RESUMEN
Rabbit bucks (bodyweight 5 kg) underwent dietary intoxication with fumonisin B series mycotoxins (FB1 + FB2 + FB3, 15 mg/kg diet) for 14 days to test the applicability of positron emission tomography-magnetic resonance (PET MR) hybrid imaging in characterizing experimentally induced mild hepatotoxicosis. 18F-fluorodeoxyglucose (18F-FDG) radiotracer-aided imaging was performed before and after FBs administration on identical animals, and at both time points, blood was sampled for haematology and clinical chemistry. Kinetic PET image analysis revealed time-activity curves with uptake maxima below 1 min in the liver, renal cortex, portal vein, lung and coarctatio aortae. In the frame of static PET image analysis, based on the standardized uptake value (SUV), the so-called metabolic liver volume (MLV, liver volume defined by over 0.9 × average liver SUV) and the total liver glycolysis (TLG, MLV multiplied by the SUVmean) were calculated. Mycotoxicosis increased total liver glycolysis (p < 0.04) after 14 days and liver tissue TLG inhomogeneity was minimal. Pearson correlation between TLG and alkaline phosphatase (ALP) was positive (0.515), while negative with LDH and AST (- 0.721 and - 0.491, respectively). Results indicate a slight hepatic mycotoxin effect and significantly increased glucose uptake intensity, which has been sensitively detected with molecular imaging (18F-FDG PET MRI) in the rabbit model.
Asunto(s)
Fluorodesoxiglucosa F18 , Fumonisinas , Hígado , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Animales , Conejos , Fumonisinas/toxicidad , Hígado/metabolismo , Hígado/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones/métodos , Glucosa/metabolismo , MasculinoRESUMEN
Fumonisin B1, T-2 toxin, and deoxynivalenol are frequently detected in feed materials. The mycotoxins induce free radical formation and, thereby, lipid peroxidation. The effects of mycotoxin exposure at the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON = 3AcDON/15-AScDON: 5 mg/kg; fumonisin B1: 20 mg/kg) and double dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg, and FB1: 40 mg/kg feed) were investigated during short-term (3 days) per os exposure in the liver of laying hens. On day 1 higher while on day 3 lower MDA concentrations were found in the low-dose group compared to the control. Fatty acid composition also changed: the proportion of monounsaturated fatty acids increased (p < 0.05) and the proportion of polyunsaturated fatty acids decreased by day 3. These alterations resulted in a decrease in the index of unsaturation and average fatty acid chain length. Histopathological alterations suggested that the incidence and severity of liver lesions were higher in the mycotoxin-treated laying hens, and the symptoms correlated with the fatty acid profile of total phospholipids. Overall, the findings revealed that mycotoxin exposure, even at the EU-recommended limits, induced lipid peroxidation in the liver, which led to changes in fatty acid composition, matched with tissue damage.
Asunto(s)
Pollos , Ácidos Grasos , Fusarium , Peroxidación de Lípido , Hígado , Micotoxinas , Animales , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Femenino , Micotoxinas/toxicidad , Alimentación Animal/análisis , Antioxidantes/metabolismoRESUMEN
In the context of nephrotoxic risks associated with environmental contaminants, this study focused on the impact of mycotoxin exposure on the renal health of laying hens, with particular attention to oxidative stress pathways. Sixty laying hens were assigned to three groups-a control group (CON), a low-dose mycotoxin group (LOW), and a high-dose mycotoxin group (HIGH)-and monitored for 72 h. Mycotoxin contamination involved T-2/HT-2 toxin, DON/3-AcDON/15-AcDON, and FB1 at their EU-recommended levels (low mix) and at double doses (high mix). Clinical assessments revealed no signs of toxicity or notable weight changes. Analysis of the glutathione redox system parameters demonstrated that the reduced glutathione content was lower than that in the controls at 48 h and higher at 72 h. Glutathione peroxidase activity increased in response to mycotoxin exposure. In addition, the gene expression patterns of key redox-sensitive pathways, including Keap1-Nrf2-ARE and the AhR pathway, were examined. Notably, gene expression profiles revealed dynamic responses to mycotoxin exposure over time, underscoring the intricate interplay of redox-related mechanisms in the kidney. This study sheds light on the early effects of mycotoxin mixtures on laying hens' kidneys and their potential for oxidative stress.
