Antioxidant-Prooxidant Properties of a New Organoselenium Compound Library

Plano, Daniel; Baquedano, Ylenia; Ibáñez, Elena; Jiménez, Iosu; Palop, Juan Antonio; Spallholz, Julian E.; Sanmartín, Carmen

doi:10.3390/molecules15107292

Cited by 92 publications

(61 citation statements)

References 49 publications

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“…Moreover, many studies reported that 50-90% of consumed selenite was lost and excreted in urine due to the short retention time in the gastrointestinal tract (52)(53)(54). It has been also evidenced that high dose supplementation of selenite may cause various adverse effects due to its pro-oxidant property, which depends on the concentration and other factors (55). Additionally, there is an emerging concern with potential adverse side effects of long-term oral Se supplementation methods that includes possible increased risk of type-2 diabetes (29).…”

Section: Resultsmentioning

confidence: 99%

Freeze-Dried Targeted Mannosylated Selenium-Loaded Nanoliposomes: Development and Evaluation

et al. 2013

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Abstract. The aim of this investigation was to develop and evaluate freeze-dried mannosylated liposomes for the targeted delivery of selenium. Dipalmitoylphosphatidylcholine, distearoylphosphatidylglycerol, and cholesterol were dissolved in a chloroform and methanol mixture and allowed to form a thin film within a rotatory evaporator. This thin film was hydrated with a sodium selenite (5.8 μM) solution to form multilamellar vesicles and homogenized under high pressure to yield unilamellar nanoliposomes. Seloaded nanoliposomes were mannosylated by 0.1%w/v mannosamine (Man-Lip-Se) prior to being lyophilized. Mannosamine concentration was optimized with cellular uptake studies in M receptor expressing cells. Non-lyophilized and lyophilized Man-Lip-Se were characterized for size, zeta potential, and entrapment efficiency. The influence of liposomal composition on the characteristics of Man-Lip-Se were evaluated using acidic and basic medium for 24 h. Thermal analysis and powder X-ray diffraction were used to determine the interaction of components within the Man-Lip-Se. The size, zeta potential and entrapment efficiency of the optimum Man-Lip-Se were observed to be 158±28.9 nm, 33.21±0.89 mV, and 77.27±2.34%, respectively. An in vitro Se release of 70-75% up to 24 h in PBS pH 6.8 and <8% Se release in acidic media (0.1 N HCl) in 1 h was observed. The Man-Lip-Se were found to withstand gastric-like environments and showed sustained release. Stable freeze-dried Man-Lip-Se were successfully formulated with a size of <200 nm, ∼75% entrapment, and achieved controlled release of Se with stability under acidic media, which may be of importance in the targeted delivery of Se to the immune system.

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Section: Resultsmentioning

confidence: 99%

Freeze-Dried Targeted Mannosylated Selenium-Loaded Nanoliposomes: Development and Evaluation

et al. 2013

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“…On the other hand, organo-Se compounds modulate extracellular redox by induction of extracellular cysteine and cell-surface thioredoxin reductase (36). The administration of Se drugs may induce either oxidant or antioxidant effects in the cells (37)(38)(39) by oxidation or reduction of thiol-containing proteins, depending on the influence of neighboring groups and redox potential (31). Se is essential for antioxidant activity but may have pro-oxidant properties at higher concentrations.…”

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confidence: 99%

Dose Effect of Rhenium (I)-diselenoether as Anticancer Drug in Resistant Breast Tumor-bearing Mice After Repeated Administrations

