Antibacterial mechanism with consequent cytotoxicity of different reinforcements in biodegradable magnesium and zinc alloys: A review

Benefits achieved by the biodegradable magnesium(Mg) and zinc(Zn) implants could be suppressed due to the invasion of infectious microbial, common bacteria, and fungi. Postoperative medications and the antibacterial properties of pure Mg and Zn are insufficient against biofilm and antibiotic-resistant bacteria, bringing osteomyelitis, necrosis, and even death. This study evaluates the antibacterial performance of biodegradable Mg and Zn alloys of different reinforcements, including silver(Ag), copper(Cu), lithium(Li), and gallium(Ga). Copper ions(Cu^(2+)) can eradicate biofilms and antibiotic-resistant bacteria by extracting electrons from the cellular structure. Silver ion(Ag^(+)) kills bacteria by creating bonds with the thiol group. Gallium ion(Ga^(3+)) inhibits ferric ion(Fe^(3+)) absorption, leading to nutrient deficiency and bacterial death. Nanoparticles and reactive oxygen species(ROS) can penetrate bacteria cell walls directly, develop bonds with receptors, and damage nucleotides. Antibacterial action depends on the alkali nature of metal ions and their degradation rate, which often causes cytotoxicity in living cells. Therefore, this review emphasizes the insight into degradation rate, antibacterial mechanism, and their consequent cytotoxicity and observes the correlation between antibacterial performance and oxidation number of metal ions.

Echinoside A from Pearsonothuria graeffei Exert the Cytotoxicity to MDA-MB-231 Cells via Mitochondrial Membrane and Modulation of PI3K/Akt/mTOR Pathway

A kind of triterpene glycosides echinoside A(EA)was extracted from sea cucumber Pearsonothuria graeffei,and its yield was about 0.78%.The purity of EA was 99.0%,and its molecular weight was 1206 Da.EA was a linear tetrasaccharide attached to a pentacyclic triterpene aglycon.It inhibited the growth of MDA-MB-231 cells in vitro.The antitumor effect was related to elevate ROS level,decrease mitochondrial membrane potential,enhance caspase-3 expression,induce cells apoptosis and arrest cell cycle at G2/M phase.EA also dose-dependently suppressed the expressions of phophorylation proteins p-PI3K,p-Akt,and p-mTOR as analyzed by western blotting.These results suggested that EA caused MDA-MB-231 cells apoptosis via intrinsic mitochondrial and PI3K/Akt/mTOR pathway.EA can be a potential anti-breast cancer agent to enhance the clinical efficacy.

New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti

Two novel compounds including a cyclohelminthol type polyketide(namely oxaleimide K,1)and a maleimide deriva-tive(namely peniroquefortine A,2),and a new natural product(namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-acetamide,3),together with four known compounds(4-7),were isolated and identified from fungus Penicillium roqueforti,which was separated from the root soil of Hypericum beanii N.Robson collected from the Shennongjia For-estry District,Hubei Province.Their structures including absolute configurations were mainly established by the NMR spectroscopy analyses and single-crystal X-ray diffraction experiment.Compound 1 represents the second example of a cyclohelminthol type polyketide,which features a rare 6/6/5/5 tetracyclic system and a branched aliphatic chain containing a terminal olefin(oct-1-en-3-yl)moiety,and compound 2 possesses an unprecedented carbon skeleton that is uniquely defined by a maleimide moiety linked to the respective 4-methylene-2-(3-methylbut-2-en-1-yl)-phenol and para-substituted aromatic moieties via the carbon-carbon bonds.Remarkably,the absolute configuration of a cyclohelminthol type polyketide as exemplified by compound 1 is determined by the single-crystal diffraction analysis for the first time,highlighting an E-configuration for the linkage of a succinimide moiety and a tetrahydro-furan moiety for 1 rather than a Z-configuration as previously reported in the biosynthesis study,which gives a new insight into the structural elucidation of this category of polyketides.Additionally,compound 1 exhibited significant cytotoxic activity against multiple tumor cells,especially against the Farage and SU-DHL-2 cells(IC_(50)<20μM,48 h).Further mechanism study revealed that compound 1 significantly induced cell cycle arrest in Farage and SU-DHL-2 cells by causing abnormal ROS level and triggering oxidative stress.

