The Effect of Combined Exposure of Fusarium Mycotoxins on Lipid Peroxidation, Antioxidant Defense, Fatty Acid Profile, and Histopathology in Laying Hens' Liver.

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.

The Effects of T-2 Toxin, Deoxynivalenol, and Fumonisin B1 on Oxidative Stress-Related Genes in the Kidneys of Laying Hens.

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.

Curcumin mitigates ochratoxin A-induced oxidative stress and alters gene expression in broiler chicken liver and kidney.

The study aimed to evaluate the effect of curcumin (CURC) supplementation on broiler chickens exposed to ochratoxin A (OTA), by examining biochemical parameters and the expression of glutathione redox system genes and their regulation. OTA reduced glutathione content in the liver while increasing glutathione peroxidase activity. CURC showed no significant effects. Kidney parameters remained mostly unaffected. Gene expression analysis revealed OTA-induced upregulation of KEAP1, NRF2, AHR, GPx4 and GSR genes in the liver. CURC supplementation led to the upregulation of GPx4 and AHR genes with OTA+CURC treatment, resulting in the downregulation of GPx4, KEAP1, NRF2 and AHR genes compared to OTA treatment alone. In the kidney, GPx4 was downregulated, and NRF2 and AHR were upregulated as an effect of OTA, while CURC upregulated the NRF2 gene only. OTA+CURC treatment led to the downregulation of GPx4, GSS and AHR genes compared to the control and downregulation of NRF2 and AHR genes compared to OTA. The results suggested that CURC is partly effective against OTA-induced oxidative stress and that the effect of OTA and CURC on the antioxidant response is regulated through the KEAP1-NRF2-ARE and AHR pathways.

Multi-Fusarium mycotoxin exposure activates Nrf2 and Ahr pathway in the liver of laying hens.

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.

The Co-Occurrence of T-2 Toxin, Deoxynivalenol, and Fumonisin B1 Activated the Glutathione Redox System in the EU-Limiting Doses in Laying Hens.

Different mycotoxins in feed lead to combined exposure, increasing adverse effects on animal health. Trichothecene mycotoxins have been associated with inducing oxidative stress, which is neutralized by the glutathione system within the antioxidant defense, depending on the dose and duration of exposure. T-2 toxin, deoxynivalenol (DON), and fumonisin B1 (FB1) are commonly found in feed commodities simultaneously. In the present study, the intracellular biochemical and gene expression changes were investigated in the case of multi-mycotoxin exposure, focusing on certain elements of the glutathione redox system. In a short-term feeding trial, an in vivo study was performed with low (EU-proposed) doses: T-2/HT-2 toxin: 0.25 mg; DON/2-AcDON/15-AcDON.: 5 mg; FB1: 20 mg/kg feed, and high doses (twice the low dose) in laying hens. The multi-mycotoxin exposure affected the glutathione system; GSH concentration and GPx activity was higher in the liver in the low-dose group on day 1 compared to the control. Furthermore, the gene expression of antioxidant enzymes increased significantly on day 1 in both exposure levels compared to the control. The results suggest that when EU-limiting doses are applied, individual mycotoxins may have a synergistic effect in the induction of oxidative stress.

New perspectives in application of kidney biomarkers in mycotoxin induced nephrotoxicity, with a particular focus on domestic pigs.

The gradual spread of Aspergilli worldwide is adding to the global shortage of food and is affecting its safe consumption. Aspergillus-derived mycotoxins, including aflatoxins and ochratoxin A, and fumonisins (members of the fusariotoxin group) can cause pathological damage to vital organs, including the kidney or liver. Although the kidney functions as the major excretory system in mammals, monitoring and screening for mycotoxin induced nephrotoxicity is only now a developmental area in the field of livestock feed toxicology. Currently the assessment of individual exposure to mycotoxins in man and animals is usually based on the analysis of toxin and/or metabolite contamination in the blood or urine. However, this requires selective and sensitive analytical methods (e.g., HPLC-MS/MS), which are time consuming and expensive. The toxicokinetic of mycotoxin metabolites is becoming better understood. Several kidney biomarkers are used successfully in drug development, however cost-efficient, and reliable kidney biomarkers are urgently needed for monitoring farm animals for early signs of kidney disease. ß2-microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) are the dominant biomarkers employed routinely in environmental toxicology research, while kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are also emerging as effective markers to identify mycotoxin induced nephropathy. Pigs are exposed to mycotoxins due to their cereal-based diet and are particularly susceptible to Aspergillus mycotoxins. In addition to commonly used diagnostic markers for nephrotoxicity including plasma creatinine, NAG, KIM-1 and NGAL can be used in pigs. In this review, the currently available techniques are summarized, which are used for screening mycotoxin induced nephrotoxicity in farm animals. Possible approaches are considered, which could be used to detect mycotoxin induced nephropathy.

