Cytotoxicity of titanium and titanium alloying elements

It is commonly accepted that titanium and the titanium alloying elements of tantalum, niobium, zirconium, molybdenum, tin, and silicon are biocompatible. However, our research in the development of new titanium alloys for biomedical applications indicated that some titanium alloys containing molybdenum, niobium, and silicon produced by powder metallurgy show a certain degree of cytotoxicity. We hypothesized that the cytotoxicity is linked to the ion release from the metals. To prove this hypothesis, we assessed the cytotoxicity of titanium and titanium alloying elements in both forms of powder and bulk, using osteoblast-like SaOS₂ cells. Results indicated that the metal powders of titanium, niobium, molybdenum, and silicon are cytotoxic, and the bulk metals of silicon and molybdenum also showed cytotoxicity. Meanwhile, we established that the safe ion concentrations (below which the ion concentration is non-toxic) are 8.5, 15.5, 172.0, and 37,000.0 μg/L for molybdenum, titanium, niobium, and silicon, respectively.

Dynamic analysis of drug-induced cytotoxicity using chip-based dielectrophoretic cell immobilization technology

Quantification of programmed and accidental cell death provides useful end-points for the anticancer drug efficacy assessment. Cell death is, however, a stochastic process. Therefore, the opportunity to dynamically quantify individual cellular states is advantageous over the commonly employed static, end-point assays. In this work, we describe the development and application of a microfabricated, dielectrophoretic (DEP) cell immobilization platform for the realtime analysis of cancer drug-induced cytotoxicity. Microelectrode arrays were designed to generate weak electro-thermal vortices that support efficient drug mixing and rapid cell immobilization at the delta-shape regions of strong electric field formed between the opposite microelectrodes. We applied this technology to the dynamic analysis of hematopoietic tumor cells that represent a particular challenge for real-time imaging due to their dislodgement during image acquisition. The present study was designed to provide a comprehensive mechanistic rationale for accelerated cell-based assays on DEP chips using real-time labeling with cell permeability markers. In this context, we provide data on the complex behavior of viable vs dying cells in the DEP fields and probe the effects of DEP fields upon cell responses to anticancer drugs and overall bioassay performance. Results indicate that simple DEP cell immobilization technology can be readily applied for the dynamic analysis of investigational drugs in hematopoietic cancer cells. This ability is of particular importance in studying the outcome of patient derived cancer cells, when exposed to therapeutic drugs, as these cells are often rare and difficult to collect, purify and immobilize.

An in vitro comparative assessment with a series of new triphenyltin(IV) 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoates endowed with anticancer activities: Structural modifications, analysis of efficacy and cytotoxicity involving human tumor cell lines

Four new triphenyltin(IV) complexes of composition Ph₃SnLH (where LH = 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoate) (1–4) were synthesized and characterized by spectroscopic (¹H, ¹³C and ¹¹⁹Sn NMR, IR, ¹¹⁹Sn Mössbauer) techniques in combination with elemental analysis. The ¹¹⁹Sn NMR spectroscopic data indicate a tetrahedral coordination geometry in non-coordinating solvents. The crystal structures of three complexes, Ph₃SnL¹H (1), Ph₃SnL³H (3), Ph₃SnL⁴H (4), were determined. All display an essentially tetrahedral geometry with angles ranging from 93.50(8) to 124.5(2)°; ¹¹⁹Sn Mössbauer spectral data support this assignment. The cytotoxicity studies were performed with complexes 1–4, along with a previously reported complex (5) in vitro across a panel of human tumor cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. The screening results were compared with the results from other related triphenyltin(IV) complexes (6–7) and tributyltin(IV) complexes (8–11) having 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoates framework. In general, the complexes exhibit stronger cytotoxic activity. The results obtained for 1–3 are also comparable to those of its o-analogs i.e. 4–7, except 5, but the advantage is the former set of complexes demonstrated two folds more cytotoxic activity for the cell line MCF-7 with ID₅₀ values in the range 41–53 ng/ml. Undoubtedly, the cytotoxic results of complexes 1–3 are far superior to CDDP, 5-FU and ETO, and related tributyltin(IV) complexes 8–11. The quantitative structure-activity relationship (QSAR) studies for the cytotoxicity of triphenyltin(IV) complexes 1–7 and tributyltin(IV) complexes 8–11 is also discussed against a panel of human tumor cell lines.

