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Nanoparticles, particularly magnesium oxide nanoparticles (MgO-NPs), are increasingly utilized in various fields, yet their potential impact on cellular systems remains a topic of concern. This study aimed to comprehensively investigate the molecular mechanisms underlying MgO-NP-induced cellular impairment in Saccharomyces cerevisiae, with a focus on cell wall integrity, endoplasmic reticulum (ER) stress response, mitochondrial function, lipid metabolism, autophagy, and epigenetic alterations. MgO-NPs were synthesized through a chemical reduction method, characterized for morphology, size distribution, and elemental composition. Concentration-dependent toxicity assays were conducted to evaluate the inhibitory effect on yeast growth, accompanied by propidium iodide (PI) staining to assess membrane damage. Intracellular reactive oxygen species (ROS) accumulation was measured, and chitin synthesis, indicative of cell wall perturbation, was examined along with the expression of chitin synthesis genes. Mitochondrial function was assessed through Psd1 localization, and ER structure was analyzed using dsRed-HDEL marker. The unfolded protein response (UPR) pathway activation was monitored, and lipid droplet formation and autophagy induction were investigated. Results demonstrated a dose-dependent inhibition of yeast growth by MgO-NPs, with concomitant membrane damage and ROS accumulation. Cell wall perturbation was evidenced by increased chitin synthesis and upregulation of chitin synthesis genes. MgO-NPs impaired mitochondrial function, disrupted ER structure, and activated the UPR pathway. Lipid droplet formation and autophagy were induced, indicating cellular stress responses. Additionally, MgO-NPs exhibited differential cytotoxicity on histone mutant strains, implicating specific histone residues in cellular response to nanoparticle stress. Immunoblotting revealed alterations in histone posttranslational modifications, particularly enhanced methylation of H3K4me. This study provides comprehensive insights into the multifaceted effects of MgO-NPs on S. cerevisiae, elucidating key molecular pathways involved in nanoparticle-induced cellular impairment. Understanding these mechanisms is crucial for assessing nanoparticle toxicity and developing strategies for safer nanoparticle applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nanotechnology is an advancing and emerging field of all environmental, medical, and industrial applications. Magnesium oxide nanoparticles have been widely used in medicine, consumer products, industrial products, textiles, ceramics, alleviation of heartburn, stomach ulcers, and bone regeneration. In the present study, acute toxicity (LC 50 ) of MgO nanoparticles and hematological and histopathological changes in Cirrhinus mrigala was analyzed. The lethal concentration for 50% of MgO nanoparticles was 4.2321 mg/L. Hematological parameters such as white blood cells, red blood cells, hematocrit, hemoglobin, platelets, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, as well as histopathological abnormalities in gills, muscle, and liver were observed on the 7th and 14th days of exposure. The WBC, RBC, HCT, Hb, and platelets count increased on the 14th day of exposure compared to the control and 7th day of exposure. The MCV, MCH, and MCHC levels decreased on the 7th day of exposure compared to the control and increased on the 14th day. Histopathological changes of MgO nanoparticles in gills, muscle, and liver highly damaged in the quantity of 3.6 mg/L compared to 12 mg/L on 7th and 14th days of exposure. This study finds the level of exposure in hematology and histopathological changes in tissues in relation to the exposure of MgO NPs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Magnesium oxide nanoparticles (MgO NPs) have a variety of applications that have contributed to their elevated popularity, however, the safety and toxic effects on humans are also of concern with these increased applications. There is insufficient data regarding the effect of MgO NPs on reproductive organs, which are crucial aspects to the body's vital physiological functions. The present study was undertaken in male and female rats to assess the reproductive toxicological potential of two doses (low versus high) of MgO NPs on testicular and ovarian tissues. The toxicity was evaluated using histological, hormonal, and oxidative parameters., Material and Methods: In this work, magnesium oxide nanoparticles (MgO NPs) were synthesized by the sol-gel route and were characterized by X ray diffraction analysis (XRD) and Fourier transform infra-red spectroscopy (FTIR). Forty-eight adult Wister albino rats were used in this experiment which were divided into groups of male and female, and then further into control, low dose MgO NPs, and high dose MgO NPs. The low dose used was 131.5 mg/kg b.w. (1/10 LD50) while the high dose used was 263 mg/kg b.w. (1/5 LD50). All doses were given orally by gastric tube. After 4 weeks, blood samples were collected to investigate the level of sex hormones and both ovarian and testicular tissues were examined for variable oxidative parameters and histopathological changes by light microscopy., Results: The obtained findings showed that high dose of MgO NPs produced considerable changes in sex hormones and stress parameters in both male and female rats in comparison to the low dose and control groups. Histomorphometric analysis demonstrated the presence of histopathological alterations in the testicular and ovarian tissues., Conclusion: The results of this study showed dose-dependent adverse effects of MgO NPs on the testis and ovary both functionally and histopathologically as compared to the control rats.

The use of metal oxide nanoparticles (NPs) is steadily spreading, leading to increased environmental exposures to many organisms, including humans. To improve our knowledge of this potential hazard, we have evaluated the genotoxic risk of cerium oxide (CeO 2 NPs) and magnesium oxide (MgONPs) nanoparticle exposures using Drosophila as an in vivo assay model. In this study, two well-known assays, such as the wing somatic mutation and recombination test (wing-spot assay) and the single-cell gel electrophoresis test (comet assay) were used. As a novelty, and for the first time, changes in the expression levels of a wide panel of DNA repair genes were also evaluated. Our results indicate that none of the concentrations of CeO 2 NPs increased the total spot frequency in the wing-spot assay, while induction was observed at the highest dose of MgONPs. Regarding the comet assay, both tested NPs were unable to induce single DNA strand breaks or oxidative damage in DNA bases. Nevertheless, exposure to CeO 2 NPs induced significant increases in the expression levels of the Mlh1 and Brca2 genes, which are involved in the double-strand break repair pathway, together with a decrease in the expression levels of the MCPH1 and Rad51D genes. Regarding the effects of MgONPs exposure, the expression levels of the Ercc1, Brca2, Rad1, mu2, and stg genes were significantly increased, while Mlh1 and MCPH1 genes were decreased. Our results show the usefulness of our approach in detecting mild genotoxic effects by evaluating changes in the expression of a panel of genes involved in DNA repair pathways.

