In vitro effects of sodium selenite supplementation on cell viability of different forms of Trypanosoma cruzi

Selenium is an essential trace element which, at adequate levels, presents different beneficial biological effects, such as cancer regression, tissue development and protection against oxidative damage. The positive effects of this element are related to the expression of selenoproteins and their ability to modulate the immune system and the oxidative stress response. In Chagas disease and sleeping sickness, selenium supplementation has shown blood parasitism reduction and the alleviation of specific aspects of the diseases, such as diminishing anemia in sleeping sickness or minimization of myocardial and right ventricular chamber damage in Chagas disease. Although the influence of selenium in trypanosomiasis has been investigated, the direct effects of sodium selenite supplementation on trypanosome cells are poorly understood. Treatment of Trypanosoma cruzi cultures with low selenium doses demonstrated different results, according to the parasite evolutive form analyzed. Epimastigote cultures supplemented with 100 nM of sodium selenite presented cell growth increment, which varies from 10 to 40% according to the parasite strain assayed. Selenium concentration around 600nM leads to a 30% increase in the amastigote form number, whereas, at the same dose, the mammal host cell presented no cellular growth alteration. For the bloodstream form, the results agree with the literature, and all sodium selenite concentrations tested, demonstrated a reduction in parasite viability. The data suggest that selenium supplementation, under specific conditions, could increase T. cruzi viability, demonstrating that a strategy for using selenium as an adjuvant in Chagas disease treatment requires additional experimentation.

Radioprotective effect of sodium selenite on mandible of irradiated rats

Abstract The purpose of this study was to test the radioprotective effect of selenium in the bone microarchitecture of irradiated rats mandibles. Forty rats were separated into 4 groups with 10 animals: control group (CG), irradiated group (IG), sodium selenite group (SSG) and sodium selenite irradiated group (SSIG). A single dose of 0.8 mg/kg sodium selenite was administered intraperitoneally in the SSG and SSIG groups. One hour later, animals of IG and SSIG groups were irradiated with 15 Gy of x-rays. Forty days after radiation a bilateral extraction of the mandibular first molars was performed. After the extraction procedure, five rats were killed after fifteen days and others five after thirty days. Micro- computed tomography was used to evaluate cortical and trabecular bone of each rat. The mean and standard deviation of each bone microarchitecture parameter were analyzed using the statistical test of two-way Analysis of Variance (ANOVA). At 15 days, the bone volume presented higher values in the CG and SSG groups (p=0.001). The same groups presented statistically significant higher values when bone volume fraction (p<0.001) and trabecular thickness (p<0.001) were analyzed. At 30 days, it was observed that in relation to the bone volume fraction, SSG group presented the highest value while SSIG group had the lowest value, with statistically significant difference (p=0.016). Sodium selenite demonstrated a median radioprotective effect in the bone microarchitecture of irradiated mandibles, which indicates the substance may be a potential radioprotective agent against chronic effects of high doses of ionizing radiation.

Resumo O propósito deste estudo foi testar o efeito radioprotetor do selênio na microarquitetura óssea de mandíbulas de ratos irradiados. Quarenta ratos foram separados em 4 grupos com 10 animais: grupo controle (GC), grupo irradiado (GI), grupo selenito de sódio (SSG) e grupo selenito de sódio irradiado (SSIG). Uma dose única de 0,8 mg/kg de selenito de sódio foi administrada intraperitonealmente nos grupos SSG e SSIG. Uma hora depois, os animais dos grupos IG e SSIG foram irradiados com 15 Gy de raios-x. Quarenta dias após a irradiação foi realizada extração bilateral dos primeiros molares inferiores. Após o procedimento de extração, cinco ratos foram mortos após quinze dias e outros cinco após trinta dias. A microtomografia computadorizada foi utilizada para avaliar o osso cortical e trabecular de cada rato. A média e o desvio padrão de cada parâmetro da microarquitetura óssea foi analisada pelo teste estatístico de Análise de Variância dois fatores (ANOVA), seguido por comparações post hoc com o teste de Tukey. Após 15 dias, o volume ósseo apresentou valores mais elevados nos grupos GC e GNS (p=0,001). Os mesmos grupos apresentaram valores estatisticamente significantes maiores quando se analisou fração de volume ósseo (p<0,001) e espessura trabecular (p<0,001). Após 30 dias, observou-se que, em relação à fração de volume ósseo, o grupo SSG apresentou o maior valor enquanto o grupo SSIG apresentou o menor valor, com diferença estatisticamente significante (p=0,016). O selenito de sódio demonstrou um efeito radioprotetor mediano na microarquitetura óssea das mandíbulas irradiadas, o que indica que a substância pode ser um potencial agente radioprotetor contra os efeitos crônicos da radioterapia.