Cytotoxic Properties on Cervical and Liver Cancer Cells of Two Plant Recipes from Burkina Faso

Cancer is one of the deadliest diseases in developing countries. In recent years, natural plant-based compounds have been used in the search for drugs to combat numerous diseases, including cancer. In this study, we evaluate the cytotoxic properties of paanfo tiben 1 and paanfo tiben 2, two traditional herbal formulations from Burkina Faso used in the treatment of cancer in Burkina Faso. To this end, the recipes were infused and freeze-dried. The dry extracts obtained were used to determine total phenolics and flavonoids content, assess antioxidant activity using the DPPH, ABTS and FRAP methods, evaluate anti-inflammatory properties by inhibiting 15-LOX, COX 1 and 2, and assess cytotoxic activity on HeLa cervical cancer and HePG2 liver cancer cell lines using the MTT test. The paanfo tiben 1 recipe showed the highest levels of total phenolics and flavonoids, as well as the best antioxidant activities, with IC50 values of 21.020 ± 0.6 µg/ml and 22.94 ± 0.57 µg/ml for DPPH and ABTS, and 165.15 mM EAA/mg dry extract for FRAP. It also exhibited the best cytotoxic activity with IC50 values of 112.02 ± 0.025 µg/ml on HeLa cells and 80.67 ± 6.08 µg/ml on HepG2 cells. On the other hand, paanfo tiben 2 exhibited the best anti-inflammatory activities through inhibition of 15-LOX and COX 1, with inhibition percentages at 100 µg/ml of 32.523% and 24.717 % respectively. These results could justify the traditional use of these two recipes by traditional health practitioners in the treatment of cancer sufferers in Burkina Faso.

Chronic toxicity and cytotoxicity of synthetic pyrethroid insecticide cis-bifenthrin

With the increasing use of synthetic pyrethroids （SPs）, the significance of ecological safety and health risk is an emerging concern, In this study, we evaluated the chronic aquatic toxicity of eis-bifenthrin （cis-BF） in Daphnia magna and its cytotoxicity in Chinese hamster ovary （CHO） cells as well as human cervical carcinoma （Hela） ceils. Chronic aquatic toxicity tests showed that cis-BF could significantly affect the reproduction of D. magna. The lowest observed effective concentration and the non-observed effective concentration of cis-BF to D. magna were 0.02 and 0.01 μg/L, respectively, and the chronic value was 0.014 μg/L. The intrinsic rate of natural increase was significantly decreased （p 〈 0.05） to 0.02 μg/L. The cytotoxicity assay demonstrated that cis-BF decreased cell viability in CHO and Hela cells in a concentration- and time-dependent manner. The IC50 values for Hela and CHO cells were 4.0 × 10^-5 and 3.2 × 10^-5 mol/L, respectively. Together, these results indicated that cis-BF induced chronic toxicity in both aquatic invertebrate animals and mammalian cells. These findings assist in understanding the impact of SPs on health and environmental safety. Considering the wide spectrum of SPs, a more comprehensive understanding of the negative effects is indispensible for planning future application and regulation of these pesticides.

Cytotoxicity Study of a Novel Implant Material Modified by Microarc Oxidation

This study examined the cytotoxicity of a new implant material modified by microarc oxidation technique. Cells on different surfaces of the implant were evaluated 2, 4 and 6 days after treatment. The results showed that cell attachment, cell morphology, and cell proliferation were influenced by the different surface treatments, and a significant increase in the osteoblast cell activity was observed on the porous MAO-Ti coating. Our results suggest that the porous MAO-Ti surface has a better biocompatibility and electrochemical performance than pure titanium surface.

