Selenium Deficiency Aggravates Aflatoxin B1-Induced Immunotoxicity in Chick Spleen by Regulating 6 Selenoprotein Genes and Redox/Inflammation/Apoptotic Signaling.

BACKGROUND: Selenium (Se) plays a protective role in aflatoxin B1 (AFB1)-induced splenic immunotoxicity in chicks. OBJECTIVE: This study was designed to reveal the underlying mechanism of Se-mediated protection against AFB1-induced splenic injury in broilers. METHODS: Four groups of 1-d-old Cobb male broilers (n = 5 cages/diet, 6 chicks/cage) were arranged in a 3-wk 2 × 2 factorial design trial whereby they were fed an Se-deficient, corn- and soy-based diet [base diet (BD), 36 µg Se/kg], BD plus 1.0 mg AFB1/kg, BD plus 0.3 mg Se/kg, or BD plus 1.0 mg AFB1/kg and 0.3 mg Se/kg (as 2-hydroxy-4-methylselenobutanoic acid). Serum and spleen were collected at week 3 to assay for cytokines, histology, redox status, selected inflammation- and apoptosis-related genes and proteins, and the selenogenome. RESULTS: Dietary AFB1 induced growth retardation and spleen injury, decreasing (P < 0.05) body weight gain, feed intake, feed conversion efficiency, and serum interleukin-1ß by 17.8-98.1% and increasing (P < 0.05) the spleen index and serum interleukin-6 by 37.6-113%. It also reduced the splenic lymphocyte number, the white pulp region, and histiocyte proliferation in Se-adequate groups. However, Se deficiency aggravated (P < 0.05) these AFB1-induced alterations by 16.2-103%. Moreover, Se deficiency decreased (P < 0.05) splenic glutathione peroxidase (GPX) activity and glutathione-S transferase and glutathione concentrations by 35.6-89.4% in AFB1-exposed groups. Furthermore, Se deficiency upregulated (P < 0.05) the apoptotic (Caspase 3 and Caspase 9) and antimicrobial (ß defensin 1 and 2) genes, but downregulated (P < 0.05) antiapoptotic (B-cell lymphoma 2) and inflammatory (E3 ubiquitin-protein ligase CBL-B) genes at the mRNA and/or protein level in AFB1 supplementation groups. Additionally, Se deficiency downregulated (P < 0.05) GPX3, thioredoxin reductase 1 (TXNRD 1), GPX4, and selenoprotein (SELENO) S, and upregulated (P < 0.05) SELENOT and SELENOU in spleen in AFB1 administered groups. CONCLUSIONS: Dietary Se deficiency exacerbated AFB1-induced spleen injury in chicks, partially through the regulation of oxidative stress, inflammatory and apoptotic signaling, and 6 selenoproteins.

Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats.

Background: Zearalenone (ZEN) can cause serious defects in development and reproduction in humans and animals. Silymarin shows antioxidant and estrogenic effects. Objective: This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities. Methods: Thirty-five 21-d-old female Sprague-Dawley rats (n = 7/diet) were fed a control diet (Ctrl) or Ctrl plus 20 mg ZEN/kg or Ctrl plus 20 mg ZEN/kg with 100, 200, or 500 mg silymarin/kg for 6 wk. Serum, livers, ovaries, and uterus were collected at week 6 for biochemistry, hormone, and redox status and selected gene and protein assays. Results: The consumption of ZEN decreased (P < 0.05) the final body weight by 17.9%, induced liver injury, increased (P < 0.05) aspartate aminotransferase and alkaline phosphatase activities, and decreased (P < 0.05) total protein and albumin concentrations in serum by 16.7-40.6%. ZEN also caused reproductive toxicity, including decreased (P < 0.05) 17ß-estradiol and increased (P < 0.05) follicle-stimulating hormone concentrations in serum by 12.7-46.3% and induced histopathologic alterations in the liver, ovaries, and uterus. Interestingly, these alterations induced by ZEN were alleviated (P < 0.05) by silymarin supplementation at 100, 200, and 500 mg/kg. Moreover, silymarin supplementation at the 3 doses mitigated (P < 0.05) ZEN-induced impairment in hepatic glutathione peroxidase activity, total antioxidant capacity, and malondialdehyde concentration by 17.6-100%. Meanwhile, silymarin supplementation at all doses upregulated (P < 0.05) phospho-ribosomal protein S6 kinase 1 (p-RPS6KB1) and 3ß-hydroxysteroid dehydrogenase (HSD3B) by 43.0-121% but downregulated (P < 0.05) AMP-activated protein kinase (AMPK) and 3α-hydroxysteroid dehydrogenase (HSD3A) in the liver relative to the ZEN group by 11.2-40.6%. In addition, silymarin supplementation at all doses elevated (P < 0.05) HSD3B by 1.8- to 2.5-fold and decreased (P < 0.05) estrogen receptor 1 (ESR1), ATP binding cassette (ABC) c1, and Abcc5 in ovaries and the uterus by 10.7-63.2%. Conclusion: Dietary silymarin supplementation at 100, 200, and 500 mg/kg protected rats from ZEN-induced hepatotoxicity and reproductive toxicity, potentially through improvement in the antioxidant capacity and regulation in the genes related to protein synthesis, ZEN metabolism, hormone synthesis, and ABC transporters in the tissues.

