ABSTRACT
With the recognition of the importance of the gut-brain axis in Parkinson's disease (PD) etiology, there is increased interest in developing therapeutic strategies that target α-synuclein, the hallmark abhorrent protein of PD pathogenesis, which may originate in the gut. Research has demonstrated that inhibiting the aggregation, oligomerization, and fibrillation of α-synuclein are key strategies for disease modification. Polyphenols, which are rich in fruits and vegetables, are drawing attention for their potential role in this context. In this paper, we reviewed how polyphenols influence the composition and functional capabilities of the gut microbiota and how the resulting microbial metabolites of polyphenols may potentially enhance the modulation of α-synuclein aggregation. Understanding the interaction between polyphenols and gut microbiota and identifying which specific microbes may enhance the efficacy of polyphenols is crucial for developing therapeutic strategies and precision nutrition based on the microbiome.
Subject(s)
Brain-Gut Axis , Gastrointestinal Microbiome , Parkinson Disease , Polyphenols , alpha-Synuclein , Parkinson Disease/metabolism , Parkinson Disease/microbiology , Parkinson Disease/drug therapy , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/physiology , Polyphenols/pharmacology , Humans , alpha-Synuclein/metabolism , Brain-Gut Axis/physiology , Animals , Brain/metabolism , Brain/drug effectsABSTRACT
Mycotoxins are a class of exogenous metabolites that are major contributors to foodborne diseases and pose a potential threat to human health. However, little attention has been paid to trace mycotoxin co-exposure situations in vivo. To address this, we devised a novel analytical strategy, both highly sensitive and comprehensive, for quantifying 67 mycotoxins in human plasma samples. This method employs isotope dilution mass spectrometry (IDMS) for approximately 40% of the analytes and utilizes internal standard quantification for the rest. The mycotoxins were classified into three categories according to their physicochemical properties, facilitating the optimization of extraction and detection parameters to improve analytical performance. The lowest limits of detection and quantitation were 0.001-0.5 µg/L and 0.002-1 µg/L, respectively, the intra-day precision ranged from 1.8% to 11.9% RSD, and the intra-day trueness ranged from 82.7-116.6% for all mycotoxins except Ecl, DH-LYS, PCA, and EnA (66.4-129.8%), showing good analytical performance of the method for biomonitoring. A total of 40 mycotoxins (including 24 emerging mycotoxins) were detected in 184 plasma samples (89 from infertile males and 95 from healthy males) using the proposed method, emphasizing the widespread exposure of humans to both traditional and emerging mycotoxins. The most frequently detected mycotoxins were ochratoxin A, ochratoxin B, enniatin B, and citrinin. The incidence of exposure to multiple mycotoxins was significantly higher in infertile males than in healthy subjects, particularly levels of ochratoxin A, ochratoxin B, and citrinin, which were significantly increased. It is necessary to carry out more extensive biological monitoring to provide data support for further study of the relationship between mycotoxins and male infertility.
ABSTRACT
To investigate the metabolic transformation of cyclopiazonic acid (CPA) in the liver of different species and to supplement accurate risk assessment information, the metabolism of CPA in liver microsomes from four animals and humans was studied using the ultra-high-performance liquid chromatography-quadrupole/time-of-flight method. The results showed that a total of four metabolites were obtained, and dehydrogenation, hydroxylation, methylation, and glucuronidation were identified as the main metabolic pathways of CPA. Rat liver microsomes exhibited the highest metabolic capacity for CPA, with dehydrogenated (C20H18N2O3) and glucuronic acid-conjugated (C26H28N2O10) metabolites identified in all liver microsomes except chicken, indicating significant species metabolic differences. Moreover, C20H18N2O3 was only detected in the incubation system with cytochromes P450 3A4 (CYP3A4). The hydroxylated (C20H20N2O4) and methylated (C21H22N2O3) metabolites were detected in all incubation systems except for the CYP2C9, with CYP3A4 demonstrating the strongest metabolic capacity. The "cocktail" probe drug method showed that CPA exhibited a moderate inhibitory effect on the CYP3A4 (IC50 value = 8.658 µM), indicating that the substrate had a negative effect on enzyme activity. Our results provide new insights to understand the biotransformation profile of CPA in animals and humans.
