RESUMEN
OBJECTIVE: To investigate the effect of selenium on cyclophosphamide (CTX)-induced spermatogenic impairment (SI) in mice and its underlying mechanism. METHODS: We equally randomized 36 male KM mice into 3 SI model and 3 control groups, the first 3 treated by intraperitoneal injection of CTX at 100 mg/kg (the SI model control group), CTX plus SI model control group, selenium deficient model group (ï¼Se SI), selenium supplemented model group (+Se SI), while latter 3 by intraperitoneal injection of normal saline (the normal control), selenium deficiency control group (ï¼Se control), selenium addition control group (+Se control), respectively, all once a week for 6 successive weeks. Then we observed the histopathological changes in the testes of all the mice by HE staining, obtained the sperm count in the epididymides, determined the expressions of glutathione peroxidase 4 (GPx4) and SLC7A11 proteins by Western blot and ferroptosis-related genes by RT-qPCR, and examined the changes in the expressions of ferroptosis-related proteins and genes in the GC2-spd cells treated with ferroptosis inhibitors and inducers in combination with different concentrations of inorganic sodium selenite (SeS) and organic selenomethionine (SeM). RESULTS: Compared with the normal controls, the SI model mice showed significantly decreased testicular and prostatic organ coefficients, reduced spermatogenic layers, increased voids, decreased serum ferritin concentration (P<0.05), and elevated transferrin concentration (P<0.05). The organ coefficients were significantly higher in the +Se SI and +Se control than in the ï¼Se SI and ï¼Se control groups (P<0.05, P<0.01), with evident pathological improvement of the testis tissue in the +Se controls. The expressions of the GPx4 and solute carrier family 7 members 11ï¼SLC7A11ï¼ genes in the testis were dramatically down-regulated in the SI model controls (P<0.01), but up-regulated in the +Se SI and +Se control compared with those in the ï¼Se SI and ï¼Se control group (P<0.01 and P<0.05), but there were no statistically significant differences between their protein expressions. The results of in vitro GC2 spd cell experiments indicated that the GPx4 gene and GPx4 protein levels in the - Se group were significantly lower than those in the normal control group (P<0.05), while the SLC7A11 gene level decreased (P<0.01). Different doses of SeS and SeM significantly increased the GPx4 protein expression compared to the average Se group. Low doses of SeM promoted a significant increase in GPx4 gene levels, while high doses of SeS increased the expression levels of SLC7A11 gene and SLC7A11 protein (P<0.05, P<0.01). The Se group showed a significant decrease in the levels of acsl4 and ptgs2 genes compared to the normal control group. SeM promoted the expression of acsl4, while SeS promoted the expression of ptgs2 and fth1 (P<0.01, P<0.05). The intervention results of GC2 spd showed that the Erastin group had a decrease in ptgs2 compared to the normal control group, while the SeS+Erastin and SeM+Erastin groups had an increase in ptgs2 gene expression compared to the Erastin group. However, the ptgs2 expression of Fer-1 was lower than that of the normal control group, and the ptgs2 gene level of SeS+Fer-1 and SeM+Fer-1 groups was lower than that of Fer-1 group (P<0.05); The gene quantity of GPx4 in the SeM+Erastin and SeM+Fer-1 groups increased compared to the Erastin and Fer-1 groups (P<0.01, P<0.05); SeM+Erastin and SeS+Erastin showed a decrease in SLC7A11 compared to the Erastin group, as well as SeM+Fer-1 and SeS+Fer-1 groups compared to the Fer-1 group, accompanied by an increase in acsl4 and fth1 (P<0.01). CONCLUSION: Selenium deficiency causes the reduction of the SLC7A11 and GPx4 gene levels, disorder of ferroptosis-related genes and down-regulation of the GPx4 protein expression in the mouse testis and spermatocytes. Selenium can promote the expression of GPx4, up-regulate the level of SLC7A11, and improve spermatogenesis in the testis of the mouse with SI. There are differences between organic SeM and inorganic SeS in regulating the ferroptosis pathway-related genes.
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Ciclofosfamida , Selenio , Espermatogénesis , Testículo , Animales , Masculino , Ciclofosfamida/efectos adversos , Ratones , Selenio/farmacología , Espermatogénesis/efectos de los fármacos , Testículo/metabolismo , Testículo/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Ferroptosis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Recuento de Espermatozoides , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Selenito de Sodio/farmacologíaRESUMEN
BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is an acute renal complication that occurs after intravascular contrast agent administration. Sodium selenite (SS) is an inorganic source of Se and has potent antioxidant properties. This study intends to examine its anti-inflammatory and antioxidant effects in CI-AKI. METHODS: A rat CI-AKI model was established with the pretreatment of SS (0.35 mg/kg). Hematoxylin-eosin staining was employed for histopathological analysis of rat kidney specimens. Biochemical analysis was conducted for renal function detection. Tissue levels of oxidative stress-related markers were estimated. Reverse transcription-quantitative polymerase chain reaction revealed the mRNA levels of proinflammatory cytokines. Western blotting showed the Nrf2 signaling-related protein expression in the rat kidney. RESULTS: SS administration alleviated the renal pathological changes and reduced the serum levels of serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin, cystatin C, and urinary level of kidney injury molecule-1 in CI-AKI rats. SS attenuated oxidative stress and inflammatory response in CI-AKI rat kidney tissues. SS activated the Nrf2 signaling transduction in the renal tissues of rats with CI-AKI. CONCLUSION: SS ameliorates CI-AKI in rats by reducing oxidative stress and inflammation via the Nrf2 signaling.
