RESUMEN

This study investigated the impact of various Ge132 (Bis-carboxyethyl germanium sesquioxide) concentrations on frozen bovine semen. Ejaculates from three bulls were pooled and divided into six groups, each one with different Ge132 concentrations (0, 500, and 1000 µg/mL) and each group was incubated in different conditions (33°C for 30 min (D: D0, D500, and D1000), and the other was immediately cooled to 4°C (R: R0-control; R500 and R1000)). Thawed semen was evaluated for sperm characteristics by CASA and flow cytometer. Results showed better motility in the immediate cooling group without Ge132 compared with high Ge132 concentrations. Values for total motility dropped after 5 and 60 min in groups with high Ge132 levels and some control groups. Linearity increased with 1000 µg/mL Ge132, while straightness differed between moments in multiple groups. Membrane integrity was higher in a control group and certain Ge132 groups. Lower O2 - generation occurred without Ge132. After oxidative stress induction, lipid peroxidation intensity increased with arachidonic acid, but D1000 had lower peroxidation than R0. Overall, Ge132 appears to have provided protection against PLM when subjected to oxidative stress, since even at high concentrations it maintained sperm metabolism.

Asunto(s)

Antioxidantes , Criopreservación , Preservación de Semen , Motilidad Espermática , Espermatozoides , Animales , Masculino , Bovinos , Criopreservación/veterinaria , Criopreservación/métodos , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Espermatozoides/efectos de los fármacos , Antioxidantes/farmacología , Motilidad Espermática/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Crioprotectores/farmacología , Peroxidación de Lípido/efectos de los fármacos , Germanio/farmacología , Semen/efectos de los fármacos , Análisis de Semen/veterinaria

RESUMEN

Severe bone defects accompanied by vascular and peripheral nerve injuries represent a huge orthopedic challenge and are often accompanied by the risk of infection. Thus, biomaterials with antibacterial and neurovascular regeneration properties are highly desirable. Here, a newly designed biohybrid biodegradable hydrogel (GelMA) containing copper ion-modified germanium-phosphorus (GeP) nanosheets, which act as neuro-vascular regeneration and antibacterial agents, is designed. The copper ion modification process serves to improve the stability of the GeP nanosheets and offers a platform for the sustained release of bioactive ions. Study findings show that GelMA/GeP@Cu has effective antibacterial properties. The integrated hydrogel can significantly boost the osteogenic differentiation of bone marrow mesenchymal stem cells, facilitate angiogenesis in human umbilical vein endothelial cells, and up-regulate neural differentiation-related proteins in neural stem cells in vitro. In vivo, in the rat calvarial bone defect mode, the GelMA/GeP@Cu hydrogel is found to enhance angiogenesis and neurogenesis, eventually contributing to bone regeneration. These findings indicate that in the field of bone tissue engineering, GelMA/GeP@Cu can serve as a valuable biomaterial for neuro-vascularized bone regeneration and infection prevention.

Asunto(s)

Germanio , Osteogénesis , Ratas , Humanos , Animales , Hidrogeles/farmacología , Cobre/farmacología , Germanio/farmacología , Fósforo/farmacología , Regeneración Ósea , Materiales Biocompatibles/farmacología , Células Endoteliales de la Vena Umbilical Humana , Antibacterianos/farmacología

RESUMEN

Hydroxyapatite (HA) is a hard mineral component of mineralized tissues, mainly composed of calcium and phosphate. Due to its bioavailability, HA is potentially used for the repair and regeneration of mineralized tissues. For this purpose, the properties of HA are significantly improved by adding natural and synthetic materials. In this sense, the germanium (Ge) mineral was loaded in HA biomaterial by cold isostatic pressure for the first time and characterization and biocompatibility using bone marrow mesenchymal stem cells (BM-MSCs) were investigated. The addition of Ge at 5% improved the solubility (3.32%), stiffness (18.34 MPa), water holding (31.27%) and biodegradation (21.87%) properties of HA, compared to control. Compared to all composite biomaterials, the drug-releasing behavior of HA-3% Ge was higher at pH 1 and 3 and the maximum drug release was obtained at pH 7 and 9 with HA-5% Ge biomaterials. Among the different mediums tested, the DMEM-medium showed a higher drug release rate, especially at 60 min. HA-Ge biomaterials showed better protein adhesion and apatite layer formation, which ultimately proves the compatibility in BM-MSCs culture. Except for higher concentrations of HA (5 and 10 mg/mL), the different concentrations of Ge and HA and wells coated with 1% of HA-1% Ge had higher BM-MSCs growth than control. All these findings concluded that the fabricated HA biomaterials loaded with Ge could be the potential biomaterial for culturing mammalian cells towards mineralized tissue repair and regeneration.