Subject(s)
Indoles , Microsomes, Liver , Microsomes, Liver/metabolism , Animals , Humans , Indoles/metabolism , Chromatography, High Pressure Liquid , Rats , Chickens/metabolism , Male , Dogs , Mass Spectrometry , Rats, Sprague-Dawley , Biotransformation , MiceABSTRACT
BACKGROUND: Percutaneous endoscopic transforaminal discectomy (PETD) is an effective method for treating lumbar disc herniation, and is typically performed under local anesthesia. However, inadequate analgesia during the procedure remains a concern, prompting the search for a medication that can provide optimal pain control with minimal impact on the respiratory and circulatory systems. OBJECTIVES: The aim of this study was to observe the effects of different doses of esketamine combined with dexmedetomidine on reducing visual analog scale (VAS) scores during surgical interventions. METHODS: One hundred two patients who underwent PETD were randomly divided into a control group (group C: normal saline + dexmedetomidine), an E1 group (0.1 mg kg-1 esketamine + dexmedetomidine), and an E2 group (0.2 mg kg-1 esketamine + dexmedetomidine). The primary outcome was the maximum visual analogue scale (VAS) (score: 0 = no pain and 10 = worst pain) at six time points. The secondary outcomes included the Assessment of Alertness/Sedation Scale (OAA/S) score and mean arterial pressure (BP), heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) at 11 time points. The incidence of adverse reactions during and 24 h after the operation and patient satisfaction with the anesthesia were also recorded. RESULTS: Compared with those in group C, the VAS scores of patients in groups E1 and E2 were lower at T6, T7, and T9 (P < 0.05). From T4 to T10, the OAA/S scores of the E1 and E2 groups were both lower than those of group C (P < 0.05), and at the T4-T6 time points, the OAA/S score of the E2 group was lower than that of group E1 (P < 0.05). At T4 and T5, the HR and BP of patients in groups E1 and E2 were greater than those in group C (P < 0.05). Compared with those in group C, the incidences of intraoperative illusion, floating sensation, postoperative dizziness, and hyperalgesia in groups E1 and E2 were significantly greater (P < 0.01). There was no significant difference in patient RR, SpO2, or postoperative satisfaction with anesthesia among the three groups (P > 0.05). CONCLUSION: The combination of esketamine and dexmedetomidine can reduce VAS scores during certain stages of this type of surgery; it has minimal impact on respiration and circulation. However, this approach is associated with increased incidences of postoperative dizziness and psychiatric side effects, which may also affect patients' compliance with surgical instructions from medical staff. Patient satisfaction was not greater with dexmedetomidine combined with esketamine than with dexmedetomidine alone. TRIAL REGISTRATION: http://www.chictr.org.cn . Identifier: ChiCTR2300068206. Date of registration: 10 February 2023.
Subject(s)
Dexmedetomidine , Diskectomy, Percutaneous , Intervertebral Disc Displacement , Ketamine , Humans , Dexmedetomidine/administration & dosage , Female , Male , Double-Blind Method , Ketamine/administration & dosage , Adult , Middle Aged , Intervertebral Disc Displacement/surgery , Diskectomy, Percutaneous/methods , Analgesics/administration & dosage , Drug Therapy, Combination , Pain Measurement , Dose-Response Relationship, Drug , Endoscopy/methods , Pain, Postoperative/drug therapy , Treatment Outcome , Lumbar Vertebrae/surgeryABSTRACT
The first paired electrolysis-enabled arylation of quinoxalin-2(1H)-ones was achieved using cyanoarenes as the arylation reagents. A variety of 3-arylquinoxalin-2(1H)-ones with various important functional groups were obtained in moderate to good yields under metal- and chemical oxidant-free conditions. With a pair of reductive and oxidative processes occurring among the substrates and reaction intermediates, the power consumption can be dramatically reduced.