Effect of omega-3 polyunsaturated fatty acid supplementation on oxidative stress parameters and sex hormone levels of modern genotype sows.

BACKGROUND: Sows are exposed to severe stress and hormonal challenges during their whole productive life. As polyunsaturated fatty acids play an important role in immune and reproductive functions, with a better understanding of their role in breeding sows' nutrition, improved performance and more sustainable pig production can be achieved. OBJECTIVES: In this study, we investigated the effects of omega-6 and omega-3 fatty acid supplementation on the antioxidant status and hormone levels of sows. METHODS: A total of 48 Danish Large white × Danish Landrace sows were supplemented either with sunflower oil (SO) as a control group or with fish oil (FO) as experimental group at the same dose of 10 g/kg feed. Blood samples were collected on day 14 of lactation, 5 days after weaning (insemination), and 30 days after insemination. To estimate antioxidant and reproductive effects, the amounts of reduced glutathione (GSH), thiobarbituric acid reactive substance, the activity of glutathione peroxidase (GPx), serum 17ß oestradiol (E2), progesterone (P4), and 6-keto prostaglandin F1α (6-keto PGF1α) levels were investigated. RESULTS: FO-based supplementation increased GPx activity on day 14 of lactation. Five days after weaning, the concentration of GSH in FO-fed sows was significantly higher than that in SO-fed sows. The E2 content of blood was significantly lower in the experimental group than in the control group for two of the three examined periods (day 14 of lactation and 30 days after insemination), whereas P4 levels were significantly higher in the experimental group 5 days after weaning. We found that 6-keto PGF1α levels were systematically lower in the experimental group throughout the trial. CONCLUSIONS: This study provides evidence of the major impact of omega-6 and -3 fatty acids on the tested hormone levels, which serve as precursors for the production of E2 and P4 but have an opposite effect on PGF2α production.

Fumonisin B Series Mycotoxins' Dose Dependent Effects on the Porcine Hepatic and Pulmonary Phospholipidome.

Male weaned piglets n = 6/group were fed Fumonisin B1+2+3 (FBs) mycotoxins at 0, 15, or 30 mg/kg diet for 3 weeks to assess the fatty acid (FA) composition of membrane lipid classes, lipid peroxidation, and histomorphological changes in the liver and lung. Growth performance and lipid peroxidation were unaltered, but histomorphological lesion scores increased in the liver. Linear dose-response was detected in liver phosphatidylcholines for C16:1n7, C18:1n9, and total monounsaturation and in lungs for C22:6n3, total n-3 and n-3:n-6, in pulmonary phosphatidylserines C20:0 and C24:0. Alterations associated with the highest FBs dose were detected in sphingomyelins (liver: total saturation ↓, total monounsaturation ↑), phosphatidylcholines (liver: total n-6 ↓, n-6:n-3 ↑; in lungs: total monounsaturation ↑, total polyunsaturation ↑), phosphatidylethanolamines (liver: total n-3 ↓; in lungs: total monounsaturation ↑ and n-6:n-3 ↑), phosphatidylserines (liver: n-6:n-3 ↑; in lungs: total saturation ↓, total polyunsatuartion ↑, and total n-6 and its ratio to n-3 ↑), and phosphatidylinositol (n-6:n-3 ↑; lungs: C22:1n9 ↑, C22:6n3 ↓, total saturation ↓, total monounsaturaion ↑). In conclusion, FBs exposures neither impaired growth nor induced substantial lipid peroxidation, but hepatotoxicity was proven with histopathological alterations at the applied exposure period and doses. FA results imply an enzymatic disturbance in FA metabolism, agreeing with earlier findings in rats.