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Lesión Renal Aguda , Medios de Contraste , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Ratas Sprague-Dawley , Transducción de Señal , Selenito de Sodio , Animales , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/patología , Estrés Oxidativo/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Masculino , Medios de Contraste/efectos adversos , Transducción de Señal/efectos de los fármacos , Selenito de Sodio/farmacología , Selenito de Sodio/uso terapéutico , Elementos de Respuesta Antioxidante , Inflamación/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Creatinina/sangreRESUMEN
Selenium (Se)-rich Cyclocarya paliurus is popular for its bioactive components, and exogenous Se fortification is the most effective means of enrichment. However, the effects of exogenous Se fortification on the nutritional quality of C. paliurus are not well known. To investigate the nutrient contents and antioxidant properties of C. paliurus following Se treatment, we used a foliar spray to apply Se in two forms-chemical nano-Se (Che-SeNPs) and sodium selenite (Na2SeO3). Sampling began 10 days after spraying and was conducted every 5 days until day 30. The Se, secondary metabolite, malondialdehyde contents, antioxidant enzyme activity, Se speciation, and Se-metabolism-related gene expression patterns were analyzed in the collected samples. Exogenous Se enhancement effectively increased the Se content of leaves, reaching a maximum on days 10 and 15 of sampling, while the contents of flavonoids, triterpenes, and polyphenols increased significantly during the same period. In addition, the application of Se significantly enhanced total antioxidant activity, especially the activity of the antioxidant enzyme peroxidase. Furthermore, a positive correlation between the alleviation of lipid peroxidation and Se content was observed, while methylselenocysteine formation was an effective means of alleviating Se stress. Finally, Na2SeO3 exhibited better absorption and conversion efficiency than Che-SeNPs in C. paliurus.
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Antioxidantes , Hojas de la Planta , Selenio , Selenito de Sodio , Antioxidantes/metabolismo , Selenio/metabolismo , Selenio/análisis , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Selenito de Sodio/farmacología , Selenito de Sodio/metabolismo , Juglandaceae/química , Flavonoides/metabolismo , Flavonoides/análisis , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Polifenoles/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Triterpenos/metabolismoRESUMEN
Background and Objectives: Selenium deficiency represents a risk factor for the occurrence of severe diseases, such as acute kidney injury (AKI). Recently, selenoprotein-p1 (SEPP1), a selenium transporter, mainly released by the liver, has emerged as a promising plasmatic biomarker of AKI as a consequence of cardio-surgery operations. The aim of the present study was to investigate, on an in vitro model of hypoxia induced in renal tubular cells, HK-2, the effects of sodium selenite (Na2SeO3) and to evaluate the expression of SEPP1 as a marker of injury. Materials and Methods: HK-2 cells were pre-incubated with 100 nM Na2SeO3 for 24 h, and then, treated for 24 h with CoCl2 (500 µM), a chemical hypoxia inducer. The results were derived from an ROS assay, MTT, and Western blot analysis. Results: The pre-treatment determined an increase in cells' viability and a reduction in reactive oxygen species (ROS), as shown by MTT and the ROS assay. Moreover, by Western blot an increase in SEPP1 expression was observed after hypoxic injury as after adding sodium selenite. Conclusions: Our preliminary results shed light on the possible role of selenium supplementation as a means to prevent oxidative damage and to increase SEPP1 after acute kidney injury. In our in vitro model, SEPP1 emerges as a promising biomarker of kidney injury, although further studies in vivo are necessary to validate our findings.
