Relationship between the nutritional state of elderly people in need of support or nursing care and jaw-opening force and tongue pressure.

[Purpose] We hypothesized that an association exists between the nutritional state of elderly people and the deterioration in the swallowing function associated with sarcopenia, which is reflected by the strength of the tongue and suprahyoid muscles. Therefore, we conducted a comparative study of the nutritional state and swallowing muscle strength. [Participants and Methods] The participants in this study were 25 elderly people in need of support or nursing care, situated at a geriatric health service facility, who were able to understand instructions and ate three meals per day orally. We evaluated the strength of the tongue muscles using a tongue pressure measurement device and the strength of the suprahyoid muscles by measuring the jaw-opening force. The nutritional state was evaluated using the Mini Nutritional Assessment. [Results] There was a significant correlation between the Mini Nutritional Assessment score and the jaw-opening force. Conversely, no correlation was found between the Mini Nutritional Assessment score and the tongue pressure. [Conclusion] The significant correlation between the Mini Nutritional Assessment score and the jaw-opening force suggests that the strength of the suprahyoid muscles, which reflects the swallowing function and jaw-opening force, deteriorates with age and is affected by the nutritional state. This suggests that the nutritional state could be an important indicator for the evaluation of the swallowing function.

Rapid Enzyme-linked Immunosorbent Assays for Diagnosis of Diabetes in a Compact Disc-shaped Microfluidic Device.

We have developed a compact disc (CD)-shaped microfluidic device for multiple, rapid enzyme-linked immunosorbent assays (ELISA). The device has a versatile design that can be adapted for the detection of various proteins by selecting the push-in-type reaction parts and appropriate reagents for each target. In this paper, we report the rapid quantification of insulin, adiponectin, and leptin, which can be used for the early diagnosis of diabetes, in human serum in only 16 min with our device.

Ascorbic acid prevents zinc oxide nanoparticle-induced intracellular oxidative stress and inflammatory responses.

Exposure to zinc oxide nanoparticles (ZnO NPs) promotes acute pulmonary toxicity through oxidative stress and inflammation. Furthermore, dissolved zinc from ZnO NPs induces the formation of intracellular reactive oxygen species (ROS). We previously reported that supplemental ascorbic acid (AA) inhibits ZnO NP-induced acute pulmonary toxicity in a rat model; however, the mechanism of this action remains unclear. Therefore, we investigated the effects of AA on ZnO NP-induced cytotoxicity in human lung carcinoma A549 cells. AA was found to suppress intracellular production of ROS, and thus reduce the subsequent inflammation of ZnO NPs. However, intracellular Zn2+ concentrations were higher in AA-treated cells than in AA-untreated cells. AA was found to react with Zn2+ but not with the ZnO NPs themselves. These results suggest the possibility that AA-chelated extracellular Zn2+ and the Zn-AA complex was readily taken up into cell. Even if the intracellular Zn2+ level was high, cytotoxicity might be reduced because the Zn-AA complex was stable. Co-treatment of AA to A549 inhibited ROS production and subsequent intracellular inflammatory responses. These results are consistent with those previously reported from an in vivo model. Thus, two possibilities can be considered about the cytotoxicity-reducing the effect of AA: antioxidant efficacy and chelating effect.

Ascorbic acid attenuates acute pulmonary oxidative stress and inflammation caused by zinc oxide nanoparticles.