Introduction: Recently, zein-coated MgO nanowires were synthesized, which could be promising as an effective antimicrobial compounds that can be combined in the preparation of a diversity of new dental formulations. However, there is a deficiency of information concerning their toxicological profile regarding the human health. Objective: This in vivo study aimed to explore the hepato- and nephrotoxicity of low versus high doses of zein-coated MgO nanowires in rats. Materials and Methods: A 21-day recurrent dose toxicity research was carried out. Wistar rats were divided into 2 main groups, males and females ( n = 18). Each group was further subdivided into 3 subgroups: control, MgO-zein nanowires low dose, MgO-zein nanowires high dose. The low dose used was 100 mg/kg while the high dose used was 200 mg/kg. Results: The results showed that MgO-zein nanowires at both doses did not affect the electrolytes levels compared to the control levels. Also, they did not produce any significant alteration in liver function markers in both rats' genders. MgO-zein nanowires at both doses did not produce any effective alteration in serum creatinine in treated rats of both genders. Moreover, very minimal histological alterations were observed in both doses of MgO-zein nanowires in liver and kidney of both genders. Conclusion: Based on the observed safety of zein-coated MgO nanowires, it can be utilized as an effective antimicrobial compound that can be combined in the preparation of a diversity of new dental formulations.KEY MESSAGESMgO NPs are globally used in multiple fields including the therapeutic field.Zein has wide pharmaceutical applications especially coating the tablet over sugar.There are no cytotoxic studies that investigate MgO-zein nanowires safety until now.

In the present scenario, the development of eco-friendly multifunctional biocidal substances with low cost and high efficiency, has become the center of focus. This study is, focused on the synthesis of magnesium oxide (MgO) and chitosan-modified magnesium oxide (CMgO) nanoparticles (NPs), via a green precipitation process. In this process, leaves extract of Plumbago zeylanica L was, used as a nucleating agent. The MgO and CMgO NPs exhibit face-centered cubic structures, as confirmed by XRD studies. Morphologically, the FESEM and TEM images showed that the MgO and CMgO NPs were spherical, with an average particle size of ~40±2 and ~37±2 nm, respectively. EDX spectra were used to identify the elemental compositions of the nanoparticles. By using FTIR spectra, the Mg-O stretching frequency of MgO and CMgO NPs were observed at 431 and 435 cm -1 , respectively. The photoluminescence (PL) spectra of MgO and CMgO NPs, revealed oxygen vacancies at 499 nm and 519 nm, respectively, due to the active radicals generated, which were responsible for their biocidal activities. The toxicity effects of the nanoparticles developed, on cell viability (antibacterial and anticancer), were measured on the MCF-7 cell line and six different types of gram-negative bacteria. The antibacterial activities of the nanoparticles on: Klebsiella pneumoniae, Escherichia coli, Shigella dysenteriae, Pseudomonas aeruginosa, Proteus vulgaris and Vibrio cholerae bacteria, were studied with the well diffusion method. The MgO and CMgO NPs were tested on breast cancer cell line (MCF-7) via an MTT assay and it proved that CMgO NPs possess higher anticancer properties than MgO NPs. Overall, CMgO NPs showed a higher amount of cytotoxicity for both the bacterial and cancer cells when compared to the MgO NPs. Toxicity studies of fibroblast L929 cells revealed that the CMgO NPs were less harmful to the healthy cells when compared to the MgO NPs. These results suggest that biopolymer chitosan-modified MgO NPs can be used for healthcare industrial applications in order to improve human health conditions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The aim of this study was to prepare, characterize, and determine the in vitro anticancer effects of platinum-doped magnesia (Pt/MgO) nanoparticles. The chemical compositions, functional groups, and size of nanoparticles were determined using X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. Pt/MgO nanoparticles were cuboid and in the nanosize range of 30-50 nm. The cytotoxicity of Pt/MgO nanoparticles was determined via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the human lung and colonic cancer cells (A549 and HT29 respectively) and normal human lung and colonic fibroblasts cells (MRC-5 and CCD-18Co repectively). The Pt/MgO nanoparticles were relatively innocuous to normal cells. Pt/MgO nanoparticles downregulated Bcl-2 and upregulated Bax and p53 tumor suppressor proteins in the cancer cells. Pt/MgO nanoparticles also induced production of reactive oxygen species, decreased cellular glutathione level, and increased lipid peroxidation. Thus, the anticancer effects of Pt/MgO nanoparticles were attributed to the induction of oxidative stress and apoptosis. The study showed the potential of Pt/MgO nanoparticles as an anti-cancer compound., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The liver is the main organ responsible for drug and xenobiotic metabolism and detoxification in the body. There are many antiepileptic drugs and nanoparticles that have been reported to cause serious untoward biological responses and hepatotoxicity. The aim of this study is to investigate the potential toxic effect of aspartic acid-coated magnesium oxide nanoparticles (Mg nano) and valproate (valp) using an in vitro three-dimensional (3D) human liver organoid model and an in vivo pentylenetetrazole (PTZ)-induced convulsion model in rats. Here, 3D human liver organoids were treated with valp or valp + Mg nano for 24 h and then incubated with PTZ for an extra 24 h. As the in vivo model, rats were treated with valp, Mg nano, or valp + Mg nano for 4 weeks and then they were treated with PTZ for 24 h. Toxicity in the liver organoids was demonstrated by reduced cell viability, decreased ATP, and increased reactive oxygen species. In the rat convulsion model, results revealed elevated serum alanine aminotransferase and aspartate aminotransferase levels. Both the in vitro and in vivo data demonstrated the potential toxic effects of valp + Mg nano on the liver tissues., (© 2020 Wiley Periodicals LLC.)

