ABSTRACT
Extensive data have reported the involvement of oxidative stress in the pathogenesis of neuropsychiatric disorders, prompting the pursuit of antioxidant molecules that could become adjuvant pharmacological agents for the management of oxidative stress-associated disorders. The 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) has been reported as an antioxidant and immunomodulatory compound that improves depression-like behavior and cognitive impairment in mice. However, the exact effect of CMI on specific brain cells is yet to be studied. In this context, the present study aimed to evaluate the antioxidant activity of CMI in H2O2-induced oxidative stress on human dopaminergic neuroblastoma cells (SH-SY5Y) and to shed some light into its possible mechanism of action. Our results demonstrated that the treatment of SH-SY5Y cells with 4 µM CMI protected them against H2O2 (343 µM)-induced oxidative stress. Specifically, CMI prevented the increased number of reactive oxygen species (ROS)-positive cells induced by H2O2 exposure. Furthermore, CMI treatment increased the levels of reduced glutathione in SH-SY5Y cells. Molecular docking studies demonstrated that CMI might interact with enzymes involved in glutathione metabolism (i.e., glutathione peroxidase and glutathione reductase) and H2O2 scavenging (i.e., catalase). In silico pharmacokinetics analysis predicted that CMI might be well absorbed, metabolized, and excreted, and able to cross the blood-brain barrier. Also, CMI was not considered toxic overall. Taken together, our results suggest that CMI protects dopaminergic neurons from H2O2-induced stress by lowering ROS levels and boosting the glutathione system. These results will facilitate the clinical application of CMI to treat nervous system diseases associated with oxidative stress.
Subject(s)
Hydrogen Peroxide/toxicity , Indoles/pharmacology , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Selenium Compounds/pharmacology , Catalytic Domain , Cell Line, Tumor , Glutathione/metabolism , Glutathione Transferase/chemistry , Glutathione Transferase/metabolism , Humans , Indoles/chemistry , Indoles/metabolism , Indoles/pharmacokinetics , Molecular Docking Simulation , Neuroprotective Agents/chemistry , Neuroprotective Agents/metabolism , Neuroprotective Agents/pharmacokinetics , Oxidoreductases/chemistry , Oxidoreductases/metabolism , Protein Binding , Reactive Oxygen Species/metabolism , Selenium Compounds/chemistry , Selenium Compounds/metabolism , Selenium Compounds/pharmacokineticsABSTRACT
Mercury accumulates at high levels in marine mammal tissues. However, its speciation is poorly understood. The main goal of this investigation was to establish the relationships among mercury species and selenium (Se) concentrations in toothed-whale muscles at different mercury levels. The concentrations of total mercury (T-Hg), methylmercury (MeHg), inorganic mercury (I-Hg) and Se were determined in the muscles of four toothed-whale species: bottlenose dolphins (n=31), Risso's dolphins (n=30), striped dolphins (n=29), and short-finned pilot whales (n=30). In each species, the MeHg concentration increased with increasing T-Hg concentration, tending to reach a plateau. In contrast, the proportion of MeHg in T-Hg decreased from 90-100% to 20-40%. The levels of T-Hg and Se showed strong positive correlations. Se/I-Hg molar ratios rapidly decreased with the increase of I-Hg and reached almost 1 in all species. These results suggested that the demethylated MeHg immediately formed Se/I-Hg equimolar complex of mercury selenide (HgSe) in their muscles. In addition, an X-ray absorption fine structure analysis (XAFS) of a bottlenose dolphin muscle confirmed that the dominant chemical form of the Se/I-Hg equimolar complex was HgSe. HgSe was mainly localized in cells near the endomysium using electron probe microanalysis (EPMA). These results suggested that the demethylated MeHg finally deposits within muscle cells of bottlenose dolphin as an inert HgSe.
Subject(s)
Dolphins/metabolism , Mercury/pharmacokinetics , Muscles/metabolism , Selenium/pharmacokinetics , Animals , Electron Probe Microanalysis , Environmental Monitoring , Female , Male , Mercury Compounds/pharmacokinetics , Methylmercury Compounds/pharmacokinetics , Selenium Compounds/pharmacokinetics , Species Specificity , Water Pollutants, Chemical/pharmacokinetics , X-Ray Absorption SpectroscopyABSTRACT
Construction of self-illuminating semiconducting nanocrystals, also called quantum dots (QDs), has attracted much attention recently due to their potential as highly sensitive optical probes for biological imaging applications. Here we prepared a self-illuminating QD system by doping positron-emitting radionuclide (64)Cu into CdSe/ZnS core/shell QDs via a cation-exchange reaction. The (64)Cu-doped CdSe/ZnS QDs exhibit efficient Cerenkov resonance energy transfer (CRET). The signal of (64)Cu can accurately reflect the biodistribution of the QDs during circulation with no dissociation of (64)Cu from the nanoparticles. We also explored this system for in vivo tumor imaging. This nanoprobe showed high tumor-targeting ability in a U87MG glioblastoma xenograft model (12.7% ID/g at 17 h time point) and feasibility for in vivo luminescence imaging of tumor in the absence of excitation light. The availability of these self-illuminating integrated QDs provides an accurate and convenient tool for in vivo tumor imaging and detection.