Asunto(s)

Germanio , Células Madre Mesenquimatosas , Animales , Materiales Biocompatibles/química , Regeneración Ósea , Calcio/metabolismo , Durapatita/farmacología , Germanio/metabolismo , Germanio/farmacología , Mamíferos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis , Andamios del Tejido/química , Agua/metabolismo

RESUMEN

The first germanium compounds which exhibited immunomodulatory and antiviral effects were sesquioxane-type germanates. To date, more than a dozen compounds containing germanium have been synthesized and are being actively studied. They include germanium carboxylates and citrates, complexes of germanium with resveratrol, daphnetin, mangiferin, chrysin, quercetin, ascorbic and nicotinic acids, amino acids, gamma-lactones, germanium-containing spirulina, yeast and others. Germanium-based compounds have shown the ability to influence the replication of various DNA/RNA viruses, stimulate the body's natural resistance, prevent the development of metabolic intoxication of various origin, increase the efficacy of vaccines, and prevent the development of excessive accumulation of reactive oxygen species, which plays a decisive role in the development of inflammatory response caused by a viral infection. It seems reasonable to say that germanium-based complex compounds effectively contribute to the preservation of high--energy bonds in the form of ATP, optimize the activity of metabolic processes by re-oxygenation, and exhibit antimicrobial activity. The purpose of this review is to summarize the pharmacological potential of various germanium-based compounds studied nowadays, taking into account their mechanisms of action, and to analyze their prospects in the development of integrated approaches in the prevention and treatment of SARS-CoV-2 infection.

Asunto(s)

COVID-19 , Germanio , Humanos , Germanio/farmacología , SARS-CoV-2 , Antivirales/química , Quercetina

RESUMEN

To improve in vivo osseointegration of pure titanium implant, Sr-Ga clavate double hydroxide (CDH) coating was grown in situ on a titanium (Ti) substrate with simple hydrothermal and calcination treatments at 500 °C. The obtained coating on the Ti substrate (Ti-CDH and Ti-CDH500) was researched by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive spectroscopy (EDS). Ti-CDH exhibited a sustained release profile of metal ions and maintained a slightly alkaline environment. The CDH coating was beneficial for osteogenic differentiation of mesenchymal stem cells (MSCs), which were reflected by the results of cellular assays, including alkaline phosphatase activity (ALP), cell mineralization capability (ARS), and osteogenesis-related gene expression. Besides, Ti-CDH could effectively improve the autophagic levels in MSCs, which further promoted osteogenic differentiation of MSCs. Hence, the Ti surface with Sr-Ga CDH modification supplied a simple and effective strategy to design biomaterials for bone generation.

Asunto(s)

Materiales Biocompatibles/farmacología , Germanio/farmacología , Hidróxidos/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Estroncio/farmacología , Titanio/farmacología , Animales , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Germanio/química , Hidróxidos/química , Osteogénesis/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Estroncio/química , Propiedades de Superficie , Titanio/química

RESUMEN

It was established that the administration of an aqueous solution of bis(µ-tartrato)di(µ-hydroxy) germanate (IV) triethanolammonium to animals daily for 2 months at a dose of the active substance of 10 mg/kg of the animal's weight leads to inhibition of the total activity of the alkaline phospholipase A2 of mononuclear cells. The results of the study can be used to correct lipid metabolism in the development of disorders in hyperlipidemia. This makes it possible to expand the scope of use of the studied substance and create new pharmaceuticals based on bis(µ-tartrato)di(µ-hydroxy) germanate (IV) triethanolammonium prevent and inhibit the development of hyperlipidemia.