ABSTRACT
The emerging mycotoxins enniatins (ENNs) and the traditional mycotoxin deoxynivalenol (DON) often co-contaminate various grain raw materials and foods. While the liver is their common target organ, the mechanism of their combined effect remains unclear. In this study, the combined cytotoxic effects of four ENNs (ENA, ENA1, ENB, and ENB1) with DON and their mechanisms were investigated using the HepG2 cell line. Additionally, a population exposure risk assessment of these mycotoxins was performed by using in vitro experiments and computer simulations. The results showed that only ENA at 1/4 IC50 and ENB1 at 1/8 IC50 coexposed with DON showed an additive effect, while ENB showed the strongest antagonism at IC50 (CI = 3.890). Co-incubation of ENNs regulated the signaling molecule levels which were disrupted by DON. Transcriptome analysis showed that ENB (IC50) up-regulated the PI3K/Akt/FoxO signaling pathway and inhibited the expression of apoptotic genes (Bax, P53, Caspase 3, etc.) via phosphorylation of FoxO, thereby reducing the cytotoxic effects caused by DON. Both types of mycotoxins posed serious health risks, and the cumulative risk of coexposure was particularly important for emerging mycotoxins.
Subject(s)
Depsipeptides , Mycotoxins , Phosphatidylinositol 3-Kinases , Trichothecenes , Humans , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Hep G2 Cells , Mycotoxins/toxicity , Mycotoxins/analysisABSTRACT
Aflatoxin B1 (AFB1) is a major mycotoxin contaminant showing in the environment and foods. In this study, the molecular initiating events (MIEs) of AFB1-induced steatohepatitis were explored in mice and human cell model. We observed dose-dependent steatohepatitis in the AFB1-treated mice, including triglyceride accumulation, fibrotic collagen secretion, enrichment of CD11b + and F4/80+ macrophages/Kupffer cells, cell death, lymphocytes clusters and remarkable atrophy areas. The gut barrier and gut-microbiota were also severely damaged after the AFB1 treatment and pre-conditioned colitis in the experimental mice aggravated the steatohepatitis phenotypes. We found that macrophages cells can be pro-inflammatorily activated to M1-like phenotype by AFB1 through an AHR/TLR4/p-STAT3 (Ser727)-mediated mitochondrial oxidative stress. The phenotypes can be rescued by AHR inhibitors in the mice model and human cell model. We further showed that this signaling axis is based on the cross-talk interaction between AHR and TLR4. Gene knock-up experiment found that the signaling is dependent on AFB1 ligand-binding with AHR, but not protein expressions of TLR4. The signaling elevated NLRP3 and two immune metabolic enzymes ICAM-1 and IDO that are associated with macrophage polarization. Results from intervention experiments with natural anti-oxidant and AHR inhibitor CH223191 suggest that the macrophage polarization may rely on AHR and ROS. Our study provides novel and critical references to the food safety and public health regulation of AFB1.
Subject(s)
Aflatoxin B1 , Fatty Liver , Animals , Humans , Mice , Intercellular Adhesion Molecule-1/metabolism , Macrophages/metabolism , Oxidative Stress , STAT3 Transcription Factor/metabolism , Toll-Like Receptor 4/metabolismABSTRACT
Childhood malnutrition remains a serious global health concern, particularly in low-income nations like Uganda. This study investigated the impact of peanut supplementation on the compositions and functions of gut microbiome with nutritional improvement. School children aged 6-9 years from four rural communities were recruited, with half receiving roasted peanut snacks while the other half served as controls. Fecal samples were collected at the baseline (day 0), day 60, and day 90. Microbial DNA was extracted, and 16S rRNA sequencing was performed, followed by the measurement of SCFA concentration in fecal samples using UHPLC. Alpha and beta diversity analyses revealed significant differences between the control and supplemented groups after 90 days of supplementation. Leuconostoc lactis, Lactococcus lactis, Lactococcus garvieae, Eubacterium ventriosum, and Bacteroides thetaiotaomicron, associated with the production of beneficial metabolites, increased significantly in the supplemented group. Acetic acid concentration also increased significantly. Notably, pathogenic bacteria, including Clostridium perfringens and Leuconostoc mesenteroides, were decreased in the supplemented group. The study indicates the potential of peanut supplementation to modulate the gut metabolome, enrich beneficial bacteria, and inhibit pathogens, suggesting a novel approach to mitigating child malnutrition and improving health status.
