RESUMO
BACKGROUND: Nano-selenium oxide (NSeO) particles are highly noticeable due to their tissue-protective and antioxidant properties. For this purpose, the effect of NSeO was evaluated on skin flap survival and flap oxidative stress markers in rats. Also, another effect of NSeO was investigated on the expression of mTOR and p-mTOR. MATERIALS AND METHODS: Fifty rats were divided into five groups of ten. Skin flap size was 3×8 cm in all groups. Groups were: (1) Sham, (2) Flap Surgery group, (3) Flap Surgery + NSeO, (4) Flap Surgery + Rapamycin (mTOR inhibitor), (5) Flap Surgery + Rapamycin + NSeO. The flap necrosis rate was computed using the paper pattern method on day seven after surgery. After day seven, flap tissues were collected for histological evaluations. Then, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Furthermore, the expression levels of mTOR and p-mTOR were measured using the Western blot method. RESULTS: Treatment with NSeO significantly reduced necrosis (P<0.05). It also resulted in a decrease in MDA level (P<0.05). Histologically, NSeO reduced inflammation and increased positive signs of tissue healing (epithelialization, neovascularization, fibroblast migration, and granulation tissue). NSeO increased SOD activity significantly (P<0.05), whereas, using rapamycin reversed these effects. Also, in all groups, mTOR changes were not significant. Additionally, p-mTOR expression was significantly reduced in groups that rapamycin was injected. CONCLUSION: NSeO can reduce flap necrosis and enhance tissue healing in rats. So, it can potentially be used clinically to promote tissue repair significantly, and its effects are independent of the mTOR pathway. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Sirolimo , Serina-Treonina Quinases TOR , Animais , Necrose , Óxidos , Ratos , Óxidos de Selênio , Superóxido DismutaseRESUMO
The abnormal tumor vasculature in solid tumors creates hypoxia and leads to compromising the delivery and anticancer efficiency of nanomedicine. Nanomaterials with intrinsic antiangiogenesis ability might normalize tumor vessels and improve the therapeutic effect of O2-related treatment like PDT. Herein, we designed and prepared ROS-responsive side-chain selenium-grafted polymers, which had potential antiangiogenic activity, as vehicles to load photodynamic therapeutic agent Ce6 and chemotherapeutic drug oridonin. Under NIR irradiation, the C-Se bonds on the side chain of polymers could be cleaved in the presence of 1O2 produced by Ce6 and further formed organic selenic acid through selenoxide elimination reaction. The generated seleninic acid could downregulate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to inhibit angiogenesis and further relieve hypoxia. The released oridonin could significantly increase the intracellular ROS concentration. Both could modulate cancer cells' microenvironment to reinforce PDT. Therefore, these nanomedicines could be a good candidate for synergistic treatments of antiangiogenesis treatment, PDT, and chemotherapy.
Assuntos
Preparações Farmacêuticas , Fotoquimioterapia , Porfirinas , Selênio , Linhagem Celular Tumoral , Células Endoteliais da Veia Umbilical Humana , Humanos , Metaloproteinase 2 da Matriz , Fármacos Fotossensibilizantes , Polímeros , Óxidos de Selênio , Fator A de Crescimento do Endotélio VascularRESUMO
The construction of reversible supramolecular self-assembly in vivo remains a significant challenge. Here, we demonstrate the redox-triggered reversible supramolecular self-assembly governed by the "check and balance" of two secondary conformations within a brushlike peptide-selenopolypeptide conjugate. The conjugate constitutes a polypeptide backbone whose side chain contains selenoether functional moieties and double bonds to be readily grafted with ß-sheet-prone short-peptide NapFFC. The backbone of the conjugate initially assumes a robust and rigid α-helical conformation, which inhibits the supramolecular assembly of the short peptide in the side chain and yields an overall irregular aggregate morphology under native/reduced conditions. Upon oxidation of the selenoether to more hydrophilic selenoxide, the backbone helix switches to a flexible and disordered conformation, which unleashes the side-chain NapFFC self-assembly into nanofibrils via the adoption of ß-sheet conformation. The reversible switch of the supramolecular morphology enables efficient loading and tumor-microenvironment-triggered release of anticancer drugs for in vivo cancer treatment with satisfactory efficacy and biocompatibility. The interplay and interaction between two well-defined secondary structures within one scaffold offer tremendous opportunity for the design and construction of functional supramolecular biomaterials.