Novel Magnesium Oxide (MgO) nanoparticles (NPs) modified with the polymer polyethylene glycol (PEG) were synthesized as carrier for the anticancer drug 2-Methoxyestradiol (2ME) to improve its clinical application. The functionalized NPs were characterized by Infrared spectroscopy with Fourier transform to elucidate the vibration modes of this conjugate, indicating the formation of the MgO-PEG-2ME nanocomposite. The studies of absorption and liberation determined that MgO-PEG-2ME NPs incorporated 98.51 % of 2ME while liberation of 2ME was constant during 7 days at pH 2, 5 and 7.35. Finally, the MgO-PEG-2ME NPs decreased the viability of the prostate cancer cell line LNCap suggesting that this nanocomposite is suitable as a drug delivery system for anticancer prostate therapy., Competing Interests: The authors have declared that no competing interests exist.

Nanoparticles (NPs) are increasingly used in different consumer-related areas, for instance in food packaging or as additives, because of their enormous potential. Magnesium oxide (MgO) is an EU-approved food additive (E number 530). It is commonly used as a drying agent for powdered foods, for colour retention or as a food supplement. There are no consistent results regarding the effects of oral MgO NP uptake. Consequently, the aim of this study was to examine the effects of MgO NPs in the HT29 intestinal cell line. MgO NP concentrations ranged from 0.001 to 100 μg/ml and incubation times were up to 24 h. The cytotoxic and genotoxic potential were investigated. Apoptotic processes and cell cycle changes were analysed by flow cytometry. Finally, oxidative stress was examined. Transmission electron microscopy indicated that there was no cellular uptake. MgO NPs had no cytotoxic or genotoxic effects in HT29 cells and they did not induce apoptotic processes, cell cycle changes or oxidative stress.

A rapid and ecofriendly fabrication of metal oxide nanoparticles using biogenic sources is the current trend being used to replace the toxic chemical method. The present study was carried out to synthesize magnesium oxide nanoparticles (MgONPs) using the marine brown algae Sargassum wighitii as the reducing and capping agent. The as-prepared MgONPs were characterized by spectroscopic and microscopic analyses. UV-visible spectrum of the MgONPs showed a sharp absorption peak at 322 nm. X- ray diffraction analysis illustrated that the MgONPs were crystalline in nature with a face-centered cubic structure. Presence of magnesium and oxygen were further confirmed by EDX profile. FTIR analysis showed the presence of functional groups specific for sulfated polysaccharides, which might be responsible for the synthesis of MgONPs. Zeta potential and dynamic light scattering analysis illustrated that the MgONPs were highly stable at 19.8 mV with an average size of 68.06 nm. MgONPs showed potent antibacterial activity and antifungal activities against human pathogens. Photocatalytic activity of MgONPs was witnessed by the quick degradation of the organic dye methylene blue on exposure to both sunlight and UV irradiation. MgONPs showed significant cytotoxicity against the lung cancer cell lines A549 in a dose dependent manner with the IC 50 value of 37.5 ± 0.34 μg/ml. Safety evaluation using peripheral blood mononuclear cells (PBMCs) illustrated the MgONPs to be non-toxic in nature. Overall, the results concluded that the MgONPs generated using marine algae have exhibited scope for multifaceted biological applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Allium cepa bioassay had been used from decades for the assessment of toxicants and their harmful effects on environment as well as human health. Magnesium oxide (MgO) particles are being utilized in different fields. However, reports on the adverse effects of MgO nanoparticles on the environment and mankind are scarce. Hence, the toxicity of MgO particles is of concern because of their increased utilization. In the current study, A. cepa was used as an indicator to assess the toxicological efficiency of MgO nano- and microparticles (NPs and MPs) at a range of exposure concentrations (12.5, 25, 50, and 100μg/mL). The toxicity was evaluated by using various bioassays on A. cepa root tip cells such as comet assay, oxidative stress and their uptake/internalization profile. Results indicated a dose dependent increase in chromosomal aberrations and decrease in mitotic index (MI) when compared to control cells and the effect was more significant for NPs than MPs (at p<0.05). Comet analysis revealed that the Deoxyribonucleic acid (DNA) damage in terms of percent tail DNA ranged from 6.8-30.1 over 12.5-100μg/mL concentrations of MgO NPs and was found to be significant at the exposed concentrations. A significant increase in generation of hydrogen peroxide and superoxide radicals was observed in accordance with the lipid peroxidation profile in both MgO NPs and MPs treated plants when compared with control. In conclusion, this investigation revealed that MgO NPs exposure exhibited greater toxicity on A. cepa than MPs., (Copyright © 2017. Published by Elsevier B.V.)