Asunto(s)

Etanolaminas/farmacología , Hiperlipidemias/tratamiento farmacológico , Compuestos Organometálicos/farmacología , Inhibidores de Fosfolipasa A2/farmacología , Fosfolipasas A2/metabolismo , Animales , Colesterol/sangre , Germanio/química , Germanio/farmacología , Hiperlipidemias/enzimología , Hiperlipidemias/patología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/enzimología , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Fosfolipasas A2/sangre , Conejos

RESUMEN

We report on the new monosubstituted aluminum Keggin-type germanotungstate (C4H12N)4[HAlGeW11O39(H2O)]·11H2O ([Al(H2O)GeW11]4-), which has been synthesized at room temperature via rearrangement of the dilacunary [γ-GeW10O36]8- polyoxometalate precursor. [Al(H2O)GeW11]4- has been characterized thoroughly both in the solid state by single-crystal and powder X-ray diffraction, IR spectroscopy, thermogravimetric analysis, and elemental analysis as well as in solution by cyclic voltammetry (CV) 183W, 27Al NMR and UV-vis spectroscopy. A study on the antibacterial properties of [Al(H2O)GeW11]4- and the known aluminum(III)-centered Keggin polyoxotungstates (Al-POTs) α-Na5[AlW12O40] (α-[AlW12O40]5-) and Na6[Al(AlOH2)W11O39] ([Al(AlOH2)W11O39]6-) revealed enhanced activity for all three Al-POTs against the Gram-negative bacterium Moraxella catarrhalis (minimum inhibitory concentration (MIC) up to 4 µg mL-1) and the Gram-positive Enterococcus faecalis (MIC up to 128 µg mL-1) compared to the inactive Al(NO3)3 salt (MIC > 256 µg mL-1). CV indicates the redox activity of the Al-POTs as a dominating factor for the observed antibacterial activity with increased tendency to reduction, resulting in increased antibacterial activity of the POT.

Asunto(s)

Aluminio/farmacología , Antibacterianos/farmacología , Complejos de Coordinación/farmacología , Enterococcus faecalis/efectos de los fármacos , Germanio/farmacología , Moraxella catarrhalis/efectos de los fármacos , Tungsteno/farmacología , Aluminio/química , Antibacterianos/síntesis química , Antibacterianos/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Germanio/química , Pruebas de Sensibilidad Microbiana , Tungsteno/química

RESUMEN

Zinc (Zn)-based alloys are considered a new class of biodegradable implant materials due to their superior chemical stability and processability compared to biodegradable magnesium (Mg) alloys. In this study, we report a new biodegradable Zn-5Ge alloy with highly desirable mechanical, corrosion, and biological properties. Microstructural characterization revealed the effective grain-refining effect of germanium (Ge) on the Zn alloy. Tensile test results indicated that the hot-rolled Zn-5Ge alloy showed an ultimate tensile strength of 237.0 MPa, a yield strength of 175.1 MPa, and an elongation of 21.6%; while as-cast pure Zn showed an ultimate tensile strength of 33.6 MPa, a yield strength of 29.3 MPa, and an elongation of 1.2%. The corrosion rates measured by potentiodynamic polarization tests in Hank's solution in ascending order are: as-cast Zn-5Ge (0.1272 mm/y) < as-cast pure Zn (0.1567 mm/y) < hot-rolled Zn-5Ge (0.2255 mm/y) < hot-rolled pure Zn (0.3057 mm/y). Immersion tests revealed that the degradation rate of as-cast Zn-5Ge is 0.042 mm/y, less than half of that of hot-rolled pure Zn and ∼62% of that of as-cast pure Zn. Moreover, the Zn-5Ge alloy showed excellent in vitro hemocompatibility and the addition of 5% Ge effectively enhanced the hemocompatibility of pure Zn. CCK-8 assay using murine preosteoblast MC3T3-E1 cells indicated that the diluted extracts at a concentration <12.5% of both the as-cast Zn-5Ge alloy and pure Zn showed grade 0 cytotoxicity; the diluted extracts at the concentrations of 50% and 25% of Zn-5Ge alloy showed a significantly higher cell viability than those of pure Zn. STATEMENT OF SIGNIFICANCE: Zinc (Zn)-based alloys are currently considered a new class of biodegradable implant materials due to their excellent processability. Here, we report a novel Zn-5Ge alloy with highly desirable mechanical, corrosion and biological properties. The tensile test results indicated that the hot-rolled Zn-5Ge alloy showed an ultimate tensile strength of 237.0 MPa, a yield strength of 175.1 MPa and an elongation of 21.6%; while as-cast pure Zn showed an ultimate tensile strength of 33.6 MPa, a yield strength of 29.3 MPa and an elongation of 1.2%. The corrosion rate measured by potentiodynamic polarization tests in Hank's solution in the ascending order is: as-cast Zn-5Ge (0.1272 mm/y) < as-cast pure Zn (0.1567 mm/y) < hot-rolled Zn-5Ge (0.2255 mm/y) < hot-rolled pure Zn (0.3057 mm/y). Immersion tests revealed that the degradation rate of the as-cast Zn-5Ge is 0.042 mm/y, less than half of that of the hot-rolled pure Zn, ∼62% of that of as-cast pure Zn. Moreover, the Zn-5Ge alloy showed excellent in vitro biocompatibility.

