra-Sensitive LC-MS/MS Method.

There are limited data on exposure to mycotoxins in Pakistan. Here, we measured exposure to deoxynivalenol (DON), a common contaminant of wheat, and aflatoxin B1 (AFB1), a known contaminant of rice, using biomarkers of exposure. Wheat (n = 195) and rice (n = 62) samples were analyzed for AFB1 and DON levels, and the corresponding urinary biomarkers were analyzed in urine samples from a rural population (n = 264, aged 4-80 years, male 58%) using ultra-sensitive liquid chromatography-tandem mass spectrometry. AFB1 was detected in 66% of rice (5.04 ± 11.94 µg/kg) and 3% of wheat samples. AFM1 (hydroxylated form of AFB1)was detected in 69% of urine samples, mean 0.023 ± 0.048 ng/mL and DON was detected in 20% of urine samples, mean 0.170 ± 0.129 ng/mL. The maximum probable daily intake for DON derived from the urinary biomarker was 59.8 ng/kg b.w./day, which is below the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives' tolerable daily intake (1000 ng/kg b.w./day). However, for aflatoxin, the derived margin of exposure (MoE) of (13.2) was well below the safe MoE (10,000) suggested by the European Food Safety Authority. The calculated aflatoxin-associated cancer risk of 0.514/105 individuals/year suggests that measures should be taken to reduce the AFB1 contamination in food, particularly rice, in Pakistan.

The contribution of PM2.5 to cardiovascular disease in China.

China is experiencing rapid urbanization and industrialization with correspondingly high levels of air pollution. Although the harm of PM2.5 has been long reported, it is only quite recently that there is increasing concern in China for its possible adverse health effects on cardiovascular disease. We reviewed the epidemiologic evidence of potential health effects of PM2.5 on cardiovascular disease reported from recent studies in China (2013 onwards). There is clear evidence for the contribution of PM2.5 to cardiovascular outcomes, including mortality, ischemic heart disease, and stroke from studies based in various regions in China. This evidence adds to the global evidence that PM2.5 contributes to adverse cardiovascular health risk and highlights the need for improved air quality in China.

Aflatoxins as a risk factor for liver cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Liver cirrhosis is characterized by fibrosis and nodule formation in the liver, due to a chronic injury, and subsequent alteration of the normal architecture of the liver. Even though there is a huge effort to elucidate the possible etiologic factors of liver cirrhosis, a significant number of cases are cryptogenic, especially in Sub Saharan Africa, where there is a high burden of aflatoxin exposure. Aflatoxins are known to cause hepatocellular carcinoma, which share similar etiologic factors with liver cirrhosis. This study aimed to assess the association between aflatoxin exposure and the risk of liver cirrhosis. METHODS: Relevant studies were identified through systematic searches conducted in Ovid MEDLINE, PubMed and Google Scholar. Also, by searching the references of retrieved articles. The abstracts and full text were screened for eligibility and the risk of bias was assessed for each study using Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies. The extracted data from included studies using Microsoft Excel were exported to Stata software version 15.0 for analyses. The overall pooled estimation of outcomes was calculated using a random-effects model of DerSimonian-Laird method at a 95% confidence level. The heterogeneity of studies was determined using I2 statistics. The presence of publication bias between studies was evaluated using the Begg's and Egger's tests and funnel plot. The protocol of this systematic review and meta-analysis was registered in the Prospero database with reference number ID: CRD42019148481. RESULTS: A total of 5 studies published between the years 2005 and 2018 that met the pre-defined inclusion and exclusion criteria were included. The meta-analysis showed that a significant increase in the risk of liver cirrhosis is associated with aflatoxin exposure (unadjusted pooled odds ratio (OR) = 3.35, 95% CI: 2.74-4.10, p = 0.000; I2 = 88.3%, p = 0.000; adjusted OR = 2.5, 95% CI: 1.84-3.39, p = 0.000; I2 = 0%, p = 0.429). CONCLUSIONS: The present meta-analysis suggests that aflatoxin exposure is associated with a higher risk of liver cirrhosis.

Identification of rhein as the metabolite responsible for toxicity of rhubarb anthraquinones.

Rhubarb is a popular food in Europe with laxative properties attributed to anthraquinones. Long term usage of rhubarb anthraquinones has been linked to colonic toxicity, including the formation of melanosis coli, which is associated with increased risk of colon cancer. The major purgative anthraquinone in rhubarb is thought to be sennoside A, which is metabolised by colonic microflora. Here, we sought to identify the toxic metabolite responsible for melanosis coli in rats dosed with rhubarb anthraquinones for up to 90 days. Three metabolites were detected in rat faeces using HPLC. Of these, rhein was identified as the metabolite that accumulated most over time. Fecal flora from treated rats were capable of greater biotransformation of sennoside A to rhein compared to that from control rats. Cell culture experiments suggested that apoptosis and autophagy induced by rhein is the likely mechanism of chronic toxicity of rhubarb anthraquinones.

