Selenomethionine modulates the JAK2 / STAT3 / A20 pathway through oxidative stress to alleviate LPS-induced pyroptosis and inflammation in chicken hearts.

Selenium (Se) is involved in many physiopathologic processes in humans and animals and is strongly associated with the development of heart disease. Lipopolysaccharides (LPS) are cell wall components of gram-negative bacteria that are present in large quantities during environmental pollution. To investigate the mechanism of LPS-induced cardiac injury and the efficacy of the therapeutic effect of SeMet on LPS, a chicken model supplemented with selenomethionine (SeMet) and/or LPS treatment, as well as a primary chicken embryo cardiomyocyte model with the combined effect of SeMet / JAK2 inhibitor (INCB018424) and/or LPS were established in this experiment. CCK8 kit, Trypan blue staining, DCFH-DA staining, oxidative stress kits, immunofluorescence staining, LDH kit, real-time fluorescence quantitative PCR, and western blot were used. The results proved that LPS exposure led to ROS explosion, hindered the antioxidant system, promoted the expression of the JAK2 pathway, and increased the expression of genes involved in the pyroptosis pathway, inflammatory factors, and heat shock proteins (HSPs). Upon co-treatment with SeMet and LPS, SeMet reduced LPS-induced pyroptosis and inflammation and restored the expression of HSPs by inhibiting the ROS burst and modulating the antioxidant capacity. Co-treatment with INCB018424 and LPS resulted in inhibited of the JAK2 pathway, attenuating pyroptosis, inflammation, and high expression of HSPs. Thus, LPS induced pyroptosis, inflammation, and changes in HSPs activity by activating of the JAK2 / STAT3 / A20 signaling axis in chicken hearts. Moreover, SeMet has a positive effect on LPS-induced injury. This work further provides a theoretical basis for treating cardiac injury by SeMet.

Bisphenol A Regulates the TNFR1 Pathway and Excessive ROS Mediated by miR-26a-5p/ADAM17 Axis to Aggravate Selenium Deficiency-Induced Necroptosis in Broiler Veins.

Selenium (Se) deficiency can affect the expression of microRNA (miRNA) and induce necroptosis, apoptosis, etc., resulting in damage to various tissues and organs. Bisphenol A (BPA) exposure can cause adverse consequences such as oxidative stress, endothelial dysfunction, and atherosclerosis. The toxic effects of combined treatment with Se-deficiency and BPA exposure may have a synergistic effect. We replicated the BPA exposure and Se-deficiency model in broiler to investigate whether the combined treatment of Se-deficiency and BPA exposure induced necroptosis and inflammation of chicken vascular tissue via the miR-26A-5p/ADAM17 axis. We found that Se deficiency and BPA exposure significantly inhibited the expression of miR-26a-5p and increased the expression of ADAM17, thereby increasing reactive oxygen species (ROS) production. Subsequently, we discovered that the tumor necrosis factor receptor (TNFR1), which was highly expressed, activated the necroptosis pathway through receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed-lineage kinase domain-like (MLKL), and regulated the heat shock proteins-related genes expressions and inflammation-related genes expressions after exposure to BPA and selenium deficiency. In vitro, we found that miR-26a-5p knockdown and increased ADAM17 can induce necroptosis by activating the TNFR1 pathway. Similarly, both N-Acetyl-L-cysteine (NAC), Necrostatin-1 (Nec-1), and miR-26a-5p mimic prevented necroptosis and inflammation caused by BPA exposure and Se deficiency. These results suggest that BPA exposure activates the miR-26a-5p/ADAM17 axis and exacerbates Se deficient-induced necroptosis and inflammation through the TNFR1 pathway and excess ROS. This study lays a data foundation for future ecological and health risk assessments of nutrient deficiencies and environmental toxic pollution.

Selenium deficiency exacerbated Bisphenol A-induced intestinal toxicity in chickens: Apoptosis and cell cycle arrest mediated by ROS/P53.

