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

ABSTRACTBackgroundSelenium (Se) plays a protective role in aflatoxin B1 (AFB1)–induced splenic immunotoxicity in chicks.ObjectiveThis study was designed to reveal the underlying mechanism of Se-mediated protection against AFB1-induced splenic injury in broilers.MethodsFour 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.ResultsDietary AFB1 induced growth retardation and spleen injury, decreasing (P < 0.05) body weight gain, feed intake, feed conversion efficiency, and serum interleukin-1β 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 (β 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.ConclusionsDietary Se deficiency exacerbated AFB1-induced spleen injury in chicks, partially through the regulation of oxidative stress, inflammatory and apoptotic signaling, and 6 selenoproteins.

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288 Se deficiency aggravates AFB1-induced immunotoxicity in chick spleen via regulating six selenoprotein and redox/inflammation/apoptotic signaling

Journal of Animal Science ◽

10.1093/jas/skz258.249 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 120-121

Author(s):

Ling Zhao ◽

Yue Feng ◽

Jiang Deng ◽

Ni-Ya Zhang ◽

Lv-hui Sun

Keyword(s):

Body Weight Gain ◽

Thioredoxin Reductase ◽

B Cell Lymphoma ◽

Underlying Mechanism ◽

Redox Status ◽

White Pulp ◽

Feed Conversion ◽

Apoptotic Signaling ◽

Protein Levels ◽

Se Deficiency

Abstract This study was designed to reveal the underlying mechanism of Se-mediated protection against aflatoxin B1 (AFB1)-induced splenic injury in broilers. Four groups of day-old Cobb male broilers (n = 5 cages/diet, 6 chicks/cage) were arranged in a 3-wk 2×2 factorial design trial that fed a Se-deficient, corn and soy–based diet (BD, 36 μg Se/kg) or the BD + 1.0 mg AFB1/kg, 0.3 mg Se/kg, or 1.0 mg AFB1/kg with 0.3 mg Se/kg (as 2-hydroxy-4-methylselenobutanoic acid). Serum and spleen were collected at wk 3 to assay for histology, cytokines, redox status, and selected inflammation- and apoptosis-related genes and proteins, and selenogenome. Dietary AFB1 induced the growth retardation and spleen injury, decreasing (P < 0.05) body weight gain, feed intake, feed conversion efficiency, and serum interleukin-1β, increasing (P < 0.05) spleen index and serum interleukin-6, and reduced the splenic lymphocyte number and white pulp region and histiocyte proliferation in Se adequate groups. However, Se deficiency aggravated (P < 0.05) these AFB1-induced changes. Moreover, Se deficiency decreased (P < 0.05) splenic glutathione peroxidases (GPX) activities and glutathione concentration in AFB1 exposed groups. Furthermore, Se deficiency also upregulated (P < 0.05) the antimicrobial (beta defensin 1 and 2) and apoptotic (Caspase 3 and Caspase 9) genes but downregulated (P < 0.05) antiapoptotic (B-cell lymphoma 2) and inflammatory (E3 ubiquitin-protein ligase CBL-B) genes at mRNA and(or) protein levels 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. In conclusions, dietary Se deficiency aggravated AFB1-induced spleen injury in chicks, partially through the regulation of the oxidative stress, inflammatory and apoptotic signaling and six selenoproteins (Supported in part by Chinese Natural Science Foundation Projects 31772636 and 31501987).

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Mitigation of Aflatoxin B1 Hepatoxicity by Dietary Hedyotis diffusa Is Associated with Activation of NRF2/ARE Signaling in Chicks

Antioxidants ◽

10.3390/antiox10060878 ◽

2021 ◽

Vol 10 (6) ◽

pp. 878

Author(s):

Ling Zhao ◽

Jiang Deng ◽

Zi-Jian Xu ◽

Wan-Po Zhang ◽

Mahmoud Mohamed Khalil ◽

...

