Nano-selenium alleviates cadmium-induced neurotoxicity in cerebrum via inhibiting gap junction protein connexin 43 phosphorylation.

Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.

Nanoselenium Alleviates Cadmium-Induced Cerebral Injury via Regulating Cerebral Metal Transporters and Metal-Regulatory Transcription Factor 1.

Cadmium (Cd) is a hazardous environmental metal that poses a global public health concern due to its high toxic potential. Nanoselenium (Nano-Se) is a nanoform of elemental Se that is widely used to antagonize heavy metal toxicity owing to its high safety margin with low doses. However, the role of Nano-Se in relieving Cd-induced brain damage is unclear. For this study, Cd-exposure-induced cerebral damage was established by using a chicken model. Administration of Nano-Se with Cd significantly decreased the Cd-mediated elevation of cerebral ROS, MDA, and H2O2 levels as well as markedly increased the Cd-mediated reduced activities of antioxidant biomarkers (GPX, T-SOD, CAT, and T-AOC). Accordingly, co-treatment with Nano-Se significantly reduced Cd-mediated increased Cd accumulation and recovered the Cd-induced biometal imbalance, notably Se and Zn. Nano-Se downregulated the Cd-induced upregulation of ZIP8, ZIP10, ZNT3, ZNT5, and ZNT6 and upregulated the Cd-mediated decreased expressions of ATOX1 and XIAP. Nano-Se also increased the Cd-mediated decreased mRNA levels of MTF1 and its target genes MT1 and MT2. Surprisingly, co-treatment with Nano-Se regulated the Cd-induced increased total protein level of MTF1 by reducing its expression. Moreover, altered selenoproteins regulation was recovered after co-treatment with Nano-Se as evidenced by increased expression levels of antioxidant selenoproteins (GPx1-4 and SelW) and Se transport-related selenoproteins (SepP1 and SepP2). The histopathological evaluation and Nissl staining of the cerebral tissues also supported that Nano-Se markedly reduced the Cd-induced microstructural alterations and well preserved the normal histological architectures of the cerebral tissue. Overall, the results of this research reveal that Nano-Se may be beneficial in mitigating Cd-induced cerebral injury in the brains of chickens. This present study provides a basis for preclinical research for its usefulness as a potential therapeutic for the treatment of neurodegeneration in the heavy-metal-induced neurotoxicity.

Lycopene ameliorates DEHP exposure-induced renal pyroptosis through the Nrf2/Keap-1/NLRP3/Caspase-1 axis.

Di (2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in plastic products, and due to its unique chemical composition, it frequently dissolves and enters the environment. Lycopene as a natural carotenoid has been shown to have powerful antioxidant capacity and strong kidney protection. This study aimed to investigate the role of the interplay between oxidative stress and the classical pyroptosis pathway in LYC alleviating DEHP-induced renal injury. ICR mice were given DEHP (500 mg/kg/d or 1000 mg/kg/d) and/or LYC (5 mg/kg/d) for 28 days to explore the underlying mechanisms of this hypothesis. Our results indicated that DEHP caused the shedding of renal tubular epithelial cells, increased the content of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the tissue, the decrease of antioxidant activity markers and the increase of oxidative stress indexes. It is gratifying that LYC alleviates DEHP-induced renal injury. The expression of nuclear factor erythrocyte 2-related factor 2 (Nrf2) and its downstream target genes is improved in DEHP induced renal injury through LYC mediated protection. Meanwhile, LYC supplementation can inhibit DEHP-induced Caspase-1/NLRP3-dependent pyroptosis and inflammatory responses. Taken together, DEHP administration resulted in nephrotoxicity, but these changes ameliorated by LYC may through crosstalk between the Nrf2/Keap-1/NLRP3/Caspase-1 pathway. Our study provides new evidence that LYC protects against kidney injury caused by DEHP.

Nano-selenium alleviates cadmium-induced cerebellar injury by activating metal regulatory transcription factor 1 mediated metal response.