Increased utilization and exposure levels of Magnesium oxide (MgO) nanoparticles (NPs) to humans and environment may raise unexpected consequences. The goal of this study was to evaluate the toxicological implications of MgO NPs and MPs after 28 day repeated oral administration in Wistar rats with three different doses (250, 500, and 1000 mg/kg). The MgO particles were characterised systematically in order to get more insights of the toxicological behaviour. MgO NPs induced significant DNA damage and aberrations in chromosomes. Moreover, hepatic enzymes released into the systemic circulation caused significant elevated levels of physiological enzymes in blood. NPs could interfere with proteins and enzymes and alter the redox balance in cell environment. Significant accumulation of Mg in all tissues and clearance via urine and faeces was noted in size dependent kinetics. Oral administration of MgO NPs altered the biochemical and genotoxic parameters in dose dependent and gender independent manner., (© 2017 Wiley Periodicals, Inc.)

The modified MgO nanoparticles (m-MgO-NPs) by a copolymer containing the malic acid and low molecular weight poly(L-lactide) (poly(L-lactide-co-malic acid), PLMA) have been successfully prepared. MgO nanoparticles (MgO-NPs) were coated by the PLMA and m-MgO-NPs were uniformly dispersed in the PLLA matrix to a novel biocomposite material (PLLA/m-MgO-NPs) with more excellent interface bonding and uniformer dispersion, compared to the PLLA/MgO-NPs. Compared to neat PLLA and PLLA/MgO-NPs film, the m-MgO-NPs not only shown the obvious neutralization effect on the acidic solution in the degradation of the PLLA and better hydrophilicity, but also exhibited the higher cell viability and decrease the toxicity to the cell in the degradation process of PLLA in vitro. In addition, m-MgO-NPs also reduced the degradation rate of the PLLA. The mechanisms for the excellent dispersion of nanoparticles, enhanced pH stability, reduced degradation rate of the PLLA and the cell viability in vitro in the case of PLLA/m-MgO-NPs have also been proposed and discussed in detail.

We report a case of hypermagnesemia associated with the use of milk of magnesia in a male patient with end-stage renal disease. After experiencing nausea and vomiting, he developed severe bradycardia and then asystole. Resuscitation efforts were successful; however, he developed atrial fibrillation with severe widening of the QRS and diffuse ST elevation, hypothermia, hypotension and apnoea requiring intubation. Initial diagnoses included ST-elevation myocardial infarction, cardiogenic and/or septic shock and hyperkalaemia. However, serum magnesium was later found to be >4.1 mmol/L (equivalent to >10 mg/dL). He underwent haemodialysis (HD) to remove serum magnesium with remarkable overall improvement. Severe hypermagnesemia can manifest with severe bradycardia and asystole, shock, hypothermia and respiratory failure and can mimic acute coronary syndromes complicated with cardiogenic shock or septic shock. Therefore, clinicians should be aware of this life-threatening condition in patients with significant renal dysfunction. Timely treatment with HD is highly effective and lifesaving., (2017 BMJ Publishing Group Ltd.)

Worldwide researchers have rising concerns about magnesium-based materials, especially magnesium oxide (MgO) nanaoparticles, due to increasing usage as promising structural materials in various fields including cancer treatment. However, there is a serious lack of information about their toxicity at the cellular and molecular levels. In this study, the toxic potentials of MgO nanoparticles were investigated on liver (HepG2), kidney (NRK-52E), intestine (Caco-2), and lung (A549) cell lines. For the toxicological assessment, the following assays were used: the particle characterization by transmission electron microscopy, the determination of cellular uptake by inductively coupled plasma-mass spectrometry, MTT and neutral red uptake assays for cytotoxicity, comet assay for genotoxicity, and the determination of malondialdehyde (MDA), 8-hydroxydeoxyguanosine, protein carbonyl, and glutathione levels by enzyme-linked immune sorbent assays for the potential of oxidative damage and annexin V-fluorescein isothiocyanate (FITC) apoptosis detection assay with propidium iodide (PI) for apoptosis. Magnesium oxide nanoparticles were taken up by the cells depending on their concentration and agglomeration/aggregation potentials. Magnesium oxide nanoparticles induced DNA (≤14.27 fold) and oxidative damage. At a concentration of ≥323.39 µg/mL, MgO nanoparticles caused 50% inhibition in cell viability by 2 different cytotoxicity assays. The cell sensitivity to cytotoxic and genotoxic damage induced by MgO nanoparticles was ranked as HepG2 < A549 < Caco-2 < NRK-52E. Although it was observed that MgO nanoparticles induced apoptotic effects on the cells, apoptosis was not the main cell death. DNA damage, cell death, and oxidative damage effects of MgO nanoparticles should raise concern about the safety associated with their applications in consumer products., (© The Author(s) 2016.)

Purpose: To examine whether a difference exists between the in vivo biocompatibility of glass-ionomer cements (GICs) containing chlorhexidine (CHX) in different concentrations., Materials and Methods: Eighty-four male Wistar rats were distributed into 7 groups (n = 12) and received subcutaneous implants of small tubes containing different materials, as follows: Ketac control (K), Ketac-CHX 10% (K10), Ketac-CHX 18% (K18), Resilience control (R), Resilience-CHX 10% (R10), Resilience-CHX 18% (R18), Control (polyethylene). The animals were then sacrificed on post-insertion days 7, 15 and 30, and tissues were examined under an optical microscope for inflammatory infiltrate, edema, necrosis, granulation tissue, multinucleated giant cells, and collagen fibers. The results were statistically analyzed using Kruskal-Wallis and Dunn's tests (p < 0.05)., Results: Groups K18 and R18 showed larger areas of intense inflammatory infiltrate, with significant differences between group C and groups K18 and R18 (p = 0.007) at 7 days, and between groups C and K18 (p = 0.017) at 15 days. In terms of tissue repair, groups K18 and R18 demonstrated a lower quantity of collagen fibers with significant differences from group C (p = 0.019) at 7 days, and between group K18 and group C (p = 0.021) at 15 days., Conclusion: The 18% concentration of CHX was shown to have a toxic effect. The 10% concentration of CHX was shown to be suitable for tissue contact. The addition of CHX to the glass-ionomer cements is a highly promising method for obtaining of an antibacterial GIC for use in clinical practice.

Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Foot-and-mouth disease (FMD) is an extremely contagious viral disease of cloven-hoofed animals that can lead to huge economic losses in the livestock production. No antiviral therapies are available for treating FMD virus (FMDV) infections in animals. The antiviral effects of magnesium oxide nanoparticles (MgO NPs) on the FMDV were investigated in cell culture. The viability of the cells after MgO NP treatment was determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The direct effects of MgO NPs on the FMDV in extracellular (virucidal assay) and also different stages of virus replication (antiviral assay) were evaluated by plaque reduction assay. The results showed that MgO NPs were safe at concentrations up to 250 µg/ml in the Razi Bovine kidney cell line. The treatments with NPs indicated that the MgO NPs exerted in vitro virucidal and antiviral activities. Plaque reduction assay revealed that MgO NPs can inhibit FMDV by more than 90% at the early stages of infection such as attachment and penetration but not after penetration. The results of this study suggested that NPs might be applied locally as an antiviral agent in early stages of infection in susceptible animals.

In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO NPs) in rats following their exposure. NPs in phosphate buffered saline + 1% Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5 mg/kg into rat lungs and evaluated for various tissue damage markers like alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post-exposure intervals. A dose-dependant increase in ALP and LDH activity was observed in BAL fluids of rat lungs than sham control at all post-exposure periods (P <0.05), and a dose-dependant infiltration of interstitial lymphocytes, peribronchiolar lymphocytic infiltration, and dilated and/or congested vessels at 1 day post-exposure period, worsened at 1 week period, and were reduced at 1 month at histology, indicating the pulmonary toxicity of MgO NPs. In conclusion, MgO NPs exposure produced a dose-dependent pulmonary toxicity in rats and was comparable with that of Quartz particles., (© 2013 Wiley Periodicals, Inc.)

The knowledge on potential harmful effects of metallic nanomaterials lags behind their increased use in consumer products and therefore, the safety data on various nanomaterials applicable for risk assessment are urgently needed. In this study, 11 metal oxide nanoparticles (MeOx NPs) prepared using flame pyrolysis method were analyzed for their toxicity against human alveolar epithelial cells A549, human epithelial colorectal cells Caco2 and murine fibroblast cell line Balb/c 3T3. The cell lines were exposed for 24 h to suspensions of 3-100 μg/mL MeOx NPs and cellular viability was evaluated using. Neutral Red Uptake (NRU) assay. In parallel to NPs, toxicity of soluble salts of respective metals was analyzed, to reveal the possible cellular effects of metal ions shedding from the NPs. The potency of MeOx to produce reactive oxygen species was evaluated in the cell-free assay. The used three cell lines showed comparable toxicity responses to NPs and their metal ion counterparts in the current test setting. Six MeOx NPs (Al2O3, Fe3O4, MgO, SiO2, TiO2, WO3) did not show toxic effects below 100 µg/mL. For five MeOx NPs, the averaged 24 h IC50 values for the three mammalian cell lines were 16.4 µg/mL for CuO, 22.4 µg/mL for ZnO, 57.3 µg/mL for Sb2O3, 132.3 µg/mL for Mn3O4 and 129 µg/mL for Co3O4. Comparison of the dissolution level of MeOx and the toxicity of soluble salts allowed to conclude that the toxicity of CuO, ZnO and Sb2O3 NPs was driven by release of metal ions. The toxic effects of Mn3O4 and Co3O4 could be attributed to the ROS-inducing ability of these NPs. All the NPs were internalized by the cells according to light microscopy studies but also proven by TEM, and internalization of Co3O4 NPs seemed to be most prominent in this aspect. In conclusion, this work provides valuable toxicological data for a library of 11 MeOx NPs. Combining the knowledge on toxic or non-toxic nature of nanomaterials may be used for safe-by-design approach.

The purpose of this research was to evaluate toxicity of uncoated magnesium oxide nanoparticles (MgO NPs), MgO NPs coated with Peanut agglutinin (PNA) lectin, and PNA alone on the promastigotes of Leishmania major (L. major) and macrophages of BALB/c mice. On the other hand, antileishmanial property of uncoated MgO NPs, lectin coated MgO NPs, and PNA lectin alone was evaluated, and also macrophage activation was investigated after treatment with these materials by measurement of nitrite, H2O2, and some interleukins. This study showed that PNA lectin and lectin coated MgO NPs had approximately no toxicity on L. major and macrophages, but some toxic effects were observed for uncoated MgO NPs, especially at concentration of 500 µg/mL. Interestingly, lectin coated MgO NPs had the highest antileishmanial activity and macrophage activation, compared with uncoated MgO NPs and PNA lectin.