Assuntos
Peptídeos , Interações Hidrofóbicas e Hidrofílicas , Oxirredução , Estrutura Secundária de Proteína , Óxidos de SelênioRESUMO
Phenylselenide substituted BOPHY probes (BOPHY-SePh and PhSe-BOPHY-SePh) were synthesized and characterized by NMR spectroscopy and single-crystal XRD. Both the probes selectively detect HOCl in water with high sensitivity over other reactive oxygen species. A fluorescence "turn-on" event was attained due to cease of the PET process through transformation of selenide to selenoxide. Both the probes react with HOCl in less than 1 s. PhSe-BOPHY-SePh probe depicted low background fluorescence due to presence of two phenylselenide groups at BOPHY. PhSe-BOPHY-SePh probe has a low detection limit (0.63 µM) than BOPHY-SePh probe (1.08 µM). The bioimaging studies of both the probes were carried out in MCF 7 cells. Both the probes exhibited a good fluorescence response for HOCl in vitro and in mammalian cells. In addition, the probes showed reversibility with all bio-thiols, which was validated in MCF 7 cells using GSH.
Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Animais , Fluorescência , Humanos , Células MCF-7 , Óxidos de SelênioRESUMO
In this study, l-methionine selenoxide (MetSeO) was used as an oxidant for the construction of peptide disulfide bonds. Excellent yields for various disulfide-containing peptides were achieved via the MetSeO oxidation method in different solvents and on a resin. Most importantly, the construction of disulfide bonds can be performed in the trifluoroacetic acid cocktail used for the cleavage of peptides from the resin, which obviates the steps of peptide purification and lyophilization. This facilitates and simplifies the synthesis of disulfide-containing peptides. Kinetic and mechanistic studies of the reaction between MetSeO and dithiothreitol (DTT, a model compound of dicysteine-containing peptide) show that the reaction is first order in both [MetSeO] and [DTT], and a reaction mechanism is proposed that can help us gain insights into the reaction of the oxidative synthesis of disulfide bonds via MetSeO oxidation.
Assuntos
Dissulfetos , Metionina , Metionina/análogos & derivados , Metionina/metabolismo , Compostos Organosselênicos , Oxirredução , Peptídeos , Óxidos de SelênioRESUMO
In the present study we have studied the incorporation and release of selenite ions (SeO32-) in hydroxyapatite nanoparticles for the treatment of bone tumors. Two types of selenium-doped hydroxyapatite (HASe) nanoparticles (NPs) with a nominal Se/(P + Se) molar ratio ranging from 0.01 up to 0.40 have been synthesized by a new and mild wet method. The two series of samples were thoroughly characterized and resulted to be slightly different in chemical composition, but they had similar properties in terms of morphology and degree of crystallinity. Selenium release from HASe was investigated under neutral and acidic conditions to simulate both healthy tissues and the low-pH environment surrounding a tumor mass, respectively. The comparison of the release profiles at two pH values clearly showed the possibility of modulating the Se release by simply changing the amount of Se in the HASe particles. The correlation between the physicochemical properties of HASe and their dissolution as a function of pH has been also investigated to facilitate future application of the NPs as chemotherapeutic adjuvant agents. Finally, the cytotoxic activity of HASe was evaluated using prostate (PC3) and breast (MDA-MB-231) cancer cells as well as healthy human bone marrow stem cells (hBMSc). HASe NPs exerted a good cytocompatibility at low concentration of Se but, with high Se doping concentration, they displayed strong cytotoxicity.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Durapatita/química , Nanopartículas/química , Selênio/química , Antineoplásicos/química , Neoplasias Ósseas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Durapatita/farmacologia , Humanos , Microscopia Eletrônica de Transmissão/métodos , Células PC-3 , Selênio/farmacologia , Óxidos de Selênio/química , Difração de Raios X/métodosRESUMO
Selenocysteine (Sec) is the 21st proteogenic amino acid in the genetic code. Incorporation of Sec into proteins is a complex and bioenergetically costly process that evokes the following question: "Why did nature choose selenium?" An answer that has emerged over the past decade is that Sec confers resistance to irreversible oxidative inactivation by reactive oxygen species. Here, we explore the question of whether this concept can be broadened to include resistance to reactive electrophilic species (RES) because oxygen and related compounds are merely a subset of RES. To test this hypothesis, we inactivated mammalian thioredoxin reductase (Sec-TrxR), a mutant containing α-methylselenocysteine [(αMe)Sec-TrxR], and a cysteine ortholog TrxR (Cys-TrxR) with various electrophiles, including acrolein, 4-hydroxynonenal, and curcumin. Our results show that the acrolein-inactivated Sec-TrxR and the (αMe)Sec-TrxR mutant could regain 25% and 30% activity, respectively, when incubated with 2 mM H2O2 and 5 mM imidazole. In contrast, Cys-TrxR did not regain activity under the same conditions. We posit that Sec enzymes can undergo a repair process via ß-syn selenoxide elimination that ejects the electrophile, leaving the enzyme in the oxidized selenosulfide state. (αMe)Sec-TrxR was created by incorporating the non-natural amino acid (αMe)Sec into TrxR by semisynthesis and allowed for rigorous testing of our hypothesis. This Sec derivative enables higher resistance to both oxidative and electrophilic inactivation because it lacks a backbone Cα-H, which prevents loss of selenium through the formation of dehydroalanine. This is the first time this unique amino acid has been incorporated into an enzyme and is an example of state-of-the-art protein engineering.