Prevention of Aflatoxin B1 Hepatoxicity by Dietary Selenium Is Associated with Inhibition of Cytochrome P450 Isozymes and Up-Regulation of 6 Selenoprotein Genes in Chick Liver.

BACKGROUND: The involvement of cytochrome P450 (CYP450) isozymes and the selenogenome in selenium-mediated protection against aflatoxin B1 (AFB1)-induced adverse effects in broilers remains unclear. OBJECTIVE: This study was designed first to determine whether selenium could reduce AFB1-induced hepatotoxic effects and then to determine whether these effects were due to changes in the CYP450 isozymes and selenogenome expression in the liver of chicks. METHODS: Male avian broilers (aged 120 d) were allocated to 4 groups with 5 replicates of 6 birds to be included in a 2-by-2 factorial trial in which the main factors included supplementation of AFB1 (<5 compared with 100 µg/kg) and selenium (0.2 compared with 0.5 mg/kg) in a corn/soybean-based diet for 4 wk. Serum biochemistry, hepatic histology, and mRNA and/or activities of hepatic antioxidant enzymes, CYP450 isozymes, and 26 selenoproteins were analyzed at week 2 and/or 4. RESULTS: Administration of AFB1 induced liver injury, decreasing (P < 0.05) total protein and albumin concentrations by 33.3-43.8% and increasing (P < 0.05) alanine aminotransferase and aspartate aminotransferase activities by 26.0-33.8% in serum, and induced hepatic necrosis and bile duct hyperplasia at week 2. AFB1 also decreased (P < 0.05) hepatic activities of glutathione peroxidase (GPX), thioredoxin reductase (TXNRD), and catalase, and the glutathione concentration by 13.1-59.9% and increased (P < 0.05) malondialdehyde, 8-hydroxydeoxyguanosine and exo-AFB1-8,9-epoxide (AFBO) DNA concentrations by 17.9-1200%. In addition, the mRNA and activity of enzymes responsible for the bioactivation of AFB1 into AFBO, which included CYP450 A1, 1A2, 2A6, and 3A4, were significantly induced (P < 0.05) by 29.2-271% in liver microsomes after 2-wk exposure to AFB1. These alterations induced by AFB1 were prevented by selenium supplementation. Dietary selenium supplementation increased (P < 0.05) mRNA and/or activities of 6 selenoprotein genes (Gpx3, Txnrd1, Txnrd2, Txnrd3, iodothyronine deiodinase 2, and selenoprotein N) in the liver of AFB1-treated groups at week 2. CONCLUSIONS: Dietary selenium protected chicks from AFB1-induced liver injury, potentially through the synergistic actions of inhibition of the pivotal CYP450 isozyme-mediated activation of AFB1 to toxic AFBO, and increased antioxidant capacities by upregulation of selenoprotein genes coding for antioxidant proteins.

Selenium mitigated aflatoxin B1-induced cardiotoxicity with potential regulation of 4 selenoproteins and ferroptosis signaling in chicks.