Asunto(s)

Implantes Absorbibles , Aleaciones , Germanio , Ensayo de Materiales , Zinc , Aleaciones/química , Aleaciones/farmacocinética , Aleaciones/farmacología , Animales , Línea Celular , Corrosión , Germanio/química , Germanio/farmacocinética , Germanio/farmacología , Ratones , Zinc/química , Zinc/farmacocinética , Zinc/farmacología

RESUMEN

Coccolithophores are globally distributed unicellular marine algae that are characterized by their covering of calcite coccoliths. Calcification by coccolithophores contributes significantly to global biogeochemical cycles. However, the physiological requirement for calcification remains poorly understood as non-calcifying strains of some commonly used model species, such as Emiliania huxleyi, grow normally in laboratory culture. To determine whether the requirement for calcification differs between coccolithophore species, we utilized multiple independent methodologies to disrupt calcification in two important species of coccolithophore: E. huxleyi and Coccolithus braarudii. We investigated their physiological response and used time-lapse imaging to visualize the processes of calcification and cell division in individual cells. Disruption of calcification resulted in major growth defects in C. braarudii, but not in E. huxleyi. We found no evidence that calcification supports photosynthesis in C. braarudii, but showed that an inability to maintain an intact coccosphere results in cell cycle arrest. We found that C. braarudii is very different from E. huxleyi as it exhibits an obligate requirement for calcification. The identification of a growth defect in C. braarudii resulting from disruption of the coccosphere may be important in considering their response to future changes in ocean carbonate chemistry.

Asunto(s)

Calcificación Fisiológica , Haptophyta/fisiología , Calcificación Fisiológica/efectos de los fármacos , Calcio/farmacología , Adhesión Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Ecología , Germanio/farmacología , Haptophyta/citología , Haptophyta/crecimiento & desarrollo , Haptophyta/ultraestructura , Fotosíntesis/efectos de los fármacos , Polisacáridos/metabolismo , Silicio/farmacología , Tubulina (Proteína)/metabolismo

RESUMEN

From the perspective of element biosafety and dietetics, the ideal alloying elements for magnesium should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group, chemically similar to its group neighbors, Si and Sn. It is a dietary trace element that naturally presents in human body. Physiological role of Ge is still unanswered, but it might be necessary to ensure normal functioning of the body. In present study, novel magnesium alloys with dietary trace element Ge were developed. Feasibility of those alloys to be used as orthopaedic implant applications was systematically evaluated. Mg-Ge alloys consisted of α-Mg matrix and eutectic phases (α-Mg + Mg2Ge). Mechanical properties of Mg-Ge alloys were comparable to current Mg-Ca, Mg-Zn and Mg-Sr biodegradable metals. As-rolled Mg-3Ge alloy exhibited outstanding corrosion resistance in vitro (0.02 mm/y, electrochemical) with decent corrosion rate in vivo (0.6 mm/y, in rabbit tibia). New bone could directly lay down onto the implant and grew along its surface. After 3 months, bone and implant were closely integrated, indicating well osseointegration being obtained. Generally, this is a pioneering study on the in vitro and in vivo performances of novel Mg-Ge based biodegradable metals, and will benefit the future development of this alloy system. STATEMENT OF SIGNIFICANCE: The ideal alloying elements for magnesium-based biodegradable metals should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group. It is a dietary trace element that naturally presents in human body. In present study, feasibility of Mg-Ge alloys to be utilized as orthopedic applications was systematically investigated, mainly focusing on the microstructure, mechanical property, corrosion behavior and biocompatibility. Our findings showed that Mg-3Ge alloy exhibited superior corrosion resistance to current Mg-Ca, Mg-Zn and Mg-Sr alloys with favorable biocompatibility. This is a pioneering study on the in vitro &in vivo performances of Mg-Ge biodegradable metals, and will benefit the future development of this alloy system.