OBJECTIVES: It is known that inhalation of zinc oxide nanoparticles (ZnO NPs) induces acute pulmonary dysfunction, including oxidative stress, inflammation, and injury, but there are no reports on how to prevent these adverse effects. We have previously reported that the pulmonary symptoms caused by ZnO NPs were associated with oxidative stress; in the present study, we therefore investigated the use of ascorbic acid (AA), which is known as vitamin C, to prevent these toxic effects. METHODS: A ZnO NP dispersion was introduced into rat lungs by intratracheal injection, and thereafter a 1% aqueous AA solution was given as drinking water. Bronchoalveolar lavage fluid was collected at 1 day and 1 week after injection, and lactate dehydrogenase (LDH) activity, heme oxygenase-1 (HO-1), and interleukin-6 (IL-6) levels were measured. In addition, expression of the chemokine cytokine-induced neutrophil chemoattractants (CINCs), HO-1, and metallothionein-1 (MT-1) genes in the lungs were determined. RESULTS: Acute oxidative stress induced by ZnO NPs was suppressed by supplying AA. Increases in LDH activity and IL-6 concentration were also suppressed by AA, as was the expression of the CINC-1, CINC-3, and HO-1 genes. CONCLUSIONS: Oral intake of AA prevents acute pulmonary oxidative stress and inflammation caused by ZnO NPs. Intake of AA after unanticipated exposure to ZnO NPs is possibly the first effective treatment for the acute pulmonary dysfunction they cause.

Singlet-oxygen-derived products from linoleate activate Nrf2 signaling in skin cells.

Linoleates are required for normal mammalian health and development, but they are also prone to oxidation, resulting in biologically active metabolites such as hydroxyoctadecadienoic acids (HODEs). To investigate the biological activity of 9-EZ-HODE, 10-EZ-HODE, 12-ZE-HODE, and 13-ZE-HODE, the metabolites of singlet-oxygen-derived products from linoleates, we assessed adaptive cytoprotection in HaCaT skin cells. Treating HaCaT cells with sublethal concentrations of 10-EZ-HODE and 12-ZE-HODE, which are singlet-oxygen-mediated specific oxidation metabolites of linoleates, but not 9-EZ-HODE and 13-ZE-HODE, caused resistance to hydrogen peroxide-induced oxidative damage. Microarray analysis of HaCaT cells revealed that 10-EZ-HODE and 12-ZE-HODE induced cellular antioxidant genes that are responsive to nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), such as heme oxygenase-1 and glutathione synthesis enzymes. Although 10-EZ-HODE and 12-ZE-HODE did not induce Nrf2 mRNA, treatment with these metabolites increased the intranuclear expression of Nrf2. These results suggest that 10-EZ-HODE and 12-ZE-HODE initiate adaptive responses that reduce the damage caused by oxidative stress.

Cellular effects of industrial metal nanoparticles and hydrophilic carbon black dispersion.

The effects of five types of metal nanoparticles, gold (Au), silver (Ag), platinum (Pt), Au-polyvinylpyrrolidone (PVP) colloid, and Pt-PVP colloid, and two types of hydrophilic carbon black on cell behavior were examined. Stable nanoparticle dispersions were prepared and applied to the culture medium of human keratinocyte (HaCaT) and human lung carcinoma (A549) cells for 6 and 24 hr. Then, the mitochondrial activity (MTT assay) and the induction of cellular oxidative stress were examined. The exposure to Au and Ag decreased mitochondrial activity. The exposure to Pt nanoparticles induced an increase in the intracellular reactive oxygen species (ROS) level. In contrast, Au-PVP, Pt-PVP, and hydrophilic carbon black did not exhibit any effects. The observed increase in the ROS level induced by the Pt nanoparticles in this study contradicted our previous findings, in which Pt did not produce chemically reactive molecules. Some nanoparticle dispersions included chemicals as the dispersant, which is used in industrial applications. In some cases, the dispersing agent may have caused some cellular effects. Adsorption of agents on the surface of the nanoparticles may be an important factor here. Hence, the cellular effects of industrial nanoparticles should be evaluated carefully.

Evaluation of cellular effects of silicon dioxide nanoparticles.