The aim of the present study was to explore the underlying mechanism of selenium (Se)-mediated detoxification of aflatoxin B1 (AFB1)-induced cardiotoxicity in chicks. A Se-deficient, corn-soybean meal-basal diet (36 µg Se/kg, BD) and three test diets (BD+1.0 mg AFB1/kg, 0.3 mg Se/kg, or 1.0 mg AFB1/kg+0.3 mg Se/kg) were used in a 3-wk 2 × 2 factorial design trial (n = 30 chicks/group). Dietary AFB1 led to induced (P < 0.05) serum creatine kinase and creatine kinase MB isoenzyme activities and heart histopathologic lesions. However, Se deficiency aggravated most of these alterations induced by AFB1. Moreover, mRNA levels of two ferroptosis activators (solute carrier family 11 Member 2 and transferrin) were upregulated (P < 0.05) in the AFB1-treated groups. Additionally, Se deficiency reduced (P < 0.05) glutathione peroxidase (GPX) 3 and thioredoxin reductase 3 mRNA and GPX activity but increased (P < 0.05) selenoprotein M and selenophosphate synthetase 2 mRNA in the heart in AFB1-administered groups. The in vitro study showed that Se alleviated (P < 0.05) AFB1-reduced cell viability and induced (P < 0.05) ROS and ferroptosis in H9C2 cardiac cells. It also downregulated (P < 0.05) two ferroptosis activators (long-chain acyl-CoA synthetase 4 and solute carrier family 11 Member 2) in the AFB1-treated groups in the H9C2 cells. In conclusion, this study illustrated that Se alleviates AFB1-induced cardiotoxicity and cardiomyocyte damage potentially related to the regulation of redox status, 4 selenoproteins, and ferroptosis-related signaling.

Yeast culture promotes the production of aged laying hens by improving intestinal digestive enzyme activities and the intestinal health status.

Yeast culture (YC) positively affects the performance of laying hens. The purpose of the present study was to explore the underlying mechanism for the YC-mediated performance improvement. Sixty 67-week-old Hy-Line Brown laying hens were randomly allocated into 2 experimental groups with 5 replicates of 6 birds each. One group was fed a control diet, whereas the other received the control diet supplemented with YC at 3.0 g/kg; treatment lasted for 8 wk. The results showed that dietary YC supplementation increased (P < 0.05) the total egg weight (11.2-13.6%) and egg-laying rate (13.0-13.5%) but decreased (P < 0.05) the feed/egg ratio by 9.3 to 11.0% during weeks 5 to 6 and 7 to 8 compared with the control. However, egg quality, including eggshell strength, eggshell thickness, egg weight, albumen height, egg yolk color, and Haugh unit, was not affected (P > 0.05) by YC supplementation. Furthermore, dietary YC supplementation increased (P < 0.05) chymotrypsin and ɑ-amylase activities by 54.8 to 62.5% in the duodenal chyme and reduced (P < 0.05) plasma endotoxin by 44.1%. YC dietary supplementation also upregulated (P < 0.05) the mRNA levels of intestinal barrier-related genes (occludin and claudin 1) and antimicrobial peptides genes (ß-defensin 1 and 7 and cathelicidin 1 and 3) in the duodenum or jejunum compared with the control. In conclusion, dietary YC supplementation improved the performance of aged laying hens, potentially through the upregulation of intestinal digestive enzyme activities and intestinal health-related gene expression.

Effect of deoxynivalenol on the porcine acquired immune response and potential remediation by a novel modified HSCAS adsorbent.

The objective of this study was to determine the immunotoxic effects of deoxynivalenol (DON) in weaning piglets, and potential efficacy of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce DON toxicity. Four groups of 21-day-old male piglets (n = 7/group) were fed a control diet or diet containing 1.0 or 3.0 mg DON/kg, or 3.0 mg DON/kg plus 0.05% modified HSCAS for 4 weeks. Compared to the control, the DON diets decreased serum porcine circovirus antibody titer and the dermal hypersensitivity response to OVA at day 21 or 28. DON also induced focal necrosis and proliferation of cortical lymphocytes and apoptosis and increased the total antioxidant capacity and reduced glutathione, protein carbonyl concentrations in thymus. DON increased thymus mRNA, protein and (or) enzyme levels, cytokines (IL-6, IL-10, and TNF-α) and apoptosis-related genes (Caspase-3), while hematopoietic cell kinase (HCK) decreased. Intriguingly, the modified HSCAS alleviated the DON-induced changes on serum antibody titer, and thymic histopathology, apoptosis, redox status, inflammation and apoptosis signaling. In conclusion, these findings help to explain the toxic effects and mechanisms of DON and demonstrated the modified HSCAS adsorbent could be used to reduce the toxicity of DON in weaning piglets.