Cytotoxicity and Apoptosis Induction in Human HepG2 Hepatoma Cells by Decabromodiphenyl Ethane

Abstract Objective To investigate the toxic effects of decabromodiphenyl ethane （DBDPE）, used as an alternative to decabromodiphenyl ether in vitro. Methods HepG2 cells were cultured in the presence of DBDPE at various concentrations （3.125-100.0 mg/L） for 24, 48, and 72 h respectively and the toxic effect of DBDPE was studied. Results As evaluated by the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays and nuclear morphological changes, DBDPE inhibited HepG2 viability in a time- and dose-dependent manner within a range of 12.5 mg/L to 100 mg/L and for 48 h and 72 h. Induction of apoptosis was detected at 12.5-100 mg/L at 48 h and 72 h by propidium iodide staining, accompanied with overproduction of reactive oxygen species （ROS）. Furthermore, N-acetyI-L-cysteine, a widely used ROS scavenger, significantly reduced DBDPE-induced ROS levels and increased HepG2 cells viability. Conclusion DBDPE has cytotoxic and anti-proliferation effect and can induce apoptosis in which ROS plays an important role

Antimicrobial activity,cytotoxicity,and phytochemical screening of Voacanga globosa(Blanco) Merr.leaf extract(Apocynaceae)

Objective:To determine the antibacterial,antifungal,antiprotozoal,cytotoxic,and phytochemical properties of ethanol extracts of leaves of Voacanga globosa(Blanco) Merr.(V.globosa). Methods:The extracts were tested against bacteria and fungus through disc diffusion assay; against protozoa through growth curve determination,antiprotozoal and cytotoxicity assays. Results:The extract revealed antibacterial activities,inhibiting the growth of Staphylococcus aureus,Bacillus cereus,Pseudomonas aeruginosa,Micrococcus luteus,and Salmonella typhimurium.Antifungal assay showed that it inhibited Candida albicans.The antiprotozoal assay against Trichomonas vaginalis and Entamoeba histolytica showed that V.globosa can inhibit the parasites,wherein the action can be comparable to metronidazole.With the in situ cell death detection kit.Trichomonas vaginalis and Entamoeba histolytica exposed to V.globosa leaf extract was observed to fluoresce simultaneously in red and yellow signals signifying apoptotic-like changes.Preliminary phytochemical screening revealed the chemical composition of plant extract containing alkaloids,saponins,2-deoxysugars,and hydrolysabie tannins.Conclusions: Thus,thus study provides scientific evidence on the traditional use of V.globosa leaf extract in treating microbial diseases.Further,the leaf extract can possibly be used to produce alternative forms of antimicrobials.

Cytotoxicity evaluation and hepatoprotective potential of bioassay guided fractions from Feronia limmonia Linn leaf

Objective:To evaluate the cytotoxicity and hepatoprotective potentials of extracts,fractions or isolated compound from the leaves of Feronia limonia(F.limonia).Methods:Qualitative phytochemical analysis of extracts,fractions or compound was performed by means of thin layer chromatography and spectroscopic assays.The%purity of compound was measured by analytical HPLC.Extracts,fractions or compound have been individually evaluated for their cytotoxicity effects(10,20,100,250,500,750 and 1 000 μg/mL).Based on the inhibitory concentration(IC_(50)) obtained from the cell viability assay,graded concentrations of extracts,fractions or isolated compound were assessed(10,20,50,100,200 μg/mL) for its hepatoprotective potential against CCl_4-induced hepatotoxicity by monitoring activity levels of serum glutamatic pyruvatic transaminase(SGPT) and serum glutamic oxaloacetic transaminase(SGOT).Results:Results indicated that the methanol extract of F.limonia was non-toxic and hepatoprotective in nature as compared with the petroleum ether extract.The acetone fraction of methanolic extract also showed similar properties but the subsequent two fractions were cytotoxic.However,the pure compound isolated from the penultimate fraction of methanolic extract was non-toxic and hepatoprotective in nature.Biochemical investigations(SCOT,SCPT) further corroborated these cytological observations.Conclusions:It can be concluded from this study that F.limonia methanol extract,some fractions and pure isolated compound herein exhibit hepatoprotective activity.However,cytotoxicity recorded in the penultimate fraction and investigation of structural details of pure compound warrants further study.

