Toxins最新文献

Zearalenone (ZEA) is a mycotoxin commonly found in moldy cereals and has a range of toxic effects that have seriously affected animal husbandry. Rutin, a natural flavonoid with antioxidant activities, has been studied for its potential involvement in mitigating ZEA-induced apoptosis in porcine endometrial stromal cells (ESCs) and its potential molecular mechanism, particularly concerning the expression of Nrf2. This study investigates the molecular pathways by which rutin alleviates ZEA-induced ESC apoptosis, focusing on the role of Nrf2. Experimental data reveal that ZEA suppresses Nrf2 nuclear translocation and reduces mitochondrial membrane potential (MMP), leading to oxidative stress, endoplasmic reticulum stress (ERS), and mitochondrial pathway-driven apoptosis. Notably, rutin mitigates ZEA-induced apoptosis through Nrf2 activation. These findings highlight Nrf2 as a critical factor in rutin's protective effects against ZEA-induced apoptosis, offering valuable insights for the clinical prevention and treatment of ZEA toxicity.

Despite the popular belief in the anti-tumor properties of Vespa bicolor venom (VBV), there is limited scientific evidence to support this claim. This study is the first to examine the anti-tumor effects of VBV on liver cancer, both alone and in combination with cisplatin (DDP), through in vitro and in vivo experiments. In vitro experiments evaluated VBV and its combination with DDP on HepG2 cell proliferation, invasion, migration, and apoptosis. Animal studies examined the tumor-suppressive effects, safety (hepatotoxicity and nephrotoxicity), and immune impact of these treatments in tumor-bearing mice. VBV monotherapy significantly inhibited the growth of HepG2 cells by suppressing their proliferation and invasion and induced apoptosis in vitro. Notably, low VBV concentrations significantly promoted the proliferation of normal liver cells (L-02), suggesting a hepatoprotective effect. In vivo, VBV monotherapy enhanced immune function and exhibited tumor suppression comparable to DDP monotherapy but did not induce significant liver or kidney damage. In addition, VBV combined with DDP synergistically enhanced the anti-tumor effects of DDP, compensating for its limited apoptosis-inducing activity and insufficient enhancement of immune function. Initial studies have shown the strong potential of VBV as an anti-liver-tumor drug, highlighting its unique clinical value.

Identifying biomarkers of mycotoxin effects in chickens will provide an opportunity for early intervention to reduce the impact of mycotoxicosis. This study aimed to identify whether serum enzyme concentrations, gut integrity, and liver miRNAs can be potential biomarkers for fumonisin B1 (FB1), deoxynivalenol (DON), and zearalenone (ZEA) toxicity in broiler birds as early as 14 days after exposure. A total of 720 male broiler chicks were distributed to six treatment groups: T1: control group (basal diet), T2 (2 FB1 + 2.5 DON + 0.9 ZEA), T3 (5 FB1 + 0.4 DON + 0.1 ZEA), T4 (9 FB1 + 3.5 DON + 0.7 ZEA), T5 (17 FB1 + 1.0 DON + 0.2 ZEA), and T6 (21 FB1 + 3.0 DON + 1.0 ZEA), all in mg/kg diet. On d14, there were no significant differences in the body weight gain (BWG) of mycotoxin treatment groups when compared to the control (p > 0.05), whereas on d21, T6 birds showed significantly reduced BWG compared to the control (p < 0.05). On d14, birds in T6 showed significant upregulation of liver miRNAs, gga-let-7a-5p (14.17-fold), gga-miR-9-5p (7.05-fold), gga-miR-217-5p (16.87-fold), gga-miR-133a-3p (7.41-fold), and gga-miR-215-5p (6.93-fold) (p < 0.05) and elevated serum fluorescein isothiocyanate-dextran (FITC-d) concentrations, aspartate aminotransferase (AST), and creatine kinase (CK) levels compared to the control (p < 0.05). On d21, T2 to T6 birds exhibited reduced serum phosphorus, glucose, and potassium, while total protein, FITC-d, AST, and CK levels increased compared to control (p < 0.05). These findings suggest that serum FITC-d, AST, CK, and liver miRNAs could serve as biomarkers for detecting mycotoxin exposure in broiler chickens.