ZnMgO nanoparticles have shown potential for medical applications as an efficient antibacterial agent. In this work, we investigate the effect of water and two commonly used cell culture media on the physicochemical properties of ZnMgO nanoparticles in correlation with their cytotoxicity. In vacuum, ZnMgO nanopowder consists of MgO (nanocubes) and ZnO (nanotetrapods and nanorods) particles. Upon exposure to water or the Luria-Bertani solution, ZnO characteristic shapes were not observable while MgO nanocubes transformed into octahedral form. In addition, water caused morphological alternations in form of disordered and fragmented structures. This effect was directly reflected in UV/vis absorption properties of ZnMgO, implying that formation of new states within the band gap of ZnO and redistribution of specific sites on MgO surfaces occurs in the presence of water. In mammalian culture cell medium, ZnMgO nanoparticles were shapeless, agglomerated, and coated with surrounding proteins. Serum albumin was found to adsorb as a major but not the only protein. Adsorbed albumin mainly preserved its α-helix secondary structure. Finally, the cytotoxicity of ZnMgO was shown to strongly depend on the environment: in the presence of serum proteins ZnMgO nanopowder was found to be safe for mammalian cells while highly toxic in a serum-free medium or a medium containing only albumin. Our results demonstrate that nanostructured ZnMgO reaches living cells with modified morphology and surface structure when compared to as-synthesized particles kept in vacuum. In addition, its biocompatibility can be modulated by proteins from biological environment.

The toxicity of metal oxide nanomaterials and their antimicrobial activity is attracting increasing attention. Among these materials, MgO is particularly interesting as a low cost, environmentally-friendly material. The toxicity of MgO, similar to other metal oxide nanomaterials, is commonly attributed to the production of reactive oxygen species (ROS). We investigated the toxicity of three different MgO nanoparticle samples, and clearly demonstrated robust toxicity towards Escherichia coli bacterial cells in the absence of ROS production for two MgO nanoparticle samples. Proteomics data also clearly demonstrate the absence of oxidative stress and indicate that the primary mechanism of cell death is related to the cell membrane damage, which does not appear to be due to lipid peroxidation., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this present study, antioxidant status was evaluated in rat serum following exposure to magnesium oxide (MgO) nanoparticles. The lungs of rats were intratracheally instilled with (single dose) phosphate-buffered saline (PBS) + 1% of Tween 80 (solvent control) or MgO or carbonyl iron (negative control) or quartz particles (positive control) at a dose of 1 and 5 mg/kg of body weight. The blood samples were collected at 1, 7, and 30 days of postinstillation of nanoparticles after their exposure, and different parameters were estimated to assess the oxidative stress induced by the instillation of MgO. Exposure of rats to MgO produced a significant (p < 0.05) dose-dependent reduction in blood total antioxidant capacity, superoxide dismutase, and catalase activity levels than PBS + 1% Tween 80 control group. This reduction in the antioxidant capacity in MgO nanoparticle-exposed rats indicates the reduction in antioxidant defense mechanisms due to the instillation of MgO. These results indicate that exposure to MgO nanoparticles induces oxidative stress by reducing the total antioxidant capacity in rats. The findings suggest possible occupational health hazard in chronic exposures.

Nano-MgO is a good bactericide but with strong alkalinity in water due to its rapid hydrolysis. To control its hydrolysis rate and keep its bactericidal properties, we synthesized nano-MgO microspheres using chitosan-alginate system in this study. The synthesized nano-MgO release-controlled microspheres (nMgO-RCM) were with 0.98-1.20mm of particle sizes. Also, their embedding ratio and loading percentage was 63.52% and 12.27%, respectively. Based on the characterization results, nano-MgO was only observed on surface of the nMgO-RCM. Its release rate from the nMgO-RCM could be controlled by the chitosan-alginate system, and the observed rate constant (k(obs)) increased from 0.0289 h(-1) to 0.0358 h(-1) with the increment of the dosage from 10 mg L(-1) to 80 mg L(-1). Furthermore, the nMgO-RCM could maintain pH value lower than 8.5 and colony counts less than 20 CFU mL(-1) for at least 120 h., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Current hazard characterisation of nanoparticles (NP) is predominantly based on in vitro test systems, being established for small molecules of drugs and chemicals. However, specific physicochemical properties of NP may result in interference with assay components, biomarkers, or detection systems. In the present study, six types of (nano)particles were screened in RAW 264.7 macrophages by common cytotoxicity methods (WST-1, LDH). Our specific focus was on the investigation of apoptosis (analysis of hypodiploid DNA, phosphatidylserine exposure, caspase 3/7 activation, and Cell Death Detection ELISA). Assays were validated by the well-known apoptosis inducer staurosporine. Our results show that ZnO, DQ12 quartz and amorphous silica are cytotoxic with strong indications for apoptotic effects in RAW 264.7 macrophages, whereas toxicity was absent for MgO. For fine as well as ultrafine TiO(2), no apoptotic effects could be detected except for induction of DNA fragmentation. The results of our study demonstrate the necessity to control on a case-by-case basis for assay interference to avoid misinterpretation of specific in vitro test findings. To obtain valid statements on the potential induction of apoptosis by specific NP the measurement of multiple endpoints is a prerequisite., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The MgO nanoparticles are widely used in many fields. However, the toxicity of these nanoparticles to cells and organs remains fairly undiscovered. In this study, the cytotoxicity of MgO nanoparticles on human umbilical vein endothelial cells (HUVECs) in vitro was examined. The morphology and size of MgO nanoparticles were analysed by the transmission electron microscope (TEM) and nanoparticle size analyser. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 h-tetrazolium bromide) assay, 4',6-diamidino-2-phenylindole (DAPI) staining analysis, NO release and total antioxidation competence (T-AOC) assay were used to evaluate the cytotoxicity of MgO nanoparticles. The results showed that most MgO nanoparticles were spherical with agglomerated state and the diameter of single particle was about 100 nm. Meanwhile, low concentration (below 200 [micro sign]g/ml) of MgO nanoparticles suspension showed no cytotoxicity by MTT assay. However, once the concentration of MgO nanoparticles was higher than 500 [micro sign]g/ml, the relative growth rate was lower than the control. The DAPI staining analysis results showed no significant difference of the cells morphology between the groups with or without MgO nanoparticles. In addition, the MgO nanoparticles significantly enhanced the NO release and T-AOC content of the HUVECs. The testing results indicated that low concentration of MgO nanoparticles exhibited non-cytotoxicity.