Subject(s)
Cadmium Compounds/chemistry , Neoplasms/diagnostic imaging , Optical Imaging , Positron-Emission Tomography , Quantum Dots , Selenium Compounds/chemistry , Sulfides/chemistry , Zinc Compounds/chemistry , Animals , Cadmium Compounds/pharmacokinetics , Copper Radioisotopes , Energy Transfer , Luminescence , Mice , Neoplasms/metabolism , Selenium Compounds/pharmacokinetics , Sulfides/pharmacokinetics , Tissue Distribution , Xenograft Model Antitumor Assays , Zinc Compounds/pharmacokineticsABSTRACT
A new PEGylation reagent enabling selective modification of free thiol groups is described in this article. The reagent was synthesized by attaching linear polyethylene glycol (PEG) N-hydroxysuccinimide to selenocystamine. The reaction was very fast, resulting in over 95% conversion yield. The active group of this new PEG-Se reagent is a diselenide, reacting with thiols via thiol/diselenide exchange reaction. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) with an unpaired cysteine at the position 18 (Cys18) was used as a model protein. It was comparatively PEGylated with the new PEG-Se reagent, as well as with commercially available maleimide (PEG-Mal) and ortho-pyridyl disulfide (PEG-OPSS) PEG reagents. The highest PEGylation yield was obtained with PEG-Mal, followed by PEG-OPSS and PEG-Se. The reaction rates of PEG-Mal and PEG-Se were comparable, while the reaction rate of PEG-OPSS was lower. Purified monoPEGylated rhG-CSF conjugates were characterized and compared. Differences in activity, stability, and in vivo performance were observed, although all conjugates contained a 20 kDa PEG attached to the Cys18. Minor conformational changes were observed in the conjugate prepared with PEG-Mal. These changes were also reflected in low in vitro biological activity and aggregate formation of the maleimide conjugate. The conjugate prepared with PEG-Se had the highest in vitro biological activity, while the conjugate prepared with PEG-OPSS had the best in vivo performance.
Subject(s)
Cysteine/chemistry , Granulocyte Colony-Stimulating Factor/chemistry , Polyethylene Glycols/chemistry , Selenium Compounds/chemistry , Animals , Cell Line , Circular Dichroism , Granulocyte Colony-Stimulating Factor/isolation & purification , Humans , Mice , Models, Molecular , Molecular Structure , Polyethylene Glycols/isolation & purification , Polyethylene Glycols/pharmacokinetics , Rats , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacokinetics , Selenium Compounds/isolation & purification , Selenium Compounds/pharmacokineticsABSTRACT
Two experiments were conducted on broiler chickens to compare the effect of a new organic Se source, 2-hydroxy-4-methylselenobutanoic acid (HMSeBA; SO), with two practical Se additives, sodium selenite (SS) and Se yeast (SY). The relative bioavailability of the different Se sources was compared on muscle (pectoralis major) total Se, selenomethionine (SeMet) and selenocysteine (SeCys) concentrations and apparent digestibility of total Se (ADSe). In the first experiment, from day (d) 0 to d21, Se sources were tested at different supplied levels and compared with an unsupplemented diet (NC). No significant effects were observed on growth performance during the experimental period. However, the different Se sources and levels improved muscle Se concentration compared with the NC, with a significant source effect in the following order: SS < SY < SO (P<0·05). Seleno-amino acids speciation results for NC, SY and SO at 0·3 mg Se/kg feed indicated that muscle Se was only present as SeMet or SeCys, showing a full conversion of Se by the bird. The second experiment (d0-d24) compared SS, SY or SO at 0·3 mg Se/kg feed. The ADSe measurements carried out between d20 and d23 were 24, 46 and 49% for SS, SY and SO, respectively, with significant differences between the organic and mineral Se sources (P<0·05). These results confirmed the higher bioavailability of organic Se sources compared with the mineral source and demonstrated a significantly better efficiency of HMSeBA compared with SY for muscle Se enrichment.