Asunto(s)

Implantes Absorbibles , Aleaciones , Sustitutos de Huesos , Germanio , Magnesio , Aleaciones/química , Aleaciones/farmacología , Animales , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Línea Celular , Corrosión , Femenino , Germanio/química , Germanio/farmacología , Humanos , Magnesio/química , Magnesio/farmacología , Conejos

RESUMEN

To investigate the effects of ß-carboxyethyl germanium sequioxide (Ge-132) and germanium dioxide (GeO2) on improving salt tolerance of evening primrose (Oenothera biennis L.), seed germination, seedling growth, antioxidase and malondialdehyde (MDA) were observed under treatments of various concentrations (0, 5, 10, 20, 30 µM) of Ge in normal condition and in 50 mM NaCl solution. The results showed that both Ge-132 and GeO2 treatments significantly increased seed germination percentage and shoot length in dose-dependent concentrations but inhibited early root elongation growth. 5-30 µM Ge-132 and 10, 20 µM GeO2 treatments could significantly mitigate even eliminate harmful influence of salt, representing increased percentage of seed germination, root length, ratio between length of root and shoot, and decreased shoot length. These treatments also significantly decreased peroxidase (POD) and catalase (CAT) activities and MDA content. The mechanism is likely that Ge scavenges reactive oxygen species - especially hydrogen peroxide (H2O2) - by its electron configuration 4S24P2 so as to reduce lipid peroxidation. This is the first report about the comparison of bioactivity effect of Ge-132 and GeO2 on seed germination and seedling growth under salt stress. We conclude that Ge-132 is better than GeO2 on promoting salt tolerance of seed and seedling.

Asunto(s)

Germanio/farmacología , Oenothera biennis/efectos de los fármacos , Compuestos Organometálicos/farmacología , Cloruro de Sodio/toxicidad , Catalasa/metabolismo , Germinación/efectos de los fármacos , Malondialdehído/metabolismo , Oenothera biennis/crecimiento & desarrollo , Oenothera biennis/metabolismo , Peroxidasa/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/crecimiento & desarrollo , Brotes de la Planta/metabolismo , Propionatos , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Estrés Fisiológico/efectos de los fármacos , Superóxido Dismutasa/metabolismo

RESUMEN

In this paper, we present the results of a study on the effects of exogenous antioxidant germanium (Ge) on seed germination and seedling growth, and its role as a radical scavenger that regulates related enzymes, including superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), under salt stress. Seeds were incubated in 0, 50, 100, 150, 200, 250 and 300 mM NaCl to determine the salt tolerance of the Lycium ruthenicum Murr seedlings and from the results, the critical and ultimate salt concentrations were chosen for the next experiment. Subsequently, two treatments (seeds soaked in Ge and Ge added to salt) with four concentrations of GeO2 (0, 5, 10 and 20 µM) were used with the critical (150 mM) and ultimate salt concentrations (250 mM). The results demonstrated that salt alone inhibited seed germination significantly (≥150 mM) and reduced seedling growth (≥200 mM). The addition of exogenous Ge to the salt solution, as well as soaking the seeds in Ge, attenuated the salt stress effects in a manner dependent on the dose of Ge, as indicated by the increased percentage of seeds that germinated and improved seedling growth. The addition of Ge also showed a significant reversal of salt stress on the activities of antioxidant enzymes, with a decrease in SOD and POD activity, but an increase in CAT activity with 150 mM NaCl, and enhancement of SOD, POD and CAT with 250 mM NaCl. Correspondingly, the level of malondialdehyde was decreased significantly by each Ge treatment under salt stress. Further, for L. ruthenicum, adding 10 Ge and seeds soaked in 5 Ge were the most effective treatments. To our knowledge, this is the first report to show the protective effects of exogenous Ge against salt-induced oxidative damage in L. ruthenicum seed germination and seedling growth. Thus, L. ruthenicum can be used in areas with salty soil and Ge can promote the plants' salt tolerance.

Asunto(s)

Antioxidantes/farmacología , Germanio/farmacología , Lycium/efectos de los fármacos , Tolerancia a la Sal/efectos de los fármacos , Cloruro de Sodio/toxicidad , Catalasa/metabolismo , Germinación/efectos de los fármacos , Lycium/crecimiento & desarrollo , Malondialdehído/metabolismo , Peroxidasa/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/crecimiento & desarrollo , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrollo , Estrés Fisiológico/efectos de los fármacos , Superóxido Dismutasa/metabolismo

RESUMEN

BACKGROUND: In mammals, adrenaline and ATP are life-essential vicinal diol and cis-diol functional groups. Here, we show that interactions between a safe organogermanium compound and these cis-diol compounds have the potential to regulate physiological functions. In addition, we represent a possible new druggable target for controlling the action of cis-diol compounds. RESULTS: We analyzed a single crystal structure of organogermanium 3-(trihydroxygermyl)propanoic acid (THGPA), a hydrolysate of safe Ge-132, in complex with catecholamine (adrenaline and noradrenaline), and evaluated the affinity between several cis-diol compounds and THGPA by NMR. An in vitro study using normal human epidermal keratinocytes was performed to investigate the inhibition of cis-diol compound-stimulated receptors by THGPA. At high concentration, THGPA inhibited the calcium influx caused by adrenaline and ATP. CONCLUSION: This study demonstrates that THGPA can modify cis-diol-mediated cell-to-cell signaling.