Analysis and Comparison of Rapid Methods for the Determination of Ochratoxin a Levels in Organs and Body Fluids Obtained from Exposed Mice.

Mycotoxins are bioaccumulative contaminants impacting animals and humans. The simultaneous detection of frequent active exposures and accumulated mycotoxin level (s) in exposed organisms would be the most ideal to enable appropriate actions. However, few methods are available for the purpose, and there is a demand for dedicated, sensitive, reliable, and practical assays. To demonstrate the issue, mice were exposed to a relevant agent Ochratoxin A (OTA), and accumulated OTA was measured by fine-tuned commercial assays. Quantitative high-performance liquid chromatography with fluorescence detection, enzyme-linked immunosorbent assay, and flow cytometry assays have been developed/modified using reagents available as commercial products when appropriate. Assays were performed on excised samples, and results were compared. Accumulated OTA could be detected and quantified; positive correlations (between applied doses of exposure and accumulated OTA levels and the results from assays) were found. Dedicated assays could be developed, which provided comparable results. The presence and accumulation of OTA following even a short exposure could be quantitatively detected. The assays performed similarly, but HPLC had the greatest sensitivity. Blood contained higher levels of OTA than liver and kidney. We demonstrate that specific but flexible and practical assays should be used for specific/local purposes, to measure the exposure itself and accumulation in blood or organs.

Effects of Fusarium Mycotoxin Exposure on Lipid Peroxidation and Glutathione Redox System in the Liver of Laying Hens.

It has been proven by several studies that Fusarium mycotoxins induce oxidative stress in animals, consequently inducing lipid peroxidation, which the glutathione system can neutralize. A short-term (3-day) in vivo feeding trial was performed with laying hens using a double dose of the EU recommendation for mycotoxin contamination (T-2 toxin 0.5 mg/kg feed; deoxynivalenol (DON) 10 mg/kg feed; fumonisin B1 (FB1) 40 mg/kg feed). Some lipid peroxidation and glutathione redox system parameters and gene expression levels were measured in the liver. The results show that FB1 significantly decreased the reduced glutathione (GSH) content and the activity of glutathione peroxidase (GPx) compared to the control and the two other mycotoxin-treated groups on day 3. Lipid peroxidation was affected by all three mycotoxins. Significantly lower values were observed in the case of conjugated dienes for all of the three mycotoxins and malondialdehyde concentration as an effect of DON on day 3. T-2 toxin and DON upregulated the expression of the GPX4 gene. The results show that Fusarium mycotoxins had different effects at the end of the trial. The FB1 exposure caused a decrease in the glutathione redox markers, while DON decreased the formation of malondialdehyde. The results suggest that the Fusarium mycotoxins investigated individually differently activated the antioxidant defense and caused low-level oxidative stress at the dose applied.

Changes of DNA Damage Effect of T-2 or Deoxynivalenol Toxins during Three Weeks Exposure in Common Carp (Cyprinus carpio L.) Revealed by LORD-Q PCR.

The present study aimed to adapt a Long-run Real-time DNA Damage Quantification (LORD-Q) qPCR-based method for the analysis of the mitochondrial genome of Common carp (Cyprinus carpio L.) and detect the DNA damaging effect of T-2 (4.11 mg kg-1) and deoxynivalenol (5.96 mg kg-1) mycotoxins in a 3-week feeding period. One-year-old Common carp were treated in groups (control, T-2 and DON). The mycotoxins were sprayed over the complete pelleted feed, and samples were taken weekly. Following the adaptation of LORD-Q PCR method for the Common carp species, the number of lesions were calculated to determine the amount of DNA damage. In the first and second weeks, the T-2 and the DON treated groups differed significantly from each other; however these differences disappeared in the third week. There was a significant difference in the DNA lesion values between weeks 1 and 3 in the deoxynivalenol-contaminated groups. While in the T-2 treated groups, the DNA lesion values were significantly reduced on weeks 2 and 3 compared to week 1. The results suggested that the trichothecene mycotoxins have a relevant DNA damaging effect.