Subject(s)
Butyrates/pharmacology , Muscles/drug effects , Selenium Compounds/pharmacology , Selenium/chemistry , Animal Feed , Animals , Antioxidants/metabolism , Butyrates/pharmacokinetics , Chickens , Diet , Oxidative Stress , Selenium Compounds/pharmacokinetics , Selenomethionine/chemistry , Sodium Selenite/pharmacology , Tissue Distribution , YeastsABSTRACT
BACKGROUND: The potential use of quantum dots (QD) in biomedical applications, as well as in other systems that take advantage of their unique physiochemical properties, has led to concern regarding their toxicity, potential systemic distribution, and biopersistence. In addition, little is known about workplace exposure to QD in research, manufacturing, or medical settings. The goal of the present study was to assess pulmonary toxicity, clearance, and biodistribution of QD with different functional groups in rats after pulmonary exposure. METHODS: QD were composed of a cadmium-selenide (CdSe) core (~5nm) with a zinc sulfide (ZnS) shell functionalized with carboxyl (QD-COOH) or amine (QD-NH2) terminal groups. Male Sprague-Dawley rats were intratracheally-instilled (IT) with saline, QD-COOH, or QD-NH2 (12.5, 5.0, or 1.25 µg/rat). On days 0, 1, 3, 5, 7, 14, and 28 post-IT, the left lung, lung-associated lymph nodes (LALN), heart, kidneys, spleen, liver, brain, and blood were collected for metal analysis of Cd content by neutron activation to evaluate clearance and biodistribution. One right lobe was ligated and fixed for microscopy and histopathological analysis. The remaining right lobes from rats in each group were subjected to bronchoalveolar lavage (BAL) to retrieve BAL fluid and cells for analysis of injury and inflammation. RESULTS: Lung injury and inflammation was found to be dose-dependent and peaked at days 7 and 14 post-exposure for both forms of QD, with slight variations in degree of toxicity at early and later time points. Both QD appeared to lose their fluorescent properties and destabilize after 1 week in the lung. Cd persisted up to 28 days for both forms of QD; however, clearance rate was slightly greater for QD-COOH over time. No Cd was detected in the liver, spleen, heart, brain, or blood at any time point. Cd appeared in the LALN and kidneys beginning at 1-2 weeks post-exposure. CONCLUSIONS: QD-COOH and QD-NH2 differed in clearance rate and differed slightly in degree of toxicity at different time points; however, the overall pattern of toxicity and biodistribution was similar between the two particles. Toxicity may be dependent on the dissolution rate and bioavailability of free Cd.
Subject(s)
Cadmium Compounds , Lung Injury/chemically induced , Lung/drug effects , Pneumonia/chemically induced , Quantum Dots , Selenium Compounds , Sulfides , Zinc Compounds , Animals , Bronchoalveolar Lavage Fluid/cytology , Cadmium Compounds/chemistry , Cadmium Compounds/pharmacokinetics , Cadmium Compounds/toxicity , Dose-Response Relationship, Drug , Inhalation Exposure , Lung/metabolism , Lung Injury/metabolism , Lung Injury/pathology , Male , Microscopy, Confocal , Microscopy, Electron, Transmission , Particle Size , Pneumonia/immunology , Pneumonia/metabolism , Pneumonia/pathology , Rats , Rats, Sprague-Dawley , Selenium Compounds/chemistry , Selenium Compounds/pharmacokinetics , Selenium Compounds/toxicity , Sulfides/chemistry , Sulfides/pharmacokinetics , Sulfides/toxicity , Surface Properties , Tissue Distribution , Zinc Compounds/chemistry , Zinc Compounds/pharmacokinetics , Zinc Compounds/toxicityABSTRACT
Quantum dots (QDs) are novel tools with multiple biological and medical applications because of their superior photoemission and photostability characteristics. However, leaching of toxic metals from QDs is of great concern. Therefore, for the successful application of QDs in bioscience, it is essential to understand their biological fate and toxicity. We investigated toxicological effects and tissue distribution of mercaptopropionic acid-conjugated cadmium selenide/cadmium sulfide (CdSe/CdS-MPA) QDs after repeated intraperitoneal injection into BALB/c mice. The mice were injected every 3 days with various doses of QDs (0, 5, 10 and 25 mg kg(-1) ). The subsequent effects of QDs on plasma levels of various biomarkers were evaluated at different time points (at 0, 1, 4, 7, 10, 13 and 15 days). Various tissue samples (spleen, liver, lung, kidneys, brain, heart and thymus) were collected for toxicity analysis, distribution testing, histopathological examination and inflammation assessment. No abnormal clinical signs or behaviors were recorded but the body weight of mice treated with 25 mg kg(-1) QDs was significantly decreased from day 7 compared with control mice. QDs were observed in the liver, spleen, lung and kidneys, but not in brain or heart. Significantly higher levels of lactate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase were found in the plasma, liver and spleen. Histopathological examination did not show any tissue toxicity but the levels of interleukin-6, a pro-inflammatory marker, were increased in the plasma, liver and spleen. All of these findings provide insight into the observed toxicological effect levels and tissue-specific distribution of CdSe/CdS-MPA QDs.