Experimental and iatrogenic poisoning by sodium selenite in pigs / Intoxicação iatrogênica e experimental por selenito de sódio em suínos

Following a case of iatrogenic selenium poisoning in a young pig, an experimental study was carry out. Sodium selenite was orally and parenterally administered to 13 pigs that were subdivided into three groups (G1, G2 and G3). The animals in groups G1 and G3 received sodium selenite intramuscularly (IM), G1 received a comercial formula, and G3 received sodium selenite mixed with distilled water at different dosages, and those in group G2 were fed commercial sodium selenite. Acute and subacute poisoning was observed in both groups, although the onset of clinical signs was slower in group G2. Only one pig (in group G1) that had received the highest dose showed a peracute course. Apathy, anorexia, dyspnea, vomiting, muscular tremors, proprioceptive deficit, ataxia and paresis of the hind limbs progressing to the front limbs evolving to tetraplegia were observed. Postmortem findings differed whether the animals received the injected (G1 and G3) or oral (G2) sodium selenite. The liver was moderately atrophic in some animals of G2. Some of the animals in groups G1 and G3 presented with lung edema. One pig in G3 had yellowish-brown areas in the ventral horns of the cervical intumescences of the spinal cord. The most important histological changes were present in the ventral horns of the cervical and lumbar intumescences of the spinal cord. In one animal, changes were present in the brainstem and mesencephalon. The initial lesion was a perivascular and astrocyte edema that progressing to lysis and death of astrocytes and neurons. In the chronic stage of the lesions, there were extensive areas of liquefaction necrosis with perivascular lymphocytic and histiocytic infiltration and occasional eosinophils. It seems that disruption of the blood-brain barrier due to astrocyte edema is the most likely mechanism of CNS lesion.(AU)

A partir de um caso de intoxicação iatrogênica por selenito de sódio injetável em suíno verificaram-se alguns aspectos patogenéticos não esclarecidos, o que ensejou o estudo experimental. Selenito de sódio foi administrado pelas vias oral e parenteral a 13 suínos, subdivididos em três grupos (G1, G2 e G3). Os grupos G1 e G3 receberam selenito de sódio por via intra-muscular (IM); (G1 - fórmula comercial e G3 - selenito de sódio misturado à água destilada, em diversas dosagens) e o grupo G2, por via oral (VO), misturado à ração. Quadros de evolução aguda e subaguda foram observados em todos os grupos, embora o início dos sintomas tenha sido mais lento no grupo G2. Um único porco (do grupo G1), que havia recebido a dose mais alta, apresentou evolução superaguda. Apatia, anorexia, dispneia, vômito, tremores musculares, déficit proprioceptivo, ataxia e paresia dos membros posteriores com progressão para os anteriores e evolução para tetraplegia foram observados. Os achados de necropsia foram diferentes entre os animais que receberam o selenito de sódio injetável (IM - G1 e G3) e oral (G2). Havia moderada atrofia hepática em alguns animais do G2. Parte dos animais dos grupos G1 e G3 apresentaram edema pulmonar. Em um suíno (G3) notaram-se áreas marrom-amareladas nos cornos ventrais da intumescência cervical. As alterações histológicas mais importantes ocorreram nos cornos ventrais do "H" medular das intumescências cervical e lombar. Em um animal, as alterações envolviam o tronco cerebral e o mesencéfalo. Inicialmente, a lesão caracterizava-se por edema perivascular e astrocitário que progredia para lise e necrose de astrócitos e neurônios. O estágio crônico das lesões caracterizava-se por extensas áreas de necrose liquefativa e infiltração perivascular linfocítica e histiocítica, com raros eosinófilos. Sugere-se que a ruptura da barreira hematoencefálica por edema astrocitário seja o mecanismo mais provável da lesão no SNC.(AU)

Estatus de selenio en equinos Criollo-Chileno a pastoreo y su respuesta a la suplementación / Selenium metabolic status and response to supplementation in grazing Chilean-Criollo horses