Encapsulation of Local Anesthetic Bupivacaine in Biodegradable Poly(DL-lactide-co-glycolide) Nanospheres: Factorial Design, Characterization and Cytotoxicity Studies

Local anesthetic agents cause temporary blockade of nerve impulses productiong insensitivity to painful stimuli in the area supplied by that nerve. Bupivacaine (BVC) is an amide-type local anesthetic widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. in this study, we prepared and characterized nanosphere formulations containing BVC. To achieve these goals, BVC loaded poly(DL-lactide-co-glycolide) (PLGA) nanospheres (NS) were prepared by nanopreciptation and characterized with regard to size distribution, drug loading and cytotoxicity assays. The 2(3-1) factorial experimental design was used to study the influence of three different independent variables on nanoparticle drug loading. BVC was assayed by HPLC, the particle size and zeta potential were determined by dynamic light scattering. BVC was determined using a combined ultrafiltration-centrifugation technique. The results of optimized formulations showed a narrow size distribution with a polydispersivity of 0.05%, an average diameter of 236.7 +/- 2.6 nm and the zeta potential -2.93 +/- 1,10 mV. In toxicity studies with fibroblast 3T3 cells, BVC loaded-PLGA-NS increased cell viability, in comparison with the effect produced by free BVC. In this way, BVC-loaded PLGA-NS decreased BVC toxicity. The development of BVC formulations in carriers such as nanospheres could offer the possibility of controlling drug delivery in biological systems, prolonging the anesthetic effect and reducing toxicity.

Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: Anti-Mycobacterium tuberculosis activity and cytotoxicity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

In vitro basal and metabolism-mediated cytotoxicity of flavonoids

The purpose of this study was to compare the basal cytotoxicity and metabolism-mediated cytotoxicity of kaempferol, quercetin and rutin. McCoy cells were exposed to various concentrations of the flavonols with and without the S9 system. The neutral red uptake assay was used to determine viability after 24 h at 35-37 degrees C. Dose-response curves were established for each flavonol in the presence and absence of external metabolizing systems. Kaempferol and quercetin were cytotoxic and provoked a dose-dependent decrease in cell viability, without the S9 system. The hepatic S9 microsomal fraction metabolized these compounds to less cytotoxic metabolites. In contrast, rutin at 500 mu g/ml failed to produce any overt signs of toxicity in either assay. (c) 2005 Elsevier Ltd. All rights reserved.

Cytotoxicity of chlorhexidine digluconate to murine macrophages and its effect on hydrogen peroxide and nitric oxide induction

Chlorhexidine, even at low concentrations, is toxic for a variety of eukaryotic cells; however, its effects on host immune cells are not well known. We evaluated in vitro chlorhexidine-induced cytotoxicity and its effects on reactive oxygen/nitrogen intermediate induction by murine peritoneal macrophages. Thioglycollate-induced cells were obtained from Swiss mice by peritoneal lavage with 5 ml of 10 mM phosphate-buffered saline, washed twice and resuspended (10(6) cells/ml) in appropriate medium for each test. Cell preparations contained more than 95% macrophages. The cytotoxicity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and the presence of hydrogen peroxide (H2O2) and nitric oxide (NO) by the horseradish peroxidase-dependent oxidation of phenol red and Griess reaction, respectively. The midpoint cytotoxicity values for 1- and 24-h exposures were 61.12 ± 2.46 and 21.22 ± 2.44 µg/ml, respectively. Chlorhexidine did not induce synthesis or liberation of reactive oxygen/nitrogen intermediates. When macrophages were treated with various sub-toxic doses for 1 h (1, 5, 10, and 20 µg/ml) and 24 h (0.5, 1, and 5 µg/ml) and stimulated with 200 nM phorbol myristate acetate (PMA) solution, the H2O2 production was not altered; however, the NO production induced by 10 µg/ml lipopolysaccharide (LPS) solution varied from 14.47 ± 1.46 to 22.35 ± 1.94 µmol/l and 13.50 ± 1.42 to 20.44 ± 1.40 µmol/l (N = 5). The results showed that chlorhexidine has no immunostimulating activity and sub-toxic concentrations did not affect the response of macrophages to the soluble stimulus PMA but can interfere with the receptor-dependent stimulus LPS.