Subject(s)
Cadmium Compounds/pharmacokinetics , Cadmium Compounds/toxicity , Quantum Dots/toxicity , Selenium Compounds/pharmacokinetics , Selenium Compounds/toxicity , Sulfides/pharmacokinetics , Sulfides/toxicity , Toxicity Tests, Acute/methods , Animals , Brain/drug effects , Brain/metabolism , Female , Heart/drug effects , Heart/physiology , Injections, Intraperitoneal , Interleukin-6/blood , Kidney/drug effects , Kidney/metabolism , L-Lactate Dehydrogenase/blood , Liver/drug effects , Liver/metabolism , Lung/drug effects , Lung/metabolism , Mice , Mice, Inbred BALB C , NADP/blood , Spleen/drug effects , Spleen/metabolism , Thymus Gland/drug effects , Thymus Gland/metabolism , Tissue DistributionABSTRACT
CdSe-core, ZnS-capped semiconductor quantum dots (QDs) are of great potential for biomedical applications. However, applications in the gastrointestinal tract for in vivo imaging and therapeutic purposes are hampered by their sensitivity to acidic environments and potential toxicity. Here we report the use of coatings with a combination of polythiol ligands and silica shell (QDs PolyT-APS) to stabilize QDs fluorescence under acidic conditions. We demonstrated the stability of water-soluble QDs PolyT-APS both in vitro, in strong acidic solutions, and in vivo. The biodistribution, stability and photoluminescence properties of QDs in the gastrointestinal tract of mice after per os administration were assessed. We demonstrated that QDs coated with current traditional materials - mercapto compounds (QDs MPA) and pendant thiol group (QDs PolyT) - are not capable of protecting QDs from chemically induced degradation and surface modification. Polythiol ligands and silica shell quantum dots (QDs PolyT-APS) are suitable for biological and biomedical applications in the gastrointestinal tract.
Subject(s)
Cadmium Compounds/pharmacokinetics , Coated Materials, Biocompatible/pharmacokinetics , Fluorescent Dyes/pharmacokinetics , Gastrointestinal Tract/metabolism , Liver/metabolism , Pancreas/metabolism , Quantum Dots , Selenium Compounds/pharmacokinetics , Administration, Oral , Animals , Cadmium Compounds/administration & dosage , Cadmium Compounds/chemistry , Female , Fluorescence , Ligands , Mice , Mice, Nude , Selenium Compounds/administration & dosage , Selenium Compounds/chemistry , Silicon Dioxide/chemistry , Sulfhydryl Compounds/chemistry , Tissue DistributionABSTRACT
Understanding the cytotoxicity of quantum dots strongly relies upon the development of new analytical techniques to gather information about various aspects of the system. In this study, we demonstrate the in vivo biodistribution and fate of CdSe quantum dots in the murine model by means of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). By comparing the hot zones of each element acquired from LA-ICP-MS with those in fluorescence images, together with hematoxylin and eosin-stained images, we are able to perceive the fate and in vivo interactions between quantum dots and rat tissues. One hour after intravenous injection, we found that all of the quantum dots had been concentrated inside the spleen, liver and kidneys, while no quantum dots were found in other tissues (i.e., muscle, brain, lung, etc.). In the spleen, cadmium-114 signals always appeared in conjunction with iron signals, indicating that the quantum dots had been filtered from main vessels and then accumulated inside splenic red pulp. In the liver, the overlapped hot zones of quantum dots and those of phosphorus, copper, and zinc showed that these quantum dots have been retained inside hepatic cells. Importantly, it was noted that in the kidneys, quantum dots went into the cortical areas of adrenal glands. At the same time, hot zones of copper appeared in proximal tubules of the cortex. This could be a sign that the uptake of quantum dots initiates certain immune responses. Interestingly, the intensity of the selenium signals was not proportional to that of cadmium in all tissues. This could be the result of the decomposition of the quantum dots or matrix interference. In conclusion, the advantage in spatial resolution of LA-ICP-MS is one of the most powerful tools to probe the fate, interactions and biodistribution of quantum dots in vivo.