Effects of deoxynivalenol on the porcine growth performance and intestinal microbiota and potential remediation by a modified HSCAS binder.

The objectives of this study were to determine the effects of deoxynivalenol (DON) on growth performance and intestinal microbiota in weaning piglets, and potential efficacy of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce DON toxicity. Four groups of 21-day-old male piglets (n = 7/group) were fed either a control diet, or diet containing 1.0 or 3.0 mg/kg DON, or 3.0 mg/kg DON plus 0.05% modified HSCAS for 28 d. Compared to the control, dietary DON at 1.0 and/or 3.0 mg/kg reduced (P < 0.05) the body weight gain (16.0-60.8%) and feed intake (18.1-38.7%) during the whole experiment, and increased (P < 0.05) the feed/gain ratio (12.8-33.8%) between d 1-28. The body weight gain and feed intake were further decreased (P < 0.05) in 3.0 mg/kg DON in comparison to 1.0 mg/kg DON during d 15-28. DON exposure reshaped gut microbial structure by drastically affecting the abundance of several bacterial phyla, families and genera, including dysbiosis of Actinobacteria, Cyanobacteria, Firmicutes, and Proteobacteria in small intestine. Notably, dietary Amdetox™ supplementation alleviated the adverse effects of DON on growth performance of piglets and improved the intestinal flora disorder. Therefore, the current study has revealed that Amdetox™, the modified HSCAS binder, can alleviate DON-induced negative effects and could be used as a promising countermeasure for reducing DON toxicity.

A Novel Modified Hydrated Sodium Calcium Aluminosilicate (HSCAS) Adsorbent Can Effectively Reduce T-2 Toxin-Induced Toxicity in Growth Performance, Nutrient Digestibility, Serum Biochemistry, and Small Intestinal Morphology in Chicks.

The objective of this study was to evaluate the ability of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce the toxicity of T-2 toxin in broilers. Ninety-six one-day-old male broilers were randomly allocated into four experimental groups with four replicates of six birds each. The four groups, 1-4, received a basal diet (BD), a BD plus 6.0 mg/kg T-2 toxin, a BD plus 6.0 mg/kg T-2 toxin with 0.05% modified HSCAS adsorbent, and a BD plus 0.05% modified HSCAS adsorbent, respectively, for two weeks. Growth performance, nutrient digestibility, serum biochemistry, and small intestinal histopathology were analyzed. Compared to the control group, dietary supplementation of T-2 toxin decreased (p < 0.05) body weight gain, feed intake, and the feed conversion ratio by 11.4%-31.8% during the whole experiment. It also decreased (p < 0.05) the apparent metabolic rates of crude protein, calcium, and total phosphorus by 14.9%-16.1%. The alterations induced by T-2 toxin were mitigated (p < 0.05) by the supplementation of the modified HSCAS adsorbent. Meanwhile, dietary modified HSCAS adsorbent supplementation prevented (p < 0.05) increased serum aspartate aminotransferase by T-2 toxin at d 14. It also prevented (p < 0.05) T-2 toxin-induced morphological changes and damage in the duodenum, jejunum, and ileum of broilers. However, dietary supplementation of the modified HSCAS adsorbent alone did not affect (p > 0.05) any of these variables. In conclusion, these findings indicate that the modified HSCAS adsorbent could be used against T-2 toxin-induced toxicity in growth performance, nutrient digestibility, and hepatic and small intestinal injuries in chicks.

The response of glandular gastric transcriptome to T-2 toxin in chicks.