Assuntos
Mutação , Selenocisteína/análogos & derivados , Selenoproteínas/química , Tiorredoxina Dissulfeto Redutase/metabolismo , Cisteína/química , Humanos , Oxirredução , Óxidos de Selênio/química , Selenocisteína/química , Selenocisteína/genética , Selenocisteína/metabolismo , Selenoproteínas/genética , Selenoproteínas/metabolismo , Tiorredoxina Dissulfeto Redutase/química , Tiorredoxinas/química , Tiorredoxinas/metabolismoRESUMO
Selenoxide elimination reaction has been widely used in the field of organic synthesis. However, few studies have been conducted to apply this reaction in biodegradable nanomedicine. In this work, the selenoxide elimination reaction was used for cancer treatment via producing excess cellular reactive oxygen species (ROS) for the first time. The ß-seleno diesters and porphyrin derivates containing nanoparticle could be responsive to the intracellular ROS and produce acrylates through the elimination reaction. The acrylates would further deplete intracellular GSH in tumor cells and finally improved the anticancer activity in the mice tumor model. Different from traditional ROS-responsive nanomedicine, the elimination product of this reaction could regenerate cytotoxic ROS and specifically disturb the redox balance of tumor cells. This work would provide attractive avenues for the development of therapeutic strategies against cancer via synthesis of well-designed biodegradable polymers.
Assuntos
Antineoplásicos/farmacologia , Compostos Organosselênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Óxidos de Selênio/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Endocitose/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In this study, PEGylated selenium nanoparticles (PSNP) was successfully prepared and combined with X-ray for effective anticancer efficacy in lung cancer cells. The particles were nanosized and observed in spherical shape. The combination of PSNP and X-ray effectively killed the cancer cells and decreased the cell viability in a concentration dependent manner. PSNP combined with X-ray showed a significantly higher apoptosis of cancer cells with around 23% of cells in late apoptosis stage. Consistently, Caspase-3 activity was significantly higher when exposed to X-ray than in the absence of X-ray. The caspase-3 activity has been doubled in the presence of X-ray and PSNPs were actively involved in the activation of effector caspase-3 and downstream target. Importantly, treatment with the combination of PSNP and X-ray showed predominant red fluorescence which is indicative of dead cells. The results clearly indicate the cytotoxic potential of PSNPâ¯+â¯X-ray combination against lung cancer cells. Overall, novel strategy of combination of PSNP and X-ray could be an alternative and effective chemo-radiotherapy.
Assuntos
Neoplasias Pulmonares/terapia , Nanopartículas , Polietilenoglicóis/química , Óxidos de Selênio/farmacologia , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quimiorradioterapia/métodos , Portadores de Fármacos/química , Humanos , Neoplasias Pulmonares/patologia , Óxidos de Selênio/administração & dosagemRESUMO
A plant factory is a closed cultivation system that provides a consistent and modified environment for plant growth. We speculated that treatment of kale (Brassica oleracea) grown in a plant factory with NaCl, Na2SeO3, or both would increase the bioactive phytochemical levels including glucosinolates (GLSs) and isothiocyanates (ITCs), the key molecules in cancer prevention. The kale was harvested and analysed after treatment with NaCl and Na2SeO3 alone or in combination for 1 or 2 weeks. Exposure to NaCl alone but not Na2SeO3 increased plant root growth. Levels of sinigrin were increased by a 2-week exposure to Na2SeO3 alone or in combination with NaCl, whereas no changes were observed in glucoraphanin and gluconasturtiin gluconasturtiin levels. Importantly, the ITC concentration was affected by 2-week treatment with both compounds. To evaluate the bioactivity of kale, HepG2 human hepatoma cells were treated with plant extract for 6 h. Only the extract of kale roots exposed to a combination NaCl and Na2SeO3 for 2 weeks showed an increased expression of nuclear factor erythroid 2-related factor (Nrf2), which regulates genes encoding antioxidant proteins. These data suggest that co-treatment with NaCl and Na2SeO3 increased the ITC content and chemopreventive effects of kale root.