Subject(s)
Cadmium Compounds/pharmacokinetics , Laser Therapy , Mass Spectrometry , Quantum Dots , Selenium Compounds/pharmacokinetics , Animals , Kidney/ultrastructure , Laser Therapy/methods , Liver/ultrastructure , Mass Spectrometry/methods , Mice , Microscopy, Fluorescence , Spleen/ultrastructure , Tissue DistributionABSTRACT
Mercury is one of the most toxic heavy metal for mammals particularly in inorganic form. In present study, 3,3'-diselenodipropionic acid (DSePA), a well-known pharmacological diselenide was evaluated for its interaction with HgCl2 and ability to prevent HgCl2-induced toxicity in experimental cellular and mice models. UV-visible, stopped flow, Fourier-transform infrared spectroscopy and 1H nuclear magnetic resonance spectroscopy studies confirmed that DSePA sequestered Hg (II) ions with stoichiometry of 1:1 and binding constant of ~104 M-1. X-ray photoelectron spectroscopy and X-ray powder diffraction analysis suggested that diselenide group of DSePA was involved in the complexation with Hg (II) ions. Further, Hg-DSePA complex degraded within 10 days to form excretable HgSe. The binding constant of DSePA and Hg (II) was comparable with that of dihydrolipoic acid, a standard disulfide compound used in heavy metal detoxification. Corroborating these observations, pre-treatment of DSePA (10 µM) significantly prevented the HgCl2 (50 µM)-induced glutathione oxidation (GSH/GSSG), decrease of thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) activities and cell death in Chinese Hamster Ovary (CHO) cells. Similarly, intraperitoneal administration of DSePA at a dosage of 2 mg/kg for 5 consecutive days prior to exposure of HgCl2 (1 mg/kg) significantly suppressed oxidative stress in renal and hepatic tissues of C57BL/6 mice. In conclusion, the protective effect of DSePA against Hg induced oxidative stress is attributed to its ability to rescue the activities of GPx, TrxR and GSH by sequestering Hg (II) ions. DSePA being a relatively safer selenium-compound for in vivo administration can be explored for mercury detoxification.
Subject(s)
Antioxidants , Mercury/toxicity , Oxidative Stress/drug effects , Propionates , Selenium Compounds , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , CHO Cells , Cricetulus , Female , Mice , Propionates/chemistry , Propionates/pharmacokinetics , Propionates/pharmacology , Selenium Compounds/chemistry , Selenium Compounds/pharmacokinetics , Selenium Compounds/pharmacologyABSTRACT
The cornea is a potential route of exposure and drug administration for nanoparticles. In this work, we use noninvasive two-photon microscopic imaging to study the distribution and permeability pathway of CdSe/ZnS core/shell quantum dots (QDs) capped with three different functional groups through the cornea. With no additional staining, the two-photon image clearly discloses that fluorescent QDs penetrate and reside within the interlamellar space of second harmonic generating collagenous stroma when the corneal epithelium barrier is injured. An in vitro cytotoxicity test using bovine corneal stromal cells incubated individually with all three kinds of QDs indicates that the cell viability decreases significantly as the QD concentration and incubation period increased. The results also show that the specific QDs influence corneal stromal cell viability up to a significant magnitude of 50% under a relatively low concentration (5-20 nM) and short exposure period (24-48 h). Furthermore, two-photon imaging shows that QDs can be retained within the cornea up to 26 days in an in vivo mouse model. On the basis of our in vivo and in vitro data, we conclude that QDs can penetrate and be retained within cornea long enough to cause consequential cytotoxicity, under the circumstance in which the corneal epithelium barrier is injured. Since corneal abrasion is quite a common situation in daily life, our work raises public attention to the potential risk of eye exposure to nanoparticles.
Subject(s)
Cadmium Compounds/toxicity , Cornea/drug effects , Quantum Dots , Selenium Compounds/toxicity , Sulfides/toxicity , Zinc Compounds/toxicity , Animals , Cadmium Compounds/pharmacokinetics , Cattle , Cell Survival/drug effects , Cells, Cultured , Cornea/cytology , Cornea/metabolism , Mice , Mice, Inbred C57BL , Selenium Compounds/pharmacokinetics , Sulfides/pharmacokinetics , Zinc Compounds/pharmacokineticsABSTRACT
BACKGROUND: Selenium (Se) is an essential micronutrient for humans, but the Se level in food plants in northern Europe is generally inadequate to meet human nutritional requirements. Commonly, food plant Se fortification is achieved by selenate fertilisation, but the effect of nitrogen (N) and sulphur (S) supply on the translocation and re-translocation of Se is unknown. Therefore the effect of N and S supply on 75selenate/75Se translocation and re-translocation during vegetative growth in spring wheat (Triticum aestivum) was studied. RESULTS: The 75Se activity in wheat varied from 148 to 549, from 277 to 1815 and from 171 to 1343 Bq 75Se in plants exposed at Zadoks growth stages Z1.4, Z1.5 and Z1.6 respectively. Approximately 85% of the plant 75Se was translocated into young leaves. High N supply enhanced the re-translocation of 75Se from the stem to maturing leaves, while S inhibited this process. The relative proportion of 75Se in L4, L5 and L6 increased with increasing N supply at low sulfate concentrations. CONCLUSION: Selenium in the stem is more re-transportable than Se in the leaves, and the re-translocation is dependent on sulfate supply. When the sulfate supply is sufficient for plant development, less 75Se is re-translocated from older to growing leaves.