Keyword(s):

Aflatoxin B1 ◽

Body Weight Gain ◽

Control Diet ◽

Protein Carbonyl ◽

Heme Oxygenase 1 ◽

High Dose ◽

Feed Conversion ◽

Quinone Oxidoreductase ◽

Vacuolar Degeneration ◽

Hedyotis Diffusa

The objective of this study was to explore the mechanism of Hedyotis diffusa (HD) in mediating the detoxification of aflatoxin B1 (AFB1)-induced hepatic injury in chicks. A total of 144 one-day-old male broilers (Cobb 500) were randomly assigned to four treatment groups (n = 6 cages/diet, 6 chicks/cage). After three days of acclimation, the broilers were fed either a control diet (Control), Control plus 0.5 mg/kg of AFB1, or Control plus 0.5 mg/kg AFB1 with 500 or 1000 mg/kg HD for two weeks. Both serum and liver were collected at the end of the feeding trial for biochemistry, histology, and NF-E2-related nuclear factor 2 (NRF2)/antioxidant response element (ARE) signaling analysis. Compared with Control, the AFB1 treatment caused liver injury and decreased (p < 0.05) body weight gain, feed intake, feed conversion ratio, and serum albumin and total protein by 6.2–20.7%. AFB1 also induced swelling, necrosis, and severe vacuolar degeneration in chicks’ livers. Notably, HD supplementation at 500 and 1000 mg/kg mitigated (p < 0.05) the alterations induced by AFB1. HD supplementation alleviated (p < 0.05) AFB1-induced impairment in hepatic glutathione peroxidase activity, protein carbonyl, and exo-AFB1-8,9-epoxide (AFBO)–DNA concentrations by 57.7–100% and increased (p < 0.05) the activities of superoxide dismutase and catalase by 23.1–40.9% more than those of AFB1 treatment alone. Furthermore, HD supplementation at the two doses upregulated (p < 0.05) NRF2, NAD(P)H: quinone oxidoreductase-1, heme oxygenase-1, glutathione cysteine ligase catalytic subunit, and glutathione-S transferase A2 and A3 in livers relative to the AFB1 group by 0.99–3.4-fold. Overall, dietary supplementation of HD at a high dose displayed better protection effects against aflatoxicosis. In conclusion, a dietary HD supplementation at 500 and 1000 mg/kg protected broilers from AFB1-induced hepatotoxicity, potentially due to the activation of NRF2/ARE signaling in the chicks.

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The effect of Silybum marianum seed, Thymus vulgaris, and Rosmarinus officinalis powders in alleviating the risks of aflatoxin B1 in young broiler chicks

Annals of Animal Science ◽

10.2478/aoas-2021-0027 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Hamid Raei ◽

Ramin Najafi ◽

Mohammad Amir Karimi Torshizi ◽

Seyyed Meysam Abtahi Froushani ◽

Fatemeh Azari Ghaleh Joogh

Keyword(s):

Aflatoxin B1 ◽

Broiler Chickens ◽

Body Weight Gain ◽

Positive Control ◽

Rosmarinus Officinalis ◽

Thigh Muscle ◽

Thymus Vulgaris ◽

Broiler Chicks ◽

Feed Conversion ◽

Silybum Marianum

Abstract This investigation was aimed to evaluate the effects of Silybum marianum seed, Thymus vulgaris, and Rosmarinus officinalis powders and their combination in alleviating the risks of aflatoxin B1 (AFB1) in young broiler chicks. One-day-old Ross 308 male broiler chickens were allocated to 6 experimental groups from d 1 to 21. The experimental dietary groups included: Negative control (NC) received the basal diet, Positive control (PC) containing 2 mg AFB1/kg diet; Positive control + 10 g/kg diet of Silybum marianum seed (SMS); Positive control + 10 g/kg diet of Thymus vulgaris (TV); Positive control + 5 g/kg diet of Rosmarinus officinalis (RO); Positive control + 10 g/kg diet of SMS + 10 g/kg diet of TV + 5 g/kg diet of RO as a blend of herbs (BH). There was no difference between feed intake and body weight gain among the experimental groups (P>0.05). In contrast, the feed conversion rate (FCR) in NC and SMS groups was lower than other groups (P<0.05). Calcium levels and high-density lipoprotein cholesterol (HDL) were lower in serum samples, but the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were higher in PC chickens (P<0.05). Increase in the thigh muscle malondialdehyde (MDA) in chickens fed AFB1 was significantly reduced in the NC, SMS, and BH chickens (P<0.05). Chickens of NC and SMS groups showed the highest response to respiratory burst of heterophile (NBT assay) and lymphocyte proliferation assays (MTT assay) (P<0.05). In conclusion, the addition of studied herbs, especially SMS, to the AFB1 contaminated diet could have a protective effect against aflatoxicosis in broiler chickens.

