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Cecal tonsil is the largest peripheral lymphoid organ of the gut-associated lymphoid tissue executing immune function. To evaluate the protective effect of selenium (Se) on the cecal tonsil of chicken exposed to aflatoxin B 1 (AFB 1 ), 144 1-day-old healthy Cobb chickens were randomly divided into four groups, and fed with basal diet (control group), 0.6 mg/kg AFB 1 (AFB 1 group), 0.4 mg/kg Se supplement (+Se group), and 0.6 mg/kg AFB 1  + 0.4 mg/kg Se supplement (AFB 1  + Se group) for 21 days, respectively. The results showed that AFB 1 significantly decreased the percentages of CD3 + , CD3 + CD4 + , CD3 + CD8 + T cells, and the CD4 + /CD8 + ratio, and suppressed the expressions of IL-2, IL-4, TNF-α, and IFN-γ mRNA in the cecal tonsil. However, Selenium (Se) supplied in the diets restored the percentages of T cell subsets, the CD4 + /CD8 + ratio, and mRNA expressions of cytokines in the AFB 1 group to be close to those in the control group, and did not exhibit obvious toxicity to the cecal tonsil. These results indicated that Se exerted protective effect against AFB 1 on the functions of cecal tonsil, and also partially uncovered a new role of Se that could protect cecal tonsil of chickens from immunotoxicity of AFB 1 .

Aflatoxin B 1 (AFB 1 ) can cause hepatotoxicity, genotoxicity, and immunosuppressive effects for a variety of organisms. Selenium (Se), as an essential nutrient element, plays important protective effects against cell apoptosis induced by AFB 1 . This research aimed to reveal the ameliorative effects of selenium on AFB 1 -induced excess apoptosis in chicken splenocytes through death receptor and endoplasmic reticulum pathways in vivo. Two hundred sixteen neonatal chickens, randomized into four treatments, were fed with basal diet (control treatment), 0.4 mg/kg Se supplement (+Se treatment), 0.6 mg/kg AFB 1 (AFB 1 treatment), and 0.6 mg/kg AFB 1  + 0.4 mg/kg Se (AFB 1  + Se treatment) during 21 days of experiment, respectively. Compared with the AFB 1 treatment, the levels of splenocyte apoptosis in the AFB 1  + Se treatment were obviously dropped by flow cytometry and TUNEL assays although they were still significantly higher than those in the control or + Se treatments. Furthermore, the mRNA expressions of CASP-3, CASP-8 and CASP-10, GRP78, GRP94, TNF-α, TNF-R1, FAS, and FASL of splenocytes in the AFB 1  + Se treatment by qRT-PCR assay were significantly decreased compared with the AFB 1 treatment. These results indicate that Se could partially ameliorate the AFB 1 -caused excessive apoptosis of chicken splenocytes through downregulation of endoplasmic reticulum and death receptor pathway molecules. This research may rich the knowledge of the detoxification mechanism of Se on AFB 1 -induced apoptosis.

Aflatoxin B 1 (AFB 1 ) is a naturally occurring secondary metabolites of Aspergillus flavus and Aspergillus parasiticus, and is the most toxic form of aflatoxins. Selenium (Se) with antioxidant and detoxification functions is one of the essential trace elements for human beings and animals. This study aims to evaluate the protective effects of Se on AFB 1 -induced tissue damage and cell cycle arrest in bursa of Fabricius (BF) of chickens. The results showed that a dietary supplement of 0.4 mg·kg -1 Se alleviated the histological lesions induced by AFB 1 , as demonstrated by decreasing vacuoles and nuclear debris, and relieving oxidative stress. Furthermore, flow cytometry studies showed that a Se supplement protected AFB 1 -induced G 2 M phase arrest at 7 days and G 0 G 1 phase arrest at 14 and 21 days. Moreover, the mRNA expression results of ATM, Chk2, p53, p21, cdc25, PCNA, cyclin D 1 , cyclin E 1 , cyclin B 3 , CDK6, CDK2, and cdc2 indicated that Se supplement could restore these parameters to be close to those in the control group. It is concluded that a dietary supplement of 0.4 mg kg -1 Se could diminish AFB 1 -induced immune toxicity in chicken's BF by alleviating oxidative damage and cell cycle arrest through an ATM-Chk2-cdc25 route and the ATM-Chk2-p21 pathway.