Silica nanoparticles (nSiO2s) are an important type of manufactured nanoparticles. Although there are some reports about the cytotoxicity of nSiO2, the association between physical and chemical properties of nSiO2s and their cellular effects is still unclear. In this study, we examined the correlation between the physiochemical properties and cellular effects of three kinds of amorphous nSiO2s; sub-micro-scale amorphous SiO2, and micro-scale amorphous and crystalline SiO2 particles. The SiO2 particles were dispersed in culture medium and applied to HaCaT human keratinocytes and A549 human lung carcinoma cells. nSiO2s showed stronger protein adsorption than larger SiO2 particles. Moreover, the cellular effects of SiO2 particles were independent of the particle size and crystalline phase. The extent of cell membrane damage and intracellular ROS levels were different among nSiO2s. Upon exposure to nSiO2s, some cells released lactate dehydrogenase (LDH), whereas another nSiO2 did not induce LDH release. nSiO2s caused a slight increase in intracellular ROS levels. These cellular effects were independent of the specific surface area and primary particle size of the nSiO2s. Additionally, association of solubility and protein adsorption ability of nSiO2 to its cellular effects seemed to be small. Taken together, our data suggest that nSiO2s do not exert potent cytotoxic effects on cells in culture, especially compared to the effects of micro-scale SiO2 particles. Further studies are needed to address the role of surface properties of nSiO2s on cellular processes and cytotoxicity.

Evaluation of cellular influences caused by calcium carbonate nanoparticles.

The cellular effects of calcium carbonate (CaCO3) nanoparticles were evaluated. Three kinds of CaCO3 nanoparticles were employed in our examinations. One of the types of CaCO3 nanoparticles was highly soluble. And solubility of another type of CaCO3 nanoparticle was lower. A stable CaCO3 nanoparticle medium dispersion was prepared and applied to human lung carcinoma A549 cells and human keratinocyte HaCaT cells. Then, mitochondrial activity, cell membrane damage, colony formation ability, DNA injury, induction of oxidative stress, and apoptosis were evaluated. Although the influences of CaCO3 nanoparticles on mitochondrial activity and cell membrane damage were small, "soluble" CaCO3 nanoparticles exerted some cellular influences. Soluble CaCO3 nanoparticles also induced a cell morphological change. Colony formation was inhibited by CaCO3 nanoparticle exposure. In particular, soluble CaCO3 nanoparticles completely inhibited colony formation. The influence on intracellular the reactive oxygen species (ROS) level was small. Soluble CaCO3 nanoparticles caused an increase in C/EBP-homologous protein (CHOP) expression and the activation of caspase-3. Moreover, CaCO3 exposure increased intracellular the Ca²âº level and activated calpain. These results suggest that cellular the influences of CaCO3 nanoparticles are mainly caused by intracellular calcium release and subsequently disrupt the effect of calcium signaling. In conclusion, there is possibility that soluble CaCO3 nanoparticles induce cellular influences such as a cell morphological change. Cellular influence of CaCO3 nanoparticles is caused by intracellular calcium release. If inhaled CaCO3 nanoparticles have the potential to influence cellular events. However, the effect might be not severe because calcium is omnipresent element in cell.

Attenuation of lipopolysaccharide (LPS)-induced cytotoxicity by tocopherols and tocotrienols.

Lipopolysaccharide (LPS) induces host inflammatory responses and tissue injury and has been implicated in the pathogenesis of various age-related diseases such as acute respiratory distress syndrome, vascular diseases, and periodontal disease. Antioxidants, particularly vitamin E, have been shown to suppress oxidative stress induced by LPS, but the previous studies with different vitamin E isoforms gave inconsistent results. In the present study, the protective effects of α- and γ-tocopherols and α- and γ-tocotrienols on the oxidative stress induced by LPS against human lung carcinoma A549 cells were studied. They suppressed intracellular reactive oxygen formation, lipid peroxidation, induction of inflammatory mediator cytokines, and cell death. Tocopherols were incorporated into cultured cells much slower than tocotrienols but could suppress LPS-induced oxidative stress at much lower intracellular concentration than tocotrienols. Considering the bioavailability, it was concluded that α-tocopherol may exhibit the highest protective capacity among the vitamin E isoforms against LPS-induced oxidative stress.

In vitro evaluation of cellular influences induced by stable fullerene C70 medium dispersion: induction of cellular oxidative stress.