Bisphenol A (BPA) is a phenolic organic synthetic compound that is used as the raw material of polycarbonate plastics, and its safety issues have recently attracted wide attention. Selenium (Se) deficiency has gradually developed into a global disease affecting intestinal function via oxidative stress and apoptosis. However, the toxic effects and potential mechanisms of BPA exposure and Se deficiency in the chicken intestines have not been studied. In this study, BPA exposure and/or Se deficiency models were established in vivo and in vitro to investigate the effects of Se deficiency and BPA on chicken jejunum. The results showed that BPA exposure and/or Se deficiency increased jejunum oxidative stress and DNA damage, activated P53 pathway, led to mitochondrial dysfunction, and induced apoptosis and cell cycle arrest. Using protein-protein molecular docking, we found a strong binding ability between P53 and peroxisome proliferator-activated receptor γ coactivator-1, thereby regulating mitochondrial dysfunctional apoptosis. In addition, we used N-acetyl-L-cysteine and pifithrin-α for in vitro intervention and found that N-acetyl-L-cysteine and pifithrin-α intervention reversed the aforementioned adverse effects. This study clarified the potential mechanism by which Se deficiency exacerbates BPA induced intestinal injury in chickens through reactive oxygen species/P53, which provides a new idea for the study of environmental combined toxicity of Se deficiency, and insights into animal intestinal health from a new perspective.

Bisphenol A exposure exacerbates tracheal inflammatory injury in selenium-deficient chickens by regulating the miR-155/TRAF3/ROS pathway.

Bisphenol A (BPA) is an endocrine disruptor. Excessive BPA intake can damage the structure and function of the respiratory tract. Dietary selenium (Se) deficiency may also cause immune tissue damage. To investigate the potential mechanism of BPA on tracheal damage in selenium-deficient chickens and the role of microRNAs (miRNAs) in this process, we established in vitro and in vivo Se deficiency and BPA exposure models and screened out miR-155 for follow-up experiments. We further predicted and confirmed the targeting relationship between miR-155 and TRAF3 using TargetScan and dual luciferase assays and found that miR-155 was highly expressed and caused inflammatory damage. Further studies showed that BPA exposure increased airway oxidative stress, activated the NF-κB pathway, and caused inflammation and immune damage in selenium-deficient chickens, but down-regulating miR-155 and NAC treatment could reverse this phenomenon. This suggested that these pathways are regulated by the miR-155/TRAF3/ROS axis. In conclusion, BPA exposure aggravates airway inflammation in selenium-deficient chickens by regulating miR-155/TRAF3/ROS. This study revealed the mechanism of BPA exposure combined with Se deficiency in tracheal inflammatory injury in chickens and enriched the theoretical basis of BPA injury in poultry.

Selenium alleviates lead-induced CIK cells pyroptosis and inflammation through IRAK1/TAK1/IKK pathway.

The toxic heavy metal lead is widely found in rivers and soils as an environmental pollutant, posing a threat to the health of aquatic organisms. Selenium is an essential trace element and a powerful antioxidant that has been shown to have anti-inflammatory and antioxidant properties as well as alleviating heavy metal poisoning. Many studies have shown that lead poisoning produces inflammatory responses and damage to the kidneys of a wide range of animals, but the effects on cellular pyroptosis and immune function and selenium antagonism in CIK cells are not clear. In this study, 500 µM Pb and 20 nM Se were applied to grass carp kidney cells, and the results showed that Pb exposure to CIK cells resulted in oxidative stress, activation of the IRAK1/TAK1/IKK pathway, up-regulation of the expression of cellular pyroptosis markers GSDMD and NLRP3, and cellular pyroptosis of CIK cells, as well as up-regulation of IL-1ß and IL-18, and the generation of cellular inflammatory response. In contrast, Se treatment significantly reduced the ROS level, the expression of cellular pyroptosis markers GSDMD, NLRP3 and inflammatory element IL-1ß and IL-18. Taken together, Se alleviated cellular pyroptosis and immune dysfunction caused by Pb exposure through oxidative stress and activation of the IRAK1/TAK1/IKK pathway. This study complements the harmful effects of the heavy metal Pb on fish and the real-life application of selenium in the healthy culture of fish as a reference will be provided.