Asunto(s)

Adenosina Trifosfato/metabolismo , Epinefrina/metabolismo , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Catecolaminas/metabolismo , Línea Celular , Cristalografía por Rayos X , Germanio/química , Germanio/farmacología , Humanos , Hidrólisis , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Propionatos

RESUMEN

Colorectal cancer, a kind of malignant cancer, has more than 1 million new patients and results in 0.5 million deaths every year globally based on the estimation of Globocan in 2008. One of the most important issues against colon cancer is tumor metastasis. Anti-angiogenesis, a form of targeted therapy uses drugs or other substances to prevent the new blood vessel formation, which is critical for tumor metastasis. In our previous studies, we have demonstrated a simple method to synthesize Chry-Ge complex through the reaction between chrysin and triphenylgermanium bromide. In this work, we investigated the mechanism of Chry-Ge induced Colo205 cell apoptosis. We found that Chry-Ge could induce apoptosis in Colo205 cells in mitochondrial-dependent pathway, cause the reorganization of cytoskeleton and induce the damage of nucleus in Colo205 cells. Besides, Chry-Ge was also found to induce membrane ultrastructural changes in Colo205 cells by AFM. Further, we found that Chry-Ge can inhibit tube formation of human umbilical vascular endothelial cell in vitro. Chry-Ge was also tested in vivo in the chicken chorioallantoic membrane (CAM) assay and found to inhibit bFGF-treated CAMs development. These results suggested that Chry-Ge could induce Colo205 cell apoptosis by mitochondrial pathway and anti-angiogenesis, highlighting the use of organic germanium agents for the treatment of colorectal cancer.

Asunto(s)

Apoptosis/efectos de los fármacos , Flavonoides/farmacología , Germanio/farmacología , Mitocondrias/efectos de los fármacos , Compuestos Organometálicos/farmacología , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Pollos , Membrana Corioalantoides/efectos de los fármacos , Colon , Células Endoteliales/efectos de los fármacos , Células Endoteliales/fisiología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neovascularización Fisiológica/efectos de los fármacos

RESUMEN

Group IV Nanowires have strong potential for several biomedical applications. However, to date their use remains limited because many are synthesised using heavy metal seeds and functionalised using organic ligands to make the materials water dispersible. This can result in unpredicted toxic side effects for mammalian cells cultured on the wires. Here, we describe an approach to make seedless and ligand free Germanium nanowires water dispersible using glutamic acid, a natural occurring amino acid that alleviates the environmental and health hazards associated with traditional functionalisation materials. We analysed the treated material extensively using Transmission electron microscopy (TEM), High resolution-TEM, and scanning electron microscope (SEM). Using a series of state of the art biochemical and morphological assays, together with a series of complimentary and synergistic cellular and molecular approaches, we show that the water dispersible germanium nanowires are non-toxic and are biocompatible. We monitored the behaviour of the cells growing on the treated germanium nanowires using a real time impedance based platform (xCELLigence) which revealed that the treated germanium nanowires promote cell adhesion and cell proliferation which we believe is as a result of the presence of an etched surface giving rise to a collagen like structure and an oxide layer. Furthermore this study is the first to evaluate the associated effect of Germanium nanowires on mammalian cells. Our studies highlight the potential use of water dispersible Germanium Nanowires in biological platforms that encourage anchorage-dependent cell growth.

Asunto(s)

Proliferación Celular/efectos de los fármacos , Germanio/farmacología , Ácido Glutámico/farmacología , Nanocables , Animales , Adhesión Celular/efectos de los fármacos , Técnicas de Cultivo de Célula , Línea Celular , Humanos , Células MCF-7 , Ratones , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión

RESUMEN

New highly cytotoxic 1-{3-[1-(5-organylsilyl-furan-2-yl)silinan-1-yl]propyl}amines and some trimethylgermyl analogues (IC50 1-7 µg mL(-1)) have been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N-allylamines in the presence of Speier's catalyst. The effects of the silacycle, the element-organic substituent in position 5 of the furan ring, and the structure of the amine on the cytotoxicity of the new compounds have been studied.