Objetivo. Dos experimentos se realizaron para determinar el estatus de selenio en equinos Criollo-Chileno a pastoreo y, evaluar la respuesta a la suplementación con Na2SeO3. Materiales y métodos. Exp.1A caballos pertenecientes a 10 criaderos del sur de Chile se les determinó la actividad sanguínea de glutatión peroxidasa (GPx, EC.1.11.1.9) (AcGPx). Los animales pertenecieron a 3 grupos, pastoreo de otoño (PO, n=40), pastoreo de otoño y suplementados con avena (PO+A, n=47), y, pastoreo de primavera (PP, n=41). Exp2Se utilizaron equinos con carencia de selenio, distribuidos en tres grupos: G1, n=7, tratado con Na2SeO3 el día 0 (Se= 0.05 mg/kg pv, im); G2, n=8, suplementado con Na2SeO3, los días 0 y 15 y GC, n=8, control. La AcGPx se determinó al día 0, 30 y 120. Resultados. La mediana (Me) de la AcGPx en todos los grupos fue menor al límite adecuado (>130 U/gHb), mayor en PO+A (Me=92, P25%=47, P75%=129 U/gHb) y PP (Me=85, P25%=45, P75%=114 U/gHb) que en PO (Me=35, P25%=20, P75%=85 U/gHb) (p<0.05). En el experimento 2 la AcGPx fue similar y menor al adecuado en todos los grupos. La suplementación con Na2SeO3 aumentó (p<0.05) la AcGPx en G1 (121±52 U/gHb) y G2 (124±69 U/gHb), sin alcanzar valores adecuados. Conclusiones. Los equinos Criollo-Chileno a pastoreo en el sur de Chile presentan carencia de Se, mayor en otoño que primavera y menor al suplementar con avena. Adicionalmente, la administración parenteral de Na2SeO3 mejora el estatus de Se, pero sin revertir el cuadro carencial.

Objective. Two experiments were conducted to determine the selenium status in grazing Chilean-Criollo horses and evaluate their response to a Na2SeO3 supplement. Material and methods. Exp.1The blood activity of glutathione peroxidase (GPx, EC.1.11.1.9) (AcGPx) was determined in horses kept grazing in 10 breeding farms from the south of Chile: PO, n= 40 horses were kept grazing during autumn (PO), 47 horses were kept grazing during autumn and supplemented with oat grain (PO+A), and 23 horses were kept grazing during spring (PP). Exp.223 horses kept on pasture were allotted into three groups: G1, n=7, supplemented with a dose of Na2SeO3 (Se= 0.05mg/kg bw, im) on day 0; G2, n=8, supplemented with similar doses of Na2SeO3, on days 0 and 15; and GC, n=8, control. AcGPx was determined on days 0, 30 and 120. Results. Median (Me) of the AcGPx on all the farms were below the adequate limit (>130 U/g Hb), being higher in PO+A (Me= 92, P25%= 47, P75%= 129 U/g Hb) and PP (Me = 85, P25%= 45, P75%=114 U/g Hb) than PO (Me= 35, P25%= 20, P75%= 85 U/g Hb) (p<0.05). Initial AcGPx was similar and below adequate in the three groups and increased after Na2SeO3 administration (p<0.05) in G1 (121 ± 52 U/g Hb) and G2 (124 ± 69 U/g Hb). Conclusions. A deficiency is observed in Chilean-Criollo horses grazing during autumn and spring in southern Chile, parenteral administration of Na2SeO3 (0.05mg/kg bw) in single or double doses improves the Se status without achieving adequate values.

Radioprotective Effect of Sodium Selenite on Developing Teeth

Radioprotective agents like selenium are used to reduce the damage caused by radiation in healthy tissues. The aim of this study was to evaluate the effect of sodium selenite on the development of the molars of offspring of rats irradiated during odontogenesis. Twenty pregnant rats were randomly divided into 4 groups: control, irradiated, selenium and selenium/irradiated. The selenium and selenium/irradiated groups received 0.3 mg/kg of sodium selenite at 18 days of pregnancy. The rats of the irradiated and selenium/irradiated groups received a single dose of 4 Gy of X rays on the abdominal region at the 19th day of pregnancy. The offspring was sacrificed at 3 and 4 days after birth for evaluation of the birefringence of the enamel organic matrix, and at 30 days for evaluation of the intercuspal dimensions of the molars. The selenium/irradiated group was similar to the irradiated group with respect to the thickness and irregularity of the enamel organic matrix region in the evaluated birefringence, as the intercuspal dimensions of the molars. In conclusion, sodium selenite had no radioprotective action on the development of the molars of offspring of rats irradiated during odontogenesis and had a toxic effect in the initial time.