This study was conducted to determine the effect of T-2 toxin on the transcriptome of the glandular stomach in chicks using RNA-sequencing (RNA-Seq). Four groups of 1-day-old Cobb male broilers (n = 4 cages/group, 6 chicks/cage) were fed a corn-soybean-based diet (control) and control supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. The histological results showed that dietary supplementation of T-2 toxin at 3.0 and 6.0 mg/kg induced glandular gastric injury including serious inflammation, increased inflammatory cells, mucosal edema, and necrosis and desquamation of the epithelial cells in the glandular stomach of chicks. RNA-Seq analysis revealed that there were 671, 1393, and 1394 genes displayed ≥2 (P < 0.05) differential expression in the dietary supplemental T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, compared with the control group. Notably, 204 differently expressed genes had shared similar changes among these three doses of T-2 toxin. GO and KEGG pathway analysis results showed that many genes involved in oxidation-reduction process, inflammation, wound healing/bleeding, and apoptosis/carcinogenesis were affected by T-2 toxin exposure. In conclusion, this study systematically elucidated toxic mechanisms of T-2 toxin on the glandular stomach, which might provide novel ideas to prevent adverse effects of T-2 toxin in chicks.

Grape Seed Proanthocyanidin Extract Alleviates AflatoxinB1-Induced Immunotoxicity and Oxidative Stress via Modulation of NF-κB and Nrf2 Signaling Pathways in Broilers.

Aflatoxin B1 (AFB1) is a widely spread mycotoxin contaminates food and feed, causing severe oxidative stress damages and immunotoxicity. Grape seed proanthocyanidin (GSPE), a natural antioxidant with wide range of pharmacological and medicinal properties. The goal of the present study was to investigate the protective effects of GSPE against AFB1-induced immunotoxicity and oxidative stress via NF-κB and Nrf2 signaling pathways in broiler chickens. For the experiment, 240 one-day old Cobb chicks were allocated into four dietary treatment groups of six replicates (10 birds per replicate): 1. Basal diet (control); 2. Basal diet + AFB1 1mg/kg contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg (GSPE); 4. Basal diet + AFB1 1 mg/kg + GSPE 250 mg/kg (AFB1 + GSPE). The results showed that GSPE significantly decreased serum inflammatory cytokines TNF-α, IFN-γ, IL-1ß, IL-10, and IL-6 induced by AFB1. Similarly, GSPE + AFB1 treated group revealed a significant decrease in mRNA expressions of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1ß, and IL-6) in the splenic tissue compared to the AFB1 treatment group. In addition, western blotting results manifested that GSPE treatment normalized the phosphorylation of nuclear factor kappa B (p65) and the degradation of IκBα protein induced by AFB1. Furthermore, GSPE enhanced the antioxidant defense system through activating the nuclear factor-erythroid-2-related factor (Nrf2) signaling pathway. The mRNA and protein expression level of Nrf2 and its down streaming associated genes were noted up-regulated by the addition of GSPE, and down-regulated in the AFB1 group. Taken together, GSPE alleviates AFB1-induced immunotoxicity and oxidative damage by inhibiting the NF-κB and activating the Nrf2 signaling pathways in broiler chickens. Conclusively, our results suggest that GSPE could be considered as a potential natural agent for the prevention of AFB1-induced immunotoxicity and oxidative damage.

Aflatoxin B1 metabolism: Regulation by phase I and II metabolizing enzymes and chemoprotective agents.

Aflatoxin B1 (AFB1) widely contaminates staple food and feed crops and is well-known as the most potent natural hepatocarcinogen in humans and domesticated animals. This review highlights significant advances in our understanding of the pivotal role of phase I and II metabolizing enzymes in the bioactivation and detoxification of AFB1 and its metabolites across species. In humans, cytochrome P450 (CYP) 1A2, CYP3A4, CYP3A5, and CYP3A7 in liver and CYP2A13 in lung are essential for the bioactivation of AFB1 to the extremely toxic exo-AFB1-8,9-epoxide (AFBO), whereas CYP1A1, CYP1A2, CYP2A6, and CYP3A4 are important in the turkey and duck, CYP1A1 and CYP2A6 are important in the chicken and quail, CYP3A11 and CYP3A13 are important in mice, and CYP2A5 are important in the hamster. In contrast, glutathione-S-transferase (GST) M1 and GSTT1 are primary responsible for detoxification of the AFB1 by catalyzing the conjugation of GSH to AFBO in humans, whereas GSTM2 in a nonhuman primate, GSTA3 in mice, GSTA5 in rats, and GSTA1, GSTA2, GSTA3 and GSTA4 in the turkey are important. Additionally, microsomal epoxide hydrolase (mEH) and aflatoxin-aldehyde reductase (AFAR) have also been shown to play key roles in AFB1 detoxification in the human, rat, and pig. Moreover, an overview of the chemoprotective agents, including synthetic compounds and naturally occurring plant compounds, which can be used to reduce aflatoxicosis is provided based on their ability to regulate these key enzymes. Collectively, this review summarizes the pivotal enzymes in the metabolism of AFB1 among humans, experimental and farm animals, as well as the chemoprotective agents that can be used to minimize risk of aflatoxicosis.