Synthesis and in vitro cytotoxicity of novel 1,4-disubstituted phthalazines

Eight novel 1,4-disubstituted phthalazines （7-14） were designed and synthesized. The structures of all the synthesized compounds were confirmed by IR,1H NMR, 13C NMR, MS and elemental analysis. Their in vitro cytotoxicity against cancer cell lines （Bel-7402 and HT- 1080） were evaluated by standard MTT assay. Among them, compounds 9 and 11 exhibited more potent cytotoxicity than cisplatin. 2007 Ping Gong. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Cytotoxicity screening of Melastoma malabathricum extracts on human breast cancer cell lines in vitro

Objective:To screen the cytotoxic activity of Melasloma malabathricum(M,malubathricum)against human breast carreer cell line(MCF-7)in vitro.Methods:A three steps extraction protocol using n-hexane,chloroform and methanol as the solvents systems was carried out on leaves,stems and flowers of M.nalabathricum.Dimethyl sulfoxide was used in extracts dilution and serial dilutions were conducted to obtain five different extract concentrations(100μg/mL,50μg/mL,25μg/mL,123μg/rnL and 6.25μg/mL).The evaluation of cell growth was determined using methylene blue assay.Results:Methanol extract from the leaves showed significant anticancer activity against MCF-7cell lines with the TC_(50)value of 7.14μg/ml while methanol and chloroform extract from the flowers exhibited a moderate activity towards MCF-7 cell line,with the IC_(50)value of 33.63μg/mL and 45.76μg/mL respectively after 72 h of treatment.Conclusions:The extracts from leaves and flowers of M.nulabatkricum showed promising anticancer activity toward human breast cancer cell lines with the lowest IC_(50)at 7.14μg/mL while the extracts from stems showed less growth inhibition activity.

Cytotoxicity of lambda-cyhalothrin on the macrophage cell line RAW 264.7

The wide use and wide-spectrum toxicity of synthetic pyrethroids （SPs） insecticides make them an emerging ecotoxicological concern. Some previous studies showed that SPs possessed cytotoxicity in some immune cells such as human lymphocytes and rat bone marrow. However, the cytotoxicity of SPs to macrophages, which are crucial to innate immunity, has not been explored. In the present report, we investigated a new pyrethroid insecticide, lambda-cyhalothrin （LCT）, which may increase the generation of reactive oxygen species （ROS） and DNA damage levels and cause cytotoxicity in RAW 264.7 cells in dose- and time-dependent manners. The results for the first time implicated increased endogenous ROS and DNA damage as co-mediators of LCT-induced cytotoxicity in macrophages. Our results also suggested that macrophages were involved in synthetic pyrethroid-induced adverse immune effects. Considering the ubiquitous environmental presence of SPs, this study provided new information relative to the potential long-term physiological and immunological effects associated with chronic exposure to SPs. Hence, the potential immunotoxicity of SPs should be considered in assessing the safety of these compounds in sensitive environmental compartments.

Cytotoxicity and genotoxicity assessment of Euphorbia hirta in MCF-7cell line model using comet assay

Objective:To evaluate the cytotoxicity and genotoxicity activity of Euphorbia hirta(E.hirta)in MCF-7 cell line model using comet assay.Methods:The cytotoxicity of E.hirta extract was investigated by employing brine shrimp lethality assay and the genotoxicity of E.hirta was assessed by using Comet assay.Results:Both toxicity tests exhibited significant toxicity result.In the comet assay,the E.hirta extract exhibited genotoxicity effects against MCF-7 DNA in a time-dependent manner by increasing mean percentage of DNA damage.The extract of E.hirta showed significant toxicity against brine shrimp with an LC_(50)value of 620.382μg/mL(24 h).Comparison with positive control potassium dichroniate signifies that cytotoxicity exhibited by the methanol extract might have moderate activity.Conclusion:The present work confirmed the cytotoxicity and genotoxicity of E.hirta.However,the observed toxicity of E.hta extracts needs to be confirmed in additional studies.

In Vitro Evaluation of Cytotoxicity and Oxidative Stress Induced by Multiwalled Carbon Nanotubes in Murine RAW 264.7 Macrophages and Human A549 Lung Cells

Objective To investigate in vitro cytotoxicity and oxidative stress response induced by multiwalled carbon nanotubes （MWCNTs）. Methods Cultured macrophages （murine RAW264.7 cells） and alveolar epithelium cells type II （human A549 lung cells） were exposed to the blank control, DNA salt control, and the MWCNTs suspensions at 2.5, 10, 25, and 100 ug/mL for 24 h. Each treatment was evaluated by cell viability, cytotoxicity and oxidative stress. Results Overall, both cell lines had similar patterns in response to the cytotoxicity and oxidative stress of MWCNTs. DNA salt treatment showed no change compared to the blank control. In both cell lines, significant changes at the doses of 25 and 100 ug/mL treatments were found in cell viabilities, cytotoxicity, and oxidative stress indexes. The reactive oxygen species （ROS） generation was also found to be significantly higher at the dose of 10 ug/mL treatment, whereas no change was seen in most of the indexes. The ROS generation in both cell lines went up in minutes, reached the climax within an hour and faded down after several hours. Conclusion Exposure to MWCNTs resulted in a dose-dependent cytotoxicity in cultured RAW264.7 cells and A549 cells, that was closely correlated to the increased oxidative stress.