Asunto(s)
Fumonisinas , Micotoxinas , Toxina T-2 , Tricotecenos , Animales , Femenino , Proteína 1 Asociada A ECH Tipo Kelch , Pollos , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Riñón , GlutatiónRESUMEN
Zearalenone (ZEN) is a mycoestrogen produced by Fusarium fungi. ZEN is a frequent contaminant in cereal-based products, representing significant health threat. The major reduced metabolites of ZEN are α-zearalenol (α-ZEL) and ß-zearalenol (ß-ZEL). Since the toxicokinetic interactions of ZEN/ZELs with cytochrome P450 enzymes (CYPs) and organic anion transporting polypeptides (OATPs) have been barely characterized, we examined these interactions applying in vitro models. ZEN and ZELs were relatively strong inhibitors of CYP3A4 and moderate inhibitors of CYP1A2 and CYP2C9. Both CYP1A2 and CYP3A4 decreased ZEN and ß-ZEL concentrations in depletion assays, while only CYP1A2 reduced α-ZEL levels. OATPs tested were strongly or moderately inhibited by ZEN and ZELs; however, these mycotoxins did not show higher cytotoxicity in OATP-overexpressing cells. Our results help the deeper understanding of the toxicokinetic/pharmacokinetic interactions of ZEN, α-ZEL, and ß-ZEL.
Asunto(s)
Micotoxinas , Transportadores de Anión Orgánico , Zearalenona , Zeranol/análogos & derivados , Zearalenona/toxicidad , Citocromo P-450 CYP1A2 , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450 , PéptidosRESUMEN
This study investigates gene expression changes in laying hens exposed to trichothecene mycotoxins, known to induce oxidative stress and affect xenobiotic transformation and antioxidants. A 3-day feeding trial tested low and high doses of T-2/HT-2 toxin, DON/3-AcDON/15-AcDON, and FB1 in hen feed. Results showed increased expression of AHR, AHRR, HSP90, and CYP1A2 genes on days 2 and 3, suggesting a response to mycotoxin exposure. High doses down-regulated CYP1A2, AHR, and AHRR on day 1. KEAP1 expression decreased on day 1 but increased dose-dependently on days 2 and 3. NRF2 was up-regulated by low and down-regulated by high doses on day 1, then increased on days 2 and 3. Antioxidant-related genes (GPX3, GPX4, GSS, GSR) showed dose-dependent responses. Low doses up-regulated GPX3 and GPX4 throughout, while high doses up-regulated GPX3 on days 2 and 3 and GPX4 on day 3. GSS was up-regulated on day 3. Results indicate that toxic metabolites formed by phase I biotransformation rapidly induce ROS formation at low doses through the AHR/Hsp90/CYP1A2 pathway at the gene expression level, but at high levels, ROS-induced oxidative stress manifests later. Study showed simultaneous activation of redox-sensitive pathways: aryl hydrocarbon receptor (Ahr) and nuclear factor erythroid-derived 2-like 2 (Nrf2) by multi-mycotoxin exposure.
Asunto(s)
Fusarium , Micotoxinas , Toxina T-2 , Femenino , Animales , Micotoxinas/toxicidad , Fusarium/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Pollos , Citocromo P-450 CYP1A2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Antioxidantes/metabolismo , Hígado/metabolismo , Toxina T-2/toxicidad , Toxina T-2/metabolismoRESUMEN
Beauvericin (BEA), cyclopiazonic acid (CPA), and sterigmatocystin (STC) are emerging mycotoxins. They appear as contaminants in food and animal feed, leading to economic losses and health risks. Human serum albumin (HSA) forms stable complexes with certain mycotoxins, including ochratoxins, alternariol, citrinin, and zearalenone. HSA binding can influence the toxicokinetics of xenobiotics, and albumin can also be considered and applied as a relatively cheap affinity protein. Therefore, we examined the potential interactions of BEA, CPA, and STC with HSA employing fluorescence spectroscopy, ultracentrifugation, ultrafiltration, and molecular modeling. Spectroscopic and ultracentrifugation studies demonstrated the formation of low-affinity BEA-HSA (Ka ≈ 103 L/mol) and moderately strong CPA-HSA and STC-HSA complexes (Ka ≈ 104 L/mol). In ultrafiltration experiments, CPA slightly displaced each site marker (warfarin, naproxen, and camptothecin) tested, while BEA and STC did not affect significantly the albumin binding of these drugs. Modeling studies suggest that CPA occupies Sudlow's site I, while STC binds to the Heme site (FA1) on HSA. Considering the interactions of CPA with the site markers, the CPA-HSA interaction may have toxicological importance.