Fullerene is one of the nanocarbons that is expected to have applications to life science, such as nanomedicines. An understanding of the cellular influences of fullerene is essential for its application to life science. Although C60 and C70 are both known as major fullerenes, most previous reports about the cellular influences of fullerene are about C60. Thus we evaluated the cellular influences caused by C70. A stable and uniform C70-medium dispersion was prepared. The dispersion was stable for the experimental period. Mitochondrial activity (MTT assay), colony forming ability (clonogenic assay), induction of oxidative stress (intracellular ROS and lipid peroxidation levels) and cellular uptake (TEM observation) in human keratinocyte HaCaT and lung carcinoma A549 cells exposed to C70 were examined. C70 did not influence mitochondrial activity. On the other hand, C70 dispersion inhibited colony formation at the concentration of 25.2 µg mL(-1). Exposure to C70 dispersion caused an increase in intracellular ROS and lipid peroxidation levels. The induction of intracellular ROS level was inhibited by pre-treatment of the cells by antioxidants. TEM observations of C70 exposed cells showed cellular uptake of C70. These results were similar to the cellular influences caused by C60 which were reported by us previously. Although C70 did not cause cell death, it caused the induction of intracellular oxidative stress.

Chromium(III) oxide nanoparticles induced remarkable oxidative stress and apoptosis on culture cells.

Chromium(III) oxide (Cr(2)O(3)) is used for industrial applications such as catalysts and pigments. In the classical form, namely the fine particle, Cr(2)O(3) is insoluble and chemically stable. It is classified as a low-toxicity chromium compound. Recently, industrial application of nanoparticles (a new form composed of small particles with a diameter of ≤100 nm, in at least one dimension) has been increasing. Cellular effects induced by Cr(2)O(3) nanoparticles are not known. To shed light upon this, the release of soluble chromium from Cr(2)O(3) nano- and fine-particles in culture medium was compared. Fine Cr(2)O(3) particles were insoluble in the culture medium; on the contrary, Cr(2)O(3) nanoparticles released soluble hexavalent chromium into the culture medium. Cr(2)O(3) nanoparticles showed severe cytotoxicity. The effect of Cr(2)O(3) nanoparticles on cell viability was higher than that of fine particles. Cr(2)O(3) nanoparticles showed cytotoxicity equal to that of hexavalent chromium (K(2)Cr(2)O(7)). Human lung carcinoma A549 cells and human keratinocyte HaCaT cells showed an increase in intracellular reactive oxygen species (ROS) level and activation of antioxidant defense systems on exposure to Cr(2)O(3) nanoparticles. Exposure of Cr(2)O(3) nanoparticles led to caspase-3 activation, showing that the decrease in cell viability by exposure to Cr(2)O(3) nanoparticles was caused by apoptosis. Cellular responses were stronger in the Cr(2)O(3) nanoparticles-exposed cells than in fine Cr(2)O(3) - and CrCl(3) -exposed cells. Cellular uptake of Cr(2)O(3) particles were observed in nano- and fine-particles. The cellular influence of the extracellular soluble trivalent chromium was lower than that of Cr(2)O(3) nanoparticles. Cr(2)O(3) nanoparticles showed cytotoxicity by hexavalent chromium released at outside and inside of cells. The cellular influences of Cr(2)O(3) nanoparticles matched those of hexavalent chromium. In conclusion, Cr(2)O(3) nanoparticles have a high cytotoxic potential.

Association of zinc ion release and oxidative stress induced by intratracheal instillation of ZnO nanoparticles to rat lung.

Zinc oxide (ZnO) nanoparticles are one of the important industrial nanoparticles. The production of ZnO nanoparticles is increasing every year. On the other hand, it is known that ZnO nanoparticles have strong cytotoxicity. In vitro studies using culture cells revealed that ZnO nanoparticles induce severe oxidative stress. However, the in vivo influence of ZnO nanoparticles is still unclear. In the present study, rat lung was exposed to ZnO nanoparticles by intratracheal instillation, and the influences of ZnO nanoparticles to the lung in the acute phase, particularly oxidative stress, were examined. Additionally, in vitro cellular influences of ZnO nanoparticles were examined using lung carcinoma A549 cells and compared to in vivo examinations. The ZnO nanoparticles used in this study released zinc ion in both dispersions. In the in vivo examinations, ZnO dispersion induced strong oxidative stress in the lung in the acute phase. The oxidative stress induced by the ZnO nanoparticles was stronger than that of a ZnCl(2) solution. Intratracheal instillation of ZnO nanoparticles induced an increase of lipid peroxide, HO-1 and alpha-tocopherol in the lung. The ZnO nanoparticles also induced strong oxidative stress and cell death in culture cells. Intracellular zinc level and reactive oxygen species were increased. These results suggest that ZnO nanoparticles induce oxidative stress in the lung in the acute phase. Intracellular ROS level had a high correlation with intracellular Zn(2+) level. ZnO nanoparticles will stay in the lung and continually release zinc ion, and thus stronger oxidative stress is induced.