In Vitro Cytotoxicity of Polyphosphoester as a Novel Injectable Alveolar Replacement Material

The aim of this study was to investigate the in vitro cytotoxicity of polyphosphoester polymer used as a novel injectable alveolar bone substitutes for controlled delivery of tetracycline. Cell culture medium was exposed to the polymer （0.01-10 mg/mL） for 24 h. The L-929 mouse fibro- blasts were then exposed to the treated cell culture medium for 24 h. Finally, cell viability and growth were assessed by using MTT assay and Alamar Blue assay. No significant cytotoxicity of the polyphosphoester against L-929 mouse fibroblasts was observed at a concentration up to 10 mg/mL （P〉0.05）. The two evaluation methods showed no significant differences （P〉0.05）. This study suggests that polyphosphoester does not demonstrate any significant toxic effects to cells in vitro and has the potential to be used both as a medical device and as scaffolds in tissue engineering applications.

CIK cells from patients with HCC possess strong cytotoxicity to multidrug-resistant cell line Bel-7402/R

ABM: To investigate the cytotoxicity of the cytokine-induced killer (CIK) cells from the post-operation patients with primary hepatocellular carcinoma (HCC) to multidrug-resistant (MDR) cell of HCC both in vitro and in vivo. METHODS: A drug-resistant cell line was established by culturing human HCC cell line Bel-7402 in complete RPMI 1640 medium with increasing concentrations of adriamycin from 10 to 2 000 nmol/L. CIK cells were obtained by inducing the peripheral blood mononuclear cells with rhlFN-γ, monoclonal anti-CD3 antibody, rhIL-1α as well as rhIL-2, which were added into the culture. To detect the cytotoxicity of the CIK cells from HCC patients, the Bel-7402/R was taken as target (T) cells and CIK cells as effect (E) cells. Cytotoxic test was performed and measured by MTT. As to in vivo test, CIK cells were transfused into patients with HCC. The tumor specimens of the patients were obtained and immunohistochemistry was carried out to detect CD3, CD45, CD45RO as well as CD68. RESULTS: A MDR 1 HCC cell line Bel-7402/R was established. Its MDR1 mRNA overexpressed which was shown by RT-PCR; the P-glycoprotein expression increased from 1.32% of parent cells to 54%. CIK cells expanded vigorously by more than 70-fold and the CD3+CD56+ increased by more than 600-fold after 3-wk incubation on average. The cytotoxicity of CIK from HCC patients to Bel-7402/R was about 50% and to L-02 below 10% (t = 8.87, P<0.01), the same as that of CIK from normal individuals. Each of the 17 patients received 1-5×1010of CIK cell transfusion. No side effects were observed. After CIK treatment, the tumor tissue nodules formed and a large amount of lymphocytes infiltrated in the liver cancer tissue and CD3, CD45, CD45RO, and CD68 increased greatly which was shown by immunohistochemistry. CONCLUSION: A stable MDR1 HCC cell line has been established which could recover from liquid nitrogen and CIK from HCC patients has strong cytotoxicity to MDR HCC cell. CIK adoptive immunotherapy is safe and has no side effects. Receivers improved their immunity to tumor evidently. CIK treatment may be a better choice for HCC patients after operation to prevent the recurrence, especially when tumors have developed drug resistance.