This paper reports data on the relative ability of CaO, CaCl2, MgO, MgCl2, TiO2, and hectorite (SHCa-1) to induce oxidative stress (as determined by lipid peroxidation, LP) in biological matrices. The effectiveness of structural (oxide form) versus soluble Ca and Mg to induce LP is compared. An assessment on cytotoxicity as affected by soluble and structural Ca, Mg, TiO2 and SHCa-1 is also addressed. LP was screened and monitored using the Thiobarbituric Acid Reactive Substances (TBARS). The extent of TBARS production was found to vary with the type and initial concentration of the soluble or structural cation, Ca or Mg respectively. Obtained results showed higher magnitude values for the latter set of experiments. In the presence of TiO2 no significant TBARS production was detected pointing out a negligible effect of TiO2 on LP. At solid concentrations ca. 100 ppm, CaO appears to be more effective than SHCa-1 to induce LP. By contrast at ca. 25 ppm, MgO appears to be more effective than the clay mineral. The SHCa-1 LP-inducing activity has been proven to closely relate to structural Ca. The prevalence of mechanisms that may induce LP but not cytotoxicity (as determined by cell growth inhibition) was also addressed. Results on cell growth inhibition as affected by soluble and structural Ca, Mg, TiO2 and hectorite provide evidence to support that structural Ca or Mg brings about significantly higher variations than soluble Ca., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The dermal absorption potential of a nanocrystalline magnesium oxide (MgO) and titanium dioxide (TiO(2)) mixture in dermatomed human skin was assessed in vitro using Bronaugh-type flow-through diffusion cells. Nanocrystalline material was applied to the skin surface at a dose rate of 50 mg/cm(2) as a dry powder, as a water suspension, and as a water/surfactant (sodium lauryl sulfate) suspension, for 8 hours. Dermal absorption of nanocrystalline MgO and TiO(2) through human skin with intact, functional stratum corneum was not detectable under the conditions of this experiment.

Although the use of periodontal dressings is currently limited, there are some indications for their use. Selection of any material that will have direct contact with live tissues, such as periodontal dressings, should be careful in order to allow surgical wound healing. The aim of this study was to evaluate the intensity of inflammatory response and bone formation in tooth sockets of rats after implantation of three periodontal dressings. After removal of the right maxillary incisors of 84 male rats, each tooth socket received implantation of a polyethylene tube, 63 of which were filled with non-eugenol periodontal dressing and the remaining 21 tubes remained empty (control group). Histological evaluation assessed the intensity of inflammatory response and presence and location of bone tissue formation at postoperative periods of 7, 14 and 28 days. Statistical analysis was performed by the Kruskal-Wallis test at 5% significance level. Regarding the inflammatory infiltrate, at 28 days, there was statistically significant difference between one of periodontal dressings and control group (p<0.05). Analysis of postoperative periods, showed that the control group presented statistically significant reduction in the inflammatory infiltrate comparing the 14- and 28-day periods (p<0.05). Regarding bone tissue formation, there was difference in control group between the 7- and 28-day periods (p<0.05). Within the experimental conditions, it may be concluded that no differences were found in the inflammatory response among the groups at 7 and 14 days and that Voco pac dressing induced a more intensive inflammatory reaction at 28 days.

Glass-ionomer cements are widely used in dentistry as restorative materials and adhesives for composite restorations. A number of genotoxicity studies have been conducted using these materials with results conflicting so far. Thus, the approach was aimed to look at 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 mouse lymphoma cells in vitro for 1 h at 37 degrees C. Data were assessed by Kruskall-Wallis non-parametric test. The results showed that all powders assayed did not show genotoxic effects. On the other hand, the liquid from Vitrebond at 0.1% dilution caused an increase of DNA injury. Significant statistically differences (P < 0.05) in cytotoxicity provoked by all powders tested were observed for exposure at 1,000 micro g mL(-1) concentration and 100 micro g mL(-1) for Ketac Molar. With respect to liquids of glass-ionomer cements evaluated, the major toxic effect on cell viability was produced at 1%, beginning at the dilution of 0.5% for Vitrebond. Taken together, these results support the notion that some components of glass-ionomer cements show both genotoxic and cytotoxic effects in higher concentrations.

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( composite function)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 microg/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 1,000 microg/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.

Background: The current hard tissue implants research aims to accelerate bone healing by designing surfaces that are bioactive. However, the role of the inflammatory response to these surfaces is so far incompletely described., Purpose: The aim of the study was to evaluate early inflammatory response in vitro to a potentially bioactive surface--an anodized surface with Mg ions incorporated (anodized/Mg)--and to compare it to a turned, a blasted, and an anodized surface., Materials and Methods: An interferometer was used for topographical characterizations. The disks were incubated with human mononuclear cells. Adherent cells were investigated with respect to number of cells, viability, differentiation, and cytokine production with and without lipopolysaccharide stimulation after 24 and 72 hours., Results: The number of adhered mononuclear cells differed significantly between the different modified surfaces, with the highest number on the anodized surface. However, there were no significant differences in cytokine production and differentiation between the different modified surfaces. The amount of anti-inflammatory mediator interleukin-10 remained over time, while the number of cells and pro-inflammatory cytokine tumor necrosis factor-alpha decreased. The cells were viable on all surfaces, respectively., Conclusion: The anodized surfaces with and without Mg ions showed an increased cell adherence, however, otherwise an inflammatory response similar to the turned and blasted surfaces. Furthermore, the potentially bioactive anodized/Mg surface showed a similar response to the TiUnite-like anodized surface despite the former having a surface roughness of a smoother character.