Subject(s)
Arachis , Bacteria , Dietary Supplements , Feces , Gastrointestinal Microbiome , Humans , Arachis/microbiology , Uganda , Child , Male , Female , Feces/microbiology , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/metabolism , RNA, Ribosomal, 16S/geneticsABSTRACT
As the world population rises, the demand for protein increases, leading to a widening gap in protein supply. There is an unprecedented interest in the development of alternative proteins, but their allergenicity has raised consumer concerns. This review aims to highlight and correlate the current research status of allergenicity studies on alternative proteins based on previously published studies. Current research keywords, hotspots and trends in alternative protein sensitization were analyzed using a mixed-method approach that combined bibliometric analysis and literature review. According to the bibliometric analysis, current research is primarily focused on food science, agriculture, and immunology. There are significant variations in the type and amount of allergens found in alternative proteins. A significant amount of research has been focused on studying plant-based proteins and the cross-reactivity of insect proteins. The allergenicity of alternative proteins has not been studied extensively or in depth. The allergenicity of other alternative proteins and the underlying mechanisms warrant further study. In addition, the lack of a standardized allergy assessment strategy calls for additional efforts by international organizations and collaborations among different countries. This review provides new research and regulatory perspectives for the safe utilization of alternative proteins in human food systems.
ABSTRACT
Aflatoxins B1 (AFB1) and antibiotic (AN) carry co-exposure risks, with the gut being a target organ for their combined effects. However, the current understanding of the impact of AN on gut and liver injury induced by AFB1 remains limited. In this study, we conducted a 9-week investigation into the implications of AN (ampicillin and penicillin) treatment on AFB1-induced intestinal and liver injury in C57BL/6J male mice fed a normal diet (ND) and a high-fat diet (HFD). The results showed that AN treatment significantly reduce the total number and diversity of intestinal species in both ND and HFD mice exposed to AFB1. Moreover, AN treatment alleviated AFB1-induced liver injury and lipid accumulation in mice on ND and HFD, while improving abnormal lipid metabolism in the liver and serum. However, AN treatment also promoted intestinal damage and reduced the levels of short-chain fatty acids in the gut. Correlation analysis demonstrated that, under the two dietary patterns, microorganisms across various genera were significantly positively or negatively correlated with alterations in liver, serum, and intestinal biochemical indexes. These genera include Akkermansia, Robinsoniella, Parabacteroides, Escherichia-Shigel, and Parabacteroides, Odoribacter. AN may alleviate long-term AFB1-induced liver injury through the regulation of intestinal microorganisms, with the effect being more pronounced in mice following an HFD pattern. These findings provide novel insights into the effects of AFB1 on the gutâliver axis under complex exposure conditions, as well as the relationship between gut microbial homeostasis and liver injury across different dietary patterns.
Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Gastrointestinal Microbiome , Mice , Male , Animals , Aflatoxin B1/toxicity , Anti-Bacterial Agents/pharmacology , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Mice, Inbred C57BL , Liver/metabolism , Diet, High-Fat/adverse effectsABSTRACT
Fumonisin B1 (FB1) is a representative form of fumonisin and is widely present in food and feed. Hydrolyzed fumonisin B1 (HFB1) emerges as a breakdown product of FB1, which is accompanied by FB1 alterations. While previous studies have primarily focused on the liver or kidney toxicity of FB1, with limited studies existing on its neurotoxicity and even fewer on the toxicity of HFB1, this study focuses on the neurotoxicity of FB1 and HFB1 exposure in mice investigated by the open field test, Morris water maze test, histopathological analysis, and nontargeted metabolomics. Further, the levels of oxidative stress-related indices, neurotransmitters, and sphingolipids in the brain were measured to analyze their correlation with behavioral outcomes. The results showed that both FB1 (5 mg/kg) and HFB1 (2.8 mg/kg) reduced autonomous exploratory behavior in mice, impaired spatial learning and memory, and caused mild abnormalities in the brain structure. Quantitative analysis further indicated that exposure to FB1 and HFB1 disrupted neurotransmitter homeostasis, exacerbated oxidative stress, and significantly increased the sphinganine/sphingosine (Sa/So) ratio. Moreover, HFB1 exhibited neurotoxic effects similar to those of FB1, emphasizing the need to pay attention to the neurotoxicity effect of HFB1. These findings underscore the importance of understanding the risks and potential neurological damage associated with FB1 and HFB1 exposure, highlighting the necessity for further research in this crucial field.