New insights into brain injury in chickens induced by bisphenol A and selenium deficiency-Mitochondrial reactive oxygen species and mitophagy-apoptosis crosstalk homeostasis.

Bisphenol A (BPA), a component of plastic products, can penetrate the blood-brain barrier and pose a threat to the nervous system. Selenium (Se) deficiency can also cause nervous system damage. Resulting from the rapid industrial development, BPA pollution and Se deficiency often coexist. However, it is unclear whether brain damage in chickens caused by BPA exposure and Se deficiency is related to the crosstalk disorder between mitophagy and apoptosis. In this study, 60 chickens (1 day old) were fed with a diet that contained 20 mg/kg BPA but was insufficient in Se (only 0.039 mg/kg) for 42 days to establish a chicken brain injury model. In vitro, the primary chicken embryo brain neurons were treated for 24 h with Se-deficient medium containing 75 µM BPA. The results showed that BPA exposure and Se deficiency inhibited the expression of the mitochondrial respiratory chain complex in brain neurons, and a large number of mitochondrial reactive oxygen species were released. Furthermore, the expression levels of mitochondrial fusion proteins (OPA1, Mfn1, and Mfn2) decreased, while the expression levels of mitochondrial fission proteins (Drp1, Mff, and Fis1) increased, thus exacerbating mitochondrial division. In addition, the results of immunofluorescence and flow cytometry analysis, as well as the elevated expressions of mitophagy related genes (PINK1, Parkin, ATG5, and LC3II/I) and pro-apoptotic markers (Bax, Cytc, Caspase3, and Caspase9) indicated that BPA exposure and Se deficiency disrupted the crosstalk homeostasis between mitophagy and apoptosis. However, this crosstalk homeostasis was restored after Mito-Tempo and Rapamycin treatment. In contrast, 3-methyladenine treatment exacerbated this crosstalk disorder. In conclusion, BPA exposure and Se deficiency can induce mitochondrial reactive oxygen species bursts and disorders of mitochondrial dynamics by destroying the mitochondrial respiratory chain complex. The result is indicative of an imbalance in mitochondrial autophagy and apoptosis crosstalk homeostasis, which damages the chicken brain.

Roles of selenoprotein K in oxidative stress and endoplasmic reticulum stress under selenium deficiency in chicken liver.

Selenoprotein K (SELENOK) is a major part of selenoprotein family. Selenoproteins have been proven playing vital roles in a variety of physiological processes. However, as a necessary supplement to the body of trace elements, how SELENOK regulates necroptosis in chicken liver has none clear claim. The purpose of this study was to cover the mechanism of SELENOK act in necroptosis of chicken liver. By feeding Se-deficiency diet for 1-day-old hyline chickens, we successfully built SELENOK-deficiency and discussed the regulation SELENOK have done. The test of liver function showed there has dysfunction appeared in the -Se groups. Results of TEM showed necroptosis occurred in the 35-Se group. After that western blot and qRT-PCR results prompted us SELENOK-deficiency caused large accumulation of ROS, enhanced endoplasmic reticulum stress, abnormally elevated HSPs family expression, and activated RIPK1-RIPK3 complex. In order to show the regulation of SELENOK in chicken liver, we artificially knocked off SELENOK gene in LMH cells. Through AO/EB staining we also found necroptosis in the siRNA-Se group. Furthermore, the results in LMH cells were coincided with those in chicken (Gallus gallus) liver. Our experiment clarified the molecular mechanism of SELENOK in the regulation and liver necroptosis, and provided reference for the healthy feeding mode of broilers.

Bisphenol A exacerbates selenium deficiency-induced pyroptosis via the NF-κB/NLRP3/Caspase-1 pathway in chicken trachea.

