Metabolic profile, bioavailability and toxicokinetics of zearalenone-14-glucoside in rats after oral and intravenous administration by liquid chromatography high-resolution mass spectrometry and tandem mass spectrometry

Zearalenone-14-glucoside (ZEN-14G), a key modified mycotoxin, has attracted a great deal of attention due to the possible conversion to its free form of zearalenone (ZEN) exerting toxicity. In this study, the toxicokinetics of ZEN-14G were investigated in rats after oral and intravenous administration. The plasma concentrations of ZEN-14G and its major five metabolites were quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The data were analyzed via non-compartmental analysis using software WinNonlin 6.3. The results indicated that ZEN-14G was rapidly hydrolyzed into ZEN in vivo. In addition, the major parameters of ZEN-14G following intravenous administration were: area under the plasma concentration-time curve (AUC), 1.80 h.ng/mL; the apparent volume of distribution (V-Z), 7.25 L/kg; and total body clearance (CL), 5.02 mL/h/kg, respectively. After oral administration, the typical parameters were: AUC, 0.16 h.ng/mL; V-Z, 6.24 mL/kg; and CL, 4.50 mL/h/kg, respectively. The absolute oral bioavailability of ZEN-14G in rats was about 9%, since low levels of ZEN-14G were detected in plasma, which might be attributed to its extensive metabolism. Therefore, liquid chromatography high-resolution mass spectrometry (LC-HRMS) was adopted to clarify the metabolic profile of ZEN-14G in rats' plasma. As a result, eight metabolites were identified in which ZEN-14-glucuronic acid (ZEN-14GlcA) had a large yield from the first time-point and continued accumulating after oral administration, indicating that ZEN-14-glucuronic acid could serve a potential biomarker of ZEN-14G. The obtained outcomes would prompt the accurate safety evaluation of ZEN-14G

Determination of aflatoxins, deoxynivalenol, ochratoxin A and zearalenone in wheat and oat based bran supplements sold in the Spanish market

The main objective of this study was to assess the exposure of Catalonian (Spain) population to AFs. Thus, two sub-objectives were considered: 1) to assess the occurrence of AFs in food marketed in Catalonia, and 2) to assess the consumption of those foods susceptible to AFs contamination by Catalonian population. AFs were analysed in a total of 603 samples considering special commodities as free-gluten, ethnic or baby foods. Analytical method consisted of an extraction and clean-up of aflatoxins step using immunoaffinity columns, and determination by HPLC with post-column photochemical derivatization and fluorescence detection. Food dietary intake was assessed using a food frequency questionnaire, administered to 1387 individuals by trained interviewers. Contamination and consumption raw datasets were combined by means of a direct method and a stochastic method, building the pseudo-parametric bootstrap confidence intervals of the main outputs. Margins of exposure (MoE) and cancer incidence were estimated for the different collectives. The highest percentages of positive samples were found in red pepper, pistachios and peanuts. Considering our results, the most exposed group was the celiac sufferer collective followed by the adolescents; however health concern should not be expected in the population groups

Review of mycotoxin reduction in food and feed: from prevention in the field to detoxification by adsorption or transformation

Mycotoxins are secondary metabolites present worldwide in agricultural commodities and produced by filamentous fungi that cause a toxic response (mycotoxicosis) when ingested by animals. Prevention of mycotoxicoses includes pre- and post-harvest strategies. The best way to reduce the mycotoxin content in food and feed is the prevention of mycotoxin formation in the field, but this is often not sufficient, so other methods are needed. To decontaminate and/or detoxify mycotoxin-contaminated food and feed, the most prevalent approach in the feed industry is the inclusion of sorbent materials in the feed thus obtaining more or less selective removal of toxins by adsorption during passage through the gastrointestinal tract. Another reliable approach is to add enzymes or microorganisms capable of detoxifying some mycotoxins. Through a comprehensive review of published reports on the strategies for mycotoxin removal, this present work aims to update our understanding of mycotoxin removal. It provides an insight into the detoxification of mycotoxin present in food and feed. In the future, more emphasis needs to be placed on adsorption of mycotoxins in the gastrointestinal tract. Concerning the enzymatic transformation of mycotoxins, further efforts are required in understanding detoxification reactions, the toxicity of transformation products and in the characterization of enzymes responsible for transformations

The status of Fusarium mycotoxins in Sub-Saharan Africa : a review of emerging trends and post-harvest mitigation strategies towards food control

Fusarium fungi are common plant pathogens causing several plant diseases. The presence of these molds in plants exposes crops to toxic secondary metabolites called Fusarium mycotoxins. The most studied Fusarium mycotoxins include fumonisins, zearalenone, and trichothecenes. Studies have highlighted the economic impact of mycotoxins produced by Fusarium. These arrays of toxins have been implicated as the causal agents of wide varieties of toxic health effects in humans and animals ranging from acute to chronic. Global surveillance of Fusarium mycotoxins has recorded significant progress in its control; however, little attention has been paid to Fusarium mycotoxins in sub-Saharan Africa, thus translating to limited occurrence data. In addition, legislative regulation is virtually non-existent. The emergence of modified Fusarium mycotoxins, which may contribute to additional toxic effects, worsens an already precarious situation. This review highlights the status of Fusarium mycotoxins in sub-Saharan Africa, the possible food processing mitigation strategies, as well as future perspectives

Mycotoxin exposure assessments in a multi-center European validation study by 24-hour dietary recall and biological fluid sampling