This study aims to investigate the role of metal regulatory transcription factor 1 (MTF1)-mediated metal response in cadmium (Cd)-induced cerebellar injury, and to evaluate the antagonistic effects of nano-selenium (Nano-Se) against Cd toxicity. A total of 80 chicks (1 d old, male, Hy-Line Variety White) were randomly allocated to 4 treatment groups for 3 months: the control group (fed with a basic diet, n = 20), the Nano-Se group (basic diet with 1 mg/kg nano-Se 1 mg/kg Nano-Se in basic diet, n = 20), the Nano-Se + Cd group (basic diet with 1 mg/kg Nano-Se and 140 mg/kg CdCl2, n = 20) and the Cd group (basic diet with 140 mg/kg CdCl2 , n = 20). The results of the experiment showed that the Purkinje cells were significantly decreased with their degradation and indistinct nucleoli after Cd exposure. Moreover, exposure to Cd caused a significant accumulation of Cd and cupper. However, the contents of Se, iron, and zinc were decreased, thereby disturbing the metal homeostasis in the cerebellum. The Cd exposure also resulted in high levels of malondialdehyde (MDA) and down regulation of selenoprotein transcriptome. Furthermore, the expressions of MTF1, metallothionein 1 (MT1), MT2, zinc transporter 3 (ZNT3), ZNT5, ZNT10, zrt, irt-like protein 8 (ZIP8), ZIP10, transferrin (TF), ferroportin 1 (FPN1), ATPase copper transporting beta (ATP7B), and copper uptake protein 1 (CTR1) were inhibited by Cd exposure. However, all these changes were significantly alleviated by the supplementation of Nano-Se. This study proved that Cd could disorder metal homeostasis and induce oxidative stress, whereas Nano-Se could relieve all these negative effects caused by Cd via activating the MTF1-mediated metal response in the cerebellum of chicken.

Lycopene alleviates di(2-ethylhexyl) phthalate-induced splenic injury by activating P62-Keap1-NRF2 signaling.

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant. It has been determined that DEHP is involved in multiple health disorders. Lycopene (Lyc) is a natural carotenoid pigment, with anti-inflammatory and antioxidant properties. However, it is not clear whether Lyc can protect the spleen from DEHP-induced oxidative damage. A total of 140 mice were randomly divided into seven groups (n = 20) and continuously gavaged with corn oil, distilled water, DEHP (500 or 1000 mg/kg BW/day) and/or Lyc (5 mg/kg BW/day) for 28 days. Histopathological and ultrastructural results showed a DEHP-induced inflammatory response and mitochondrial injuries. Moreover, DEHP exposure induced redox imbalance, which resulted in the up-regulation of ROS activity and MDA content, and the down-regulation of T-AOC, T-SOD and CAT in the DEHP groups. Simultaneously, our results also demonstrated that DEHP-induced kelch-like ECH-associated protein 1 (Keap1) expression was downregulated, and the expression levels of P62, nuclear factor erythroid 2-related factor (NRF2) and their downstream target genes were up-regulated. However, the supplementary Lyc reverted these changes to normal levels. Together, Lyc prevented DEHP-induced splenic injuries by regulating the P62-Keap1-NRF2 signaling pathway. Hence, the protective effects of Lyc might be a therapeutic strategy to ameliorate DEHP-induced splenic damage.

Cadmium induced Fak -mediated anoikis activation in kidney via nuclear receptors (AHR/CAR/PXR)-mediated xenobiotic detoxification pathway.

Cadmium (Cd) is a toxic heavy metal of considerable toxicity, possessing a serious environmental problem that threatening food safety and human health. However, the underlying mechanisms of Cd-induced nephrotoxicity and detoxification response remain largely unclear. Cd was administered at doses of 35, 70, and 140 mg/kg diet with feed for 90 days and produced potential damage to chickens' kidneys. The results showed that Cd exposure induced renal anatomical and histopathological injuries. Cd exposure up-regulated cytochrome P450 enzymes (CYP450s), activated nuclear xenobiotic receptors (NXRs) response, including aryl hydro-carbon receptor (AHR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR) by low and moderate doses of Cd, and induced an increase in CYP isoforms expression. Cd exposure down-regulated phase II detoxification enzymes (glutathione-S-transferase (GST), glutathione peroxidase (GSH-PX) activities, and glutathione (GSH) content), and GST isoforms transcription . Furthermore, ATP-binding cassette (ABC) transporters, multidrug resistance protein (MRP1), and P-glycoprotein (P-GP) levels were elevated by low dose, but high dose inhibited the P-GP expression. Activation of detoxification enzymes lost their ability of resistance as increasing dose of Cd, afterwards brought into severe renal injury. Additionally, Cd suppressed focal adhesion kinase (Fak) and integrins protein expression as well as activated extrinsic pathway and intrinsic pathways, thereby producing anoikis. In conclusion, these results indicated that Cd induced Fak-mediated anoikis activation in the kidney via nuclear receptors (AHR/CAR/PXR)-mediated xenobiotic detoxification pathway.