Selenium deficiency can lead to multiple tissue and organ damage in the body and could coexist with chronic toxic exposures. Contamination from Bisphenol A (BPA) exposure can induce the occurrence of various injuries including pyroptosis. However, it is not clear whether selenium deficiency and BPA exposure affect tracheal tissue pyroptosis in chickens. To investigate whether selenium deficiency and BPA exposure induce chicken tracheal tissue pyroptosis via the NF-κB/NLRP3/Caspase-1 pathway and the effect of their combined exposure on tissue injury, we developed a model of relevant chicken tracheal injury. Sixty broilers were divided into four groups: the control group (C group), selenium-deficient group (SeD group), BPA-exposed group (BPA group) and combined exposure group (SeD + BPA group). The study examined the expression indicators of markers of pyroptosis (NLRP3&GSDMD), NF-κB pathway-related inflammatory factors (NF-κB, iNOS, TNF-α, COX-2), pyroptosis-related factors (ASC, Caspase-1, IL-1ß, IL-18), and some heat shock proteins and interleukins (HSP60, HSP90, IL-6, IL-17) in the samples. The results showed that the expression of the above indicators was significantly upregulated in the different treatment groups (P < 0.05). In addition, the expression levels of the above related indicators were more significantly up-regulated in the combined selenium-deficient and BPA-exposed group compared to the group in which they were individually exposed. It was concluded that selenium deficiency and BPA exposure induced tracheal tissue pyroptosis in chickens through NF-κB/NLRP3/Caspase-1 pathway, and BPA exposure exacerbated selenium deficiency-induced tracheal pyroptosis. The present study provides new ideas into studies related to the co-exposure of organismal micronutrient deficiency and chronic toxicants.

The decrease of selenoprotein K induced by selenium deficiency in diet improves apoptosis and cell progression block in chicken liver via the PTEN/PI3K/AKT pathway.

Selenoprotein K (SELK) is imperative for normal development of chicken. It does regulate to chicken's physiological function. However, the injury of SELK-deficiency done on chicken liver and its underlying mechanism involved has not yet been covered. Therefore, we built SELK- deficiency model by feeding diet which contained low concentration of selenium (Se) to discuss SELK's regulation mechanism. Through using TUNEL, TEM, western blot and qRT-PCR we found apoptosis occurred in chicken liver in the SELK-deficiency groups. In the meanwhile, our study showed there were differentially expressed of the PTEN/PI3K/AKT pathway, calcium homeostasis, endoplasmic reticulum healthy and cell cycle progression in SELK-deficiency chicken liver tissues. In order to claim the regulation mechanism of SELK, we set SELK-knock down model in the LMH. The results in vitro were coincided with those in vivo. In the SELK-deficiency groups, the PTEN/PI3K/AKT pathway was activated and then induced ERS which eventually resulted in apoptosis in chicken liver. As the same time, the PTEN/PI3K/AKT pathway also regulated the combined effective of MDM2-p53, which leaned liver cells to G1/S blocking. Our findings support the potential of SELK in maintain the health of chicken liver, and indicate that adding proper amount of Se on the daily dietary may alleviate the deficiency of selenium.

Selenium deficiency induced apoptosis via mitochondrial pathway caused by Oxidative Stress in porcine gastric tissues.

Selenium (Se) is an essential nutrient for the body, which can ensure GSH-Px activity and has antioxidant effect. Se deficiency may lead to apoptosis in various tissues and organs in animals. Pigs as major livestock in the farming industry, Se deficiency can cause various types of diseases such as white muscle disease, and mulberry heart disease.The aim of this experiment was to investigate the effect and mechanism of Se deficiency on apoptosis in porcine gastric tissue. Forty weaned piglets were randomly divided into Se deficiency group and control group, and fed with low Se diet and normal diet for six weeks respectively. The histochemical characteristics, antioxidant indexes, apoptotic genes and apoptotic protein expression of gastric cells in Se-deficient piglets were detected. The results of antioxidant index, TUNEL, RT-PCR and Western blot showed that Se deficiency decreased the activities of CAT, SOD and GSH-Px, increased the apoptotic rate of porcine gastric tissue, increased the expression of Bax and Caspase-3, and decreased the expression of Bcl-2. The results demonstrated that Se deficiency could induce apoptosis in porcine gastric tissue cells through oxidative stress-induced mitochondrial pathway. The stomach was a key target of Se deficiency and may play a key role in the response to Se deficiency. Our study may provide new ideas for the prevention and treatment of swine gastric diseases caused by Se deficiency and is beneficial to the development of pig farming industry.