Association of the physical and chemical properties and the cytotoxicity of metal oxide nanoparticles: metal ion release, adsorption ability and specific surface area.

Association of cellular influences and physical and chemical properties were examined for 24 kinds of industrial metal oxide nanoparticles: ZnO, CuO, NiO, Sb(2)O(3), CoO, MoO(3), Y(2)O(3), MgO, Gd(2)O(3), SnO(2), WO(3), ZrO(2), Fe(2)O(3), TiO(2), CeO(2), Al(2)O(3), Bi(2)O(3), La(2)O(3), ITO, and cobalt blue pigments. We prepared a stable medium dispersion for each nanoparticle and examined the influence on cell viability and oxidative stress together with physical and chemical characterizations. ZnO, CuO, NiO, MgO, and WO(3) showed a large amount of metal ion release in the culture medium. The cellular influences of these soluble nanoparticles were larger than insoluble nanoparticles. TiO(2), SnO(2), and CeO(2) nanoparticles showed strong protein adsorption ability; however, cellular influences of these nanoparticles were small. The primary particle size and the specific surface area seemed unrelated to cellular influences. Cellular influences of metal oxide nanoparticles depended on the kind and concentrations of released metals in the solution. For insoluble nanoparticles, the adsorption property was involved in cellular influences. The primary particle size and specific surface area of metal oxide nanoparticles did not affect directly cellular influences. In conclusion the most important cytotoxic factor of metal oxide nanoparticles was metal ion release.

Evaluation of cellular influences of platinum nanoparticles by stable medium dispersion.

Platinum nanoparticles have industrial application, for example in catalysis, and are used in consumer products such as cosmetics and supplements. Therefore, among the many nanoparticles, platinum is one of the more accessible nanoparticles for consumers. Most platinum nanoparticles that are used in cosmetics and supplements which have an anti-oxidant activity are modified particles. However, the cellular influences of pristine platinum nanoparticles are still unclear, although it has been reported that platinum nanoparticles induce oxidative stress. In this study, we investigated the cellular influences induced by pure pristine platinum nanoparticles. Platinum nanoparticles of 100% purity were dispersed in a cell culture medium and stable medium dispersion was obtained. The platinum nanoparticle medium dispersion was applied to two kinds of cultured cells, A549 and HaCaT cells, and the cellular influences were examined. Cell viability (MTT assay), cell proliferation (clonogenic assay), apoptosis induction (caspase-3 activity), intracellular ROS level (DCFH assay), and lipid peroxidation level (DPPP assay) were measured as markers of cellular influences. Transmission electron microscope observation showed cellular uptake of platinum nanoparticles. However, the platinum nanoparticles did not drive any markers. It is known that some metal oxide nanoparticles such as NiO and CuO show severe cytotoxicity via metal ion release. Compared with these toxic nanoparticles, the platinum nanoparticles used in this study did not release platinum ions into the culture media. These results suggest that the physically and chemically inactive cellular influences of platinum nanoparticles are small.

Cellular responses induced by cerium oxide nanoparticles: induction of intracellular calcium level and oxidative stress on culture cells.