Lycopene prevents DEHP-induced testicular endoplasmic reticulum stress via regulating nuclear xenobiotic receptors and unfolded protein response in mice.

Lycopene (LYC) is a potent antioxidant synthesized by red vegetables or plants. Di-2-ethylhexyl phthalate (DEHP) is frequently detected in diverse agricultural environments and considered as a reproductive toxicant. The present research was designed to assess the potential mechanisms of DEHP-induced testicular toxicity and the treatment efficacy of LYC. In this study, after the oral administration of LYC at the dose of 5 mg per kg b.w. per day, mice were given 500 or 1000 mg per kg b.w. per day of DEHP. This research suggested that LYC prevented the DEHP-induced disorder at the levels of activity and content of CYP450 enzymes. LYC attenuated DEHP-caused enhancement in nuclear xenobiotic receptors (NXRs) and the phase I metabolizing enzymes (CYP1, CYP2, CYP3, etc.) levels. Furthermore, endoplasmic reticulum (ER) stress was induced by DEHP and triggered unfolded protein response (UPR). Interestingly, LYC could effectively ameliorate these "hit". The present study suggested that LYC prevents DEHP-induced ER stress in testis via regulating NXRs and UPRER.

The protective effect of nnano-selenium against cadmium-induced cerebellar injury via the heat shock protein pathway in chicken.

Cadmium (Cd) is one of the toxic environmental heavy metals that poses health hazard to animals due to its toxicity. Nano-Selenium (Nano-Se) is a Nano-composite form of Se, which has emerged as a promising therapeutic agent for its protective roles against heavy metals-induced toxicity. Heat shock proteins (HSPs) play a critical role in cellular homeostasis. However, the potential protective effects of Nano-Se against Cd-induced cerebellar toxicity remain to be illustrated. To investigate the toxic effects of Cd on chicken's cerebellum, and the protective effects of Nano-Se against Cd-induced cerebellar toxicity, a total of 80 male chicks were divided into four groups and treated as follows: (A) 0 mg/kg Cd, (B) 1 mg/kg Nano-Se (C) 140 mg/kg Cd + 1 mg/kg Nano-Se (D) 140 mg/kg Cd for 90 days. We tested heat shock protein pathway-related factors including heat shock factors (HSFs) HSF1, HSF2, HSF3 and heat shock proteins (HSPs) HSP10, HSP25, HSP27, HSP40, HSP60, HSP70 and HSP90 expressions. Histopathological results showed that Cd treatment caused degradation of Purkinje cells. In addition, HSFs and HSPs expression decreased significantly in the Cd group. Nano-Se co-treatment with Cd enhanced the expression of HSFs and HSPs. In summary, our findings explicated a potential protective effect of Nano-Se against Cd-induced cerebellar injury in chicken, suggesting that Nano-Se is a promising therapeutic agent for the treatment of Cd toxicity.

Comparison of nanoparticle-selenium, selenium-enriched yeast and sodium selenite on the alleviation of cadmium-induced inflammation via NF-kB/IκB pathway in heart.

Cadmium (Cd) has been confirmed as an environmental contaminant, which potential threats health impacts to humans and animals. Selenium (Se) as a beneficial element that alleviates the negative effects of Cd toxicity. Se mainly exists in two forms in food nutrients including organic Se usually as (Se-enriched yeast (SeY)) and inorganic Se (sodium selenite (SSe)). Nanoparticle of Se (Nano-Se), a new form Se, which is synthesized by the bioreduction of Se species, which attracted significant attention recently. However, compared the superiority alleviation effects of Nano-Se, SeY or SSe on Cd-induced toxicity and related mechanisms are still poorly understood. The purpose of this study was to compare the superiority antagonism effects of Nano-Se, SeY and SSe on Cd-induced inflammation response via NF-kB/IκB pathway in the heart. The present study demonstrated that exposed to Cd obviously increased the accumulation of Cd, disruption of ion homeostasis and depressed the ratios of K+/Na+ and Mg2+/Ca2+ via ion chromatography mass spectrometry (ICP-MS) detecting the heart specimens. In the results of histological and ultrastructure observation, typical inflammatory infiltrate characteristics and mitochondria and nuclear structure alterations in the hearts of Cd group were confirmed. Cd treatment enhanced the inducible nitric oxide synthase (iNOS) activities and NOS isoforms expression via NF-kB/IκB pathway to promote inflammation response. However, the combined treatment of Cd-exposed animals with Nano-Se was more effective than SeY and SSe in reversing Cd-induced histopathological changes and iNOS activities increased, reducing Cd accumulation and antagonizing Cd-triggered inflammation response via NF-kB/IκB pathway in chicken hearts. Overall, Se applications, especially Nano-Se, can be most efficiently used for relieving cardiotoxicity by exposed to Cd compared to other Se compound.