Agentes radioprotetores, como o selênio, são utilizados para reduzir os danos causados pela radiação nos tecidos sadios. O objetivo nesse estudo foi avaliar o efeito do selenito de sódio no desenvolvimento de molares de filhotes de ratas irradiadas. Vinte ratas grávidas foram aleatoriamente divididas em 4 grupos: controle, irradiado, selênio e selênio/irradiado. Os animais dos grupos selênio e selênio/irradiado receberam 0.3 mg/kg de selenito de sódio aos 18 dias de gestação. Os animais dos grupos irradiado e selênio/irradiado receberam dose única de 4 Gy de radiação X na região abdominal aos 19 dias de gestação. Os filhotes foram sacrificados aos 3 e 4 dias após o nascimento para avaliação da birrefringência da matriz orgânica do esmalte, e aos 30 dias para avaliação das dimensões dos molares. Os resultados do grupo selênio/irradiado foram similares aos do irradiado, tanto em relação à espessura e irregularidade região da matriz orgânica do esmalte quanto às dimensões dos molares. Dessa forma, foi possível concluir que o selenito de sódio não exerceu ação radioprotetora no desenvolvimento de molares de filhotes de ratas irradiadas durante a odontogênese e apresentou efeito tóxico nos tempos iniciais.

Role of selenium in protection of liver cirrhosis

Selenium is an essential trace element and has been shown to protect the rats against dietary liver necrosis. This study was designed to evaluate the effects of selenium supplementation on different biochemical parameters in thioacetamide induced cirrhotic rats. For this purpose 24 male Albino wistar rats were divided into four groups [n=6]. Group 1, remained healthy control rats, Group 2, received thioacetamide [at a dose of 200mg/kg b.w, i.p, for 12 weeks, twice a week] in first phase and saline in second phase, Group 3, received thioacetamide [200mg/kg b.w, i.p for 12 weeks, twice a week] in first phase and sodium selenite [1mg/kg b.w, i.p. for 12 weeks, three times a week] in second phase and Group 4, received sodium selenite [1mg/kg b.w, i.p. for 12 weeks, three times a week] in first phase and saline in second phase. Biochemical analysis was evaluated by total and direct bilirubin, liver specific enzymes, and antioxidant enzymes. Marked increase in total and direct bilirubin and ALT activity was the indicative markers of liver cirrhosis while reduced antioxidant activity [SOD and GSH] and increased MDA and Catalase levels were observed in cirrhotic group. Sodium selenite supplementation markedly reduced total bilirubin and ALT activity and restored the antioxidant enzymes [SOD and GSH] and MDA and catalase activity. These results indicate that sodium selenite successively attenuates the thioacetamide induced liver cirrhosis

Differentiation of human labia minora dermis-derived fibroblasts into insulin-producing cells

Recent evidence has suggested that human skin fibroblasts may represent a novel source of therapeutic stem cells. In this study, we report a 3-stage method to induce the differentiation of skin fibroblasts into insulin-producing cells (IPCs). In stage 1, we establish the isolation, expansion and characterization of mesenchymal stem cells from human labia minora dermis-derived fibroblasts (hLMDFs) (stage 1: MSC expansion). hLMDFs express the typical mesenchymal stem cell marker proteins and can differentiate into adipocytes, osteoblasts, chondrocytes or muscle cells. In stage 2, DMEM/F12 serum-free medium with ITS mix (insulin, transferrin, and selenite) is used to induce differentiation of hLMDFs into endoderm-like cells, as determined by the expression of the endoderm markers Sox17, Foxa2, and PDX1 (stage 2: mesenchymal-endoderm transition). In stage 3, cells in the mesenchymal-endoderm transition stage are treated with nicotinamide in order to further differentiate into self-assembled, 3-dimensional islet cell-like clusters that express multiple genes related to pancreatic beta-cell development and function (stage 3: IPC). We also found that the transplantation of IPCs can normalize blood glucose levels and rescue glucose homeostasis in streptozotocin-induced diabetic mice. These results indicate that hLMDFs have the capacity to differentiate into functionally competent IPCs and represent a potential cell-based treatment for diabetes mellitus.

The effects of selenium on tumor growth in epithelial ovarian carcinoma / 부인종양

OBJECTIVE: Epidemiological studies suggest that selenium protects against the development of several cancers. Selenium (sodium selenite) has been reported to interfere with cell growth and proliferation, and to induce cell death. In this study, we tested whether selenium could have growth-inhibiting effect in ovarian cancer cells and an orthotopic animal model. METHODS: Cell growth in selenium-treated cells was determined in human ovarian cancer cells, A2780, HeyA8, and SKOV3ip1 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Animal experiment of selenium with paclitaxel was performed using SKOV3ip1 cells in nude mice to evaluate their inhibiting effect for tumor growth. In addition, another animal experiment of paclitaxel with or without selenium was performed to assess the effect of survival and food intake in mice. RESULTS: The in vitro growth of selenium-treated cells was significantly decreased dose-dependently in A2780, HeyA8, and SKOV3ip1 cells. Therapy experiment in mice was started 1 week after injection of the SKOV3ip1 cells. Treatment with selenium (1.5 mg/kg, 3 times/week) and paclitaxel injection showed no addictive effect of the inhibition of tumor growth. However, combination of selenium and paclitaxel showed the slightly increased food intake compared with paclitaxel alone. CONCLUSION: Although selenium has growth-inhibiting effect in ovarian carcinoma cells in vitro, there is no additive effect on tumor growth in mice treated with combination of paclitaxel and selenium. However, food intake is slightly higher in selenium-treated mice during chemotherapy.