The Effects of Mixed Fusarium Mycotoxins at EU-Permitted Feed Levels on Weaned Piglets' Tissue Lipids.

At exactly the individual permitted EU-tolerance dietary limits, fumonisins (FB: 5 mg/kg diet) and mixed fusariotoxins (DZ: 0.9 mg deoxynivalenol + 0.1 mg zearalenone/kg diet, and FDZ: 5 mg fumonisins + 0.9 mg deoxynivalenol + 0.1 mg zearalenone/kg diet) were administered to piglets (n = 6/group) for three weeks. Bodyweights of intoxicated piglets increased, while feed conversion ratios decreased. In FDZ, both the absolute and relative weight of the liver decreased. In the renal-cellular membrane, the most pronounced alterations were in FDZ treatment, followed by individual FB exposure. In both treatments, high proportions of C20:0 and C22:0 with low fatty acid (FA) unsaturation were found. In hepatocyte phospholipids, FDZ toxins exerted antagonistic interactions, and FB had the strongest increasing effect on FA monounsaturation. Among all investigated organs, the spleen lipids were the least responsive, in which FDZ expressed synergistic reactions on C20:0 (↑ FDZ vs. FB) and C22:0 (↓ FDZ vs. DZ). The antioxidant defense of the kidney was depleted (↓ glutathione concentration by FB-exposure). Blood plasma indicated renal injury (profound increase of urea and creatinine in FB vs. DZ and FDZ). FB strongly increased total-cholesterol and low density lipoprotein concentrations, whereas FDZ synergistically increased gamma-glutamyltransferase, alkaline-phosphatase, calcium and phosphorus levels. Summarized, individual and combined multiple fusariotoxins modified the membrane lipid profile and antioxidant defense of splanchnic organs, and serum biochemicals, without retarding growth in piglets.

Role of the glutathione redox system in the susceptibility of pheasants (Phasianus colchicus) to ochratoxin A.

The purpose of the present study was to investigate the effects of different dietary concentrations of ochratoxin A (OTA) on the growth, feed intake, mortality, blood plasma protein content and some parameters of lipid peroxidation and the glutathione redox system of pheasant chicks in a three-week long trial. A total of 320 seven-day-old female pheasants were randomly assigned to four treatment groups (n = 40 in each), fed with a diet artificially contaminated with OTA [control (<0.02 mg/kg), 0.88 mg/kg, 1.14 mg/kg and 1.51 mg/kg] for 21 days (up to 28 days of age). The pheasant chicks were sacrificed at early (12, 24 and 72 h) and late (7, 14 and 21 days) stages of mycotoxin exposure to check the effect of OTA. Minimal feed refusal was found in the medium- and high-dose toxin groups (-9.8 and -7.9%, respectively), and body weight gain was nearly the same in all groups. The glutathione redox system was activated mainly in the liver, confirmed by significantly increased reduced glutathione content and glutathione peroxidase activity during the late phase of mycotoxin exposure and at a high-dose treatment. The results suggest that pheasants have low susceptibility to OTA, and activation of the glutathione redox system has importance in this tolerance.

Susceptibility of Broiler Chickens to Deoxynivalenol Exposure via Artificial or Natural Dietary Contamination.

Multi-mycotoxin contamination of poultry diets is a recurrent problem, even if the mycotoxins levels are below EU recommendations. Deoxynivalenol (DON) is one of the main studied mycotoxins due to its risks to animal production and health. When evaluating the effects of DON, one must consider that under practical conditions diets will not be contaminated solely with this mycotoxin. In the present study, broiler chickens were fed diets with negligible mycotoxin levels or with naturally or artificially contaminated diets containing approximately 4000 µg/kg DON. Birds were sampled at D14 and D28. Naturally-contaminated diets caused the most harm to the birds, especially the young ones, which presented decreased jejunal villus height and increased lesions, down-regulation of a peptide transporter. At D28 broiler chickens seemed to have adapted to the dietary conditions, when no differences were observed in villus morphometry, together with up-regulation of a carbohydrate transporter. However, intestinal lesions remained present in these older birds.