Collery

Santoni

Ciccolini

et al. 2016

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Abstract. Rhenium (I)-diselenoether has shown promising antiproliferative efficacy in both in vitro and in vivo models. However, the maximal tolerated dose and dose-effect relationships have not been fully addressed for this compound. Here, we evaluated the tolerance and efficacy of three dose-levels (namely 10, 40 and 100 mg/kg) intraperitoneally administered daily over 28 days in mice bearing the resistant MDA-MB231 breast cancer cell line.The upper dose was found to be toxic and was reduced to 60 mg/kg. The 10 mg/kg dose well tolerated, whereas 40 mg/kg was associated with 10% mortality (LD 10 ). Both 10 and 40 mg/kg dosing achieved a significantly similar regression of tumor growth compared with untreated animals. This study suggests that 10 mg/kg daily is the recommended dose for rhenium (I) diselenoether.Rhenium(I)-diselenoether has been proposed as an anticancer agent (1-6). This compound features a central atom of rhenium bound to 3,7-diselenanonanedioic acid ligand in which the two selenium atoms secure a tight complexation of the Re, while the carboxylic group, as sodium salt, allows water solubility. This amphiphilic complex is a hydrophilic drug, soluble in water, easy to administer and lipophilic with a good distribution in tissues after oral administration (2).Re is a heavy transition metal (atomic number 75, atomic mass 186.21 g/mol), with the widest range of oxidation states of any element (−3, −1, +1, +2, +3, +4, +5, +6 +7), providing it with unique properties. It was demonstrated with Re-diselenoether drug that Re formed DNA adducts with one or two guanine bases (3), like cisplatin, but with an octahedral configuration and not a square-planar one. The uptake of Re in the nucleus of malignant cells has also been demonstrated after exposure to Re-diselenoether complex (2). Other Re-based drugs have also shown a high activity against a variety of tumor cell lines, with a good selectivity for cancer cells (7,8). One common mechanism of action could be related to the binding of Re with guanine and adenine bases of DNA (9-12). In contrast with cisplatin, the binding with the DNA bases is reversible (13). Re also binds with proteins (14,15). However, other properties of Re compounds have been identified, like the inhibition of some cysteine proteases (16). We hypothesize that the Re atom could be used either for oxidation or reduction of cell components due to its great number of oxidation states. Re cluster compounds were screened for their biological activities as antioxidants (17) and proposed to protect erythrocytes from hemolytic anemia (18). These Re compounds affected the peroxidation level, the activity of superoxide dismutase, the antioxidant factor and the index of resistance of erythrocytes to hemolysis as a function of the concentration range in the pre-incubation medium of erythrocytes (19,20 (22) and with dichlorotetra-μ-isobutyratodirhenium (III) complex (23) and the cluster Re compound with gamma-aminobutyric acid ligand (24). This synergism was however not observed with the Re (I)-di...

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“…the substantial role of human selenoproteins in antioxidant defense system and cancer protection. [3,4] In all living cells, there exists a constant balance between the generation of reactive oxygen species (ROS) and their destruction via antioxidant defense mechanisms. [5,6] ROS, including superoxide radical anions, hydroxyl radicals and hydrogen peroxide, participate in a variety of normal biochemical functions, as well as in abnormal pathological processes causing the cellular damage.…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic characterization, photoinduced processes and cytotoxic properties of substitutedN-ethyl selenadiazoloquinolones

Barbieriková

Bella

Sekeráková

et al. 2013

J. Phys. Org. Chem.

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a 7-R-9-ethyl-6,9-dihydro-6-oxo- [1,2,5]selenadiazolo [3,4-h]quinolines (R = H, COOC 2 H 5 , COOCH 3 , COOH and COCH 3 , E1h-E5h) and 6-ethyl-6,9-dihydro-9-oxo-[1,2,5]selenadiazolo[3,4-f]quinoline (E1f) were characterized by UV/vis, FT-IR and fluorescence spectroscopy. The electronic absorption spectra of the derivatives E1h-E3h and E5h in the aprotic solvents dimethylsulfoxide (DMSO) and acetonitrile (ACN) reveal low-energy absorption maxima with l max > 400 > nm, shifted hypsochromically in water. In DMSO, N-ethyl selenadiazoloquinolones behave as strong fluorescent agents (l em ≥ 550 nm) with the exception of the carboxylic acid derivative E4h which shows only poor emission. Photoinduced reactions of N-ethyl selenadiazoloquinolones were investigated by means of electron paramagnetic resonance (EPR) spectroscopy. Photoexcitation of N-ethyl selenadiazoloquinolones in aerated DMSO with either 385 nm or 400 nm wavelengths, monitored by EPR spin trapping technique, results in the generation of superoxide radical anions; under an inert atmosphere, the generation of methyl radicals originating from the solvent predominates. Upon exposure at either 365 nm, 385 nm or 400 nm, aerated ACN solutions of selenadiazoloquinolones in the presence of sterically hindered amines produce nitroxide radicals via a reaction with photogenerated singlet oxygen. The 7-substituted derivatives of 9-ethyl-6,9-dihydro-6-oxo-[1,2,5]selenadiazolo[3,4-h] quinoline behave as photosensitizers activating molecular oxygen upon photoexcitation and possess the sufficient photochemical stability under the given experimental conditions. The cytotoxic effects of non-photoactivated and UVA photoactivated N-ethyl substituted selenadiazoloquinolones on cancer (human HeLa and murine L1210) and non-cancer (NIH-3T3) cell lines were monitored by the MTT test. The derivative E2h demonstrates the highest cytotoxic/photocytotoxic activity on the neoplastic cell lines.

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Antioxidant-Prooxidant Properties of a New Organoselenium Compound Library

Cited by 92 publications

References 49 publications

Freeze-Dried Targeted Mannosylated Selenium-Loaded Nanoliposomes: Development and Evaluation

Freeze-Dried Targeted Mannosylated Selenium-Loaded Nanoliposomes: Development and Evaluation

Dose Effect of Rhenium (I)-diselenoether as Anticancer Drug in Resistant Breast Tumor-bearing Mice After Repeated Administrations

Spectroscopic characterization, photoinduced processes and cytotoxic properties of substitutedN-ethyl selenadiazoloquinolones

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