Cerium oxide (CeO(2)) is an important metal oxide used for industrial products. Many investigations about the cellular influence of CeO(2) nanoparticles have been done, but results are contradictory. It has been reported that CeO(2) nanoparticles have an anti-oxidative effect in cells, but it has also been reported that CeO(2) nanoparticles induce oxidative stress. We investigated the potential influence on cells and the mechanisms induced by CeO(2) nanoparticles in vitro. We prepared a stable CeO(2) culture medium dispersion. Cellular responses in CeO(2) medium-exposed cells were examined. Cellular uptake of CeO(2) nanoparticles was observed. After 24-h exposure, a high concentration of CeO(2) nanoparticles (∼200 mg/ml) induced an increase in the intracellular level of reactive oxygen species (ROS); a low concentration of CeO(2) nanoparticles induced a decrease in the intracellular ROS level. On the other hand, exposure of CeO(2) nanoparticle for 24 h had little influence on the cell viability. Exposure of CeO(2) nanoparticles increased the intracellular Ca(2+) concentration and also Calpain was activated. These results suggest that CeO(2) nanoparticles have a potential to induce intracellular oxidative stress and increase the intracellular Ca(2+) level, but these influences are small.

Angiogenic and vasoprotective effects of adrenomedullin on prevention of cognitive decline after chronic cerebral hypoperfusion in mice.

BACKGROUND AND PURPOSE: Although subcortical vascular dementia, the major subtype of vascular dementia, is caused by a disruption in white matter integrity after cerebrovascular insufficiency, no therapy has been discovered that will restore cerebral perfusion or functional cerebral vessels. Because adrenomedullin (AM) has been shown to be angiogenic and vasoprotective, the purpose of the study was to investigate whether AM may be used as a putative treatment for subcortical vascular dementia. METHODS: A model of subcortical vascular dementia was reproduced in mice by placing microcoils bilaterally on the common carotid arteries. Using mice overexpressing circulating AM, we assessed the effect of AM on cerebral perfusion, cerebral angioarchitecture, oxidative stress, white matter change, cognitive function, and brain levels of cAMP, vascular endothelial growth factor, and basic fibroblast growth factor. RESULTS: After bilateral common carotid artery stenosis, mice overexpressing circulating AM showed significantly faster cerebral perfusion recovery due to substantial growth of the capillaries, the circle of Willis, and the leptomeningeal anastomoses and reduced oxidative damage in vascular endothelial cells compared with wild-type mice. Vascular changes were preceded by upregulation of cAMP, vascular endothelial growth factor, and basic fibroblast growth factor. White matter damage and working memory deficits induced by bilateral common carotid artery stenosis were subsequently restored in mice overexpressing circulating AM. CONCLUSIONS: These data indicate that AM promotes arteriogenesis and angiogenesis, inhibits oxidative stress, preserves white matter integrity, and prevents cognitive decline after chronic cerebral hypoperfusion. Thus, AM may serve as a strategy to tackle subcortical vascular dementia.

α-Tocopheryl phosphate: uptake, hydrolysis, and antioxidant action in cultured cells and mouse.

α-Tocopheryl phosphate (α-TP), a water-soluble analogue of α-tocopherol, is found in humans, animals, and plants. α-TP is resistant to both acid and alkaline hydrolysis and may exert its own function in this form in vivo. In this study, the uptake, hydrolysis, and antioxidant action of α-TP were measured using α-TP with a deuterated methyl group, CD(3), at position 5 of the chroman ring (α-TP(CD3)). The hydrolysis of α-TP(CD3) was followed by measuring α-tocopherol containing the CD(3) group, α-T(CD3), in comparison to unlabeled α-tocopherol, α-T(CH3). α-TP(CD3) was incubated with cultured cells, and the intracellular α-T(CD3) formed was measured with HPLC-ECD and GC-MS. α-TP(CD3) was also administered to mice for 4 weeks by mixing in the diet, and α-T(CD3) was measured in plasma, liver, brain, heart, and testis to compare with endogenous unlabeled α-T(CH3). It was found that α-TP(CD3) was taken in and hydrolyzed readily to α-T(CD3) in cultured cells and in mice. The hydrolysis of α-TP(CD3) in cell culture medium was not observed. α-TP protected primary cortical neuronal cells from glutamate-induced cytotoxicity, and α-TP given to mice reduced the levels of lipid peroxidation products in plasma and liver. These results suggest that α-TP is readily hydrolyzed in vivo to α-T, which acts as an antioxidant, and that α-TP may be used as a water-soluble α-T precursor in intravenous fluids, in eye drops, or as a dietary supplement.