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Curcumin Protects an SH-SY5Y Cell Model of Parkinson’s Disease Against Toxic Injury by Regulating HSP90

Cellular Physiology and Biochemistry ◽

10.1159/000495326 ◽

2018 ◽

Vol 51 (2) ◽

pp. 681-691 ◽

Cited By ~ 13

Author(s):

Qiuling Sang ◽

Xiaoyang Liu ◽

Libo Wang ◽

Ling Qi ◽

Wenping Sun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Cell Proliferation ◽

Parkinson's Disease ◽

Cell Model ◽

B Cell Lymphoma ◽

Underlying Mechanism ◽

Protective Role ◽

Enzyme Linked Immunosorbent Assay ◽

Western Blot Assay ◽

The Impact

Background/Aims: We aimed to explore the protective role of curcumin (Cur) in a cell model of Parkinson’s disease (PD) and its underlying mechanism. Methods: In this study, genes concerned with PD-related keywords were screened within DiGSeE database. The association network between Cur and selected genes was downloaded from STITCH, with the interactions analyzed by STRING. We built a mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y cell model of PD. Cell morphology was observed under an electron microscope. MTT assay was applied to detect cell proliferation rate. Western blot assay was conducted to determine the level of apoptotic markers, including cleaved caspase 3, Bcl-2-associated X protein (Bax) and B-cell lymphoma-extra-large (Bcl-xl). Tyrosine hydroxylase (TH), dopamine transporter (DAT) protein levels and dopamine (DA) concentration were identified as dopaminergic neuron markers and measured by western blotting or Enzyme-linked immunosorbent assay (ELISA). Results: Cur rescued the toxicity effects of MPP+ on SH-SY5Y cells, by controlling morphological change, promoting cell proliferation and inhibiting apoptosis. Of all PD-related genes, HSP90 played an important role in Cur-gene network. HSP90 protein level was elevated by MPP+, whereas Cur could reverse this effect. Silencing of HSP90 significantly attenuated the curative effect introduced by Cur, while HSP90 overexpression enhanced the impact of Cur on PD. Conclusion: Cur can effectively inhibit the toxic effect of MPP+ on SH-SY5Y cells and significantly reduce the adverse effects of MPP+ on dopaminergic neurons via up-regulation of HSP90.

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Selenium status highly regulates selenoprotein mRNA levels for only a subset of the selenoproteins in the selenoproteome

Bioscience Reports ◽

10.1042/bsr20080146 ◽

2009 ◽

Vol 29 (5) ◽

pp. 329-338 ◽

Cited By ~ 137

Author(s):

Roger A. Sunde ◽

Anna M. Raines ◽

Kimberly M. Barnes ◽

Jacqueline K. Evenson

Keyword(s):

Thioredoxin Reductase ◽

Selenium Deficiency ◽

Underlying Mechanism ◽

Pcr Analysis ◽

Mrna Levels ◽

Nonsense Mediated Decay ◽

Liver And Kidney ◽

Se Deficiency ◽

Selenoprotein Mrnas ◽

Se Status

Gpx (glutathione peroxidase)-1 enzyme activity and mRNA levels decrease dramatically in Se (selenium) deficiency, whereas other selenoproteins are less affected by Se deficiency. This hierarchy of Se regulation is not understood, but the position of the UGA selenocysteine codon is thought to play a major role in making selenoprotein mRNAs susceptible to nonsense-mediated decay. Thus in the present paper we studied the complete selenoproteome in the mouse to uncover additional selenoprotein mRNAs that are highly regulated by Se status. Mice were fed on Se-deficient, Se-marginal and Se-adequate diets (0, 0.05 and 0.2 μg of Se/g respectively) for 35 days, and selenoprotein mRNA levels in liver and kidney were determined using microarray analysis and quantitative real-time PCR analysis. Se-deficient mice had liver Se concentrations and liver Gpx1 and thioredoxin reductase activities that were 4, 3 and 3% respectively of the levels in Se-adequate mice, indicating that the mice were Se deficient. mRNAs for Selh (selenoprotein H) and Sepw1 (selenoprotein W) as well as Gpx1 were decreased by Se deficiency to <40% of Se-adequate levels. Five and two additional mRNAs were moderately down-regulated in Sedeficient liver and kidney respectively. Importantly, nine selenoprotein mRNAs in liver and fifteen selenoprotein mRNAs in the kidney were not significantly regulated by Se deficiency, clearly demonstrating that Se regulation of selenoprotein mRNAs is not a general phenomenon. The similarity of the response to Se deficiency suggests that there is one underlying mechanism responsible. Importantly, the position of the UGA codon did not predict susceptibility to Se regulation, clearly indicating that additional features are involved in causing selenoprotein mRNAs to be sensitive to Se status.