Efeitos da suplementação com fósforo em caprinos no semiárido do nordeste brasileiro / Effect of phosphorus supplementation for goats in the Brazilian semiarid region

To evaluate the effect of phosphorus supplementation for goats grazing for the semiarid region, one group of 16 recently weaned Moxotó goats was supplemented with a mineral supplement containing Na, Cl, Zn, Cu, Se, Co, and P during 240 days. Another similar group was supplemented with a similar mineral supplement without P. The mean daily consumption of supplement by animal was of 7.09±2.77g and 7.67±3.14g for the groups with and without P, respectively. The mean weight gain of the P supplemented group (45.20±5.56g) was significantly higher (P<0.05) than the non-supplemented group (40.03±2.80g). The average total P in soil was 30.8mg/kg and in the pasture 0.13 percent in dry matter. These results demonstrate the occurrence of P deficiency in some areas of the Brazilian semiarid region.

The Effect of Sodium Selenite on Breast Cancer-Related Lymphedema

OBJECTIVE: To investigate the effects of complex decongestive physiotherapy (CDPT) with sodium selenite compared to the effects of CDPT without sodium selenite for the treatment of breast cancer-related lymphedema (BCRL). METHOD: Patients (n=40) who were diagnosed with BCRL were randomly assigned to the two groups: sodium selenite group or the non-sodium selenite group. In the sodium selenite group, sodium selenite was administered for 100 days concurrently with CDPT. In the non-sodium selenite group, only CDPT was administered. The main outcome measurements included limb circumference (proximal, distal and total) to indicate volume changes, the visual analogue scale (VAS) and the short form-36 version 2 questionnaire (SF-36) scores to evaluate the quality of life (QoL) pre-treatment, 100 days post-treatment and 130 days post-treatment for each patient. RESULTS: The sodium selenite group experienced volume reduction of 8.22% and 9.21%, at 100 and 130 days post-treatment, respectively. The non-sodium selenite group experienced 5.57% and 6.11% reduction in swelling at the same periods. Between the two groups, more significant volume reduction was observed in the affected distal limbs of patients assigned to the sodium selenite group compared to patients in the non-sodium group. However, the VAS and the SF-36 scores were not significantly different between the two groups. CONCLUSION: Sodium selenite therapy in combination with CDPT is effective in reducing the volume of upper limb in BCRL, and significantly reduce the volume of the affected distal upper limb compared to CDPT alone.

The curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning.</p><p><b>METHODS</b>In present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats), 20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 µmol/kg sodium selenite group (40 rats), 0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats). All rats except for control group inhaled passively 250 mg/m(3) carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope.</p><p><b>RESULTS</b>Compared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite, shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P < 0.05 or P < 0.01), when tested on the 3rd day after exposure. Except from methylprednisolone sub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P < 0.05). Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05 or P < 0.01). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure, DDC group administrated at 4 h or 30 h and tested on the 7th day after exposure, DDC group administrated at 30h and tested on the 3rd day after exposure, and methylprednisolone with DDC group administrated at 30 h and tested on the 7th day after exposure) increased significantly (P < 0.05 or P < 0.01). As compared with carbonyl nickel group, the ultrastructure observation indicated that the nucleus and other organelles of liver cells in methylprednisolone, DDC and methylprednisolone with DDC groups administrated at 4h and tested on the 3rd day were access to normal levels.</p><p><b>CONCLUSION</b>The results of present study showed that methylprednisolone, DDC and methylprednisolone with DDC could improve obviously the repair of rat liver cell damage induced by acute carbonyl nickel poisoning, and the curative effects of early treatment were better than those of later treatment.</p>