Efficacy of 2-hydroxy-4-methylthiobutanoic acid compared to DL-Methionine on growth performance, carcass traits, feather growth, and redox status of Cherry Valley ducks.

The objective of this study was to compare the bio-efficacy of 2-hydroxy-4-methylthiobutanoic acid (DL-HMTBA) with that of DL-methionine (DLM) as sources of methionine in terms of the growth performance, carcass traits, feather growth, and redox statuses of Cherry Valley ducks. Six hundred and thirty male ducks were randomly allotted to 9 dietary treatment groups with 7 replicates of 10 birds each. The first group received a basal diet (BD) without methionine addition that was deficient in the total number of sulfur amino acids. In Groups 2 to 5 and Groups 6 to 9, the BD was supplemented with 4 increasing doses of methionine as either DLM or DL-HMTBA. The trial was run from ages 1 to 42 d. Dietary supplementation with DLM and DL-HMTBA improved body weight gain and feed intake as well as weights of carcasses, breast meat, and feathers compared with the BD. No significant difference was observed between the 2 methionine sources on growth performance, carcass traits, and feather growth. Concentrations of some redox markers in the pectoralis major muscle were improved by addition of methionine to the BD. However, a significant difference was observed between DLM and DL-HMTBA in this respect, as the supplementation of DL-HMTBA significantly increased the total antioxidant capacity, the activities of glutathione peroxidase, and the concentration of reduced glutathione in the pectoralis major muscle, compared with DLM. No significant difference between methionine sources was found with regard to the concentrations of oxidized glutathione and malondialdehyde in the pectoralis major muscle. Both DLM and DL-HMTBA increased malondialdehyde concentrations in the pectoralis major muscle compared with the BD. In conclusion, these results indicated that DLM and DL-HMTBA have equal biological value for the growth performance, carcass traits, and feather growth of Cherry Valley duck. Moreover, the improved antioxidant capacity observed with DL-HMTBA makes this a better candidate than DLM for lowering the oxidation process in the meat during post-mortem storage and thereby contributes to a better duck meat quality.

Individual and Combined Occurrence of Mycotoxins in Feed Ingredients and Complete Feeds in China.

The objective of this study was to investigate the individual and combined contamination of aflatoxin B1 (AFB1), zearalenone (ZEN) and deoxynivalenol (DON) in feedstuffs from different Provinces of China between 2016 and 2017. A total of 1569 samples, including 742 feed ingredients and 827 complete pig feed samples, were collected from various regions of China for mycotoxins analysis. The results showed that individual occurrence rates of AFB1, ZEN, and DON were more than 83.3%, 88%, and 74.5%, respectively, in all the tested samples. DON was the most prevalent contaminant, followed by ZEN and AFB1, with the average concentrations ranging from 450.0-4381.5 µg/kg, 2.3-729.2 µg/kg, and 1.3-10.0 µg/kg, respectively. Notable, 38.2%, 10.8%, and 0.6% of complete pig feeds were contaminated with DON, ZEN, and AFB1 over China's regulatory limits, respectively. Moreover, over 75.0% analyzed samples were co-contaminated with two or three mycotoxins. In conclusion, the current study revealed that the feedstuffs in China were severely contaminated with DON, followed by ZEN and AFB1 during the past two years. These findings highlight the importance of monitoring mycotoxins in livestock feed and implementing feed management and bioremediation strategies to reduce mycotoxin exposure.

Response of the hepatic transcriptome to aflatoxin B1 in ducklings.