Assuntos
Brassica , Isotiocianatos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Raízes de Plantas/efeitos dos fármacos , Óxidos de Selênio/metabolismo , Transdução de Sinais , Cloreto de Sódio/farmacologia , Cromatografia Líquida de Alta Pressão , Glicosídeo Hidrolases/metabolismo , Células Hep G2 , Humanos , Raízes de Plantas/enzimologia , Raízes de Plantas/crescimento & desenvolvimentoRESUMO
The effects of selenium, putrescine, and cadmium on the contents of glucosinolates, total phenolics, flavonoids, carotenoids, chlorophyll, anthocyanin, malondialdehyde, hydrogen peroxide, and antioxidant capacities as well as gene regulation of phenolics, flavonoids, carotenoids, and glucosinolates biosynthesis were investigated in turnip plants. Selenium dioxide (SeO2) treatment significantly induced the amount of gluconasturtiin, glucobrassicanapin, glucoallysin, glucobrassicin, 4-methoxyglucobrassicin, and 4-hydroxyglucobrassicin. Cadmium chloride (CdCl2)- and putrescine-treated plants had considerably enhanced gluconasturtiin and 4-hydroxyglucobrassicin levels, respectively. Total phenolic and flavonoid content as well as antioxidant capacities were significantly increased in SeO2-treated plants. Lutein was higher in control plants followed by, in decreasing order, SeO2-, putrescine-, and CdCl2-treated plants. The chlorophyll content was significantly decreased and anthocyanin, MDA, and H2O2 levels were significantly increased with CdCl2 treatment. Moreover, plants treated with selenium and cadmium showed significant induction of genes related to glucosinolate, phenolic, and carotenoid biosynthesis. These results demonstrated that SeO2 significantly increased the contents of health-promoting compounds and enhanced the antioxidant capacities of turnip plants.
Assuntos
Brassica napus/química , Brassica napus/efeitos dos fármacos , Cloreto de Cádmio/farmacologia , Putrescina/farmacologia , Óxidos de Selênio/farmacologia , Carotenoides/análise , Carotenoides/biossíntese , Clorofila/análise , Flavonoides/análise , Glucosinolatos/análise , Glucosinolatos/biossíntese , Promoção da Saúde , Luteína/análise , Malondialdeído/análise , Fenóis/análiseRESUMO
The correlation among selenium uptake, the content of bioactive compounds in sprouts, and biological activities triggered in cultured human cells by sprout extracts was investigated. Seeds of Brassica crops and rye were treated with SeO2 water solution. The selenium levels in sprouts increased from 1.0-4.1 to 53.3-382 µg/g dw with no influence on plant physiology according to the indices used. Neither the composition of glucosinolates (GL) in Brassica sprouts nor the myrosinase activity nor the composition of GL breakdown lipophilic products were significantly affected. In all Brassica sprouts, conversion to health-promoting isothiocyanates (ITC) and indoles corresponded to only 1% of total GLs. Low ITC concentration may explain observed lack of induction of glutathione S-transferases (GST) and quinone oxidoreductase (NQO) detoxifying enzymes in HT29 cells exposed to sprout extracts. The insignificant impact on cell growth and genome function suggests that Brassica sprouts may be safe vehicle of selenium to combat its dietary deficiency.