Cytotoxicity study of some Ti alloys used as biomaterial

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ascorbic acid potentiates the cytotoxicity of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genotoxicity, cytotoxicity and gene expression in patients undergoing elective surgery under isoflurane anaesthesia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Familial cancer: depressed NK-cell cytotoxicity in healthy and cancer affected members

Este estudo se reporta às funções de células natural killer (NK), como adesão, lise e citotoxicidade e de subpopulações de células T em uma família com alta prevalência de pacientes com câncer e que apresentaram: glioblastoma, leucemia mielóide crônica, osteoblastoma, melanoma e carcinomas gástrico, pancreático e cólon retal. Quinze membros dessa família foram estudados, sendo 13 sadios, acompanhados por 5 anos e dois com câncer: glioblastoma e leucemia mielóide crônica. Duas pessoas sadias, no momento da avaliação, desenvolveram posteriormente osteoblastoma mandibular ou melanoma maligno. Como controle, foram avaliados 19 indivíduos saudáveis de faixa etária equivalente. A determinação de linfócitos T CD3+ e de suas subpopulações CD4+ e CD8+ foi realizada empregando-se anticorpos monoclonais e a atividade citotóxica de células NK, avaliada pelo teste de single-cell contra células alvo da linhagem eritroleucêmica K562. Os resultados mostraram que as percentagens de células T totais (CD3+), da subpopulação CD4+ e da relação CD4/CD8 foram significativamente menores nos indivíduos da família estudada em comparação aos valores observados no grupo controle. em todos os membros dessa família a percentagem de formação de conjugados entre células NK-células alvo foi inferior ao valor mínimo observado nos controles. Essa alteração poderia estar relacionada a defeito na expressão de moléculas de adesão, presentes na membrana de células NK, como provável causa das alterações funcionais dessas células. A herança dos mecanismos determinantes desta deficiência pode ser um fator de risco, com valor prognóstico para o desenvolvimento de cancer.

Genotoxicity and cytotoxicity of glass ionomer cements on Chinese hamster ovary (CHO) cells

Glass ionomer cements are widely used in dentistry as restorative materials and adhesives for composite restorations. However, the results of genotoxicity studies using these materials are inconclusive in literature. The goal of this study was to examine the genotoxic and cytotoxic potential of three different glass ionomer cements available commercially (Ketac Cem, Ketac Molar and Vitrebond) by the single cell gel (comet) assay and trypan blue exclusion test, respectively. For this, such materials were exposed to Chinese hamster ovary (CHO) cells in vitro for 1 h at 37 degrees C. Data were assessed by Kruskall-Wallis nonparametric test. The results showed that the powder from Ketac Molar displayed genotoxicity only in the maximum concentration evaluated (100 mu g/mL). In the same way, the liquid from Vitrebond at 0.1% dilution caused an increase of DNA injury. Significant differences (P < 0.05) in cytotoxicity provoked by all powders tested of glass ionomer cements were observed for exposure at 1000 mu g/mL concentration. With respect to liquids of glass ionomer cements evaluated, the major toxic effect on cell viability was produced at 10%, beginning at the dilution of 0.5% for Vitrebond. Taken together, we conclude that some components of glass ionomer cements show both genotoxic and cytotoxic effects.

Diuron-Induced Rat Bladder Epithelial Cytotoxicity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cytotoxicity and Regenerative Proliferation as the Mode of Action for Diuron-Induced Urothelial Carcinogenesis in the Rat

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)