Subject(s)
Fumonisins , Mice , Animals , Fumonisins/analysis , Spatial Memory , Sphingolipids , Liver/metabolismABSTRACT
Per- and Polyfluoroalkyl Substances (PFAS) are a diverse class of industrial chemicals that have been used for decades in industrial and commercial applications. Due to their widespread usages, persistence in the environment, and bioaccumulation in animals and humans, great public health concerns have been raised on adverse health risks of PFAS. In this study, ten PFAS were selected according to their occurrence in different water bodies. The wild-type worms were exposed to individual PFAS at 0, 0.1, 1,10, 100, and 200 µM, and the toxic effects of PFAS on growth, development, fecundity, and behavior at different life stages were investigated using a high-throughput screening (HTS) platform. Our results showed that perfluorooctanesulfonic acid (PFOS), 1H,1H, 2H, 2H-perfluorooctanesulfonamidoacetic acid (NEtFOSAA), perfluorobutanesulfonic (PFBS), and perfluorohexanesulfonic acid (PFHxS) exhibited significant inhibitive effects on the growth in the L4 larva and later stages of worms with concentrations ranging from 0.1 to 200 µmol/L. PFOS and PFBS significantly decreased the brood size of worms across all tested concentrations (p < 0.05), and the most potent PFAS is PFOS with BMC of 0.02013 µM (BMCL, 1.6e-06 µM). During adulthood, all PFAS induced a significant reduction in motility (p < 0.01), while only PFOS can significantly induce behavior alteration at the early larvae stage. Furthermore, the adverse effects occurred in larval stages were found to be the most susceptible to the PFAS exposure. These findings provide valuable insights into the potential adverse effects associated with PFAS exposure and show the importance of considering developmental stages in toxicity assessments.
Subject(s)
Alkanesulfonic Acids , Fluorocarbons , Humans , Animals , Adult , Caenorhabditis elegans , Alkanesulfonic Acids/toxicity , Fluorocarbons/toxicity , BioaccumulationABSTRACT
Aflatoxins are among the most important mycotoxins due to their widespread occurrence and adverse impacts on humans and animals. These toxins and/or their metabolites cannot be destroyed with cooking or boiling methods. Therefore, consumption of aflatoxin-contaminated food may lead to impaired growth, compromised immunity, stomach and liver cancer, and acute toxicity. These adverse effects along with food wastage might have detrimental consequences on a country's economy. Several studies from Pakistan reported a high prevalence of aflatoxins in food and feed commodities (Range; milk = 0.6-99.4%, cereals, and grains = 0.38-41%, animal feed = 31-100%). Notably, Pakistan reported very high figures of impaired child growth-stunted 40.2%, wasted 17.7% and underweight 28.9%-that could be associated with the higher aflatoxin prevalence in food items. Importantly, high aflatoxins prevalence, i.e. 100%, 69% and 60.5%, in children has been reported in Pakistan. Food and feed are more prone to aflatoxin contamination due to Pakistan's hot and humid climate; however, limited awareness, inadequate policy framework, and weak implementation mechanisms are the major obstacles to effective control. This review will discuss aflatoxins prevalence, associated risk factors, adverse health effects, required regulatory regime, and effective control strategies adopting the One Health approach to ensure food safety and security.
ABSTRACT
Aflatoxin B1 (AFB1), the most potent mycotoxin and Group 1 human carcinogen, continues to pose a significant public health burden, particularly in developing countries. Increasing evidence has shown the gut microbiota as a key mediator of AFB1 toxicity through multiple interactive host-microbiota activities. In our previous study we observed that disturbances in bacterial pyruvate metabolism might have a significant impact on AFB1 in the host. To further investigate the impact of the pyruvate pathway on AFB1 toxicity in C. elegans, we engineered two bacterial strains (triple-overexpressed and triple-knockout strains with aceB, lpd, and pflB). Additionally, we employed two mutant worm strains (pyk-1 and pdha-1 mutants) known to affect pyruvate metabolism. Our results revealed that the co-metabolism of pyruvate by the host and bacterial strains synergistically influences AFB1 toxicity. Remarkable, we found that bacterial pyruvate metabolism, rather than that of the host, plays a pivotal role in modulating AFB1 toxicity in C. elegans. Our study sheds light on the role of gut microbiota involved in pyruvate metabolism in influencing AFB1 toxicity in C. elegans.