To explore AFB₁-induced damage of the small intestine, the changes in structure and expression of TLRs (Toll-like Receptors) in the small intestine of chickens were systematically investigated. Ninety healthy neonatal Cobb chickens were randomized into a control group (0 mg/kg AFB₁) and an AFB₁ group (0.6 mg/kg AFB₁). The crypt depth of the small intestine in the AFB₁ group was significantly increased in comparison to the control chickens, while the villus height and area were evidently decreased, as well as the villus:crypt ratio and epithelial thickness. The histopathological observations showed that the villi of the small intestine exposed to AFB₁ were obviously shedding. Based on ultrastructural observation, the absorptive cells of small intestine in the AFB₁ group exhibited fewer microvilli, mitochondrial vacuolation and the disappearance of mitochondrial cristae, and junctional complexes as well as terminal web. Moreover, the number of goblet cells in the small intestine in the AFB₁ group significantly decreased. Also, AFB₁ evidently decreased the mRNA expression of TLR2-2, TLR4, and TLR7 in the small intestine. Taken together, our study indicated that dietary 0.6 mg/kg AFB₁ could induce histopathological injuries and ultrastructural changes, and depress levels of TLR mRNA in the chicken small intestine., Competing Interests: The authors declare no conflict of interest.

Aflatoxin B 1 shows potent hepatotoxic, carcinogenic, genotoxic, immunotoxic potential in humans and many species of animals. The aim of this study was to clarify the underlying mechanism of G 0 G 1 phase and G 2 M phase arrest of cell cycle in the bursa of Fabricius in broilers exposed to dietary AFB 1 . 144 one-day-old healthy Cobb broilers were randomly divided into two groups and fed on control diet and 0.6 mg·Kg -1 AFB 1 diet for 3 weeks. Histological observation showed that AFB 1 induced the increase of nuclear debris and vacuoles in lymphoid follicle of BF. Results of flow cytometry studies showed that bursal cells arrested in G 2 M phase at 7 days of age and blocked in G 0 G 1 phase at 14 and 21 days of age following exposure to AFB 1 . The qRT-PCR analysis indicated that cell cycle arrested in G 2 M phase via ATM-Chk2-cdc25-cyclin B/cdc2 pathway, and blocked in G 0 G 1 phase through ATM-Chk2-cdc25-cyclin D/CDK6 pathway and ATM-Chk2-p21-cyclin D/CDK6 route. In a word, our results provided new insights that AFB 1 diet induced G 2 M and G 0 G 1 phase blockage of BF cells in different periods, and different pathways were activated in different arrested cell cycle phase.

Aflatoxin B 1 (AFB 1 ) is the most toxic among the mycotoxins and causes detrimental health effects on human and animals. Selenium (Se) plays an important role in chemopreventive, antioxidant, anticarcinogen, and detoxification and involved in cell cycle regulation. The aim of this study was to explore the molecular mechanisms of selenium involved in inhibition of G 2 /M cell cycle arrest of broiler's jejunum. A total of 240 one-day-old healthy Cobb broilers were randomly divided into four groups and fed with basal diet (control group), 0.6 mg/kg AFB 1 (AFB 1 group), 0.4 mg/kg Se (+Se group), and 0.6 mg/kg AFB 1 + 0.4 mg/kg Se (AFB 1 + Se group) for 21 days, respectively. The histological observation and morphological analysis revealed that 0.4 mg/kg Se prevented the AFB 1 -associated lesions of jejunum including the shedding of the apical region of villi, the decreased villus height, and villus height/crypt ratio. The cell cycle analysis by flow cytometry showed that 0.4 mg/kg Se ameliorated the AFB 1 -induced G 2 /M phase arrest in jejunal cells. Moreover, the expressions of ATM, Chk2, p53, Mdm2, p21, PCNA, Cdc25, cyclin B, and Cdc2 analyzed by immunohistochemistry and qRT-PCR demonstrated that 0.4 mg/kg Se restored these parameters to be close to those in the control group. In conclusion, Se promoted cell cycle recovery from the AFB 1 -induced G 2 /M phase arrest by the molecular regulation of ATM pathway in the jejunum of broilers. The outcomes from the present study may lead to a better understanding of the nature of selenium's essentiality and its protective roles against AFB 1 .