AQP2 as a target of lycopene protects against atrazine-induced renal ionic homeostasis disturbance.

Atrazine (ATR), a ubiquitous environmental contaminant in water and soil, causes environmental nephrosis. To reveal the toxic effect of ATR on the kidney and the potential chemical nephroprotective effect of lycopene (LYC), Kun-Ming mice of specific pathogen-free (SPF) grade were treated with LYC (5 mg kg-1) and/or ATR (50 mg kg-1 or 200 mg kg-1) for 21 days. The degree of renal injury was evaluated by measuring the ion concentration, ATPase activities and the mRNA expressions/levels of associated ATPase subunits. In addition, the expression of renal aquaporins (AQPs) was analyzed. The results showed that the renal tubular epithelial cells of ATR-exposed mice were swollen, the glomeruli were significantly atrophied, and the ion concentrations were obviously changed. The activity of Na+-K+-ATPase and the transcription of its subunits were downregulated. The activity of Ca2+-Mg2+-ATPase and the transcription of its subunits were upregulated. The expression of AQPs, especially the critical AQP2, was affected. Notably, ATR-induced nephrotoxicity was significantly improved by LYC supplementation. Therefore, LYC could protect the kidney against ATR-induced nephrotoxicity via maintaining ionic homeostasis, reversing the changes in ATPase activity and controlling the expression of AQPs on the cell membrane. These results suggested that AQP2 was a target of LYC and protected against ATR-induced renal ionic homeostasis disturbance.

Lycopene attenuates di(2-ethylhexyl) phthalate-induced mitophagy in spleen by regulating the sirtuin3-mediated pathway.

Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. Di(2-ethylhexyl) phthalate (DEHP) is regarded as a universal environmental pollutant. To clarify the potential protective effect of Lyc on DEHP-induced splenic injury, 140 male mice were randomized into seven groups: control (distilled water), vehicle control (corn oil per day), Lyc (5 mg per kg BW per day), DEHP (500 or 1000 mg per kg BW per day), and DEHP combined Lyc group, respectively. All experimental animals were treated by oral gavage for 28 days. The results that showed DEHP exposure significantly up-regulated the mRNA and protein expression of the sirtuin family (except SIRT4-5), PGC-1α, OPA1, Drp1, MFN1/2, NRF1, TFAM, Parkin and PINK in DEHP-treated alone groups and the SOD2 and LC3-II protein expression were also in accordance with the above changes. These were accompanied with an increase of the number of inflammatory cells and rate of mitochondrial damage, and autophagosome formation in the spleen. Notably, Lyc supplementation facilitated all these changes to effectively return to the normal level, indicating that Lyc exerts protective effects against DEHP-induced splenic toxicity. Altogether, the protective effects of Lyc may be a strategy to ameliorate DEHP-induced spleen damage.

Comparative study on protective effect of different selenium sources against cadmium-induced nephrotoxicity via regulating the transcriptions of selenoproteome.