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THE EFFECT OF (Morinda citrifolia L.) MEAL IN DIET ON PERFORMANCE OF BROILER

Jurnal Agroindustri ◽

10.31186/j.agroind.2.1.21-27 ◽

2012 ◽

Vol 2 (1) ◽

pp. 21-27

Author(s):

Yosi Fenita

Keyword(s):

Body Weight ◽

Body Weight Gain ◽

Morinda Citrifolia ◽

Feed Consumption ◽

Feed Conversion ◽

Randomized Design ◽

Different Levels ◽

Effect Of Feeding ◽

Average Body ◽

Average Body Weight

The objective of the research was to evaluate to effect of feeding mengkudu on performances of broilers. The research design used was completely randomized design. One hundred broilers were distributed into five treatments. The treatments were different levels of mengkudu meal (0, 0.75%, 1.5%, 2.25 % and 3%). The observed measured were feed consumption, average body weight (gain) and feed conversion. Results showed that feeding mengkudu (Morinda Citrifolia L.) no effect significant (P>0.05) on feed consumption, average body weight and feed conversion. In conclusion, feeding mengkudu meal up to 3% (in diet) does not negatively affect feed consumption, average body weight, and feed conversion.

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Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells

Current Bioactive Compounds ◽

10.2174/1573407214666180727093612 ◽

2020 ◽

Vol 16 (1) ◽

pp. 85-89

Author(s):

Mahesh M. Gouda ◽

Ashwini Prabhu ◽

Varsha Reddy S.V. ◽

Rafa Jahan ◽

Yashodhar P. Bhandary

Keyword(s):

Epithelial Cells ◽

Lung Injury ◽

Molecular Mechanisms ◽

A549 Cells ◽

Plasminogen Activator Inhibitor ◽

Underlying Mechanism ◽

Protective Role ◽

Alveolar Epithelial Cells ◽

Cellular Damage

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation. Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression. Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin. Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

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Supplementing Garlic Nanohydrogel Optimized Growth, Gastrointestinal Integrity and Economics and Ameliorated Necrotic Enteritis in Broiler Chickens Using a Clostridium perfringens Challenge Model

Animals ◽

10.3390/ani11072027 ◽

2021 ◽

Vol 11 (7) ◽

pp. 2027

Author(s):

Doaa Ibrahim ◽

Tamer Ahmed Ismail ◽

Eman Khalifa ◽

Shaimaa A. Abd El-Kader ◽

Dalia Ibrahim Mohamed ◽

...

Keyword(s):

Growth Performance ◽

Clostridium Perfringens ◽

Broiler Chickens ◽

Body Weight Gain ◽

Economic Benefits ◽

Production Costs ◽

Broiler Chicks ◽

Necrotic Enteritis ◽

Feed Conversion ◽

Intestinal Lesion

Necrotic enteritis (NE) caused by Clostridium perfringens (C. perfringens) results in impaired bird growth performance and increased production costs. Nanotechnology application in the poultry industry to control NE outbreaks is still not completely clarified. Therefore, the efficacy of dietary garlic nano-hydrogel (G-NHG) on broilers growth performance, intestinal integrity, economic returns and its potency to alleviate C. perfringens levels using NE challenge model were addressed. A total of 1200 male broiler chicks (Ross 308) were assigned into six groups; four supplemented with 100, 200, 300 or 400 mg of G-NHG/kg diet and co-challenged with C. perfringens at 21, 22 and 23 d of age and two control groups fed basal diet with or without C. perfringens challenge. Over the total growing period, the 400 mg/kg G-NHG group had the most improved body weight gain and feed conversion efficiency regardless of challenge. Parallel with these results, the mRNA expression of genes encoding digestive enzymes (alpha 2A amylase (AMY2A), pancreatic lipase (PNLIP) and cholecystokinin (CCK)) and intestinal barriers (junctional adhesion molecule-2 (JAM-2), occludin and mucin-2 (Muc-2)) were increased in groups fed G-NHG at higher levels to be nearly similar to those in the unchallenged group. At 14 d post challenge, real-time PCR results revealed that inclusion of G-NHG led to a dose-dependently decrease in the C. perfringens population, thereby decreasing the birds’ intestinal lesion score and mortality rates. Using 400 mg/kg of G-NHG remarkably ameliorated the adverse effects of NE caused by C. perfringens challenge, which contributed to better growth performance of challenged birds with rational economic benefits.