Effects of sodium selenite on the expressions of beta-catenin and its target cyclin D1 in colorectal cancer cells HCT 116 and SW480 / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effects of sodium selenite on the expressions of beta-catenin and cyclin D1 in colorectal cancer cells HCT 116 and SW480.</p><p><b>METHODS</b>HCT 116 and SW480 cells were treated by 10 micromol/L sodium selenite at different time points. The expressions and transcription of beta-catenin and cyclin D1 were detected by Western blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. Meanwhile, the impact of MG132 (a proteasome inhibitor) pretreatment on the expressions of beta-catenin and cyclin D1 was observed through Western blot analysis. The interaction between beta-catenin and T cell factor 4 (TCF4) after selenite treatment was evaluated using co-immunoprecipitation assay.</p><p><b>RESULTS</b>Sodium selenite inhibited the expression of beta-catenin and transcription of its target such as cyclin D1. MG132 pretreatment prevented the inhibition of beta-catenin signaling triggered by selenite in HCT 116 and SW480 cells. Furthermore, selenite treatment disrupted the interaction between beta-catenin and TCF4 in HCT 116 and SW480 cells.</p><p><b>CONCLUSIONS</b>Sodium selenite can lower the expression levels of beta-catenin and its target cyclin D1, during which the proteasome-mediated degradative pathway may be involved. The decreased interaction between beta-catenin and TCF4 due to sodium selenite may be also involved in the regulation of beta-catenin signaling.</p>

Therapeutic effect of sodium selenite and zinc sulphate as sup-plementary with meglumine antimoniate[glucantime] against cutaneous leishmaniasis in BALB/C Mice

Successful therapy of leishmaniasis depends on effective cellular immune response. We evaluated the effectiveness of sodium selenite and zinc sulphate as known immunomodulator materials, in combination with Glucantime in treatment of cutaneous leishmaniasis lesions resulting from Leishmania major in susceptible animal model. Thirty three female mice weighing 18-20 g at the age of 7-8 week infected with L. major were randomly divided into 3 groups: group1: treated by sodium selenite [0.35 mg/kg for 30 days], group2: treated by zinc sulphate [2 mg/kg for 30 days] and group3: treated by distilled water [0.01 ml/gr body weight for 30 days] as control. All groups received Glucantime as a standard anti- leishmanial agent [60 mg/kg, ip] for 14 days. To assess the results of treatment measurement of lesions size and parasitological tests were done weekly. The lesion sizes increased continuously in sodium selenite group .Although, in zinc group did not increase compared to baseline but with considering the time- group interaction there was no significant difference between zinc and control group during this study. There was no difference between lesion sizes and Leishmanial loads in the interventional and control groups, respectively. Sodium selenite and zinc sulphate at mentioned doses and duration of treatment did not show any treatment effect on cutaneous leishmaniasis caused by L. major in BALB/c mice. Increasing the dose of supplements and considering the follow up period after treatment can help more certain conclusion

Analysis of the Effective Fraction of Sun Ginseng Extract in Selenite Induced Cataract Rat Model

PURPOSE: To compare the protective effects of saponin and non-saponin Sun-ginseng extract fractions in a selenite-induced rat cataract model. METHODS: A total of 101 Sprague-Dawley rat pups were divided into four groups by treatment: Sun-ginseng, saponin fraction, non-saponin fraction, and control. For induction of cataracts, sodium selenite 15 nmol/g was injected subcutaneously in 13 day-old rat pups. Sun-ginseng extract 100 microgram/g (Group I, Ginseng Science, Seoul, Korea), saponin fraction 100 microgram/g (Group II), non-saponin fraction 100 microgram/g (Group III), and phosphate buffered saline (Control group) were injected intraperitoneally every two days for a total of seven injections. The rats were sacrified and their lenses were dissected and photographed at day 7 and 14, and the cataracts were graded according to the ratio of the cataract area to the total lens area. The blind method was used for the evaluation of the cataract area. RESULTS: At day 14, cataract formation rates (CFR) were 33.3% in group I, 76.4% in group II, 41.2% in group III, and 77.7% in the control group. The mean cataract area (MCA) was 13.4+/-20.8% in group I, 14.4+/-11.7% in group II, 5.7+/-7.7% in group III, and 15.8+/-12.1% in the control group. Group III showed statistically significant results compared with those of control group (CFR p=0.001, MCA p=0.001). We observed significantly lower incidence and smaller mean cataract area in Group I and Group III at day 7 compared with the control group (Group I, CFR p=0.018; Group III, CFR p=0.032, MCA p=0.005). CONCLUSIONS: The protective effects of Sun-ginseng extract are caused by the components in the non-saponin fraction, not by those in the saponin fraction, in a selenite-induced cataract rat model.