Objective: This in vitro study characterized the hemolysis and cytotoxicity of ZUT, an experimental glass ionomer cement (GIC) sealer with an added antimicrobial-containing zeolite (0.2% Zeomic w/w)., Study Design: ZUT, Ketac-Cem (GIC component of ZUT), Ketac-Endo, and two AH 26 sealer formulations were tested at various times after mixing. Hemolysis produced by standardized specimens was determined spectrophotometrically (n = 6/material). Cytotoxicity was assessed by using a Millipore Filter test with a HeLa cell monolayer (n = 10/material). Tests were repeated, and results were analyzed with a one-way analysis of variance (alpha = .05)., Results: Disks of AH 26 containing silver produced the most hemolysis of all test groups (P < .0001). Compared to controls, GICs and AH 26 formulations were noncytotoxic at 1 and 6 hours after mixing, respectively (P > .05). Addition of Zeomic did not increase the cytotoxic and hemolytic activity of Ketac-Cem (P > .05)., Conclusion: Overall results suggest ZUT is less cytotoxic than AH 26 and possesses characteristics similar to the other GIC formulations tested.

Isofrax and Insulfrax are two new synthetic vitreous fibers (SVFs) developed for high-temperature insulation (1800-2300 degrees F) applications. In an attempt to significantly reduce or eliminate the potential of adverse health effects, these two fibers were specifically designed to have high solubility and, thus, low in vivo biodurability. In this paper, we review the effects of chemical composition on biodurability, in vitro fiber dissolution rates (K(dis)), and the relevance and relationship of K(dis) to pulmonary fibrosis and lung tumors in chronic rat inhalation studies. We also examine the correlations between K(dis) and weighted in vivo half-life (t(0.5)) of long fibers (>20 microm) and their relation to pulmonary effects in chronic rat inhalation bioassays. Predictions for outcomes of inhalation bioassays and development of nonsignificant risk levels of exposure are provided. Additionally, justification for the use of inhalation versus noninhalation animal data is provided as is a brief review of human health effects of SVFs. We conclude, inter alia, that Isofrax and Insulfrax have low biodurability, would not be expected to produce either pulmonary fibrosis or lung tumors in a well-designed animal inhalation bioassay, have weighted half-lives beneath the threshold established by the European Union for classification as a carcinogen, and based on epidemiological data for SVFs would not be expected to result in incremental cancer in human cohorts. Finally, it is estimated that approximately 90% of workplace exposure concentrations of these materials would be beneath 1 f/cc. At a concentration of 1 f/cc, neither fiber would be expected to result in an incremental working lifetime cancer risk greater than 10(-5)., (Copyright 1999 Academic Press.)

Purpose of this investigation was to determine the cytocompatibility of various periodontal dressing materials by means of human primary gingival fibroblasts (HGF), human osteoblast-like cells (HObl) derived from the alveolar bone, and permanent 3T3 mouse fibroblasts (3T3). Cell culture medium extracts (time periods of extraction: day 1 and between day 2 and day 8 after setting) as well as solid specimens of the following materials were investigated: Coe-pak, Voco pac, Peripac, and Barricaid. Responses of cultures exposed for 24 h and 48 h to these materials were monitored by the fluorescent dyes H33342 and sulforhodamin 101 as well as by light microscopy. It was found that most extracts of Voco pac, Peripac, and Barricaid did not inhibit growth of HGF. Coe-Pak, however, clearly reduced the proliferation of HGF compared to untreated controls. Peripac decreased growth of HObl whereas Coe-Pak, Voco pac, and Barricaid caused no cytotoxic alterations in any of the test assays. Contrary to HGF and HObl, 3T3 cells were much more irritated by the test materials. But the light-curing resinous material Barricaid reduced proliferation of 3T3-fibroblasts only slightly. Our data indicate that Barricaid is exceedingly cytocompatible, whereas all other materials revealed moderate or severe cytotoxic effects according to the cell type.

With the aid of laser-Doppler-flowmetry we are able to determine changes in the microcirculation of the tooth pulp. This method can also be used for testing the histocompatibility of dental materials. The zinkoxiphosphate cement Tenet and the glass ionomer cement Ketac-Cem are examined for tissue tolerance. This is done by determining the incisal and apical changes in pulpal microcirculation. Tenet has almost no discernible effect on pulpal microcirculation. Ketac-Cem causes a longlasting hyperaemia in half of the cases which seems to depend on the depth of cavity preparation.

Laser-Doppler-flowmetry enables us to assess microcirculatory changes in the tooth pulp. This method can also be used for testing the histocompatibility of dental materials. The acid components of Tenet and Ketac-Cem are examined for tissue tolerance. This is done by assessing the incisal and apical changes in pulpal microcirculation. The phosphoric acid of Tenet causes an almost complete collapse of the incisal microcirculation just a short time after its application. The tartrate of Ketac-Cem causes long-lasting hyperaemia, whereas the acryl-maleinate-copolymer has no discernible effects.

It is well known that infection-induced stones (apatite, struvite), uric acid and cystine calculi in the urinary tract can be managed by the use of certain chemical solutions. We investigated the effects of various acidic and alkaline solutions on the rabbit urothelium. Acidic solutions (pH: 4.2) caused more urothelial injury as compared to alkaline solutions (pH: 7.6). Ureteral injury was more severe than the bladder injury. Magnesium-containing solutions caused less injury to the urothelium.