Aflatoxin B1 is known as a mycotoxin that develops various health problems of animals, the effects of AFB1 on thymus and bursa of Fabricius in chickens are not clear. The objective of this study was to investigate the apoptosis of thymus and bursa of Fabricius in broilers fed with AFB1 . Two hundred Avian broilers were randomly divided into four groups of 50 each, namely control group and three AFB1 groups fed with 0.15 mg, 0.3 mg, and 0.6 mg AFB1 /kg diet, respectively. In this study, flow cytometer and immunohistochemical approaches were used to determine the percentage of apoptotic cells and the expression of Bax, Bcl-2, and Caspase-3. The results showed that consumption of AFB1 diets results in increased percentage of apoptotic cells and increased expression of Caspase-3 in both thymus and bursa of Fabricius. The expression of Bax was increased and the expression of Bcl-2 was decreased in the thymus, but no significant changes in Bax and Bcl-2 expression were observed in the bursa of Fabricius when broilers fed with AFB1 . These findings suggest that adverse effects of AFB1 on thymus and bursa of Fabricius in broilers were confirmed by increased apoptotic cells and abnormal expression of Caspase-3. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1113-1120, 2016., (© 2015 Wiley Periodicals, Inc.)

Aflatoxin B1 (AFB1) has potent hepatotoxic, carcinogenic, genotoxic, immunotoxic and other adverse effects in human and animals. The aim of this study was to investigate the molecular mechanism of G2/M cell cycle arrest induced by AFB1 in the jejunum of broilers. Broilers, as experimental animals, were fed 0.6 mg/kg AFB1 diet for 3 weeks. Our results showed that AFB1 reduced the jejunal villus height, villus height/crypt ratio and caused G2/M cell cycle arrest. The G2/M cell cycle was accompanied by the increase of ataxia telangiectasia mutated (ATM), p53, Chk2, p21 protein and mRNA expression, and the decrease of Mdm2, cdc25C, cdc2, cyclin B and proliferating cell nuclear antigen protein and mRNA expression. In conclusion, AFB1 blocked G2/M cell cycle by ATM pathway in the jejunum of broilers., Competing Interests: The authors declare no conflict of interest.

The effects of aflatoxin B1 (AFB1) exposure and sodium selenite supplementation on cell apoptosis of jejunum in broilers were studied. A total of 240 one-day-old male AA broilers were randomly assigned four dietary treatments containing 0 mg/kg of AFB1 (control), 0.3 mg/kg AFB1 (AFB1), 0.4 mg/kg supplement Se (+ Se) and 0.3 mg/kg AFB1 + 0.4 mg/kg supplement Se (AFB1 + Se), respectively. Compared with the control broilers, the number of apoptotic cells, the expression of Bax and Caspase-3 mRNA were significantly increased, while the expression of Bcl-2 mRNA and the Bcl-2/Bax ratio were significantly decreased in AFB1 broilers. The number of apoptotic cells and the expression of Caspase-3 mRNA in AFB1 + Se broilers were significantly higher than those in the control broilers, but significantly lower than those in AFB1 broilers. There were no significant changes in the expression of Bax mRNA between AFB1 + Se and control broilers; the expression of Bcl-2 mRNA and the Bcl-2/Bax ratio in AFB1 + Se broilers were significantly lower than those in the control broilers, but significantly higher than those in AFB1 broilers. In conclusion, 0.3 mg/kg AFB1 in the diet can increase cell apoptosis, decrease Bcl-2 mRNA expression, and increase of Bax and Caspase-3 mRNA expression in broiler's jejunum. However, supplementation of dietary sodium selenite at the concentration of 0.4 mg/kg Se may ameliorate AFB1-induced apoptosis by increasing Bcl-2 mRNA expression, and decreasing Bax and Caspase-3 mRNA expression.

To investigate the effects of sodium selenite against aflatoxin B1 (AFB 1), 200 male Avian broilers, divided into five groups, were fed with basal diet (control group), 0.3 mg/kg AFB1 (AFB1 group), 0.3 mg/kg AFB1 + 0.2 mg/kg Se (+Se group I), 0.3 mg/kg AFB1 + 0.4 mg/kg Se (+Se group II) and 0.3 mg/kg AFB1 + 0.6 mg/kg Se (+Se group III), respectively. Compared with the control group, decreased relative weight of bursa of Fabricius and contents of serum immunoglobulin, more vacuoles and debris in the bursal lymphoid follicle, and increased percentage of apoptotic bursal cells were observed in the AFB1 group. Sodium selenite, however, could increase the relative weight of bursa of Fabricius and contents of serum immunoglobulin, and ameliorate histopathological lesions. The percentages of apoptotic bursal cells, through flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, in the three +Se groups were lower than those in the AFB 1 group. Compared with the AFB 1 group, moreover, the mRNA expressions of Bax and Caspase-3 by qRT-PCR in the three +Se groups were decreased, while the expression of Bcl-2 was increased. The results indicate that sodium selenite in diet can protect chicken from AFB 1-induced impairment of humoral immune function by reducing bursal histopathological lesions and percentages of apoptotic bursal cells., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study was aimed to assess the protective effect of sodium selenite on the ileum mucosal immunologic injury induced by AFB1. One hundred eighty-one-day-old healthy male Avian broilers were divided into four groups of three replicates and 15 birds per replicate and fed with basal diet (control group), 0.3 mg/kg AFB1 (AFB1 group), 0.4 mg/kg Se (+Se group), and 0.3 mg/kg AFB1 + 0.4 mg/kg Se (AFB1 + Se group) respectively. The numbers of IgA(+) cells of ileum were determined by immunohistochemistry as well as the contents of sIgA, IgA, IgG, and IgM in the mucosa of ileum by ELISA. Compared with those in the control group, the numbers of IgA(+) cells as well as the sIgA, IgA, IgG, and IgM contents were decreased in the AFB1 group. However, compared with those in the AFB1 group, the numbers of IgA(+) cells as well as the sIgA, IgA, IgG, and IgM contents were increased in the AFB1 + Se group, and these data had no difference between AFB1 + Se group and control group. It was concluded that 0.3 mg/kg AFB1 could reduce the humoral immune function of the ileum mucosa, but 0.4 mg/kg supplemented dietary selenium could protect the mucosal humoral immune function from AFB1-induced impairment.