Selenomethionine ameliorates LPS-induced intestinal immune dysfunction in chicken jejunum.

Selenomethionine (SeMet) is a widely used food supplement. However, the research on the effect of SeMet on intestinal immune function is not enough. Therefore, in this experiment, SeMet was added to the diet of chickens, and lipopolysaccharide (LPS) was used as harmful stimulation to study the effect of SeMet on intestinal immune function in chickens. We chose chicken jejunum as the research object. The results showed that LPS treatment decreased the expressions of selenoproteins and induced inflammatory reaction, cytokine disorder, decreases of immunoglobulin levels, heat shock protein expression disorder, and decreases of defensin expression levels in jejunum. However, dietary SeMet can effectively alleviate the above injury caused by LPS. Our results showed that SeMet could improve the intestinal immunity in chickens, and feeding SeMet could alleviate the intestinal immune dysfunction caused by LPS. The application range of SeMet in feed can be roughly given through our experiment; i.e. 0.35-0.5 mg/kg SeMet was effective. We speculated that dietary SeMet could effectively alleviate the intestinal immune dysfunction caused by harmful stimulation and help to resist the further damage caused by harmful stimulation.

Antagonistic effect of selenium on lead-induced neutrophil apoptosis in chickens via miR-16-5p targeting of PiK3R1 and IGF1R.

Environmental contamination by heavy metals, such as lead (Pb), can lead to severe immune dysfunction. MicroRNAs (miRNAs) are involved in regulating immunity. Whether Pb can regulate neutrophil apoptosis through miRNA, and whether selenium (Se) can antagonize this response are still unknown. We treated neutrophils with 12.5 µM (CH3OO)2Pb and 1 µM Na2SeO3 for 3 h, after which apoptosis was evaluated using acrideine orange/ethidium bromide (AO/EB) dual fluorescent staining and flow cytometry. The results showed that neutrophil apoptosis was significantly increased following Pb exposure, and that this response was prevented upon Se addition. Pb up-regulates miR-16-5p and leads to the subsequent down-regulation of the target genes phosphoinositide-3-kinase regulatory subunit 1 (PiK3R1), insulin-like growth factor 1 receptor (IGF1R), and phosphatidylinositol 3 kinase (Pi3K)-protein kinase B (AKT), followed by activation of the tumor protein P53 (P53)-B-cell lymphoma-2 (Bcl-2)/Bcl-2-Associated X protein (Bax)-cytochrome c (Cytc)-Caspase 9 (mitochondrial apoptotic pathway) and the tumor necrosis factor receptor superfamily member 6 (Fas)-Fas-associated death domain protein (Fadd)-Caspase 8 (death receptor pathway). Pb also triggered oxidative stress and indirectly activated the mitochondrial apoptotic pathway. We conclude that miR-16-5p plays a key role in the apoptosis of neutrophils exposed to Pb by down-regulating the expression of PiK3R1 and IGFR1, thereby activating the mitochondrial apoptotic pathway and death receptor pathway. Se can prevent Pb-induced apoptosis.

The antagonistic effect of Se on the Pb-weakening formation of neutrophil extracellular traps in chicken neutrophils.

Neutrophils represent an important part of the body's innate immunity and can resist the invasion of pathogenic microorganisms by releasing neutrophil extracellular traps (NETs). In this study, we investigated the toxic effects of lead (Pb) on the release of NETs, the antagonism of selenium (Se) on Pb toxicity and the potential molecular mechanisms. Our model was an in vitro exposure model for the addition of Se, Pb or both in the culture medium and was based on the separation of neutrophils from the peripheral blood of healthy chickens. Phorbol-myristate-acetate (PMA) was used as a stimulant. The scanning electron microscopy and fluorescence microscopy results showed that Pb weakened the PMA-induced formation of NETs. Exposure to Pb reduced the expression of the extracellular regulated protein kinase (ERK) pathway and the respiratory burst. Exposure to Pb also attenuated the release of Ca2+ in the endoplasmic reticulum mediated by the inositol 1,4,5-trisphosphate receptor (IP3R). These are two ways by which Pb decreases the formation of NETs. Pb also attenuates the expression levels of myeloperoxidase (MPO) and neutrophil elastase (NE), and attenuates histone removal by affecting the expression of different protein kinase C (PKC) isoforms. In contrast, Se can reduce the toxic damage caused by Pb. These results indicate that exposure to Pb decreases the formation of NETs, while Se can antagonize the toxicity of Pb to allow the formation of NETs.