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Túbulos Renales Proximales , Daño por Reperfusión , Selenoproteína P , Humanos , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/etiología , Biomarcadores/análisis , Línea Celular , Supervivencia Celular , Técnicas In Vitro , Túbulos Renales Proximales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Selenoproteína P/sangre , Selenoproteína P/metabolismo , Selenito de Sodio/farmacologíaRESUMEN
It is known that selenium (Se) is an essential trace element, important for the growth and other biological functions of fish. One of its most important functions is to contribute to the preservation of certain biological components, such as DNA, proteins, and lipids, providing protection against free radicals resulting from normal metabolism. The objective of this study was to evaluate and optimize selenium accumulation in the native yeast Rhodotorula mucilaginosa 6S. Sodium selenite was evaluated at different concentrations (5-10-15-20-30-40 mg/L). Similarly, the effects of different concentrations of nitrogen sources and pH on cell growth and selenium accumulation in the yeast were analyzed. Subsequently, the best cultivation conditions were scaled up to a 2 L reactor with constant aeration, and the proteome of the yeast cultured with and without sodium selenite was evaluated. The optimal conditions for biomass generation and selenium accumulation were found with ammonium chloride and pH 5.5. Incorporating sodium selenite (30 mg/L) during the exponential phase in the bioreactor after 72 h of cultivation resulted in 10 g/L of biomass, with 0.25 mg total Se/g biomass, composed of 25% proteins, 15% lipids, and 0.850 mg total carotenoids/g biomass. The analysis of the proteomes associated with yeast cultivation with and without selenium revealed a total of 1871 proteins. The results obtained showed that the dynamic changes in the proteome, in response to selenium in the experimental medium, are directly related to catalytic activity and oxidoreductase activity in the yeast. R. mucilaginosa 6S could be an alternative for the generation of selenium-rich biomass with a composition of other nutritional compounds also of interest in aquaculture, such as proteins, lipids, and pigments.
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Proteómica , Rhodotorula , Selenio , Rhodotorula/metabolismo , Rhodotorula/crecimiento & desarrollo , Rhodotorula/efectos de los fármacos , Selenio/metabolismo , Selenio/farmacología , Proteómica/métodos , Biomasa , Reactores Biológicos/microbiología , Selenito de Sodio/metabolismo , Selenito de Sodio/farmacología , Concentración de Iones de Hidrógeno , Proteoma/metabolismo , Proteínas Fúngicas/metabolismoRESUMEN
Tumor cells are characterized by a delicate balance between elevated oxidative stress and enhanced antioxidant capacity. This intricate equilibrium, maintained within a threshold known as redox homeostasis, offers a unique perspective for cancer treatment by modulating reactive oxygen species (ROS) levels beyond cellular tolerability, thereby disrupting this balance. However, currently used chemotherapy drugs require larger doses to increase ROS levels beyond the redox homeostasis threshold, which may cause serious side effects. How to disrupt redox homeostasis in cancer cells more effectively remains a challenge. In this study, we found that sodium selenite and docosahexaenoic acid (DHA), a polyunsaturated fatty acid extracted from marine fish, synergistically induced cytotoxic effects in colorectal cancer (CRC) cells. Physiological doses of DHA simultaneously upregulated oxidation and antioxidant levels within the threshold range without affecting cell viability. However, it rendered the cells more susceptible to reaching the upper limit of the threshold of redox homeostasis, facilitating the elevation of ROS levels beyond the threshold by combining with low doses of sodium selenite, thereby disrupting redox homeostasis and inducing MAPK-mediated paraptosis. This study highlights the synergistic anticancer effects of sodium selenite and DHA, which induce paraptosis by disrupting redox homeostasis in tumor cells. These findings offer a novel strategy for more targeted and less toxic cancer therapies for colorectal cancer treatment.
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Neoplasias Colorrectales , Ácidos Docosahexaenoicos , Homeostasis , Sistema de Señalización de MAP Quinasas , Oxidación-Reducción , Especies Reactivas de Oxígeno , Selenito de Sodio , Ácidos Docosahexaenoicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Selenito de Sodio/farmacología , Humanos , Oxidación-Reducción/efectos de los fármacos , Homeostasis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Línea Celular Tumoral , Estrés Oxidativo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Antioxidantes/farmacología , Sinergismo Farmacológico , Antineoplásicos/farmacología , ParaptosisRESUMEN
This study aimed to investigate the protective effects of nanoparticle selenium (SeNP) and sodium selenite (SS) on preventing oxidative stress during the freezing process of dog semen. A total of six dogs were used in the study. The ejaculate was collected from dogs three times at different times by massage method. A total of 18 ejaculates were used and each ejaculate was divided in five experimental groups. The experimental groups were designed to tris extender containing no antioxidants control, 1 µg/mL SeNP1, 2 µg/mL SeNP2, and 1 µg/mL SS1 and 2 µg/mL SS2. Extended semen were equilibrated for 1 h at 4°C, then frozen in liquid nitrogen vapour and stored in liquid nitrogen (~-196°C). After thawing, semen samples were evaluated in terms of CASA motility and kinematic parameters, spermatozoa plasma membrane integrity and viability (HE Test), spermatozoa morphology (SpermBlue) and DNA fragmentation (GoldCyto). Antioxidant enzyme activity (glutathione peroxidase; GPX, superoxide dismutase; SOD, catalase; CAT) and lipid peroxidation (malondialdehyde; MDA) were evaluated in frozen-thawed dog sperm. When the results were evaluated statistically, the progressive motility, VCL, and VAP kinematic parameters in the SeNP1 group were significantly higher than the control group after thawing (p < .05). The highest ratio of plasma membrane integrity and viable spermatozoa was observed in the SeNP1 group, but there was no statistical difference found between the groups (p > .05). Although the ratio of total morphological abnormality was observed to be lower in all groups to which different selenium forms were added, compared to the control group, no statistical difference was found. Spermatozoa tail abnormality was significantly lower in the SeNP1 group than in the control and SS2 group (p < .05). The lowest ratio of fragmented DNA was observed in the SeNP1 group, but there was no statistical difference was found between the groups (p > .05). Although there was no statistical difference between the groups in the evaluation of sperm antioxidant profile, the highest GPX, SOD and CAT values and the lowest lipid peroxidation values were obtained in the SeNP1 group. As a result, it was determined that 1 µg/mL dose of SeNP added to the tris-based extender in dog semen was beneficial on spermatological parameters, especially sperm kinematic properties and sperm morphology, and therefore nanoparticle selenium, a nanotechnology product, made a significant contribution to the freezing of dog semen.