Protective effect of Na2SeO3 against cerebral ischemia-reperfusion injury to the hippocampal neurons in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effects of selenium on rat hippocampal neurons against ischemia-reperfusion (IR) injury.</p><p><b>METHODS</b>Thirty-two rats were randomly divided into sham-operated group, IR group and selenium-treated group, and in the latter two groups, cerebral IR injury was induced by middle cerebral artery occlusion; Na2SeO3 treatment was administer in selenium-treated group. At 14 days after reperfusion, the brain tissues were harvested from the rats and hippocampal neuron injuries were observed by TUNEL and Methylene Blue staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nerve growth factor (NGF) in the hippocampal tissues were measured by ELISA.</p><p><b>RESULTS</b>Compared with IR group, the rats in selenium-treated group showed no significant increase in the expression of m-NGF (P>0.05), but pro-NGF expression was significantly increased (P<0.05) in the hippocampal tissue. Na2SeO3 treatment significantly inhibited the expressions of TNF-α and IL-1β and decreased the apoptosis of hippocampal neurons following cerebral IR injury (P<0.05).</p><p><b>CONCLUSION</b>Selenium produces antiapoptotic effect to protect the hippocampal neurons following cerebral IR injury possibly not by increasing the level of m-NGF but by decreasing the expressions of the inflammatory factors.</p>

Preventive effect of onion juice on selenite-induced experimental cataract.

Purpose: To evaluate the effects of onion juice on sodium-selenite induced cataract formation. Materials and Methods: Thirty-two 10-day-old Wistar-albino rat pups were divided into four equal groups. Group 1 received only subcutaneous saline injection. In Group 2, sodium-selenite (30 nmol / g body weight) was injected subcutaneously. In Group 3, subcutaneous sodium-selenite was injected and one drop 50% diluted fresh juice of crude onion was instilled every 8 h into the right eye for 14 days; the left eye received no treatment. Group 4 rats were similar to those of Group 3, the only difference being that of undiluted fresh juice of crude onion. The development of cataract was assessed. Rat lenses were analyzed for total antioxidant (TA) level, and for activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD). Results: Both eyes of all rats in Group 1 did not exhibit cataract formation . In Group 2, all rats developed Grade 3 cataract in the lenses of both eyes. The difference in exhibited cataract in the lens of the right eyes in all rats between Group 2 and any eyes of groups 3 or 4 were significant ( P = 0.001). The mean TA level and mean activities of SOD and GPX in Group 2 rat lenses were significantly lower than the values in lenses of all rats in Group 1 ( P = 0.001, 0.003, 0.001), and in the lenses of the right eyes of rats in Groups 3 and 4 ( P = 0.001, 0.020, 0.001). Conclusion: Instillation of onion juice into the rat eyes can effectively prevent selenite-induced cataract formation. This effect was associated with increased TA level, SOD and GPX activities in the lens.

Effect of sodium selenite on bone repair in tibiae of irradiated rats

This study evaluated the radioprotective effect of sodium selenite on the bone repair process in tibiae of female rats. For such purpose, 100 female Wistar rats (Rattus norvegicus, albinus) were randomly assigned to 4 groups (n=25), according to the treatment received: administration of distilled water (control); administration of sodium selenite; gamma radiation; and administration of sodium selenite plus gamma radiation. A bone defect was prepared on both tibiae of all animals. Three days after surgery, the gamma radiation and selenium/gamma radiation groups received 8 Gy gamma rays on the lower limbs. Five animals per group were sacrificed 7, 14, 21, 28 days after surgery for evaluation of the repair process by bone volumetric density analysis. The 5 animals remaining in each group were sacrificed 45 days postoperatively for examination of the mature bone by scanning electron microscopy. Based on all analyzed parameters, the results of the present study suggest that sodium selenite exerted a radioprotective effect in the bone repair of tibia of irradiated rats.

Este estudo avaliou o efeito radioprotetor de selenito de sódio no processo de reparação óssea em tíbias de ratas. Para isto, 100 ratas Wistar (Rattus norvegicus, albinus) foram aleatoriamente divididas em 4 grupos (n=25), de acordo com o tratamento recebido: administração de água destilada (controle); administração de selenito de sódio; irradiação gama; e administração de selenito de sódio mais irradiação gama. Um defeito ósseo foi realizado em ambas as tíbias de todos os animais. Três dias após a cirurgia, apenas os animais dos grupos irradiado e selênio/irradiado receberam 8 Gy de radiação gama na região dos membros inferiores. Cinco animais por grupo foram sacrificados 7, 14, 21 e 28 dias após a cirurgia para avaliação do processo de reparo ósseo pela análise da densidade óssea volumétrica. Os cinco animais remanescentes em cada grupo foram sacrificados aos 45 dias do pós-operatório para avaliação da maturação óssea por meio da microscopia eletrônica de varredura. Baseado em todos os parâmetros analisados, os resultados do presente estudo sugerem que o selenito de sódio exerceu efeito radioprotetor no reparo ósseo de tíbias de ratas irradiados.