Prevalence and Exposure Assessment of Aflatoxins Through Black Tea Consumption in the Multan City of Pakistan and the Impact of Tea Making Process on Aflatoxins.

Aflatoxins are the highly toxic secondary metabolites of certain fungi, being mainly produced by Aspergillus flavus and Aspergillus parasiticus. Aflatoxins are classified as group 1 category carcinogens by the International Agency for Research on Cancer (IARC). A large number of food commodities are reported to be contaminated with aflatoxins. Tea is the world's second most consumed beverage and the consumption of tea is increasing day by day. Besides being a source of several health promoting substances, tea leaves are also reported to be contaminated with aflatoxins. However, not a single study is reported from Pakistan regarding the level of aflatoxins in commercially available black tea samples. The current study aimed to quantify the level of aflatoxins in commercially available branded and non-branded black tea samples. The estimated daily intake (EDI) of aflatoxins through branded and non-branded black tea consumption and the health risk assessment based on margin of exposure (MOE) approach was assessed. Furthermore, the impact of local tea making processes on the concentration of aflatoxins in tea beverage (filtrate) was also investigated.

Preliminary study on the relationship between aflatoxin-bovine serum albumin adducts in blood and aflatoxin M1 levels in milk of dairy cows.

The aflatoxin (AF) albumin adduct is often used as a biomarker for aflatoxin exposure in humans. An ELISA method previously used for aflatoxin serum albumin in human blood was used to analyse bovine serum samples (n = 22) collected from dairy cattle during an aflatoxin mitigation study in Kenya. Albumin adduct data were compared with aflatoxin M1 (AFM1) levels in corresponding milk samples from these cows. The concentration ranged from < LOD to 487.9 pg/mL for AFM1 and < LOD and 96.3 pg/mg for aflatoxin-albumin. This study indicates that aflatoxin-albumin adducts could be used as a measure of chronic aflatoxin exposure in dairy cattle.

In vitro effects of single and binary mixtures of regulated mycotoxins and persistent organochloride pesticides on steroid hormone production in MA-10 Leydig cell line.

Epidemiological studies have shown strong deterioration in male reproductive health globally due to compromised testosterone production leading to altered spermatogenesis and poor sperm quality. However, the effects and mechanisms through which mycotoxins and persistent organochloride pesticides contribute to poor reproductive health in males remain unclear. The effects of single and binary combinations of ochratoxin A, deoxynivalenol, zearalenone, alpha-zearalenol, beta-zearalenol and 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane on testicular steroidogenesis were evaluated using the MA-10 Leydig cell line after 48 h of exposure. Zearalenone exposure, especially at 16 µM, had a stimulatory effect on progesterone secretion (4.7 ±â€¯0.48 ng/mL compared to 0.60 ±â€¯0.07 ng/mL in control), but inhibited testosterone production after 48 h compared to the solvent control. Ochratoxin A treatment significantly increased both progesterone and testosterone levels. Combination of alpha-zearalenol with beta-zearalenol showed a synergistic stimulation of progesterone hormone level at 1 and 8 µM. The results presented here show that the MA-10 Leydig cell line is a useful model for assessing the effects of xenoestrogens on testicular steroidogenesis. In addition, the inhibitory effects of zearalenone, alpha-zearalenol and beta-zearalenol on testosterone production was enhanced by co-exposure with 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane, further compounding the threat posed by these mycotoxins to male reproductive health.

The effect of individual and mixtures of mycotoxins and persistent organochloride pesticides on oestrogen receptor transcriptional activation using in vitro reporter gene assays.

The mycotoxins zearalenone (ZEN) and alpha-zearalenone (α-ZOL), which are common contaminants of agri-food products, are known for their oestrogenic potential. In addition to mycotoxins, food may also contain pesticides with oestrogenic properties such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (p,p'-DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE), raising the question on the potential effects of individual and combinations of these xeno-oestrogens on the action of natural oestrogens. The present study employed a mammalian reporter gene assay to assess the effects individual and binary combinations of these environmental and food-borne contaminants on oestrogen nuclear receptor (ER) transactivation. As expected, α-ZOL and ZEN exhibited the strongest oestrogenic potency (EC50: 0.27 ±â€¯0.121 nM and 1.32 ±â€¯0.0956 nM, respectively) whereas p,p'-DDT and p,p'-DDE had weak ER agonistic activity with the maximal response of 28.70 ±â€¯2.97% and 18.65 ±â€¯1.77%, respectively. Concurrent treatment of the mycotoxins and/or pesticides, individually or in binary combination, with 17ß-oestradiol (E2) showed either additive, synergistic or antagonistic interactive effects on E2-mediated ER response, depending on the combination ratios, the concentration range of xeno-oestrogens, and the concentration of E2. This study highlights the importance of assessing the mixture effects of chemical contaminants in risk assessment, especially in the area of reproductive and developmental toxicity.