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Antioxidantes , Criopreservación , Selenio , Preservación de Semen , Selenito de Sodio , Espermatozoides , Animales , Perros , Masculino , Selenito de Sodio/farmacología , Selenito de Sodio/administración & dosificación , Selenio/farmacología , Selenio/administración & dosificación , Selenio/química , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Criopreservación/veterinaria , Criopreservación/métodos , Espermatozoides/efectos de los fármacos , Antioxidantes/farmacología , Motilidad Espermática/efectos de los fármacos , Nanopartículas , Estrés Oxidativo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Análisis de Semen/veterinaria , Fragmentación del ADN/efectos de los fármacos , Crioprotectores/farmacología , CongelaciónRESUMEN
BACKGROUND: The rising incidence of prostate cancer in the U.S. necessitates innovative therapeutic approaches to this disease. Though extensive research has studied Selenium as an anticarcinogen against prostate cancer, results have varied due to overlooked experimental confounds. Recent studies have identified differential effects of various selenium compounds on prostate cancer cells. This study leverages Mixture Design Response Surface Methodology to characterize the ideal combination of select Se forms against the PC-3 prostate cancer cell line. METHODS: The PC-3 cell line was chosen as a model for its representation of advanced-stage malignancy. Three Se compounds-sodium selenite, methylseleninic acid, and nano-selenium-were selected for their promising antineoplastic potential. Nano-Se particles were synthesized and subsequently characterized by transmission electron microscopy. Cells were cultured, treated with Se compounds, and assessed for viability using an Alamar Blue Assay. IC50 values of individual Se compounds were determined, and treatment combinations evaluated. In collaboration with statical modeling experts, MDRSM was utilized to optimize Se compound combinations. RESULTS: Absolute IC50 values were identified for methylseleninic acid (5.01 µmol/L), sodium selenite (13.8 µmol/L), and nano-selenium (14.6 µmol/L). Combining methylseleninic acid and sodium selenite resulted in only 5% PC-3 cell viability, whereas individual treatments reduced viability by approximately 45%. Among the tested mixtures, the 50:50 combination of MSA and sodium selenite most effectively decreased PC-3 cell viability. Regression analysis indicated the special cubic model had a strong fit (multiple r² = 0.9853), predicting maximum cell viability reduction from the methylseleninic acid and selenite mixture. CONCLUSION: The specific form of Selenium plays a pivotal role in determining its physiological effects and therapeutic potential against prostate cancer. All three selenium compounds showed variable antineoplastic effects, with a 50:50 mixture of methylseleninic acid and selenite exhibiting optimal results. Nano-selenium, when combined with selenite, showed no additive effect, implying a shared mechanism of action. Our research underscores the critical need to consider Se compound forms as distinct entities in prostate cancer treatment and encourages further exploration of Se compounds against prostate cancer.
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Supervivencia Celular , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Supervivencia Celular/efectos de los fármacos , Células PC-3 , Antineoplásicos/farmacología , Antineoplásicos/química , Selenio/farmacología , Selenio/química , Compuestos de Organoselenio/farmacología , Compuestos de Organoselenio/química , Ensayos de Selección de Medicamentos Antitumorales , Selenito de Sodio/farmacología , Nanopartículas/química , Propiedades de Superficie , Relación Dosis-Respuesta a DrogaRESUMEN
In this study, we investigated the effects of different types of selenium (Se) (sodium selenite [SS], yeast selenium [YS], and nano-selenium [NS]) on the toxicity, growth, Se accumulation, and transformation of Lucilia sericata maggots (LSMs). We found that the 50% lethal concentration of LSMs exposed to SS was 2.18 and 1.96 times that of YS and NS, respectively. LSM growth was significantly promoted at exposure concentrations of 10-50 mg kg-1 in group SS and 10-30 mg kg-1 in group YS, whereas NS inhibited LSMs growth at all concentrations (p < 0.05). Total Se content in LSMs, conversion efficiency to organic and other forms of Se, and bioaccumulation factor of Se were the highest in the SS group when exposed to 50 mg kg-1 (81.6 mg kg-1, 94.6%, and 1.63, respectively). Transcriptomic results revealed that LSMs significantly upregulated the amino acid (alanine, aspartate, glutamic, and tyrosine) and tricarboxylic acid cycle signaling pathways (p < 0.05) on exposure to Se, resulting in a significant increase in LSMs biomass and quality. In conclusion, our study indicates that LSMs exhibit good tolerance to SS and can convert it into bioorganic or other forms of Se.