A 65-Day Fumonisin B Exposure at High Dietary Levels Has Negligible Effects on the Testicular and Spermatological Parameters of Adult Rabbit Bucks.

A 65-day study was undertaken to test the effects of two doses (10 and 20 mg/kg) of dietary fumonisin Bs (FB) on the rabbit male reproduction system. Body and testicular weight was not affected by the intoxication, neither the fatty acid composition of the testicular total phospholipids; the testis histological analysis failed to reveal any toxic effect. The FBs increased the testicular concentration and activity of reduced glutathione and glutathione peroxidase and decreased initial phase lipid peroxidation (conjugated dienes and trienes) in a dose dependent manner. Sperm morphology and chromatin condensation were monitored on Feulgen-stained smears. No significant differences were observed between the treatment groups and between sampling time points. The live cell ratio in the sperm (as assessed with flow cytometry) was not different among groups at any of the five sampling timepoints and was also identical within groups. Similarly, the spermatozoa membrane lipid profile was also identical in all three groups after the total intoxication period. In summary, it was demonstrated that FBs in an unrealistic and unjustified high dose still do not exert any drastic harmful effect on the leporine, male reproduction system, meanwhile slightly augmenting testicular antioxidant response.

Modification of the effects of aflatoxin B1 on the glutathione system and its regulatory genes by zeolite.

The purpose of the present study was to use oxidative stress markers for investigating the effect of zeolite (315 mg/kg of complete feed) in the case of aflatoxin B1 contamination (92 µg/kg complete feed). In a 21-day feeding trial with broiler chickens, oxidative stress parameters such as conjugated dienes, conjugated trienes, malondialdehyde, reduced glutathione content and glutathione peroxidase activity were not changed significantly by supplementation with this mycotoxin absorbent. The relative gene expression of transcription factors KEAP1 and NRF2 was not modified by the absorbent either. Still, the expression of GSS, GSR and GPX4 genes increased significantly due to the aluminosilicate supplementation. The results suggest that zeolite reduced lipid peroxidation in the blood plasma but not in the red blood cell haemolysate or the kidney. The relative expression of the genes encoding the glutathione redox system also changed as a result of zeolite supplementation, but these changes were not found at the protein level.

A preliminary study on changes in heat shock protein 70 levels induced by Fusarium mycotoxins in rats: in vivo study.

The heat shock protein (Hsp70) level was assessed after 14 days of oral gavage-exposure to fumonisin B1 (FB1: 150 µg/animal/day), deoxynivalenol (DON: 30 µg/animal/day) and zearalenone (ZEN: 150 µg/animal/day), alone or in combinations (in additive manner: FD = FB1 + DON, FZ = FB1 + ZEN, DZ = DON + ZEN and FDZ = FB1 + DON + ZEN) in the liver, kidneys and lung of 24 adult male Wistar rats (n = 3/group). The liver was the most responsive tissue, as compared with kidney and lung. Except of DZ-treatment, mycotoxins elevated the Hsp70 levels in livers. The highest Hsp70-levels (≈ twofold) were in the DON, FD, FZ and FDZ treatments (additive effects). In the kidney, alterations (↑ ≈ twofold) were detected in ZEN, FD, FZ and DZ treatments. The least responsive organ was the lung (↑ only in FDZ, antagonistic effect). DON and ZEA exposures have altered the reduced glutathione concentration (↓) and glutathione peroxidase activity (↓) in the blood serum. The serum malondialdehyde level increased only after exposure to FD (synergistic effect), as compared with the DZ group (antagonistic effect). When the blood clinical chemistry was assessed, significant alterations were in alanine aminotransferase (80% increase in FDZ, antagonistic effect) and total protein (↓ ZEN). Results varied according to the organ, toxin type and interactions. Furthermore, oxidative stress was not the only key player behind the Hsp70 increase, in which another mechanism is suggested.

Individual and Combined Effects of Aflatoxin B1 and Sterigmatocystin on Lipid Peroxidation and Glutathione Redox System of Common Carp Liver.