Assuntos
Brassica/metabolismo , Dieta , Germinação , Glucosinolatos/metabolismo , Isotiocianatos/metabolismo , Plântula/metabolismo , Selênio/metabolismo , Anticarcinógenos/farmacologia , Antioxidantes/metabolismo , Técnicas de Cultura de Células , Glutationa Transferase/metabolismo , Glicosídeo Hidrolases/metabolismo , Células HT29 , Humanos , Indóis/metabolismo , Indóis/farmacologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Extratos Vegetais/farmacologia , Selênio/deficiência , Óxidos de Selênio/metabolismoRESUMO
In vitro antiproliferative effects of selenium nanoparticles (nanoSe(0), 10-40 µmol/L) on HeLa (human cervical carcinoma) cells and MDA-MB-231 (human breast carcinoma) cells were examined by optical microscopic inspection and MTT assay in the present study. The nanoSe(0) effectively inhibited the growth of MDA-MB-231 cells and HeLa cells in a dose-dependent manner. The morphology analysis with atomic force microscope showed that the HeLa cells treated with 10 µmol/L nanoSe(0) were rough and shrunken with truncated lamellipodia at terminal part of the cells. Flow cytometric analysis demonstrated that HeLa cells were arrested at S phase of the cell cycle after exposed to nanoSe(0) (10 µmol/L). Taken together, our results suggested that nanoSe(0) may be more helpful in cancer chemoprevention as a potential anticancer drug.
Assuntos
Anticarcinógenos/farmacologia , Ácido Ascórbico/farmacologia , Nanopartículas/química , Fase S/efeitos dos fármacos , Compostos de Selênio/farmacologia , Anticarcinógenos/química , Apoptose/efeitos dos fármacos , Ácido Ascórbico/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Citometria de Fluxo , Células HeLa , Humanos , Microscopia de Força Atômica , Compostos de Selênio/química , Óxidos de Selênio , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologiaRESUMO
A set of human tumor cell lines was characterized in terms of the GPx isoenzymes GPx1, -2, -3 and -4. Semiquantitative PCR was used to investigate the GPx mRNA transcripts and the GPx activity was determined photometrically. As a result of culturing under standard conditions, diverse distribution of GPx mRNA and basic GPx activity was found in the investigated cell lines. PCR results showed nearly ubiquitous existence of the isoenzymes GPx1 and GPx4. GPx2 mRNA transcript was only detected in the colonic cell line CaCo-2. After detection of the GPx3 mRNA transcripts in most of the tested cell lines, an ELISA was performed to investigate if the GPx3 protein is present as well. However, the GPx3 protein could not be detected. Glutathione peroxidases contain the amino acid selenocysteine in their active centre. Selenocysteine contains selenium instead of sulfur in cysteine. Therefore, the influence of selenium on GPx activity and GPx isoenzyme distribution was investigated. Cell culturing with additional selenium showed a clear elevation of GPx activity in Mono Mac 6 cells but no gain of mRNA transcripts or any change in the isoenzyme's distribution.
Assuntos
Linhagem Celular Tumoral/enzimologia , Glutationa Peroxidase/metabolismo , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Isoenzimas/metabolismo , Reação em Cadeia da Polimerase , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Padrões de Referência , Compostos de Selênio/farmacologia , Óxidos de SelênioRESUMO
The organ-specific accumulation, spatial distribution, and chemical speciation of selenium (Se) were previously unknown for any species of cactus. We investigated Se in Opuntia ficus-indica using inductively coupled plasma mass spectrometry, microfocused x-ray fluorescence elemental and chemical mapping (µXRF), Se K-edge x-ray absorption near-edge structure (XANES) spectroscopy, and liquid chromatography-mass spectrometry (LC-MS). µXRF showed Se concentrated inside small conic, vestigial leaves (cladode tips), the cladode vasculature, and the seed embryos. Se K-edge XANES demonstrated that approximately 96% of total Se in cladode, fruit juice, fruit pulp, and seed is carbon-Se-carbon (C-Se-C). Micro and bulk XANES analysis showed that cladode tips contained both selenate and C-Se-C forms. Inductively coupled plasma mass spectrometry quantification of Se in high-performance liquid chromatography fractions followed by LC-MS structural identification showed selenocystathionine-to-selenomethionine (SeMet) ratios of 75:25, 71:29, and 32:68, respectively in cladode, fruit, and seed. Enzymatic digestions and subsequent analysis confirmed that Se was mainly present in a "free" nonproteinaceous form inside cladode and fruit, while in the seed, Se was incorporated into proteins associated with lipids. µXRF chemical mapping illuminated the specific location of Se reduction and assimilation from selenate accumulated in the cladode tips into the two LC-MS-identified C-Se-C forms before they were transported into the cladode mesophyll. We conclude that Opuntia is a secondary Se-accumulating plant whose fruit and cladode contain mostly free selenocystathionine and SeMet, while seeds contain mainly SeMet in protein. When eaten, the organic Se forms in Opuntia fruit, cladode, and seed may improve health, increase Se mineral nutrition, and help prevent multiple human cancers.