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Selenio , Selenito de Sodio , Animales , Selenito de Sodio/farmacología , Selenito de Sodio/metabolismo , Selenio/metabolismo , Saccharomyces cerevisiae/metabolismo , Larva/metabolismo , BioacumulaciónRESUMEN
The research was carried out in order to find ways to optimize the system of protection of spring wheat crops. In the conducted studies, the effect of combinations of sodium selenite and various pesticides, differing in the specifics of action and biological activity, on the yield and quality of spring wheat of the Yubileinaya 80 variety was studied. Currently, there is a need to achieve a sufficient effect of the action of chemical plant protection products and to obtain a minimum impact on human health and the environment. The purpose of the research is to study the influence of various combinations of chemical plant protection products and methods of using sodium selenite on the yield and grain quality indicators of spring wheat variety Yubileinaya 80. The studies were carried out under the conditions of a vegetative experiment with spring wheat variety Yubileinaya 80. Two methods of using sodium selenite and chemical plant protection agents of different specifics of action were studied: fungicide, herbicide, and insecticide, which were applied in different combinations and at different times. As a result of the studies, the phytotoxicity of the studied preparations of chemical plant protection was revealed, which apparently manifests itself as a result of inhibition of the morphometric indicators of the growth of the root system and vegetative organs of wheat plants, resulting in a violation of the processes of accumulation of assimilates and their outflow to the reproductive organs. Optimal combinations of pesticides and sodium selenite have been established, allowing to obtain reliable changes in yield and quality indicators of wheat grain. It was revealed that the use of selenium treatment before sowing seeds contributed to a decrease in the phytotoxicity of the studied pesticides, as a result of stimulating the processes of absorption by plants and the redistribution of nitrogen to the reproductive organs of wheat, which had a positive effect not only on the yield and quality of spring wheat of the Yubileynaya 80 variety, but also on the external surface microstructure of the fruit shell of the grain. The noted features of the surface of the fruit shell of the grain will reduce losses during grain processing and obtain processed products from such grain of higher quality.
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Plaguicidas , Selenio , Humanos , Selenio/farmacología , Triticum , Plaguicidas/toxicidad , Selenito de Sodio/farmacología , Grano ComestibleRESUMEN
Matrine (MT), an active ingredient derived from Sophor flavescens Ait, is used as a therapeutic agent to treat liver disease and cancer. However, the serious toxic effects of MT, including nephrotoxicity, have limited its clinical application. Here, we explored the involvement of ferroptosis in MT-induced kidney injury and evaluated the potential efficacy and underlying mechanism of sodium selenite (SS) in attenuating MT-induced nephrotoxicity. We found that MT not only disrupts renal structure in mice but also induces the death of NRK-52E cells. Additionally, MT treatment resulted in significant elevations in ferrous iron, reactive oxygen species (ROS) and lipid peroxidation levels, accompanied by decreases in glutathione (GSH) and glutathione peroxidase (GPx) levels. SS effectively mitigated the alterations in ferroptosis-related indicators caused by MT and prevented MT-induced nephrotoxicity as effectively as Fer-1 in vivo and in vitro. SS also reversed the MT-induced reduction in GPX4, CTH and xCT protein levels. However, the glutathione peroxidase 4 (GPX4) inhibitor RSL3 and knockdown of GPX4, CTH, or xCT via siRNA abolished the protective effect of SS against MT-induced nephrotoxicity, indicating that SS exhibited antiferroptotic effects via the GSH-GPX4 antioxidant system. Overall, MT-induced ferroptosis triggers nephrotoxicity, and SS is a promising therapeutic drug for alleviating MT-induced renal injury by activating the GSH-GPX4 axis.
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Alcaloides , Antioxidantes , Ferroptosis , Glutatión , Matrinas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Quinolizinas , Selenito de Sodio , Animales , Ferroptosis/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Quinolizinas/farmacología , Selenito de Sodio/farmacología , Glutatión/metabolismo , Ratones , Antioxidantes/farmacología , Antioxidantes/metabolismo , Alcaloides/farmacología , Masculino , Ratas , Especies Reactivas de Oxígeno/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Ratones Endogámicos C57BL , Línea CelularRESUMEN
BACKGROUND: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM: To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.