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TRPM4 in Cancer—A New Potential Drug Target

Biomolecules ◽

10.3390/biom11020229 ◽

2021 ◽

Vol 11 (2) ◽

pp. 229

Author(s):

Anna Borgström ◽

Christine Peinelt ◽

Paulina Stokłosa

Keyword(s):

Anticancer Drug ◽

Drug Target ◽

Transient Receptor Potential ◽

Human Cancer ◽

Receptor Potential ◽

B Cell Lymphoma ◽

Underlying Mechanism ◽

Monovalent Cation ◽

Transient Receptor Potential Melastatin ◽

And Migration

Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, liver, breast, urinary bladder, cervical, and endometrial cancer. In several types of cancer TRPM4 is overexpressed and contributes to cancer hallmark functions such as increased proliferation and migration and cell cycle shift. Hence, TRPM4 is a potential prognostic cancer marker and a promising anticancer drug target candidate. Currently, the underlying mechanism by which TRPM4 contributes to cancer hallmark functions is under investigation. TRPM4 is a Ca2+-activated monovalent cation channel, and its ion conductivity can decrease intracellular Ca2+ signaling. Furthermore, TRPM4 can interact with different partner proteins. However, the lack of potent and specific TRPM4 inhibitors has delayed the investigations of TRPM4. In this review, we summarize the potential mechanisms of action and discuss new small molecule TRPM4 inhibitors, as well as the TRPM4 antibody, M4P. Additionally, we provide an overview of TRPM4 in human cancer and discuss TRPM4 as a diagnostic marker and anticancer drug target.

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Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression, evoking oxidative stress, and activating inflammation and apoptosis

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-021-00587-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Shuang Li ◽

Wenjuan Sun ◽

Kai Zhang ◽

Jiawei Zhu ◽

Xueting Jia ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

The Body ◽

Terminal Deoxynucleotidyl Transferase ◽

Antioxidant Systems ◽

Tunel Staining ◽

White Pulp ◽

Sibling Pairs ◽

Se Deficiency ◽

Spleen Index

Abstract Background The immune system is one aspect of health that is affected by dietary selenium (Se) levels and selenoprotein expression. Spleen is an important immune organ of the body, which is directly involved in cellular immunity. However, there are limited reports on Se levels and spleen health. Therefore, this study established a Se-deficient pig model to investigate the mechanism of Se deficiency-induced splenic pathogenesis. Methods Twenty-four pure line castrated male Yorkshire pigs (45 days old, 12.50 ± 1.32 kg, 12 full-sibling pairs) were divided into two equal groups and fed Se-deficient diet (0.007 mg Se/kg) or Se-adequate diet (0.3 mg Se/kg) for 16 weeks. At the end of the trial, blood and spleen were collected to assay for erythroid parameters, the osmotic fragility of erythrocytes, the spleen index, histology, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining, Se concentrations, the selenogenome, redox status, and signaling related inflammation and apoptosis. Results Dietary Se deficiency decreased the erythroid parameters and increased the number of osmotically fragile erythrocytes (P < 0.05). The spleen index did not change, but hematoxylin and eosin and TUNEL staining indicated that the white pulp decreased, the red pulp increased, and splenocyte apoptosis occurred in the Se deficient group. Se deficiency decreased the Se concentration and selenoprotein expression in the spleen (P < 0.05), blocked the glutathione and thioredoxin antioxidant systems, and led to redox imbalance. Se deficiency activated the NF-κB and HIF-1α transcription factors, thus increasing pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α), decreasing anti-inflammatory cytokines (IL-10, IL-13, and TGF-β) and increasing expression of the downstream genes COX-2 and iNOS (P < 0.05), which in turn induced inflammation. In addition, Se-deficiency induced apoptosis through the mitochondrial pathway, upregulated apoptotic genes (Caspase3, Caspase8, and Bak), and downregulated antiapoptotic genes (Bcl-2) (P < 0.05) at the mRNA level, thus verifying the results of TUNEL staining. Conclusions These results indicated that Se deficiency induces spleen injury through the regulation of selenoproteins, oxidative stress, inflammation and apoptosis.

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