Echis ocellatus envenomings are a public health problem in West Africa, leading to bleeding and hypocoagulability. The aim of this study was to assess the hemostasis disorders associated with E. ocellatus envenoming. Envenomed patients with an abnormal whole blood clotting test (WBCT) were prospectively included at Tanguiéta, Benin. A WBCT with a sequential reading (i.e., at 20, 30, and 60 min), viscoelastic analysis (VA) using the Quantra analyzer, and blood count were performed on admission. VA and the WBCT were also assessed at 4, 8, 12, 24, 48, and 72 h after antivenom administration. Nineteen patients were included. On admission, the main results were an absence of a clot on VA and a slight decrease in platelets. Clot time gradually decreased over time while clot stiffness, fibrinogen, and platelet contributions to stiffness increased. Sequential reading improved the sensitivity of the WBCT. At H48, all patients with recurrence bleeding after antivenom administration had an abnormal WBCT while patients with a normal WBCT never had bleeding during their follow-up. VA allows the identification of various hemostasis disorders. Hypofibrinogenemia was the main disorder that persisted for several days after treatment. A WBCT with a sequential reading is an effective alternative for monitoring hypocoagulability in the absence of a laboratory.

Aspergillus carbonarius is considered one of the main fungi responsible for black and sour rot in grapes, as well as the production of the carcinogenic mycotoxin ochratoxin A. The global regulatory methyltransferase protein LaeA controls the production of various secondary metabolites in Aspergillus species, as well as influences sexual and asexual reproduction and morphology. The goal of this study was to investigate the role of the regulatory gene AclaeA in physiology, virulence, and ochratoxin A (OTA) production by deleting this gene from the genome of a wild-type A. carbonarius strain. The evaluation data on the morphological characteristics, virulence experiments in three different grape varieties, and OTA analysis of ΔAclaeA mutants showed that the growth and the OTA production by ΔAclaeA strains were significantly reduced. The mutant strains were also less virulent, producing 40-50% less conidia in three different cultivars of grape berries. Additionally, the gene AclaeA was considerably repressed after the application of three commercial biopesticides (Trianum-P^®, Vacciplant^®, and Serenade^® Max) and the essential oils (EOs) cinnamon, geranium, and thyme, which were also shown to inhibit OTA biosynthesis in A. carbonarius. The study of the regulatory gene AclaeA can contribute to a broader understanding of the role of secondary metabolites during A. carbonarius-grape interactions, as well as the discovery of the mode of action of biological plant protection products and EOs against this mycotoxigenic fungus.

Zearalenone (ZEN) has been detected in both pet food ingredients and final products, causing acute toxicity and chronic health problems in pets. Therefore, the early detection of mycotoxin contamination in pet food is crucial for ensuring the safety and well-being of animals. This study aims to develop a rapid and cost-effective method using an electronic nose (E-nose) and machine learning algorithms to predict whether ZEN levels in pet food exceed the regulatory limits (250 µg/kg), as set by Chinese pet food legislation. A total of 142 pet food samples from various brands, collected between 2021 and 2023, were analyzed for ZEN contamination via liquid chromatography-tandem mass spectrometry. Additionally, the "AIR PEN 3" E-nose, equipped with 10 metal oxide sensors, was employed to identify volatile compounds in the pet food samples, categorized into 10 different groups. Machine learning algorithms, including liner regression, k-nearest neighbors, support vector machines, random forests, XGBoost, and multi-layer perceptron (MLP), were used to classify the samples based on their volatile profiles. The MLP algorithm showed the highest discrimination accuracy at 86.6% in differentiating between pet food samples above and below the ZEN threshold. Other algorithms showed moderate accuracy, ranging from 77.1% to 84.8%. The ensemble model, which combined the predictions from all classifiers, further improved the classification performance, achieving the highest accuracy at 90.1%. These results suggest that the combination of E-nose technology and machine learning provides a rapid, cost-effective approach for screening ZEN contamination in pet food at the market entry stage.

Objective: In some regions of the globe, accidental food confusion regarding plants can cause severe poisoning events and deaths. The aim of this study was to report on those confusions from the Marseille Poison Control Centre's (PCC) experience from 2002 to 2023.

Results: Over 22 years, 2197 food confusion events were managed with 321 different species. The most frequently involved plant was Nerium oleander (289 cases, 13.1%), then Cucurbitaceae genus (3.3%), Colchicum autumnale (3.3%), Prunus amygdalus (3%), Mahinot esculenta (3%), Cytisus laburnum (2.6%), Aesculus hippocastanum (2.5%) and Narcissus Jonquilla (2%). Many botanical confusion events were also reported (n = 1386, 63%), but with fewer than five identical species. Only one death was reported for this review, in an event involving Aconitum napellus. Two antidotes were used for all the series: Datura genus and Prunus dulcis.