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Infecciones por Helicobacter , Helicobacter pylori , Selenio , Animales , Ratones , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Selenito de Sodio/farmacología , Ratones Endogámicos C57BL , Citotoxinas , Infecciones por Helicobacter/metabolismoRESUMEN
Selenium (Se), an essential trace element, plays an important role in the antioxidative defense mechanism, and it has been proven to improve fertility and reproductive efficiency in dairy cattle. The present study evaluated the potential protective action of Se supplement of in vitro maturation (IVM) media on the maturation and subsequent development of bovine cumulus-oocyte complexes (COCs) exposed to heat stress (HS). The treatment with Se improved the viability of cumulus cells (CCs) and oocytes (P < 0.05). The proportion of oocytes reached metaphase II (MII) and those arrested at metaphase I (MI) was greater and lower in treatment than control respectively (P < 0.05). Supplementation with Se increased the percentage of cleaved embryos, total blastocysts, and blastocyst/cleavage ratio (P < 0.05). Moreover, the upregulation of CCND1, SEPP1, GPX-4, SOD, CAT, and downregulation of GRP78, CHOP, and BAX in both Se-treated CCs and oocytes were recorded. The upregulation of NRF2 was detected in Se-treated CCs other than in oocytes, which showed upregulation of IGF2R and SOX-2 as the markers of quality as well. Se supplement in IVM media improved the viability, maturation, and the level of transcripts related to antioxidant defense and quality of heat-treated oocytes, which coincided with greater subsequent development outcomes. Se ameliorated the viability of CCs along with upregulation of antioxidative candidate gene expression and downregulation of apoptosis-related ones to support their protective role on restoring the quality of oocytes against compromising effects of HS.
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Técnicas de Maduración In Vitro de los Oocitos , Selenito de Sodio , Bovinos , Animales , Femenino , Selenito de Sodio/farmacología , Selenito de Sodio/metabolismo , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Oocitos , Respuesta al Choque Térmico , Células del Cúmulo/fisiologíaRESUMEN
Selenium contributes to physiological functions through its incorporation into selenoproteins. It is involved in oxidative stress defense. A selenium deficiency results in the onset or aggravation of pathologies. Following a deficiency, the repletion of selenium leads to a selenoprotein expression hierarchy misunderstood. Moreover, spirulina, a microalga, exhibits antioxidant properties and can be enriched in selenium.. Our objective was to determine the effects of a sodium selenite or selenium-enriched spirulina supplementation. Thirty-two female Wistar rats were fed for 12 weeks with a selenium-deficient diet. After 8 weeks, rats were divided into 4 groups and were fed with water, sodium selenite (20 µg Se/kg body weight), spirulina (3 g/kg bw), or selenium-enriched spirulina (20 µg Se/kg bw + 3 g spirulina/kg bw). Another group of 8 rats was fed with normal diet during 12 weeks. Selenium concentration and antioxidant enzyme activities were measured in plasma, urine, liver, brain, kidney, heart, and soleus. Expression of GPx (1, 3), Sel (P, S, T, W), SEPHS2, TrxR1, ApoER2, and megalin were quantified in liver, kidney, brain, and heart. We showed that a selenium deficiency leads to a growth delay, reversed by selenium supplementation despite a minor loss of weight in week 12 for SS rats. All tissues displayed a decrease in selenium concentration following deficiency. The brain seemed protected. We demonstrated a hierarchy in selenium distribution and selenoprotein expression. A supplementation of sodium selenite improved GPx activities and selenoprotein expression while a selenium-enriched spirulina was more effective to restore selenium concentration especially in the liver, kidney, and soleus.
Asunto(s)
Desnutrición , Selenio , Spirulina , Ratas , Femenino , Animales , Antioxidantes/metabolismo , Selenito de Sodio/farmacología , Spirulina/metabolismo , Ratas Wistar , Selenoproteínas/metabolismo , Suplementos Dietéticos , Glutatión Peroxidasa/metabolismoRESUMEN
Perfluoro octane sulfonate (PFOS) and cadmium (Cd) are toxic elements in the environment. As a micronutrient trace element, selenium (Se) can mitigate the adverse effects induced by PFOS and Cd. However, few studies have examined the correlation between Se, PFOS and Cd in fish. The present study focused on the antagonistic effects of Se on PFOS+Cd-induced accumulation in the liver of zebrafish. The fish was exposed to PFOS (0.08mg/L), Cd (1mg/L), PFOS+ Cd (0.08 mg/L PFOS+1 mg/L Cd), L-Se (0.07mg/L Sodium selenite +0.08mg/L PFOS+1mg/L Cd), M-Se (0.35mg/L Sodium selenite + 0.08mg/L PFOS+ 1 mg/L Cd), H-Se (1.75 mg/L Sodium selenite + 0.08 mg/L PFOS+ 1mg/L Cd) for 14d. The addition of selenium to fish exposed to PFOS and Cd has been found to have significant positive effects. Specifically, selenium treatments can alleviate the adverse effects of PFOS and Cd on fish growth, with a 23.10% improvement observed with the addition of T6 compared to T4. In addition, selenium can alleviate the negative effects of PFOS and Cd on antioxidant enzymes in zebrafish liver, thus reducing the liver toxicity caused by PFOS and Cd. Overall, the supplementation of selenium can reduce the health risks to fish and mitigate the injuries caused by PFOS and Cd in zebrafish.