Asunto(s)

Antineoplásicos/química , Antineoplásicos/farmacología , Germanio/química , Germanio/farmacología , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Animales , Antineoplásicos/síntesis química , Línea Celular Tumoral , Humanos , Metilación , Ratones , Células 3T3 NIH , Neoplasias/tratamiento farmacológico , Compuestos de Organosilicio/síntesis química

RESUMEN

The development of protease's inhibitors is an active field of research in the pharmaceutical industry. As concerns the design of new inhibitors, the theoretical study of the binding patterns and energies of known metal binding groups (MBGs) toward Zn(2+) using quantum-chemical calculations may offer a better understanding of their interaction models and may be useful for the improvement and design of novel ZBGs. Here the properties of gem-Ge(OH)(2)-based compounds as ZBG were assessed theoretically using DFT calculations. [Zn(Imdz)(2) R - OH(2)](2+) complexes (Imdz =imidazole rings; R = imidazole ring, acetic acid molecule or acetate anion) were used to partially reproduce the coordination sphere in metalloproteases (ACE, amgiotensin converting enzyme, and TLN, thermolysine) being inhibited by related compounds (i.e., silanediols). The MBG- Zn(2+) interaction was analyzed through the energy of the reaction: [Zn(Imdz)(2) R - OH(2)](2+) + L → [Zn(Imdz)(2) R - L](2+) + H(2)O using DFT (M06L/cc-pVDZ) in gas-phase and in solution (IEF-PCM). Although the functional used (M06L) has proven its efficiency to study systems containing transition metal governed by non-covalent interactions, dispersion effects were implemented by the correction of the computed energies using the DFT-D3 program. Accounting for dispersion effects produced a systematic increase of c.a. 13 kJ mol(-1) on the energies, whereas the effect of solvent goes in the opposite direction (i.e., BE under the IEF-PCM model are on average 125 kJ mol(-1) lower). The Ge(OH)(2) - Zn(2+) interaction seems to be similar (or even stronger) than the Si(OH)(2) -Zn(2+). Their better performance as ZBG is explained by the combined NBO-AIM analysis. The results of this work may encourage the preparation, isolation, and experimental assay of the chelating properties of these compounds, which may propose a new family of protease's inhibitors.

Asunto(s)

Quelantes/química , Simulación por Computador , Diseño Asistido por Computadora , Diseño de Fármacos , Germanio/química , Hidróxidos/química , Modelos Moleculares , Péptido Hidrolasas/química , Inhibidores de Proteasas/química , Zinc/química , Sitios de Unión , Dominio Catalítico , Quelantes/farmacología , Electrones , Transferencia de Energía , Germanio/farmacología , Hidróxidos/farmacología , Imidazoles/química , Ligandos , Estructura Molecular , Inhibidores de Proteasas/farmacología , Unión Proteica , Conformación Proteica , Relación Estructura-Actividad

RESUMEN

In the present study, the protective effects of dietary Spirulina (SP) and germanium-containing Spirulina (GeSP) were compared in rats with liver injury induced by an intraperitoneal injection of d-galactosamine and lipopolysaccharide (GalN/LPS). Wistar rats were fed one of the following diets: the basal diet (GalN/LPS-CON group; n 6), the basal diet supplemented with 5 % SP or GeSP (GalN/LPS-SP and GalN/LPS-GeSP group, respectively; n 7 each). After administering these diets for 7 d, each rat was intraperitoneally injected with GalN/LPS. Increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were suppressed in the GalN/LPS-GeSP group (GalN/LPS-CON v. GalN/LPS-GeSP: ALT 1052 (sem 187) v. 509 (sem 88) IU/l and AST 2183 (sem 368) v. 1170 (sem 196) IU/l) following the injection of GalN/LPS. Plasma levels of interferon-γ (IFN-γ) and TNF-α in GeSP-fed rats were significantly lower when compared with those in the GalN/LPS-CON group (GalN/LPS-CON v. GalN/LPS-GeSP: IFN-γ 142·8 (sem 17·5) v. 66·8 (sem 9·7) pg/ml and TNF-α 72·3 (sem 15·4) v. 31·2 (sem 6·8) pg/ml). However, the decrease in these levels observed in the GalN/LPS-SP group was not as prominent as those observed in the GalN/LPS-GeSP group. Furthermore, the increase in liver catalase (CAT) and glutathione peroxidase (GPx) activities, as well as the level of oxidised glutathione (GSSG), was more suppressed in GeSP-fed rats (GalN/LPS-CON v. GalN/LPS-GeSP: CAT 457 (sem 47) v. 262 (sem 54) U/mg liver protein; GPx 1·30 (sem 0·11) v. 0·53 (sem 0·09) U/mg liver protein; GSSG 2·18 (sem 0·33) v. 1·31 (sem 0·24) mmol/kg liver) after the injection of GalN/LPS. These changes were more pronounced in the GalN/LPS-GeSP group than in the GalN/LPS-SP group. These results suggest that GeSP could afford a significant protective effect in the alleviation of GalN/LPS-induced hepatic damage. In addition, the results indicate that GeSP is more effective than SP.