Evaluation of acute oxidative stress induced by NiO nanoparticles in vivo and in vitro.

OBJECTIVES: Nickel oxide (NiO) is an important industrial material, and it is also a harmful agent. The toxicity of NiO is size-related: nanoparticles are more toxic than fine-particles. The toxic mechanism induced by NiO nanoparticles remains unexplained, and the relationship between in vitro and in vivo NiO toxicity results is unclear. In the present study, we focused on the oxidative stress caused by NiO nanoparticles by examining and comparing in vitro and in vivo acute responses induced by NiO nanoparticles. METHODS: Cellular responses induced by black NiO nanoparticles with a primary particle size of 20 nm, were examined in human lung carcinoma A549 cells. In vivo responses were examined by instillation of NiO nanoparticles into rat trachea. Bronchoalveolar lavage fluid (BALF) was collected after intratracheal instillation at different time points, and concentrations of lipid peroxide heme oxygenase-1 (HO-1), surfactant protein-D (SP-D) and lactate dehydrogenase (LDH) in BALF were measured. RESULTS: The levels of intracellular reactive oxygen species and lipid peroxidation in A549 cells increased with increasing exposure to NiO nanoparticles, and increases in gene expressions of HO-1 and SP-D were observed in A549 cells. The lipid peroxide level in BALF significantly increased after 24 h instillation but decreased three days later. LDH leakage was also observed three days later. CONCLUSIONS: NiO nanoparticles induce oxidative stress-related lung injury. In vivo and in vitro oxidative stress was induced resulting in activation of antioxidant systems. Based on these responses, we conclude that the results of the in vivo and in vitro studies tend to correspond.

Cytoprotective effects of vitamin E homologues against glutamate-induced cell death in immature primary cortical neuron cultures: Tocopherols and tocotrienols exert similar effects by antioxidant function.

Glutamate plays a critical role in pathological cell death within the nervous system. Vitamin E is known to protect cells from glutamate cytotoxicity, either by direct antioxidant action or by indirect nonantioxidant action. Further, α-tocotrienol (α-T3) has been reported to be more effective against glutamate-induced cytotoxicity than α-tocopherol (α-T). To shed more light on the function of vitamin E against glutamate toxicity, the protective effects of eight vitamin E homologues and related compounds, 2,2,5,7,8-pentamethyl-6-chromanol (PMC) and 2-carboxy-2,5,7,8-pentamethyl-6-chromanol (Trolox), against glutamate-induced cytotoxicity on immature primary cortical neurons were examined using different protocols. Glutamate induced the depletion of glutathione and generation of reactive oxygen species and lipid hydroperoxides, leading to cell death. α-, ß-, γ-, and δ-T and -T3; PMC; and Trolox all exerted cytoprotective effects against glutamate-induced cytotoxicity, and a longer preincubation time increased both the cellular content and the cytoprotective effects of T more significantly than those of T3, the effect of preincubation being relatively small for T3 and PMC. The protective effect of Trolox was less potent than that of PMC. The cytoprotective effects of α-T and α-T3 corresponded to their intracellular content. Further, lipid peroxidation products were measured after reduction with triphenylphosphine followed by saponification with potassium hydroxide. It was found that glutamate treatment increased the formation of hydroxyeicosatetraenoic acid, hydroxyoctadecadienoic acid, and 8-F(2)-isoprostane 2α, which was suppressed by α-T. This study shows that vitamin E protects cells from glutamate-induced toxicity primarily by direct antioxidant action and that the apparent higher capacity of T3 compared to T is ascribed to the faster uptake of T3 compared to T into the cells. It is suggested that, considering the bioavailability, α-T should be more effective than α-T3 against glutamate toxicity in vivo.