Discussion: The most implicated plant was Nerium oleander. This is explained by its distribution. This rate is very low compared to that of suicide attempts with this plant. Many cases were symptomatic (53.6%), but very few of them described severe symptoms (only 0.5% severe poisonings). Few patients needed to be admitted to intensive care (0.4%), and even fewer needed an antidote (two cases). Only one death occurred, involving Aconitum napellus. Food confusions were more common than suicide attempts with plants, but seem to be less severe. However, death and serious complications can occur, so it is important to identify and manage the plants concerned.

Material and methods: For each food confusion event managed between 2002 and 2023 at the Southeastern France PCC based in Marseille, we performed a retrospective review. This PCC is responsible for the Provence-Alpes-Côte d'Azur Region, Corsica Island and Indian Ocean French overseas territories. For each case, severity was calculated with the Poison Severity Score (PSS).

King cobra (Ophiophagus hannah) venom comprises a diverse array of proteins and peptides. However, the roles and properties of these individual components are still not fully understood. Among these, Cysteine-rich secretory proteins (CRiSPs) are recognized but not fully characterized. This study investigates the biological effects of Opharin, the CRiSP from king cobra venom (KCV). The effects of Opharin on cytokine production, specifically on IL-1β, IL-6, IL-8, TNF-α, and IL-10 release, were evaluated over 24 h in monocyte-derived macrophage (MDM) cells. Notably, the levels of these inflammatory cytokines were significantly increased over 24 h, with values higher than those observed in cells treated with crude KCV at most time points. Additionally, the in vivo Miles assay in mice revealed that Opharin increased vascular permeability by 26% compared to the negative control group. These findings highlight the Opharin's role in severe inflammatory and vascular responses observed in king cobra envenomation. Still, further research is essential to elucidate the pharmacological and toxicological effects of venom components, ultimately enhancing the clinical management of envenomation.

Cyanobacteria, also known as blue-green algae, are a diverse phylum of photosynthetic, Gram-negative bacteria and one of the largest microbial taxa. These organisms produce cyanotoxins, which are secondary metabolites that can have significant impacts on both human health and the environment. While toxins like Microcystins and Cylindrospermopsins are well-documented and have been extensively studied, other cyanotoxins, including those produced by Lyngbya and Nostoc, remain underexplored. These lesser-known toxins can cause various health issues in humans, including neurotoxicity, hepatotoxicity, and dermatotoxicity, each through distinct mechanisms. Moreover, recent studies have shown that cyanobacteria can be aerosolized and transmitted through the air over long distances, providing an additional route for human exposure to their harmful effects. However, it remains an area that requires much more investigation to accurately assess the health risks and develop appropriate public health guidelines. In addition to direct exposure to toxins, cyanobacteria can lead to harmful algal blooms, which pose further risks to human and wildlife health, and are a global concern. There is limited knowledge about these lesser-known cyanotoxins, highlighting the need for further research to understand their clinical manifestations and improve society's preparedness for the associated health risks. This work aims to review the existing literature on these underexplored cyanotoxins, which are associated with human intoxication, elucidate their clinical relevance, address significant challenges in cyanobacterial research, and provide guidance on mitigating their adverse effects.

Cheese is vulnerable to contamination with mycotoxins, particularly ochratoxin A (OTA) and aflatoxin M1 (AFM1). This study aims to develop and validate an analytical method for the detection and quantification of OTA and AFM1 in cheese and to assess their prevalence and associated risks. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was validated for detecting these mycotoxins in 41 cheese samples, including firm-ripened, spreadable, and plant-based alternatives. The results showed that OTA was detected exclusively in grated Parmigiano Reggiano cheese, while AFM1 was found in both Parmigiano Reggiano and Pecorino cheeses. This study goes beyond analytical method development by providing a preliminary exposure assessment and risk characterization for OTA and AFM1 in cheese, bridging the gap between analytical chemistry and public health implications. This study identified potential health risks associated with OTA, particularly for children and adolescents categorized as high consumers of Parmigiano Reggiano cheese. The findings underscore the need for monitoring of OTA and AFM1 in cheese and further research to establish regulatory limits for these contaminants.