Asunto(s)

Antioxidantes/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Suplementos Dietéticos , Germanio/uso terapéutico , Hepatitis/tratamiento farmacológico , Hígado/efectos de los fármacos , Spirulina/química , Alanina Transaminasa/sangre , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Aspartato Aminotransferasas/sangre , Catalasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Galactosamina , Germanio/farmacología , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Hepatitis/etiología , Hepatitis/metabolismo , Interferón gamma/sangre , Lipopolisacáridos , Hígado/enzimología , Hígado/metabolismo , Masculino , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/sangre

RESUMEN

We study the cytotoxicity of indium chloride (InCl3) in Chinese hamster lung fibroblasts, the V79 cells, using MTT assay. The results showed that InCl3 did not induce significant cytotoxicity at various concentrations tested. In addition, the frequency of micronuclei (MN) was assayed to evaluate the genotoxic effects of InCl3 in V79 cells. InCl3 at concentrations ranged 0.1-1 µM significantly increased MN frequency in a concentration-dependent manner. Both catalase and superoxide dismutase at concentrations of 75 and 150 µg/mL significantly inhibited InCl3-induced MN. Similarly, Germanium oxide (GeO2) and dimercaprol expressed antigenotoxic effects. From these findings, it is concluded that InCl3 is a potent genotoxic chemical, which may be mediated partly by inducing oxidative stress. The significance of this study shows that the workers in the semiconductor factories should be cautious in exposing to the hazardous genotoxic InCl3.

Asunto(s)

Fibroblastos/efectos de los fármacos , Indio/toxicidad , Pulmón/citología , Especies Reactivas de Oxígeno/metabolismo , Animales , Catalasa/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cricetinae , Cricetulus , Daño del ADN , Dimercaprol/farmacología , Fibroblastos/metabolismo , Depuradores de Radicales Libres/farmacología , Germanio/farmacología , Pruebas de Micronúcleos , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/farmacología

RESUMEN

Physical-chemical parameters such as purity, structure, chemistry, length, and aspect ratio of nanoparticles (NPs) are linked to their toxicity. Here, synthetic imogolite-like nanotubes with a set chemical composition but various sizes and shapes were used as models to investigate the influence of these physical parameters on the cyto- and genotoxicity and cellular uptake of NPs. The NPs were characterized using X-ray diffraction (XRD), small angle X-ray scattering (SAXS), and atomic force microscopy (AFM). Imogolite precursors (PR, ca. 5 nm curved platelets), as well as short tubes (ST, ca. 6 nm) and long tubes (LT, ca. 50 nm), remained stable in the cell culture medium. Internalization into human fibroblasts was observed only for the small particles PR and ST. None of the tested particles induced a significant cytotoxicity up to a concentration of 10(-1) mg·mL(-1). However, small sized NPs (PR and ST) were found to be genotoxic at very low concentration 10(-6) mg·mL(-1), while LT particles exhibited a weak genotoxicity. Our results indicate that small size NPs (PR, ST) were able to induce primary lesions of DNA at very low concentrations and that this DNA damage was exclusively induced by oxidative stress. The higher aspect ratio LT particles exhibited a weaker genotoxicity, where oxidative stress is a minor factor, and the likely involvement of other mechanisms. Moreover, a relationship among cell uptake, particle aspect ratio, and DNA damage of NPs was observed.

Asunto(s)

Aluminio/farmacología , Roturas del ADN de Doble Cadena/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Germanio/farmacología , Nanotubos/química , Aluminio/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Daño del ADN , Relación Dosis-Respuesta a Droga , Fibroblastos/citología , Germanio/química , Humanos , Tamaño de la Partícula , Relación Estructura-Actividad