Subject(s)
Fertilizers , Nitrogen/metabolism , Selenium Compounds/pharmacokinetics , Selenium/pharmacokinetics , Sulfur/metabolism , Triticum/metabolism , Biological Transport , Plant Leaves/metabolism , Plant Stems/metabolism , Selenic Acid , Triticum/growth & developmentABSTRACT
Rheumatoid Arthritis is an inflammatory disease primarily involves the inflamed synovium, affecting about 0.5-1 % population worldwide. It is the assumption from many years that oxidative stress is involved in the pathophysiology of inflammatory disorders like RA and many others. The significance of micronutrients in arthritis is linked to their role as a cofactor for the activation of selenoenzymes. Dietary interventions can manage the clinical symptoms of RA like pain, swelling and tenderness of joints and their associated disability along the progression of disease. This review highlights the antioxidant potential of selenium in treatment of RA along with the scientific evidence that Se supplementation can reduce disease progression by managing its clinical symptoms.
Subject(s)
Antioxidants/chemistry , Arthritis, Rheumatoid/drug therapy , Selenium Compounds/chemistry , Animals , Antioxidants/pharmacokinetics , Eating , Enzyme Activation , Gastrointestinal Absorption , Humans , Micronutrients/chemistry , Micronutrients/pharmacology , Nanostructures/chemistry , Oxidative Stress , Selenium Compounds/pharmacokineticsABSTRACT
BACKGROUND: Extensive research is being carried out globally to design and develop new selenium compounds for various biological applications such as antioxidants, radio-protectors, anti-carcinogenic agents, biocides, etc. In this pursuit, 3,3'-diselenodipropionic acid (DSePA), a synthetic organoselenium compound, has received considerable attention for its biological activities. SCOPE OF REVIEW: This review intends to give a comprehensive account of research on DSePA so as to facilitate further research activities on this organoselenium compound and to realize its full potential in different areas of biological and pharmacological sciences. MAJOR CONCLUSIONS: It is an interesting diselenide structurally related to selenocystine. It shows moderate glutathione peroxidase (GPx)-like activity and is an excellent scavenger of reactive oxygen species (ROS). Exposure to radiation, as envisaged during radiation therapy, has been associated with normal tissue side effects and also with the decrease in selenium levels in the body. In vitro and in vivo evaluation of DSePA has confirmed its ability to reduce radiation induced side effects into normal tissues. Administration of DSePA through intraperitoneal (IP) or oral route to mice in a dose range of 2 to 2.5 mg/kg body weight has shown survival advantage against whole body irradiation and a significant protection to lung tissue against thoracic irradiation. Pharmacokinetic profiling of DSePA suggests its maximum absorption in the lung. GENERAL SIGNIFICANCE: Research work on DSePA reported in fifteen years or so indicates that it is a promising multifunctional organoselenium compound exhibiting many important activities of biological relevance apart from radioprotection.
Subject(s)
Antioxidants/pharmacology , Propionates/pharmacology , Radiation-Protective Agents/pharmacology , Selenium Compounds/pharmacology , Animals , Antioxidants/chemical synthesis , Antioxidants/pharmacokinetics , Antioxidants/toxicity , Humans , Oxidation-Reduction/drug effects , Propionates/chemical synthesis , Propionates/pharmacokinetics , Propionates/toxicity , Radiation-Protective Agents/chemical synthesis , Radiation-Protective Agents/pharmacokinetics , Radiation-Protective Agents/toxicity , Reactive Oxygen Species/metabolism , S-Nitrosothiols/metabolism , Selenium Compounds/chemical synthesis , Selenium Compounds/pharmacokinetics , Selenium Compounds/toxicityABSTRACT
Quantum dots have potential in biomedical applications, but concerns persist about their safety. Most toxicology data is derived from in vitro studies and may not reflect in vivo responses. Here, an initial systematic animal toxicity study of CdSe-ZnS core-shell quantum dots in healthy Sprague-Dawley rats is presented. Biodistribution, animal survival, animal mass, hematology, clinical biochemistry, and organ histology are characterized at different concentrations (2.5-15.0 nmol) over short-term (<7 days) and long-term (>80 days) periods. The results show that the quantum dot formulations do not cause appreciable toxicity even after their breakdown in vivo over time. To generalize the toxicity of quantum dots in vivo, further investigations are still required. Some of these investigations include the evaluation of quantum dot composition (e.g., PbS versus CdS), surface chemistry (e.g., functionalization with amines versus carboxylic acids), size (e.g., 2 versus 6 nm), and shape (e.g., spheres versus rods), as well as the effect of contaminants and their byproducts on biodistribution behavior and toxicity. Combining the results from all of these studies will eventually lead to a conclusion regarding the issue of quantum dot toxicity.