Dose-dependent Cytotoxicity and Oxidative Stress Induced by "Naked" Fe_3O_4 Nanoparticles in Human Hepatocyte

The dose-dependent cytotoxicity effect on human hepatocyte（HL-7702 cells） induced by ＂naked＂ Fe3O4 nanoparticles was assessed through cell viabilities and lactate dehydrogenase（LDH） activities. Three important oxi dative indexes of the cells by glutathione peroxidase（GSH-Px）, superoxide dismutase（SOD） and malondialde hyde（MDA） were determined. The good correlation of the cell viabilities with their GSH-Px, SOD and MDA levels indicated that the cytotoxicity is related to activation of oxidative stress induced by Fe3O4 nanoparticles. The oxida tive stress also leads to corresponding DNA damage in a similar dose-dependent manner, followed by the changes of cell cycle and cell apoptosis. Such work provides important experimental data for the safety evaluation of superpa ramagnetic Fe3O4 nanoparticles.

Cytotoxicity effect assessment of acid purified carbon nanotubes modified with cetyltrimethyl ammonium bromide

The cytotoxicities of single-walled carbon nanotubes （SWNTs） and acid purified single-walled carbon nanotubes （SWNT-COOH） were investigated by spectroscopic analysis. Cell viability and cell apoptosis were applied to assessing the cytotoxicity of SWNT-COOH, cetyltrimethyl ammonium bromide （CTAB） and acid purified carbon nanotubes modified with cetyltrimethyl ammonium bromide （SWNT-COOH/CTAB）. The results indicate that SWNTs are more toxic than SWNT-COOH. Concentration and time-curve analyses indicate that cytotoxicity of SWNT-COOH/CTAB is more related to the toxicity of the surfactant CTAB. The cytotoxicity effect of CTAB and SWNT-COOH/CTAB is acceptable at low concentrations （0.5-25μg/mL）. The cytotoxicity observation suggests that SWNT-COOH/CTAB can safely applied to biomedical field at low concentrations （0.5-25μg/mL）.

Effect of Inhalational Anesthetics on Cytotoxicity and Intracellular Calcium Differently in Rat Pheochromocytoma Cells (PC12)

Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in rat pheochromocytoma cells （PC12） in a concentration- and time-dependent manner with unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum （ER） via activation of inositol 1,4,5-trisphosphate （IP3） receptors. Alzheimer＇s presenilin-1 （PS 1） mutation increased activity of IP3 receptors and therefore rendered cells vulnerable to isoflurane-induced cytotoxicity. Sevoflurane and desflurane had less ability to disrupt intracellular calcium homeostasis and thus being less potent pared the cytotoxic effects of various inhaled to cause cytotoxicity. This study examined and com-anesthetics on PC12 cells transfected with the Alzheimer＇s mutated PS 1 （L286V） and the disruption of intracellular calcium homeostasis. PC 12 cells transfected with wild type （WT） and mutated PS 1 （L286V） were treated with equivalent of 1 MAC of isoflurane, sevoflurane and desflurane for 12 h. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in cytosolic space （[Ca^2＋]c） were determined after exposing different types of cells to various inhalational anesthetics. The effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in L286V PC12 cells were also determined. The results showed that isoflurane at 1 MAC for 12 h induced cytoxicity in L286V but not WT PC12 cells, which was also associated with greater and faster elevation of peak [Ca^2＋]c in L286V than in the WT cells. Xestospongin C significantly ameliorated isoflurane cytotoxicity in L286V cells, as well as inhibited the calcium release from the ER in L286V cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar cytotoxicity or elevation of peak [Ca^2＋]c in L286V PC 12 cells. These results suggested that isoflurane induced cytoxicity by partially causing abnormal calcium release from the ER via activation of IP3 receptors in L286V PC12 cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar elevation of [Ca^2＋]c or neurotoxicity in PC 12 cells transfected with the Alzheimer＇s PS 1 mutation.

Neodymium Oxide Induces Cytotoxicity and Activates NF-κB and Caspase-3 in NR8383 Cells

We investigated whether Nd_2O_3 treatment results in cytotoxicity and other underlying effects in rat NR8383 alveolar macrophages.Cell viability assessed by the MTT assay revealed that Nd_2O_3 was toxic in a dose-dependent manner, but not in a time-dependent manner. An ELISA analysis indicated that exposure to Nd203 caused cell damage and enhanced synthesis and release of inflammatory chemokines. A Western blot analysis showed that protein expression levels of caspase-3, nuclear factor-KB （NF-KB） and its inhibitor IKB increased significantly in response to Nd203 treatment. Both NF-KB and caspase-3 signaling were activated, suggesting that both pathways are involved in Nd203 cytotoxicity.