This study was conducted to determine the effects of aflatoxin B1 (AFB1) on the hepatic transcriptome in ducklings through RNA-sequencing (RNA-Seq). Twenty four, 1-day-old ducklings were divided into 4 treatment groups. Each group received an oral dose of AFB1 at 0, 10, 20, 40 µg/kg BW per day for 2 weeks. Administration of 20 and 40 µg/kg BW of AFB1 significantly decreased body weight, feed intake, serum total protein and albumin, while increasing serum aspartate aminotransferase and alanine aminotransferase activities, and hepatic histopathological lesions. Furthermore, RNA was extracted from the liver of ducklings administrated 0 and 40 µg/kg BW of AFB1. Two RNA-Seq libraries were created from pooled samples and produced over 149 M reads, totaling 14.9 Gb of sequence. Approximately 96,953 predicted transcripts were assembled, 749 of which had significant differential expressions (≥ 2-fold) between the control and AFB1 treatment. GO and KEGG pathway analysis results showed that many genes involved in phase I metabolism, phase II detoxification, oxidation-reduction process, carcinogenesis, apoptosis and cell cycle, and fatty acid metabolism were affected by AFB1 exposure. Conclusion, this study determined the hepatic transcriptome responded to AFB1 exposure, and provide candidate genes can be targeted to prevent and/or reduce aflatoxicosis in ducklings.

Curcumin Prevents Aflatoxin B1 Hepatoxicity by Inhibition of Cytochrome P450 Isozymes in Chick Liver.

This study was designed to establish if Curcumin (CM) alleviates Aflatoxin B1 (AFB1)-induced hepatotoxic effects and to determine whether alteration of the expression of cytochrome P450 (CYP450) isozymes is involved in the regulation of these effects in chick liver. One-day-old male broilers (n = 120) were divided into four groups and used in a two by two factorial trial in which the main factors included supplementing AFB1 (< 5 vs. 100 µg/kg) and CM (0 vs. 150 mg/kg) in a corn/soybean-based diet. Administration of AFB1 induced liver injury, significantly decreasing albumin and total protein concentrations and increasing alanine aminotransferase and aspartate aminotransferase activities in serum, and induced hepatic histological lesions at week 2. AFB1 also significantly decreased hepatic glutathione peroxidase, catalase, and glutathione levels, while increasing malondialdehyde, 8-hydroxydeoxyguanosine, and exo-AFB1-8,9-epoxide (AFBO)-DNA concentrations. In addition, the mRNA and/or activity of enzymes responsible for the bioactivation of AFB1 into AFBO-including CYP1A1, CYP1A2, CYP2A6, and CYP3A4-were significantly induced in liver microsomes after 2-week exposure to AFB1. These alterations induced by AFB1 were prevented by CM supplementation. Conclusively, dietary CM protected chicks from AFB1-induced liver injury, potentially through the synergistic actions of increased antioxidant capacities and inhibition of the pivotal CYP450 isozyme-mediated activation of AFB1 to toxic AFBO.

Individual and combined cytotoxic effects of aflatoxin B1, zearalenone, deoxynivalenol and fumonisin B1 on BRL 3A rat liver cells.

This study was performed to determine the individual and combined cytotoxic effects of Aflatoxin B1 (AFB1), zearalenone (ZEA), deoxynivalenol (DON) and fumonisin B1 (FB1) on BRL 3A rat liver cells. After the mycotoxins treated the BRL 3A cells for 12, 24 and 48 h, cell viability was determined using the MTT assay. The cytotoxicity of individual mycotoxins on BRL 3A cell viability in decreasing order were DON > AFB1 > ZEA > FB1. The central composite design (CCD) was used to assess the toxicity of binary and ternary mixtures of these mycotoxins. The mixtures of AFB1+ZEA and AFB1+DON showed the synergetic toxic effects on BRL 3A cells. These toxins decreased the viability of cells by inducing intracellular reactive oxygen species (ROS) production and promoting apoptosis in the BRL 3A cells. This effect was mediated by an upregulation of the stress and apoptotic genes Hsp70, p53, Bax, Caspase-3 and Caspase-8, along with a downregulation of the antiapoptotic gene Bcl-2. In conclusion, our results suggested that the coexistence of AFB1 and ZEA or DON in agricultural products could be more hepatotoxic than individually, suggests that the toxicological interactions of these toxins need to be better understood to assess health risks.