The aim of this study was to investigate the effects of aflatoxin B1 (AFB1) exposure and sodium selenite supplementation on the histology, cell proliferation and cell cycle of jejunum in broilers. A total of 240 1-day-old male AA broilers were divided into four groups of 60 each, fed with basal diet (control group), 0.3 mg/kg AFB1 (AFB1 group), 0.4 mg/kg supplement Se (Se group), and 0.3 mg/kg AFB1 + 0.4 mg/kg supplement Se (AFB1 + Se group) for 21 days, respectively. Compared with the control group, decreased jejunal villus height, villus height/crypt ratio, and proliferation cell nuclear antigen (PCNA)-positive cells, and G2/M phase arrest and shedded epithelial cells on the tip of jejunal villus were observed in AFB1 groups at 7 and 14 days of age. However, the villus/crypt ratio, PCNA-positive cells and cell percentage of G0/G1, S, and G2/M phases had no significant differences between AFB1 group and control group at 21 days. Simultaneous supplementation with sodium selenite restored these parameters to be close to those in control group. In conclusion, 0.3 mg/kg AFB1 in the diet inhibits the development of broiler's jejunum by reducing cellular proliferation and inducing G2/M arrest during only the first 2 weeks after hatching. Supplementation of dietary sodium selenite at the concentration of 0.4 mg/kg Se had protective action against these toxic effects of AFB1.

The aim of this work was to assess the protective effect of sodium selenite on the ileum mucosal immunologic toxicity induced by aflatoxin B1 (AFB1). One hundred and eighty one-day-old healthy male avian broilers were divided into four groups of three replicates and 15 birds per replicate and fed with basal diet (control group), 0.3 mg/kg AFB1 (AFB1 group), 0.4 mg/kg Se (+Se group), and 0.3 mg/kg AFB1+0.4 mg/kg Se (AFB1+Se group), respectively. The ileac T-cell subsets were determined by the methods of flow cytometry (FCM), and the mRNA contents of interleukin-2 (IL-2), interleukin-6(IL-6), and tumor necrosis factor-alpha (TNF-α) by quantitative real-time PCR. Compared with those in control group, the percentages of CD3+, CD3+CD4+, CD3+CD8+ intraepithelial lymphocytes (IELs) and LPLs, the CD4+/CD8+ ratio of IELs, and the mRNA contents of IL-2, IL-6, and TNF-α were decreased in AFB1 group. However, compared with those in AFB1 group, these parameters of AFB1+Se group were increased to be close to those in control group. It was concluded that 0.3 mg/kg AFB1 could reduce the cellular immune function of the ileum mucosa, but 0.4 mg/kg supplemented dietary selenium showed protective effects on AFB1-induced immunologic injury.

