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Carmona-Aparicio L.,National Institute of Pediatrics | Perez-Cruz C.,CINVESTAV | Zavala-Tecuapetla C.,National Institute of Neurology and Neurosurgery MVS | Granados-Rojas L.,National Institute of Pediatrics | And 7 more authors.
International Journal of Molecular Sciences | Year: 2015

Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen and nitrogen species and antioxidant defenses. It is involved in the physiopathology of degenerative and chronic neuronal disorders, such as epilepsy. Experimental evidence in humans and animals support the involvement of oxidative stress before and after seizures. In the past few years, research has increasingly focused on the molecular pathways of this process, such as that involving transcription factor nuclear factor E2-related factor 2 (Nrf2), which plays a central role in the regulation of antioxidant response elements (ARE) and modulates cellular redox status. The aim of this review is to present experimental evidence on the role of Nrf2 in this neurological disorder and to further determine the therapeutic impact of Nrf2 in epilepsy. © 2015 by the authors; licensee MDPI, Basel, Switzerland. Source

Lopez T.,Metropolitan Autonomous University | Lopez T.,National Institute of Neurology and Neurosurgery MVS | Lopez T.,National Autonomous University of Mexico | Ortiz-Islas E.,National Institute of Neurology and Neurosurgery MVS | And 6 more authors.
Journal of Materials Science | Year: 2015

Copper complexes containing inorganic ligands were loaded on a functionalized titania (F-TiO2) to obtain drug delivery systems. The as-received copper complexes and those released from titania were tested as toxic agents on different cancer cell lines. The sol–gel method was used for the synthesis and surface functionalization of the titania, as well as for loading the copper complexes, all in a single step. The resultant Cu/F-TiO2 materials were characterized by several techniques. An “in vitro” releasing test was developed using an aqueous medium. Different concentrations (15.6–1000 µg mL−1) of each copper complex, those loaded on titania (Cu/F-TiO2), functionalized titania, and cis-Pt as a reference material, were incubated on RG2, C6, U373, and B16 cancer cell lines for 24 h. The morphology of functionalized titania and the different Cu/F-TiO2 materials obtained consists of aggregated nanoparticles, which generate mesopores. The amorphous phase (in dominant proportion) and the anatase phase were the structures identified through the X-ray diffraction profiles. These results agree with high-resolution transmission electron microscopy. Theoretical studies indicate that the copper compounds were released by a Fickian diffusion mechanism. It was found that independently of the copper complex and also the cell line used, low concentrations of each copper compound were sufficient to kill almost 100 % of cancer cells. When the cancer cells were treated with increasing concentrations of the Cu/F-TiO2 materials the number of survival cells decreased. Both copper complexes alone as well as those loaded on TiO2 had higher toxic effect than cis-Pt. © 2015, Springer Science+Business Media New York. Source

Lopez T.,Metropolitan Autonomous University | Lopez T.,National Institute of Neurology and Neurosurgery MVS | Lopez T.,Tulane University | Ortiz E.,National Institute of Neurology and Neurosurgery MVS | And 3 more authors.
Materials Chemistry and Physics | Year: 2014

In the present paper we report the preparation and characterization of functionalized-TiO2 (F-TiO2) to obtain a biocompatible material to be used as carrier of alternative anticancer agents: copper acetate and copper acetylacetonate. The sol-gel procedure was used to prepare the fuctionalized titania material through hydrolysis and condensation of the titanium's butoxide. Sulfate, amine and phosphate ions served as functional groups which were anchored to the titania's surface. Mineral acids and gamma amine butyric acid were the precursors and they were added at the initial step of the synthesis. The copper complexes were loaded on titania and were also added to the reactor synthesis from the beginning. Infrared and ultraviolet-visible spectroscopies were the principal techniques used to the characterization of F-TiO2 and copper complexes loaded on titania materials. Transmission Electronic Microscopy (TEM) was used to complement the characterization's studies. The biocompatibility of F-TiO2 was evaluated by treating different cancer cell lines with increased concentration of this compound. The amine, the sulfate and the phosphate on the titania's surface, as well as the integral structures of the metal complexes on titania were well identified by infrared and ultraviolet-visible spectroscopies. The TEM photographs of Cu(acac)2/F-TiO2 and Cu(Oac) 2/F-TiO2 materials showed the formation of nanoparticles, which have sizes ranging from 4 to 10 nm, with no morphology alterations in comparison with F-TiO2 nanoparticles, suggesting that the presence of low quantities of copper do not affect the structure of the nanoparticles. The Energy Dispersive Spectroscopy (EDS) confirms the presence of copper on the titania's nanoparticles. The biological results indicate that there is more than 90% cell survival, thus suggesting that F-TiO2 does not cause damage to the cells. Therefore, highly biocompatible titania was obtained by functionalizing its surface with those ions which in a certain way are similar to the hydrophilic heads of phospholipids in the double layer of the cell membrane. © 2014 Elsevier B.V. All rights reserved. Source

Lopez T.,Metropolitan Autonomous University | Lopez T.,National Institute of Neurology and Neurosurgery MVS | Lopez T.,Tulane University | Ortiz-Islas E.,National Institute of Neurology and Neurosurgery MVS | And 2 more authors.
International Journal of Nanomedicine | Year: 2013

The anticancer properties of pure copper (II) acetate and copper (II) acetylacetonate, alone and loaded on functionalized sol-gel titania (TiO2), were determined in four different cancer cell lines (C6, RG2, B16, and U373), using increasing concentrations of these compounds. The copper complexes were loaded onto the TiO2 network during its preparation by the sol-gel process. Once copper-TiO2 materials were obtained, these were characterized by several physical-chemical techniques. An in vitro copper complex-release test was developed in an aqueous medium at room temperature and monitored by ultraviolet spectroscopy. The toxic effect of the copper complexes, alone and loaded on TiO2, was determined using a cell viability 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, when cancer cells were treated with increasing concentrations (15.75-1000 mg/mL) of these. Characterization studies revealed that the addition of copper complexes to the TiO2 sol-gel network during its preparation, did not generate changes in the molecular structure of the complexes. The surface area, pore volume, and pore diameter were affected by the copper complex additions and by the crystalline phases obtained. The kinetic profiles of both copper complexes released indicated two different stages of release: The first one was governed by first-order kinetics and the second was governed by zero-order kinetics. The cell viability assay revealed a cytotoxic effect of copper complexes, copper-TiO2, and cisplatin in a dose-dependent response for all the cell lines; however, the copper complexes exhibited a better cytotoxic effect than the cisplatin compound. TiO2 alone presented a minor cytotoxicity for C6 and B16 cells; however, it did not cause any toxic effect on the RG2 and U373 cells, which indicates its high biocompatibility with these cells. © 2013 Lopez et al, publisher and licensee Dove Medical Press Ltd. Source

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