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Selenio , Oligoelementos , Animales , Pez Cebra , Selenio/farmacología , Cadmio/toxicidad , Selenito de Sodio/farmacología , OctanosRESUMEN
Silver nanoparticles (AgNP) are the dominant nanomaterials in commercial products and the medical field, but the widespread occurrence of AgNP has become a global threat to human health. Growing studies indicate that AgNP exposure can induce vascular endothelial toxicity by excessive oxidative stress and inflammation, which is closely related to cardiovascular disease (CVD), but the potential intrinsic mechanism remains poorly elucidated. Thus, it has been crucial to control the toxicological effects of AgNP in order to improve their safety and increase the outcome of their applications.Multiple researches have demonstrated that sodium selenite (Se) possesses the capability to counteract the toxicity of AgNP, but the functional role of Se in AgNP-induced CVD is largely unexplored. The aim of this study was to explore the potential protective effect of Se on AgNP-induced vascular endothelial lesion and elucidate the underlying mechanisms. An in vivo model of toxicity in animals was established by the instillation of 200 µL of AgNP into the trachea of rats both with (0.2 mg/kg/day) and without Se treated. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated with AgNP (0.3 µg/mL ) and Se for a duration of 24 h. Utilizing transmission electron microscopy, we observed that the internalization of AgNP-induced endothelial cells was desquamated from the internal elastic lamina, the endoplasmic reticulum was dilated, and the medullary vesicle formed. Se treatment reduced the levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), inhibited the release of pro-inflammatory cytokines (specifically tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6), improved endothelial cell permeability, integrity, and dysfunction, and prevented damage to the aortic endothelium caused by AgNP. Importantly, we found that Se showed the capacity against AgNP with biological functions in guiding the intracellular reactive oxygen species (ROS) scavenging and meanwhile exhibiting anti-inflammation effects. Se supplementation decreased the intracellular ROS release and suppressed NOD-like receptor protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB) mediated inflammation within AgNP-intoxicated rats and HUVECs. The anti-oxidant stress and anti-inflammatory effects of Se were at least partly dependent on nuclear factor erythroid 2-related factor 2 (Nrf2). Overall, our results indicated that the protectiveness of Se against AgNP-induced vascular endothelial toxicity injury was at least attributed to the inhibition of oxidative ROS and pro-inflammatory NF-κB/NLRP3 inflammasome by activating the Nrf2 and antioxidant enzyme (HO-1) signal pathway.
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Antioxidantes , Células Endoteliales de la Vena Umbilical Humana , Inflamación , Nanopartículas del Metal , Factor 2 Relacionado con NF-E2 , Transducción de Señal , Plata , Selenito de Sodio , Plata/química , Plata/farmacología , Animales , Nanopartículas del Metal/química , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Selenito de Sodio/farmacología , Transducción de Señal/efectos de los fármacos , Ratas , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Antioxidantes/farmacología , Masculino , Ratas Sprague-Dawley , Estrés Oxidativo/efectos de los fármacosRESUMEN
As a beneficial nutrient and essential trace element, selenium plays a significant role in plant growth functions and human protein biosynthesis. Plant selenium enrichment is mainly obtained from both natural soil and exogenous selenium supplementation, while human beings consume selenium-enriched foods for the purposes of selenium supplementation. In this study, different types of selenium fertilizers were sprayed onto Lycium barbarum in Ningxia, and transcriptomics and metabolomics techniques were used to explore the effects of selenium on the fruit differentials and differential genes in Lycium barbarum. Taking the "Ning Qiyi No.1" wolfberry as the research object, sodium selenite, nano-selenium, and organic selenium were sprayed at a concentration of 100 mg·L-1 three times from the first fruiting period to the harvesting period, with a control treatment comprising the spraying of clear water. We determined the major metabolites and differential genes of the amino acids and derivatives, flavonoids, and alkaloids in ripe wolfberries. We found that spraying selenium significantly enhanced the Lycium barbarum metabolic differentiators; the most effective spray was the organic selenium, with 129 major metabolic differentiators and 10 common metabolic pathways screened after spraying. Nano-selenium was the next best fertilizer we screened, with 111 major metabolic differentiators, the same number as organic selenium in terms of differential genes and common metabolite pathways. Sodium selenite was the least effective of the three, with only 59 of its major metabolic differentials screened, but its differential genes and metabolites were enriched for five common pathways.