Subject(s)
Cadmium Compounds/pharmacokinetics , Cadmium Compounds/toxicity , Quantum Dots , Selenium Compounds/pharmacokinetics , Selenium Compounds/toxicity , Selenium/pharmacokinetics , Selenium/toxicity , Animals , Materials Testing , Metabolic Clearance Rate , Organ Specificity , Rats , Rats, Sprague-Dawley , Sulfides , Tissue DistributionABSTRACT
Semiconductor quantum dots (QDs) have recently been used to deliver and monitor biomolecules, such as drugs and proteins. However, QDs alone have a low efficiency of transport across the plasma membrane. In order to increase the efficiency, we used synthetic nona-arginine (SR9), a cell-penetrating peptide, to facilitate uptake. We found that SR9 increased the cellular uptake of QDs in a noncovalent binding manner between QDs and SR9. Further, we investigated mechanisms of QD/SR9 cellular internalization. Low temperature and metabolic inhibitors markedly inhibited the uptake of QD/SR9, indicating that internalization is an energy-dependent process. Results from both the pathway inhibitors and the RNA interference (RNAi) technique suggest that cellular uptake of QD/SR9 is predominantly a lipid raft-dependent process mediated by macropinocytosis. However, involvement of clathrin and caveolin-1 proteins in transducing QD/SR9 across the membrane cannot be completely ruled out.
Subject(s)
Drug Delivery Systems/methods , Oligopeptides/administration & dosage , Quantum Dots , Biological Transport , Blotting, Western , Cadmium Compounds/administration & dosage , Cadmium Compounds/pharmacokinetics , Caveolins/antagonists & inhibitors , Caveolins/genetics , Caveolins/metabolism , Cell Line, Tumor , Clathrin Heavy Chains/antagonists & inhibitors , Clathrin Heavy Chains/genetics , Clathrin Heavy Chains/metabolism , Humans , Microscopy, Fluorescence , Oligopeptides/pharmacokinetics , Pinocytosis , RNA, Small Interfering/genetics , Selenium Compounds/administration & dosage , Selenium Compounds/pharmacokinetics , Sulfides/administration & dosage , Sulfides/pharmacokinetics , Zinc Compounds/administration & dosage , Zinc Compounds/pharmacokineticsABSTRACT
The retention behavior of selenites, selenates, seleno-DL-methionine, selenocystine, selenocystamine, selenourea, dimethyl selenide, and dimethyl diselenide was investigated by means of biomimetic liquid chromatography. For this purpose, two immobilized artificial membrane (IAM) columns, namely, IAM.PC.DD2 and IAM.PC.MG, and two immobilized plasma protein columns, human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP) columns, were employed using different mobile phase conditions in respect to pH and buffer composition. In general, satisfactory interrelations between retention factors obtained with the two IAM stationary phases and HSA/AGP columns were obtained. Large differences were observed between biomimetic retention factors and octanol-water logD values, since the latter fail to describe electrostatic interactions. In contrast, despite the column diversity, the net retention outcome on all four biomimetic columns was quite similar, especially in the presence of phosphate-buffered saline, which by its effective shielding alleviates the differences between the stationary phases. Of the two IAM columns, IAM.PC.DD2 showed better performance when compared with HSA and AGP columns as well as to octanol-water partitioning. Biomimetic chromatographic indices were further used to estimate the percentage of human oral absorption and plasma protein binding of the eight selenium species investigated, according to equations previously reported in the literature. The estimated values of human oral absorption imply moderate absorption only for dimethyl diselenide, which also may exhibit considerable plasma protein binding. Moderate affinity for plasma proteins should also be expected for dimethyl selenide and selenocystamine.
Subject(s)
Biomimetics/methods , Chromatography, Liquid/methods , Organoselenium Compounds/pharmacokinetics , Selenium/pharmacokinetics , Absorption , Humans , Membranes, Artificial , Models, Biological , Organoselenium Compounds/analysis , Orosomucoid/chemistry , Selenic Acid , Selenium/analysis , Selenium Compounds/analysis , Selenium Compounds/pharmacokinetics , Serum Albumin/chemistry , Sodium Selenite/analysis , Sodium Selenite/pharmacokineticsABSTRACT
The final goal of this study is to develop multi-functional organic/inorganic hybrid nanoparticles, which can be utilized as biomedical imaging probes and drug delivery carriers. As an initial step toward this goal, we encapsulated CdSe/ZnS quantum dots (QDs) into poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) micelles using a solid dispersion method. The size and fluorescent intensity of QDs encapsulated in PEG-PLA micelles depended on the amount of incorporated QDs. For example, when the amount of QDs increased from 0.1 to 1.0 microg, the mean diameter increased from 24.2 +/- 6.0 to 211.2 +/- 6.5 nm and the fluorescent intensity changed from 10.2 +/- 1.0 to 469.9 +/- 15.6 (RFU). Stability studies showed that the size and zeta-potential (ZP) of QDs encapsulated in PEG-PLA micelles (QEMs) did not change significantly in response to a change in pH conditions or under a 10% serum condition. We also tested the cytotoxicity and cellular uptake of the QEMs. The viability of HeLa cells treated with micelles for 24 h was 80-100% in various concentration ranges of micelles. Confocal laser scanning microscopic images showed that the QEMs penetrated into the cells, particularly into the cytosolic compartments. Our results suggest that the QEMs may be a promising multi-functional nanocarrier for biomedical imaging and drug delivery.