Subject(s)
Gastrointestinal Microbiome , Mycotoxins , Animals , Humans , Caenorhabditis elegans , Aflatoxin B1/toxicity , Bacteria/metabolismABSTRACT
Aflatoxins are a group of potent fungal metabolites produced by Aspergillus and commonly contaminate groundnuts and cereal grains. Aflatoxin B1 (AFB1), the most potent mycotoxin, has been classified as Group 1 human carcinogen because it can be metabolically activated by the cytochrome P450 (CYP450) in the liver to form AFB1-DNA adducts and induce gene mutations. Increasing evidence has shown the gut microbiota as a key mediator of AFB1 toxicity through multiple interactive host-microbiota activities. To identify specific bacterial activity that modulates AFB1 toxicity in Caenorhabditis (C.) elegans, we established a 3-way (microbe-worm-chemical) high-throughput screening system using C. elegans fed E. coli Keio collection on an integrated robotic platform, COPAS Biosort. We performed 2-step screenings using 3985 Keio mutants and identified 73 E. coli mutants that modulated C. elegans growth phenotype. Four genes (aceA, aceB, lpd, and pflB) involved in the pyruvate pathway were identified from the screening and confirmed to increase the sensitivity of all animals to AFB1. Taking together, our results indicated that disturbances in bacterial pyruvate metabolism might have a significant impact on AFB1 toxicity in the host.
Subject(s)
Aflatoxins , Microbiota , Animals , Humans , Aflatoxin B1/toxicity , Aflatoxin B1/metabolism , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Cytochrome P-450 Enzyme System/metabolism , Aflatoxins/toxicityABSTRACT
Here we report that macrophage AHR/TLR/STAT signaling axis is implicated in the colon colitis induced by non-canonical AHR ligand aflatoxin B1 (AFB1). In BALB/c mice gavaged with 5, 25 and 50 µg/kg body weight/day AFB1, we observed severe colitis featured by over-recruitment of myeloid lineage immune cells such as monocytes/macrophage in colon lamina propria. Stressed and damaged colon epithelial cells were observed in low-dose group, while twisted and shortened intestinal crypts being found in middle dose group. Severe tissue damage was induced in the high-dose group. Dose-dependent increases of ROS, NO, and decrease of mitochondrial ROS-suppressor STAT3 were observed in the exposure groups. Further investigation in AFB1-treated human macrophage model found: (1) functional adaptations such as elevation of TNF-alpha and IL-6 secretion, stimulation of phagocytosis, elevation of LTE4 level; (2) overall inflammatory status confirmed by RNA-sequence analysis, in line with up-regulation of immune functional proteins such as ICAM-1, IDO-1, NF-kB-p65, NLRP3, COX-2 and iNOS; (3) mRNA disruption of mitochondrial oxidative phosphorylation complex I units and STATs; (4) perturbation of AHR/TLR/STAT3 signaling axis, including elevated AHR, TLR2, TLR4, and decreased STAT3, p-STAT3 Ser727. Mechanism investigation revealed regulatory links of ligand-dependent AHR/TLR4/STAT3. AHR-TLR4 together regulate MyD88, and STAT3 may be directly regulated by MyD88 (TLR4 downstream molecule) upon AHR/TLR4 binding with ligands. Solely protein level changes of AHR/TLR4 cannot regulate STAT3. Our study suggests that macrophage AHR/TLR4/STAT3 is involved with the colitis induced by sub-acute exposure to AFB1. Future follow-up study will focus on the intervention of the colitis using AHR-anti-inflammatory ligands.