Aflatoxin B1 (AFB1), which causes hepatocellular carcinoma and immune-suppression, is commonly found in feedstuffs. To evaluate the ability of selenium (Se) to counteract the deleterious effects of AFB1, two hundred 1-day-old male avian broilers, divided into five groups, were fed with basal diet (control group), 0.3 mg/kg AFB1 (AFB1 group), 0.3 mg/kg AFB1+0.2 mg/kg Se (+Se group I), 0.3 mg/kg AFB1+0.4 mg/kg Se (+Se group II) and 0.3 mg/kg AFB1+0.6 mg/kg Se (+Se group III), respectively. Compared with control group, the relative weight of spleen in the AFB1 group was decreased at 21 days of age. The relative weight of spleen in the three +Se groups was higher than that in the AFB1 group. By pathological observation, the major spleen lesions included congestion in red pulp and vacuoles appeared in the lymphatic nodules and periarterial lymphatic sheath in the AFB1 group. In +Se groups II and III, the incidence of major splenic lesions was decreased. The percentages of CD3+, CD3+CD4+ and CD3+CD8+ T cells in the AFB1 group were lower than those in control group from 7 to 21 days of age, while there was a marked increase in the three +Se groups compared to the AFB1 group. The results indicated that sodium selenite could improve the cellular immune function impaired by AFB1 through increasing the relative weight of spleen and percentages of splenic T cell subsets, and alleviating histopathological spleen damage.

For evaluating the ability of selenium (Se) in counteracting the adverse effects of aflatoxin B₁ (AFB₁), two hundred 1-day-old male Avian broilers, divided into five groups, were fed with basal diet (control group), 0.3 mg/kg AFB₁ (AFB₁ group), 0.3 mg/kg AFB₁+0.2 mg/kg Se (+Se group I), 0.3mg/kg AFB₁+0.4 mg/kg Se (+Se group II) and 0.3mg/kg AFB₁+0.6 mg/kg Se (+Se group III), respectively. Compared with control group, the decreased relative weight of thymus and percentages of mature thymocytes, congestion in medulla and much debris in cortex of thymus, and the increased apoptotic thymocytes were observed in AFB1 group. However, supplied dietary sodium selenite could increase the relative weight of thymus and percentages of mature thymocytes, and alleviate histopathological lesions. Compared with AFB1 group, the percentages of apoptotic thymocytes detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method and flow cytometry method in three +Se groups were decreased, the expression of Caspase-3 and Bax, through quantitative real-time PCR and immunohistochemical method, in three +Se groups were decreased, while the expression of Bcl-2 was increased. The results indicate that sodium selenite supplied in the diet, through a mechanism of apoptosis regulation, may ameliorated AFB₁-induced lesions of thymus and accordingly improve the impaired cellular immune function., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The aim of this study was to investigate the possible protective role of sodium selenite on aflatoxin B1-induced oxidative stress and apoptosis in spleen of broilers. Two hundred one-day-old male broilers, divided into five groups, were fed with basal diet (control group), 0.3 mg/kg AFB1 (AFB1 group), 0.3 mg/kg AFB1 + 0.2 mg/kg Se (+Se group I), 0.3 mg/kg AFB1 + 0.4 mg/kg Se (+Se group II) and 0.3 mg/kg AFB1 + 0.6 mg/kg Se (+Se group III), respectively. According to biochemical assays, AFB1 significantly decreased the activities of glutathione peroxidase, total superoxide dismutase, glutathione reductase, catalase and the level of glutathione hormone, while it increased the level of malondialdehyde. Moreover, AFB1 increased the percentage of apoptosis cells by flow cytometry and the occurrence of apoptotic cells by TUNEL assay. Simultaneous supplementation with sodium selenite restored these parameters to be close to those in control group. In conclusion, sodium selenite exhibited protective effects on AFB1-induced splenic toxicity in broilers by inhibiting oxidative stress and excessive apoptosis.

Cecal tonsil is the largest peripheral lymphoid organ of the gut-associated lymphoid tissue executing immune function. To evaluate the protective effect of selenium (Se) on the cecal tonsil of chicken exposed to aflatoxin B1 (AFB1), 144 1-day-old healthy Cobb chickens were randomly divided into four groups, and fed with basal diet (control group), 0.6 mg/kg AFB1 (AFB1 group), 0.4 mg/kg Se supplement (+Se group), and 0.6 mg/kg AFB1 + 0.4 mg/kg Se supplement (AFB1 + Se group) for 21 days, respectively. The results showed that AFB1 significantly decreased the percentages of CD3+, CD3+CD4+, CD3+CD8+ T cells, and the CD4+/CD8+ ratio, and suppressed the expressions of IL-2, IL-4, TNF-α, and IFN-γ mRNA in the cecal tonsil. However, Selenium (Se) supplied in the diets restored the percentages of T cell subsets, the CD4+/CD8+ ratio, and mRNA expressions of cytokines in the AFB1 group to be close to those in the control group, and did not exhibit obvious toxicity to the cecal tonsil. These results indicated that Se exerted protective effect against AFB1 on the functions of cecal tonsil, and also partially uncovered a new role of Se that could protect cecal tonsil of chickens from immunotoxicity of AFB1. [ABSTRACT FROM AUTHOR]