Assuntos
Suplementos Nutricionais , Secas , Alimentos Fortificados , Opuntia/metabolismo , Plantas Tolerantes a Sal/metabolismo , Selênio/metabolismo , Cloreto de Sódio/farmacologia , Ácidos , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/metabolismo , Endopeptidase K/metabolismo , Frutas/efeitos dos fármacos , Frutas/metabolismo , Espectrometria de Massas , Opuntia/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Extratos Vegetais , Reprodutibilidade dos Testes , Plantas Tolerantes a Sal/efeitos dos fármacos , Compostos de Selênio/metabolismo , Compostos de Selênio/farmacologia , Óxidos de Selênio , Espectrometria por Raios X , Espectrofotometria Atômica , Espectroscopia por Absorção de Raios XRESUMO
The aim of this study was to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced oxidative stress in erythrocytes, compared to Se or Zn treatment alone in rats exposed to Cd. For this purpose, 30 adult male Wistar albino rats were equally divided into control and four treated groups received either 200ppm Cd (as CdCl(2)), 200ppm Cd+500ppm Zn (as ZnCl(2)), 200ppm Cd+0.1ppm Se (as Na(2)SeO(3)), or 200ppm Cd+500ppm Zn+0.1ppm Se in their drinking water for 35 days. Marked alterations of antioxidative system were found in Cd-treated rats. Activities of catalase (CAT) and glutathione peroxidise (GSH-Px) as well as the total glutathione (GSH) contents in erythrocytes were significantly decreased, whereas the activity of total superoxide dismutase (SOD) was significantly increased. The treatment of Cd-exposed rats with Se alone had no significant effect on the Cd-induced increase in the SOD activity but increased significantly the CAT and GSH-Px activities and partially reversed Cd-induced depletion of GSH levels in erythrocytes. The treatment of Cd-exposed animals with Zn alone partially reversed Cd-induced increase in SOD activity and Cd-induced decrease in GSH-Px activity. The combined treatment of Cd-exposed animals with Se and Zn was more effective than that with either of them alone in reversing Cd-induced decrease in CAT and GSH-Px activities and Cd-induced increase in SOD activity. This treatment also partially restored Cd-induced depletion of GSH. These results could be important for the further development of better treatments for people and/or animals exposed to Cd.
Assuntos
Antioxidantes/farmacologia , Cloreto de Cádmio/toxicidade , Cloretos/farmacologia , Eritrócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Selênio/farmacologia , Compostos de Zinco/farmacologia , Animais , Catalase/sangue , Catalase/efeitos dos fármacos , Eritrócitos/metabolismo , Glutationa/sangue , Glutationa/efeitos dos fármacos , Glutationa Peroxidase/sangue , Glutationa Peroxidase/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Óxidos de Selênio , Superóxido Dismutase/sangue , Superóxido Dismutase/efeitos dos fármacosRESUMO
Allylic hydroxylated derivatives of the C18 unsaturated fatty acids were prepared from linoleic acid (LA) and conjugated linoleic acids (CLAs). The reaction of LA methyl ester with selenium dioxide (SeO(2)) gave mono-hydroxylated derivatives, 13-hydroxy-9Z,11E-octadecadienoic acid, 13-hydroxy-9E,11E-octadecadienoic acid, 9-hydroxy-10E,12Z-octadecadienoic acid and 9-hydroxy-10E,12E-octadecadienoic acid methyl esters. In contrast, the reaction of CLA methyl ester with SeO(2) gave di-hydroxylated derivatives as novel products including, erythro-12,13-dihydroxy-10E-octadecenoic acid, erythro-11,12-dihydroxy-9E-octadecenoic acid, erythro-10,11-dihydroxy-12E-octadecenoic acid and erythro-9,10-dihydroxy-11E-octadecenoic acid methyl esters. These products were purified by normal-phase short column vacuum chromatography followed by high-performance liquid chromatography (HPLC). Their chemical structures were characterized by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR). The allylic hydroxylated derivatives of LA and CLA exhibited moderate in vitro cytotoxicity against a panel of human cancer cell lines including chronic myelogenous leukemia K562, myeloma RPMI8226, hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7 cells (IC(50) 10-75 microM). The allylic hydroxylated derivatives of LA and CLA also showed toxicity to brine shrimp with LD(50) values in the range of 2.30-13.8 microM. However these compounds showed insignificant toxicity to honeybee at doses up to 100 microg/bee.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ácido Linoleico/química , Ácido Linoleico/farmacologia , Ácidos Linoleicos Conjugados/síntese química , Ácidos Linoleicos Conjugados/farmacologia , Animais , Antineoplásicos/química , Artemia/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Hidroxilação , Dose Letal Mediana , Ácido Linoleico/síntese química , Ácidos Linoleicos Conjugados/química , Compostos de Selênio/química , Óxidos de SelênioRESUMO