A novel strain of Cellulosimicrobium funkei can biologically detoxify aflatoxin B1 in ducklings.

Two experiments were conducted to screen microorganisms with aflatoxin B1 (AFB1 ) removal potential from soils and to evaluate their ability in reducing the toxic effects of AFB1 in ducklings. In experiment 1, we screened 11 isolates that showed the AFB1 biodegradation ability, and the one exhibited the highest AFB1 removal ability (97%) was characterized and identified as Cellulosimicrobium funkei (C. funkei). In experiment 2, 80 day-old Cherry Valley ducklings were divided into four groups with four replicates of five birds each and were used in a 2 by 2 factorial trial design, in which the main factors included administration of AFB1 versus solvent and C. funkei versus solvent for 2 weeks. The AFB1 treatment significantly decreased the body weight gain, feed intake and impaired feed conversion ratio. AFB1 also decreased serum albumin and total protein concentration, while it increased activities of alanine aminotransferase and aspartate aminotransferase and liver damage in the ducklings. Supplementation of C. funkei alleviated the adverse effects of AFB1 on growth performance, and provided protective effects on the serum biochemical indicators, and decreased hepatic injury in the ducklings. Conclusively, our results suggest that the novel isolated C. funkei strain could be used to mitigate the negative effects of aflatoxicosis in ducklings.

Effects of dietary tin on growth performance, hematology, serum biochemistry, antioxidant status, and tin retention in broilers.

Tin (Sn) is widely used in daily life and distributed in many tissues and nutrients. Although over-ingestion of Sn can cause health problems, relatively little attention has been given to the toxic effects of Sn in livestock health and productivity. This study was performed to investigate the toxic effects of prolonged high intake of dietary Sn on broilers. 150 one-day-old Avian broilers were randomly divided into five treatment groups, with five replicates of six birds. For 6 weeks, each group was fed a corn-soybean basal diet (BD) or BD + Sn (as SnCl2) at 120, 240, 480, or 720 mg/kg, respectively. Compared with the control, hepatic glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities were significantly decreased when supplemented with Sn up to 480 mg/kg, while malondialdehyde (MDA) was increased until Sn supplementation at 720 mg/kg. Moreover, dietary Sn supplementation at 720 mg/kg decreased BW gain, feed intake, and impaired feed conversion ratio. The 720 mg Sn/kg group also increased activities of alkaline phosphatase (AKP), while decreased hemoglobin (HGB), red blood cell (RBC), and hematocrit (HCT) in the blood. Furthermore, the accumulation of Sn in various tissues was dose dependent on Sn ingestion. It was found that the tibia and feather are the two main tissues for Sn accumulation, followed by the liver, kidney, and other tissues in broilers. In conclusion, the adverse effects on broilers were induced when diets supplemented with Sn up to 480 mg/kg. Sn levels also managed to accumulate in the tibia and feather of broilers.

Hepatotoxic effects of mycotoxin combinations in mice.

This study was performed to assess the individual and combined toxic effects of aflatoxin B1 (AFB1), zearalenone (ZEA) and deoxynivalenol (DON) within the liver of mice. A total of 56 4-week-old weanling female mice were divided into seven groups (n = 8). For 2 weeks, each group received an oral administration of either solvent (control), AFB1, ZEA, DON, AFB1 + ZEA, AFB1 + DON or ZEA + DON per day. The results showed that AFB1, ZEA and DON induced liver injury, indicated by elevated relative liver weight, activities of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), as well as decreased albumin (ALB) and/or total protein (TP) concentration in the serum. These mycotoxins also decreased hepatic total antioxidant capacity (T-AOC), and/or increased the concentration of malondialdehyde (MDA). Moreover, AFB1 + DON displayed synergistic effects, while AFB1 + ZEA displayed antagonistic effects on those parameters previously described. Furthermore, the apoptotic potential was demonstrated associated with an upregulation of the apoptotic genes Caspase-3 and Bax, along with a downregulation of the antiapoptotic gene Bcl-2 in liver. In conclusion, this study provides a better understanding of the toxic effects of AFB1, ZEA, DON, alone or in combinations on the liver of mice, which could contribute to the risk assessment of these mycotoxins in food and feed.