Subject(s)
Aflatoxin B1 , Colitis , Animals , Mice , Humans , Aflatoxin B1/toxicity , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Ligands , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Follow-Up Studies , Reactive Oxygen Species/metabolism , Colitis/chemically induced , Colitis/metabolism , NF-kappa B/genetics , Macrophages/metabolism , STAT3 Transcription Factor/metabolismABSTRACT
Human exposure to aflatoxins (AFs) and zearalenone (ZEA) has not been sufficiently investigated. Here, we analyzed the exposure level and health risks posed by AFs (B1, B2, G1, G2) and ZEA through cooking oil consumption in Shandong, China. The individual daily consumption of cooking oil was calculated through 2745 questionnaires during 2017-2019. The average contamination levels of mycotoxins were estimated by examining 60 cooking oil samples. For the peanut oil, AFs ranged from <0.2 to 274 µg/kg, with a positive rate of 66.6% (20/30). Average levels of 36.62 µg/kg AFB1 and 44.43 µg/kg total AFs were found. Over-the-limit level (20 µg/kg) of AFB1 was detected in 8/30 samples. Estimated daily intake (EDI) and margin of exposure (MOE) for age-stratified population groups showed that children are facing highest adverse health risk with AFB1 (MOE 5.88-6.39). The liver cancer incidences attributable to AFB1 exposure are non-negligible as 0.896, 0.825, and 0.767 cases per 100,000 for 6-14 age group, 15-17 age group, and adult labor-intensive workers. Over-the-limit level (60 µg/kg) ZEA contamination was detected in 25/30 corn oil samples with a 50th percentile value of 97.95 µg/kg. Our health risk assessment suggested significant health risks of enterohepatic (inflammation and cancer), reproductive, and endocrine systems posed by AFs and ZEA. However, the health risk of immunotoxicity is unclear because currently animal study data are not available for the immunotoxicity induced after long-term exposure. In general, the health risks posed by mycotoxins are non-negligible and long-term mycotoxin surveillance is necessary.
Subject(s)
Aflatoxins , Mycotoxins , Zearalenone , Animals , Adult , Child , Humans , Mycotoxins/analysis , Aflatoxins/analysis , Plant Oils/analysis , Vegetables , Food Contamination/analysisABSTRACT
Aflatoxins are potent carcinogenic and immunomodulatory mycotoxins, and exposure may lead to deleterious effects on human health. This study aimed to detect aflatoxin M1 (AFM1) as biomarker of exposure and determine associated risk factors in children attending a specialized-childcare hospital in Lahore. Urine samples collected from 238 children (1-11 years) during winter (January-mid-March 2020) and hot-humid summer (August-September 2020) were tested for AFM1 presence using ELISA. Data on potential risk factors were also collected. Of 238 samples, 156 (65.5%) were positive for urinary AFM1. Season was significantly associated (OR = 2.64; 95% CI = 1.49-4.79; p = 0.001) with AFM1 positivity; prevalence was higher in hot-humid months (74.6%) than winter (57.3%). The place of living was also significantly associated (OR = 2.21; 95% CI = 1.25-3.97; p = 0.007), and urinary AFM1 positivity was higher in urban children (71.1%) compared to rural (58.3%). Median value for creatinine-adjusted AFM1 was 1.9 ng/mg creatinine (Q1-Q3 = 0.82-6.0 ng/mg creatinine), while non-creatinine-adjusted AFM1 was 0.57 ng/mL (Q1-Q3 = 0.23-1.4 ng/mL). Significantly higher urinary AFM1 levels were detected in children; age ≤2 years (p = 0.037), who consumed more milk (p = 0.048), and who presented to the nutrition clinic (p = 0.003). These findings highlight the need for an effective control program to reduce the AFM1 burden in children.
Subject(s)
Aflatoxin M1 , Aflatoxins , Humans , Child, Preschool , Animals , Aflatoxin M1/analysis , Pakistan , Food Contamination/analysis , Milk/chemistry , Aflatoxins/analysisABSTRACT
Fumonisins comprise structurally related metabolites mainly produced by Fusarium verticillioides and Fusarium proliferatum. Contamination with fumonisins causes incalculable damage to the economy and poses a great risk to animal and human health. Fumonisins and their covert products are found in cereals and cereal products. Food processing significantly affects the degradation of toxins and the formation of covert toxins. However, studies on fumonisins and their covert mycotoxins remain inadequate. This review aims to summarize changes in fumonisins and the generation of covert fumonisins during processing. It also investigates the toxicity and determination methods of fumonisins and covert fumonisins, and elucidates the factors affecting fumonisins and their covert forms during processing. In addition to the metabolic production by plants and fungi, covert fumonisins are mainly produced by covalent or noncovalent binding, complexation, or physical entrapment of fumonisins with other substances. The toxicity of covert fumonisins is similar to that of free fumonisins and is a non-negligible hazard. Covert fumonisins are commonly found in food matrices, and methods to analyze them have yet to be improved. Food processing significantly affects the conversion of fumonisins to their covert toxins.