Cadmium (Cd) is a ubiquitous environmental pollutant, which mainly input to the aquatic environment through discharge of industrial and agricultural waste, can be a threat to human and animal health. Selenium (Se) possesses a beneficial role in protecting animals and ameliorating the toxic effects of Cd. However, the comparative antagonistic effects of different Se sources such as inorganic, organic Se and nano-form Se on Cd toxicity are still under-investigated. Hence, the purpose of this study was to evaluate the comparative of Se sources antagonism on Cd-induced nephrotoxicity via oxidative stress and selenoproteome transcription. In the present study, Cd-diet disturbed in the system balance of 5 trace elements (Zinc (Zn), copper (Cu), Iron (Fe), Se, Cd) and impaired renal function. Se sources, including nano- Se (NS), Se- yeast (SY), sodium selenite (SS) and mixed selenium (MS) significantly recovered the balance of 4 trace elements (Zn, Cu, Cd, Se) and renal impaired indexes (blood urea nitrogen (BUN) and creatinine (CREA)). Histological appearance of Cd-treated kidney indicated renal tubular epithelial vacuoles, particle degeneration and enlarged capsular space. Ultrastructure observation results illustrated that Cd-induced mitochondrial cristae reduction, membrane disappearance, and nuclear deformation. Treatment with Se sources, NS appeared a better impact on improving kidney tissues against the pathological alterations resulting from Cd administration. Meanwhile, NS reflected a significant impact on relieving Cd-induced kidney oxidative damage, and significantly restored the antioxidant defense system of the body. Our findings also showed NS ameliorated the Cd-induced downtrends expression of selenoproteome and selenoprotein synthesis related transcription factors. Overall, NS was the most effective Se source in avoiding of Cd cumulative toxicity, improving antioxidant capacity and regulating of selenoproteome transcriptome and selenoprotein synthesis related transcription factors expression, which contributes to ameliorate Cd-induced nephrotoxicity in chickens. These results demonstrated diet supplement with NS may prove to be an effective approach for alleviating Cd toxicity and minimizing Cd -induced health risk.

Potential Role of Lycopene in the Inhibition of Di(2-ethylhexyl) Phthalate-Induced Ferroptosis in Spleen Via Modulation of Iron Ion Homeostasis.

Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical and widely used as a plasticizer. Humans can be exposed to DEHP through direct contact or environmental contamination. Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. 140 male mice were assigned into control, vehicle control, Lyc (5 mg/kg BW/d), DEHP (500 and 1000 mg/kg BW/d, respectively), and DEHP + Lyc groups and treated with an oral gavage that lasted 28 d. The ultrastructural results showed that DEHP induced pathological changes and mitochondrial injuries. We further revealed that DEHP exposure destroyed the Fe2+ imbalance homeostasis and, consequently, increases of lipid peroxidation and inhibition of cysteine/glutamate antiporter, all of which were involved in the process of ferroptsis. Moreover, the supplementation of Lyc significantly inhibited the ferroptsis changes mentioned above. Altogether, these results indicated that DEHP exposure triggered splenic cell death via ferroptosis; meanwhile, they also shed new evidence on a potential clue for the intervention and prevention of DEHP-related diseases.

Selenium sources differ in their potential to alleviate the cadmium-induced testicular dysfunction.

Cadmium (Cd), a major environmental contaminant, is closely associated with male reproductive health. Selenium (Se) has been recognized as an effective chemo-protectant against Cd toxicity, but the underlying mechanisms remain unclear. The objective of present study was to illustrate the toxic effect of Cd on testis, and then compare the antagonistic effect among different Se sources on growth performance, testicular damage, ion homeostasis, antioxidative potential, and the expression of selenotranscriptome and biosynthetic related factors in Cd-treated chicken. Male chickens were fed with (Ⅰ) Control group: basal diet; (Ⅱ) Cd group: basal diet with 140 mg/kg CdCl2; (Ⅲ) YSe + Cd group: basal diet with 140 mg/kg CdCl2 and 3 mg/kg Yeast-Se; (Ⅳ) NSe + Cd group: basal diet with 140 mg/kg CdCl2 and 1 mg/kg Nano-Se; (Ⅴ) SSe + Cd group: basal diet with 140 mg/kg CdCl2 and 3 mg/kg Na2SeO3. It was observed that different Se treatments dramatically alleviated Cd-induced testicular developmental disorder, ion homeostasis disorder, hormone secretion disorder and oxidative stress. Simultaneously, Se mitigated Cd-induced testicular toxicity by regulating selenoprotein biosynthetic related factors to promote selenoprotein transcription. Finally, this study indicated that dietary supplementation of Yeast-Se produced an acceptable Se form to protect testis from Cd exposure.

Selenium mitigates cadmium-induced crosstalk between autophagy and endoplasmic reticulum stress via regulating calcium homeostasis in avian leghorn male hepatoma (LMH) cells.