Subject(s)
Cadmium Compounds/chemistry , Micelles , Nanocomposites/chemistry , Polyethylene Glycols/chemistry , Quantum Dots , Selenium Compounds/chemistry , Zinc Compounds/chemistry , Cadmium Compounds/pharmacokinetics , Cadmium Compounds/pharmacology , Cell Survival/drug effects , Drug Stability , HeLa Cells , Humans , Hydrogen-Ion Concentration , Microscopy, Confocal , Particle Size , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/pharmacology , Selenium Compounds/pharmacokinetics , Selenium Compounds/pharmacology , Zinc Compounds/pharmacokinetics , Zinc Compounds/pharmacologyABSTRACT
Galvanostatic stripping chronopotentiometry (GSC) was developed and applied for the determination of selenium in human plasma. In this work GSC based on composite carbon electrode coated by a gold layer was optimized concerning various electrochemical parameters (coating procedure, electrolysis potential, electrolysis time, dissolution current). Along with this, the sample preparation was optimized with respect to mineralization conditions (type and concentration of decomposition agent, temperature, time). The human plasma samples mineralized in an autoclave under the optimized conditions (160 degrees C, 100 min, 22 mol/l HNO3) were appropriately diluted by background electrolyte solution (0.100 mol/l H2SO4 + 0.001 mol/l HCl) and directly analyzed by the optimized GSC method. The proposed method was characterized by excellent performance parameters, the limit of detection was 0.2 ng/ml, accuracy <5%, reproducibility <4%. The proposed method was applied for the investigation of the relationship between atopic dermatitis and selenium concentration in human plasma. Here, patients suffering from atopic dermatitis were monitored during their treatment with a pharmaceutical preparation containing inorganic selenium (Zinkosel). After six months therapy increased levels of selenium in plasma were detected in 76% of the patients with an improvement of the clinical state in 65% of the patients.
Subject(s)
Dermatitis, Atopic/blood , Selenium Compounds/pharmacokinetics , Selenium/blood , Dermatitis, Atopic/drug therapy , Electrochemistry , Humans , Indicators and Reagents , Potentiometry , Reference Standards , Reproducibility of Results , Selenium Compounds/therapeutic use , SolutionsABSTRACT
The purpose of this study was to investigate the interactions between different selenium (Se) compounds including sodium selenite (SS), selenium-enriched yeast (SY), and nano-selenium (NS) and various essential trace elements involved in the antioxidant systems, and to evaluate the effects on laying performance and egg quality. A total of 288 21-week-old Hyline Sophie hens were allotted to four dietary treatments: (1) basal diet without Se supplementation; (2) basal diet supplemented with 0.3 mg/kg Se of SS; (3) basal diet supplemented with 0.3 mg/kg Se of SY; (4) basal diet supplemented with 0.3 mg/kg Se of NS. Each treatment had eight replicates with nine hens per replicate. The trial lasted for 35 days. Results demonstrated that NS supplementation decreased the egg production (EP) and increased the feed conversion rate (FCR) and eggshell thickness and that SY changed the egg shape index (p < 0.05). Supplementation with three Se compounds significantly increased serum Se concentration and glutathione peroxidase (GSH-Px) activity in all treatment groups, as well as total superoxide dismutase (T-SOD) activity in the SY and NS groups. Yolk iron (Fe) and copper (Cu) concentrations in the NS group were also increased with Se supplementation. While the serum zinc (Zn) concentration decreased in the NS and SY groups, as well as the yolk manganese (Mn) concentration in the SY group. And the total antioxidant capability (T-AOC) of yolk with 3 days of storage in the SY and NS groups, malondialdehyde (MDA) value in the NS group, and the T-SOD activity and MDA value of yolk with 10 days of storage in the SY group also decreased. Thus, the source of Se compounds may influence the balance between Se and other trace elements including Zn, Mn, Fe, and Cu, which is important for proper antioxidant defense in blood and egg yolk of laying hens.