Endogenous Hydrogen Sulfide Promotes Apoptosis via Mitochondrial Pathways in the Livers of Broilers with Selenium Deficiency Exudative Diathesis Disease.

Hydrogen sulfide (H2S), an endogenous gasotransmitter, plays an important role in apoptosis. Exudative diathesis (ED) disease is associated with dietary selenium (Se) deficiency in broilers. The liver is one of the target organs of Se deficiency; however, little is known about the effect of H2S on apoptosis via mitochondrial pathways in the livers of broilers with ED disease. In the present study, we aimed to investigate the correlation between endogenous H2S and mitochondrial-mediated apoptosis in the livers of broilers with ED disease, as induced by Se deficiency. One hundred twenty healthy, 1-day-old broilers were randomly assigned to one of two groups (60 each) based on diet: Basal diet (control group, 0.2 mg/kg Se) or a low-Se diet (-Se group, 0.033 mg/kg Se). At day 20, 15 broilers of a similar weight were sacrificed from the control group, while the same number of broilers were euthanatized from the -Se group when displaying typical symptoms of ED between days 18 and 25. The livers were collected, and apoptosis was measured using a TUNEL assay. Additionally, H2S concentration, the expression of H2S synthases of cystathionine γ-lyase (CSE), cystathionine ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as mitochondrial apoptosis-related genes of Bcl-2, Bax, Bak, Cyt-C, Caspase-9, Caspase-3, and p53, were examined in livers. The results indicated that Se deficiency could induce apoptosis in the livers of broilers. Swelling, fractures, and vacuolization were visible in the mitochondrial cristae in the livers of the -Se group. The expression of H2S synthase-related genes and H2S concentration was significantly enhanced (P < 0.05) in the livers of the -Se group compared to controls. Moreover, a low-Se diet downregulated (P < 0.05) the level of Bcl-2 and upregulated (P < 0.05) the levels of Bax, Bak, Cyt-C, Caspase-9, Caspase-3, and p53. These results suggest that an H2S increase in the livers of ED broilers, which was induced by Se deficiency, is related to apoptosis mediated by mitochondrial pathways.

Selenium Supplementation Changes the Ion Profile in the Pancreas of Chickens Treated with Cadmium.

Increasing evidence indicates that selenium (Se) could antagonize metal toxicity, including cadmium (Cd) toxicity. However, the effects of Se on Cd-induced changes in the ion profile in the pancreas of chickens have not been reported. In the present study, 128 Hy-Line brown laying chickens were divided into the control group, Se-treated group, Se/Cd-treated group, and Cd-treated group, and we detected the concentrations of 28 ions in the four groups by inductively coupled plasma mass spectrometry. In the Cd-treated group, the accumulation of Cd in the pancreas was 836.8 times higher that than in the control group (27,353.71 ppb/32.69 ppb). Meanwhile, the Ca, Ti, Fe, Mo, Li, Al, and Pb levels increased and the Cr, Mn, Ni, Cu, Zn, Se, Sr, and Sb levels decreased due to sub-chronic Cd poisoning. The Fe, Mo, Ba, and Pb levels decreased in the Se/Cd-treated group. Our findings suggest that Cd can accumulate in the chicken pancreas and affect the ion profiles, whereas Se can ameliorate the accumulation of Cd and change the ion profiles in the chicken pancreas.

The Protective Effect of Selenium on the Chicken Pancreas against Cadmium Toxicity via Alleviating Oxidative Stress and Autophagy.