The European Food Consumption Validation (EFCOVAL) project includes 600 men and women from Belgium, the Czech Republic, France, the Netherlands, and Norway, who had given serum and 24-hour urine samples, and completed 24-hour dietary recall (24-HDR) interviews. Consumption, according to 24-HDR, was matched against the European Food Safety Authority (EFSA) databases of mycotoxin contaminations, via the FoodEx1 standard classifications, producing an indirect external estimate of dietary mycotoxin exposure. Direct, internal measurements of dietary mycotoxin exposure were made in serum and urine by ultra-performance liquid chromatography coupled to tandem mass spectrometry. For the first time, mycotoxin exposures were thoroughly compared between two 24-HDRs, and two 24-hour urine samples collected during the same days covered by the 24-HDRs. These measurements were compared to a single-time point serum measurement to investigate evidence of chronic mycotoxin exposure. According to 24-HDR data, all 600 individuals were exposed to between 4 and 34 mycotoxins, whereof 10 found to exceed the tolerable daily intake. Correlations were observed between two time points, and significant correlations were observed between concentrations in serum and urine. However, only acetyldeoxynivalenol, ochratoxin A, and sterigmatocystin were found to have significant positive correlations between 24-HDR exposures and serum, while aflatoxin G1 and G2, HT-2 toxin, and deoxynivalenol were associated between concurrent 24-HDR and 24-hour urine. Substantial agreements on quantitative levels between serum and urine were observed for the groups Type B Trichothecenes and Zearalenone. Further research is required to bridge the interpretation of external and internal exposure estimates of the individual on a time scale of hours. Additionally, metabolomic profiling of dietary mycotoxin exposures could help with a comprehensive assessment of single time-point exposures, but also with the identification of chronic exposure biomarkers. Such detailed characterization informs population exposure assessments, and aids in the interpretation of epidemiological health outcomes related to multi-mycotoxin exposure

Regulation of 3β-Hydroxysteroid Dehydrogenase/∆5-∆4 Isomerase: A Review

This review focuses on the expression and regulation of 3β-hydroxysteroi ddehydrogenase/Δ5-Δ4 isomerase (3β-HSD), with emphasis on the porcine version. 3β-HSD is often associated with steroidogenesis, but its function in the metabolism of both steroids and xenobiotics is more obscure. Based on currently available literature covering humans,rodents and pigs, this review provides an overview of the present knowledge concerning the regulatory mechanisms for 3β-HSD at all omic levels. The HSD isoenzymes are essential in steroid hormone metabolism, both in the synthesis and degradation of steroids. They display tissue-specific expression and factors influencing their activity, which therefore indicates their tissue-specific responses. 3β-HSD is involved in the synthesis of a number of natural steroid hormones, including progesterone and testosterone, and the hepatic degradation of the pheromone androstenone. In general, a number of signaling and regulatory pathways have been demonstrated to influence 3β-HSD transcription and activity, e.g., JAK-STAT, LH/hCG, ERα, AR, SF-1 and PPARα. The expression and enzymic activity of 3β-HSD are also influenced by external factors, such as dietary composition. Much of the research conducted on porcine 3β-HSD is motivated by its importance for the occurrence of the boar taint phenomenon that results from high concentrations of steroids such as androstenone. This topic is also examined in this review

Different methods to counteract mycotoxin production and its impact on animal health

Mycotoxins can cause serious adverse effects on animal health. This may lead to great economic losses in animal husbandry. In this review, the most common methods to counteract mycotoxins are presented, including several pre- and post-harvest strategies as well as an overview of the different mycotoxin detoxifying agents. The current legislation regarding maximum, guidance or action levels of mycotoxin contamination in various feedstuffs is also mentioned. It allows the agricultural industry to interpret feed analysis results and to decide whether to undertake actions or not

Mycotoxin exposure and human cancer risk : a systematic review of epidemiological studies

In recent years, there has been an increasing interest in investigating the carcinogenicity of mycotoxins in humans. This systematic review aims to provide an overview of data linking exposure to different mycotoxins with human cancer risk. Publications (2019 and earlier) of case–control or longitudinal cohort studies were identified in PubMed and EMBASE. These articles were then screened by independent reviewers and their quality was assessed according to the Newcastle–Ottawa scale. Animal, cross‐sectional, and molecular studies satisfied criteria for exclusion. In total, 14 articles were included: 13 case–control studies and 1 longitudinal cohort study. Included articles focused on associations of mycotoxin exposure with primary liver, breast, and cervical cancer. Overall, a positive association between the consumption of aflatoxin‐contaminated foods and primary liver cancer risk was verified. Two case–control studies in Africa investigated the relationship between zearalenone and its metabolites and breast cancer risk, though conflicting results were reported. Two case–control studies investigated the association between hepatocellular carcinoma and fumonisin B1 exposure, but no significant associations were observed. This systematic review incorporates several clear observations of dose‐dependent associations between aflatoxins and liver cancer risk, in keeping with IARC Monograph conclusions. Only few human epidemiological studies investigated the associations between mycotoxin exposures and cancer risk. To close this gap, more in‐depth research is needed to unravel evidence for other common mycotoxins, such as deoxynivalenol and ochratoxin A. The link between mycotoxin exposures and cancer risk has mainly been established in experimental studies, and needs to be confirmed in human epidemiological studies to support the evidence‐based public health strategies