The possible abiotic reduction of selenite to form elemental Se was studied under controlled conditions in the presence of ferrous iron. The reduction of selenite and formation of Se (0) was found to be a surface-mediated reaction by iron oxides. Without the presence of the reactive surface of freshly precipitated iron oxides, the reduction reaction could not be detected, even under a well controlled low oxygen environment (30 ppmv). Our results clearly illustrate the crucial role of iron oxide in this redox process. In lake sediments, the complex sediment matrix seems to strongly adsorb SeO(2-) and make it less available for reduction into Se(0). When lake sediments were submitted to UV irradiation to eliminate bacteria, the percentage of iron oxides increased and it was found that higher levels of iron oxides, generated by the UV treatment, correlated with the higher formation of Se(0). Moreover, the results of our field studies on two distinctively different lake sediments also showed a strong influence of iron oxides on the formation of elemental Se, which agrees well with our laboratory simulations.
Assuntos
Compostos Férricos/química , Selênio/química , Sedimentos Geológicos/química , Concentração de Íons de Hidrogênio , Cinética , Oxirredução , Oxigênio/química , Ácido Selênico , Compostos de Selênio/química , Óxidos de Selênio , Selenito de Sódio/química , Propriedades de Superfície , Raios Ultravioleta , Água/químicaRESUMO
The effects of selenium (Se) on antioxidant defense system in liver and kidneys of rats with cadmium (Cd)-induced toxicity were examined. Cd exposure (15 mg Cd/kg b.m./day as CdCl(2) for 4 weeks) resulted in increased lipid peroxidation (LP) in both organs (p<0.005 and p<0.01). Vitamin C (Vit C) was decreased in the liver (p<0.005), whereas vitamin E (Vit E) was increased in the liver and kidneys (p<0.005 and p<0.05) of Cd-exposed animals. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were decreased in both tissues (p<0.05 and p<0.005), whereas catalase (CAT) activity was decreased only in liver (p<0.005). Glutathione S-transferase (GST) increased in both tissues (p<0.005 and p<0.01). Treatment with Se (0.5 mg Se/kg b.m./day as Na(2)SeO(3) for 4 weeks) significantly increased liver and kidneys SOD and GSH-Px activities (p<0.05 to p<0.005), as well as CAT and GST activities only in the liver (p<0.01). In animals exposed to Se, both the concentrations of Vit C (p<0.01) and Vit E (p<0.005) were increased in both tissues. Co-treatment with Se resulted in reversal of oxidative stress with significant decline in analyzed tissues Cd burden. Our results show that Se may ameliorate Cd-induced oxidative stress by decreasing LP and altering antioxidant defense system in rat liver and kidneys and that Se demonstrates the protective effect from cadmium-induced oxidative damage.
Assuntos
Antioxidantes/farmacologia , Cloreto de Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Selênio/farmacologia , Animais , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Cloreto de Cádmio/metabolismo , Catalase/metabolismo , Poluentes Ambientais/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Rim/enzimologia , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Ratos , Óxidos de Selênio , Superóxido Dismutase/metabolismo , Vitamina E/metabolismoRESUMO
[reaction: see text] An efficient synthetic route to Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones has been developed. 3-Aryl-1-(3-bromo-5-chloro-2-hydroxyphenyl)-2-propen-1-one or 2-aryl-8-bromo-6-chlorochroman-4-one could be reacted under Mannich conditions yielding 2-aryl-8-bromo-6-chloro-3-methylenechroman-4-one, which was further converted to the target compound via an aza-Michael reaction followed by an SeO(2) oxidation. This procedure represents a new method to introduce a primary aminomethyl group at the 3-position of a 2-arylchromone scaffold. The Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones can, e.g., be used in the synthesis of chromone-based beta-turn peptidomimetics.