Cadmium (Cd) is a toxic heavy metal and widespread in environment and food, which is adverse to human and animal health. Food intervention is a hot topic because it has no side effects. Selenium (Se) is an essential trace element, found in various fruits and vegetables. Many previous papers have described that Se showed ameliorative effects against Cd. However, the underlying mechanism of antagonistic effect of Se against Cd-induced cytotoxicity in avian leghorn male hepatoma (LMH) cells is unknown, the molecular mechanism of Se antagonistic effect on Cd-induced and calcium (Ca2+) homeostasis disorder and crosstalk of ER stress and autophagy remain to be explored. In order to confirm the antagonistic effect of Se on Cd-induced LMH cell toxicity, LMH cells were treated with CdCl2 (2.5 µM) and Na2SeO3 (1.25 and 2.5 µM) for 24 h. In this study, Cd exposure induced cell death, disrupted intracellular Ca2+ homeostasis and Ca2+ homeostasis related regulatory factors, interfered with the cycle of cadherin (CNX)/calreticulin (CRT), and triggered ER stress and autophagy. Se intervention inhibited Cd-induced LDH release and crosstalk of ER stress and autophagy via regulating intracellular Ca2+ homeostasis. Moreover, Se mitigated Cd-induced Intracellular Ca2+ overload by Ca2+/calmodulin (CaM)/calmodulin kinase IV (CaMK-IV) signaling pathway. Herein, CNX/CRT cycle played a critical role for the protective effect of Se on Cd-induced hepatotoxicity. Based on these findings, we demonstrated that the application of Se is beneficial for prevention and alleviation of Cd toxicity.

Selenium prevent cadmium-induced hepatotoxicity through modulation of endoplasmic reticulum-resident selenoproteins and attenuation of endoplasmic reticulum stress.

Cadmium (Cd), a heavy metal contaminant, exists in humans and animals throughout life and closely associate with severe hepatotoxicity. Selenium (Se) has been recognized as an effective chemo-protectant of Cd, but the underlying mechanisms remain unclear. The objective of the present study is to illustrate the antagonistic effect of Se against Cd-induced hepatotoxicity. Primary hepatocytes were cultured in the presence of 5 µM Cd, 1 µM Se and the mixture of 1 µM Se and 5 µM Cd for 24 h. Cell viability and morphology, antioxidant status, endoplasmic reticulum (ER) stress response and selenotranscriptome were assessed. It was observed that Se treatment dramatically alleviated Cd-induced hepatocytes death and morphological change. Simultaneously, Se mitigated Cd-induced oxidative stress by reducing ROS production, increasing reduced glutathione (GSH) level and increasing selenoenzyme (glutathione peroxidase, GPX) activity. Cd induced hepatotoxicity via disordering ER-resident selenoproteins transcription and triggering ER stress and unfolded protein response. Supplementary Se evidently relieved hepatocytes injury via modulating ER-resident selenoproteins transcription to inhibit ER stress. Collectively, our findings showed a potential protection of Se against Cd-induced hepatotoxicity via suppressing ER stress response.

Selenoprotein W as a molecular target of d-amino acid oxidase is regulated by d-amino acid in chicken neurons.

Selenoprotein W (SelW) is an important member of the avian selenoprotein family. It is well known for its important role in protecting neurons from oxidative stress during neuronal development. d-Amino acid (d-serine), as a neurotransmitter in the central nervous system (CNS), can mediate neurotoxicity. d-Amino acid oxidase (DAAO) is responsible for regulating the d-serine levels in cells. However, the correlation between SelW and DAAO is not clear yet. To investigate the regulations between SelW and DAAO, chicken embryo monolayer neurons were treated with d-serine and/or Se. In this study, we predicted molecular binding between SelW and DAAO. These results showed that the 9-16, 18, 41-47 and 66 residues of SelW could combine with the DAAO, which suggested that chicken SelW might be the target of DAAO. We determined the DAAO activity and the mRNA expression of SelW in in vitro cultured chicken embryo primitive neuron cells. d-Serine influenced the activity of DAAO and, moreover, a significant increase in the mRNA expression of SelW was found in neurons treated with Se. Notably, we also observed changes in the expression of SelW and DAAO when neurons were treated with various concentrations of d-serine and Se. In conclusion, these data suggest that d-serine could regulate the mRNA expression of SelW by interfering with the activity of DAAO in chicken embryo neurons.