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Lycium , Selenio , Humanos , Lycium/química , Selenio/análisis , Frutas/química , Selenito de Sodio/farmacología , Selenito de Sodio/metabolismo , Metabolómica/métodos , Perfilación de la Expresión Génica , FertilizaciónRESUMEN
The effect of heavy metal cadmium (Cd) on testicular function is recognized. However, the mechanism involved is not well-established. In the present study, we analyzed the testicular transcriptomic changes induced by acute Cd exposure of adult rats with and without supplementation of antioxidants selenium (Se) and/or coenzyme Q10 (CoQ). Cd significantly decreased serum testosterone and two steroidogenic proteins SCARB1 and STAR. RNA-Seq analyses of testicular RNAs revealed specific activation of oxidative stress-, inflammation-, MAPK- and NF-κB-related signaling molecules. In addition, Cd treatment down-regulated gene for I, III and IV complexes of mitochondrial electron transport chain and up-regulated genes for NADPH-oxidase, major cascade in ROS production. The decrease in steroidogenesis and increase in inflammation may result from oxidative stress since supplementation of Se and CoQ, but not with either alone, almost completely prevented these changes, including overall alterations in transcriptome. Cd exposure induced total of 1192 differentially expressed genes (DEGs), which was reduced to 29 without considering confounding factors associated with Se/CoQ, a 97.6% protection rate. In conclusion, Cd exposure inhibited Leydig cell steroidogenesis by down-regulating SCARB1 and STAR through increasing oxidative stress and inflammation, but Se plus CoQ synergistically prevented all the changes induced by the Cd exposure.
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Cadmio , Selenio , Masculino , Ratas , Animales , Cadmio/toxicidad , Selenito de Sodio/farmacología , Transcriptoma , Antioxidantes/farmacología , Selenio/farmacología , Estrés Oxidativo , Inflamación , Perfilación de la Expresión GénicaRESUMEN
Dietary selenium (Se) sources affects the structure of the rumen microbial community and rumen fermentation. This study evaluated the effects of sodium selenite (SS) and bio-nanostructured selenium (SeNSM) on rumen fermentation and structure of rumen microbial community of lactating Barki ewes. Twenty one lactating Barki ewes were assigned into three groups based on their body weight and milk yield. The experiment lasted for 50 days, whenever, the control group was fed basal diet; group SS received basal diets plus sodium selenite as inorganic source of Se; and group SeNSM received basal diet plus organic selenium bio-nanostructured. Ruminal pH and volatile Fatty Acids (VFA) was lower (P < 0.05) in SeNSM group compared to control. Principle Coordinate Analysis separated the microbial communities into three clusters based on feeding treatment. The bacterial community was dominated by phylum Bacteroidetes and Firmicutes that were affected (P < 0.05) by Se sources. Specifically Bacteriodetes was higher (P < 0.05) in SS and SeNSM groups; and Firmicutes was higher (P < 0.05) in the control group. Moreover, the predominant bacterial genera were Prevotella, Rikenellaceae RC9 gut group, Unclassified_Bacteroidales, which were higher (P < 0.05) in SeNSM group. The methanogenic community belonged to phylum Euryarchaeota and was significantly decreased (P < 0.05) by Se supplementation. Principal component analysis based on rumen fermentation parameters, and relative abundances of bacteria and methanogens revealed three distinct clusters. These findings suggest that Se supplementation affected the relative abundances of dominant bacterial groups, declined rumen methanogens and SeNSM supplementation showed some positive impacts on some fibrolytic bacteria.
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Microbiota , Selenio , Ovinos , Animales , Femenino , Selenito de Sodio/farmacología , Suplementos Dietéticos/análisis , Selenio/farmacología , Selenio/metabolismo , Rumen/metabolismo , Lactancia , Fermentación , Dieta/veterinaria , Bacterias , FirmicutesRESUMEN
T-2 toxin, is a monotrichous mycotoxin commonly found in animal feed and agricultural products that can damage tissues and organs through oxidative stress. Selenium is a trace element with favorable antioxidant effects. However, it is unclear whether T-2 toxin-induces ferroptosis in LMH cells and whether Na2SeO3 has a protective role in this process. To investigate the process of hepatic injury by T-2 toxin and its antagonistic effect by Na2SeO3, we used 20 ng/mL T-2 toxin as well as 160 nmol/L Na2SeO3 to treat the LMH cells. The results demonstrated that exposure to the T-2 toxin induced iron death by increasing the quantity of ROS, leading to oxidative damage, decreasing the quantities of SOD, GPx, and T-AOC, and increasing the accumulation of MDA and H2O2, which resulted in the accumulation of Fe2+ and the down-regulation of the manifestation of linked genes and proteins including FTH1, Gpx4, NQO-1, and HO-1. After the addition of Na2SeO3, the PI3K/AKT/Nrf2 pathway is activated by regulating the selenoproteins gene level, and the above abnormal changes are reversed. In summary, Na2SeO3 alleviated T-2 toxin-induced iron death via the PI3K/AKT/Nrf2 pathway. These study not only broaden the cytotoxic knowledge regarding T-2 toxin, but also serve as a foundation for the use of Na2SeO3 in daily life.