Protective effects of melatonin as an eye drops against selenite-induced cataract in rat pups

The aim of the present study is to investigate the possible role of melatonin, when administered as an eye drops, in the selenite-induced cataractogenesis in rat pups. Sixty Wistar albino rats [13 days old] were allocated into three groups [20 animals each]. group A injected subcutaneously with normal saline and received no other treatment served as control; group B injected with [40 micro mol/g body weight] sodium selenite subcutaneously, and treated with 1 drop of melatonin eye drops, specially formulated for this purpose, twice daily for 30 days; group C injected with sodium selenite as in group B, but treated with single drop of normal saline, twice daily for 30 days. The stage of cataract development was examined with slit-lamp photographs. Alter 30 days the pups were sacrificed and their eyeballs enucleated for histological examination. The results demonstrated that melatonin eye drops decreased the nuclear cataract formation after 15 and 21 days of treatment, compared to saline treated group. Histological evaluations of enucleated lenses revealed that treatment with melatonin drops clearly indicated recovery of the lenticular tissues and retained their ordinary shape. These findings demonstrate that melatonin when administered as an eye drops protects the lens of rat pups against selenite-induced cataract

Mechanism for downregulation of cytochrome c oxidase subunit IV in NB4 cells induced by sodium selenite / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the mechanism and significance of cytochrome c oxidase subunit IV (COX IV) downregulation during apoptosis of NB4 cells induced by sodium selenite.</p><p><b>METHODS</b>NB4 cells were treated with 20 micromol/L sodium selenite at different time points. COX IV protein and mRNA were detected by Western blot and RT-PCR, respectively. NB4 cells were pretreated with reactive oxygen species (ROS) scavenger before selenite exposure, and then COX IV protein expression and caspase-3 activation were detected by Western blot. NB4 cells were pretreated with caspase-3 inhibitor before selenite exposure, and then COX IV protein expression was detected by Western blot. NB4 cells were transiently transfected with vectors to interfere with the expression of COX IV, and then the apoptosis induced by selenite was analyzed by flow cytometry.</p><p><b>RESULTS</b>Sodium selenite induced evident downregulation of COX IV protein in NB4 cells, while its mRNA level was almost unchanged. ROS scavenger completely reversed selenite-induced COX IV downregulation and caspase-3 activation. Caspase-3 inhibitor partially reversed selenite-induced COX IV downregulation. Interference with COX IV expression dramatically enhanced selenite-induced apoptosis of NB4 cells.</p><p><b>CONCLUSIONS</b>COX IV is remarkably downregulated during selenite-induced apoptosis of NB4 cells. ROS mediates COX IV downregulation and caspase-3 activation, while caspase-3 is partially involved in COX IV downregulation. COX IV interference markedly increases the sensitivity of NB4 cells to selenite-induced apoptosis.</p>

Effect of Glutathione With Sea Tangle Extract on Prevention of Selenite-Induced Cataract Formation in Rats

PURPOSE: To evaluate antioxidative and preventive effects of sea tangle extract on selenite-induced cataract formation. METHODS: Eighty SD rat pups were randomized into 8 groups. Group 1 received no injection of reagent (normal); Group 2 to 8 received injection of selenite (15 micromol/Kg, s.c.) was injected. In group 2 (control) and group 3, normal saline (i.p.) and ascorbic acid (i.p.) was injected on days 3~31. In groups 4~8, sea tangle extract (i.p.) was injected at a concentration of 12.5, 25, 50, 100, 200 mg/kg, respectively. Development of cataract was assessed and photographed weekly under slit lamp. Rat lenses were analyzed for antioxidant enzymes, glutathione peroxidase (GPx), superoxide dismutase and malondialdehyde. Furthermore, an amino acid analysis of sea tangle extract was performed. RESULTS: Significant differences (p<0.05) were seen in cataract development in group 7. Dense nuclear cataracts developed in 8 of 10 of the control group (group 2); Group 4~8 developed nuclear cataract with proportion of 6/10, 3/10, 2/10, 1/10, and 6/10 rats. In sea tangle injected group, levels of GPx were higher than in the ascorbic acid and control groups. In particular, group 7, injected with 100 mg/kg of sea tangle extract, showed significantly high level of enzyme. Results of the amino acid analysis showed sea tangle includes glutamate-glycine-cysteine, major constituents of glutathione (GSH). CONCLUSIONS: The glutamate-glycine-cysteine in sea tangle is supposed to increase the level of lens GSH and this may contribute to lowering cataract development. This study strongly supports the activity of sea tangle as an endogenous antioxidant and anticataract agent.