The purpose of the study was to evaluate the short-term effects of aflatoxin B1 (AFB1 100 µg/kg feed) and sterigmatocystin (STC 1000 µg/kg feed) exposure individually and in combination (100 µg AFB1 + 1000 µg STC/kg feed) on the parameters of lipid peroxidation and glutathione redox system both in biochemical and gene expression levels in one-year-old common carp. Lipid peroxidation parameters were slightly affected, as significant differences were observed only in conjugated diene and triene concentrations. Reduced glutathione content decreased more markedly by STC than AFB1 or AFB1+STC, but glutathione peroxidase activity did not change. Expression of gpx4a, gpx4b, gss, and gsr genes was down-regulated due to STC compared to AFB1 or AFB1+STC, while an induction was found as effect of AFB1+STC in the case of gpx4a, but down-regulation for gpx4b as compared to AFB1. Expression of the glutathione biosynthesis regulatory gene, gss, was higher, but glutathione recycling enzyme encoding gene, gsr, was lower as an effect of AFB1+STC compared to AFB1. These results are supported by the changes in the expression of transcription factors encoding genes, nrf2, and keap1. The results revealed that individual effects of AFB1 and STC on different parameters are synergistic or antagonistic in multi-toxin treatment.

Effects of Single and Repeated Oral Doses of Ochratoxin A on the Lipid Peroxidation and Antioxidant Defense Systems in Mouse Kidneys.

Ochratoxin-A (OTA) is a carcinogenic and nephrotoxic mycotoxin, which may cause health problems in humans and animals, and it is a contaminant in foods and feeds. The purpose of the present study is to evaluate the effect of oral OTA exposure on the antioxidant defense and lipid peroxidation in the kidney. In vivo administration of OTA in CD1, male mice (1 or 10 mg/kg body weight in a single oral dose for 24 h and repeated daily oral dose for 72 h or repeated daily oral dose of 0.5 mg/kg bodyweight for 21 days) resulted in a significant elevation of OTA levels in blood plasma. Some histopathological alterations, transcriptional changes in the glutathione system, and oxidative stress response-related genes were also found. In the renal cortex, the activity of the glutathione-system-related enzymes and certain metabolites of the lipid peroxidation (conjugated dienes, trienes, and thiobarbituric reactive substances) also changed.

Short-term effects of deoxynivalenol, T-2 toxin, fumonisin B1 or ochratoxin on lipid peroxidation and glutathione redox system and its regulatory genes in common carp (Cyprinus carpio L.) liver.

The effects of a single oral dose of 1.82 mg kg-1 bw of T-2 and HT-2 toxin (T-2), 1.75 mg kg-1 bw deoxynivalenol (DON) and 15-acetyl DON, 1.96 mg kg-1 bw fumonisin B1 (FB1) or 1.85 mg kg-1 bw ochratoxin A (OTA) were investigated in common carp juveniles on lipid peroxidation, the parameters of the glutathione redox system including the expression of their encoding genes in a short-term (24 h) experiment. Markers of the initiation phase of lipid peroxidation, conjugated dienes, and trienes, were slightly affected by DON and OTA treatment at 16-h sampling. The termination marker, malondialdehyde, concentration increased only as an effect of FB1. Glutathione content and glutathione peroxidase activity showed significantly higher levels in the T-2 and FB1 groups at 8 h, and in the DON and FB1 groups at 16 h. The expression of glutathione peroxidase genes (gpx4a, gpx4b) showed a dual response. Downregulation of gpxa was observed at 8 h, as the effect of DON, FB1, and OTA, but an upregulation in the T-2 group. At 16 h gpx4a upregulated as an effect of DON, T-2, and FB1, and at 24 h in the DON and T-2 groups. Expression of gpx4b downregulated at 8 h, except in the T-2 group, and upregulation observed as an effect of T-2 at 24 h. The lack of an increase in the expression of nrf2, except as the effect of DON at 8 h, and a decrease in the keap1 expression suggests that the antioxidant defence system was activated at gene and protein levels through Keap1-Nrf2 independent pathways.