Cadmium (Cd) is a highly toxic heavy metal that can affect human and animal health. Selenium (Se) is an essential microelement that can protect various organs against toxic heavy metals. Although many studies have investigated the adverse effect of Cd in rats and several other animals, little is known regarding the mechanisms of Cd-induced autophagy in the chicken pancreas and the antagonistic effect of Se on Cd. In the current study, we fed chickens Se, Cd, or Se and Cd supplements to establish the Se and Cd interaction model and to measure the concentrations of Se and Cd in the chicken pancreas. The ultrastructure changes of the chicken pancreas were also observed, and we detected oxidative stress indexes in each group. The expression levels of autophagy-related genes were also examined. We found that Cd exposure could increase the concentration of Cd, the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); and the total antioxidant capacity (T-AOC) content in the chicken pancreas. The protein expression levels of dynein, Beclin1, LC3-1, LC3-2, and Atg5 were increased and that of TOR was decreased under Cd exposure conditions. However, the changes induced by Cd were significantly alleviated by Se. This study suggested that Cd could accumulate in the chicken pancreas and lead to oxidative stress and autophagy. Se was shown to antagonize Cd toxicity though reducing Cd accumulation, alleviating oxidative stress, and inhibiting autophagy. This study revealed a concrete mechanism for the Se antagonism of Cd and might provide a new clue for the detoxification of Cd poisoning.

Ameliorative Effects of Selenium on Cadmium-Induced Oxidative Stress and Endoplasmic Reticulum Stress in the Chicken Kidney.

The harmful influences of dietary cadmium (Cd) on the chicken kidney and the protective role of selenium (Se) against Cd-induced nephrotoxicity in the chicken are relatively unexplored subjects. The aim of this study was to investigate the ameliorative role of Se on the effects of Cd-induced oxidative stress, endoplasmic reticulum stress, and apoptosis in chicken kidneys. For this study, 100-day-old chickens received Se (as 10 mg Na2SeO3/kg dry weight of diet), Cd (as 150 mg CdCl2/kg dry weight of diet), or Cd + Se in their diets for 60 days. Then, the histopathological changes, Cd and Se contents, levels of oxidative stress, inducible nitric oxide synthase-nitric oxide (iNOS-NO) system activity, levels of endoplasmic reticulum (ER) stress, results of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay of apoptosis, and expression levels of Bcl-2 and caspase 3 in the kidney were examined. The results showed that Cd exposure caused histopathological and ultrastructural damage and apoptosis of the kidneys. Cd administration significantly increased the accumulation of Cd, the malondialdehyde (MDA) content, NO production, iNOS activity, iNOS expression levels, expression levels of ER stress-related genes (GRP78, GRP94, ATF4, ATF6, and IRE) and the pro-apoptosis gene caspase 3, and the rate of apoptosis. Cd administration markedly decreased the Se content, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, and anti-apoptosis gene Bcl-2 expression levels. Co-treatment with Se and Cd obviously reduced the accumulation of Cd, Cd-induced histopathological and ultrastructural changes, oxidative stress, iNOS-NO system activity, ER stress, caspase 3 expression levels, and the rate of apoptosis in the kidneys. These results suggested that Cd exposure caused renal injury and that Se ameliorated Cd-induced nephrotoxicity in chickens.

Manganese-induced effects on testicular trace element levels and crucial hormonal parameters of Hyline cocks.

Manganese (Mn) is an essential element required for normal development and reproduction. However, little is known about the reproductive toxicity of Mn in birds. To investigate the Mn-induced toxicity on testicular trace element levels and crucial hormonal parameters on male reproduction in birds, 50-day-old male Hyline cocks were fed either a commercial diet or a Mn-supplemented diet. The changes in contents of copper (Cu), iron (Fe), zinc (Zn), and calcium (Ca) in testis were detected. Hormonal parameters were evaluated including the levels of testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) in the serum. The mRNA levels of luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR) were determined in this study. The results showed that Mn was accumulated in testis, and the content of Cu, Fe, Zn, and Ca decreased. Exposure to Mn significantly lowered the content of T, LH, FSH, and the mRNA expression levels of LHR and FSHR. Levels of T3 and T4 appeared with a decreased tendency, and TSH presented no obvious regularity. It indicated that Mn exposure resulted in the disbalance of testicular trace elements and influenced hormone levels in the molecular level, which may be possible underlying reproductive toxicity mechanism induced by Mn.