Aluminum nanoparticle exposure in L1 larvae results in more severe lethality toxicity than in L4 larvae or young adults by strengthening the formation of stress response and intestinal lipofuscin accumulation in nematodes

Toxicity of Al(2)O(3)-NPs, as compared to that of Al(2)O(3), to L1-larval, L4-larval or young adult nematodes was evaluated. When exposure was performed at L1-larval stage, the significant increases of lethality, stress response, and intestinal lipofuscin autofluorescence were observed in 6.3-203.9 mg/L of Al(2)O(3)-NPs exposed nematodes. In contrast, when exposure was performed at L4-larval or young adult stage, the significant increases of lethality and intestinal lipofuscin autofluorescence were observed in 12.7-203.9 mg/L of Al(2)O(3)-NPs exposed nematodes, and the significant inductions of stress response were detected in 25.5-203.9 mg/L of Al(2)O(3)-NPs exposed nematodes. Moreover, the lethality was significantly correlated with the stress response and the intestinal lipofuscin autofluorescence in Al(2)O(3)-NPs exposed nematodes. These data imply that Al(2)O(3)-NPs exposure in L1 larvae causes more severe lethality toxicity than in L4 larvae or young adults by strengthening the formation of stress response and intestinal lipofuscin accumulation in nematodes.     

Transmissions of serotonin,dopamine, and glutamate are required for the formation of neurotoxicity from Al2O3-NPs in nematode Caenorhabditis elegans

Abstract

In this study, we investigated genetic mechanisms of neurotransmitters in regulating the formation of adverse effects on locomotion behavior in Al₂O₃ nanoparticles (NPs)-exposed Caenorhabditis elegans. Al₂O₃-NPs exposure caused the decrease of locomotion behavior with head thrash and body bend as endpoints. Interestingly, the neurotransmitters of glutamate, serotonin, and dopamine were required for the adverse effects of Al₂O₃-NPs on locomotion behavior in nematodes. Glutamate transporter EAT-4, serotonin transporter MOD-5, and dopamine transporter DAT-1 might serve as the molecular targets of Al₂O₃-NPs for neurotoxicity formation. Moreover, the behavioral response of nematodes to Al₂O₃-NPs exposure was primarily mediated by non-NMDA glutamate receptors GLR-2 and GLR-6, ionotropic serotonin receptor MOD-1, and D1-like dopamine receptor DOP-1. Therefore, Al₂O₃-NPs exposure influences locomotion behavior of nematodes primarily by impinging on their glutamatergic, serotoninergic, and dopaminergic systems. Our data will shed light on questions surrounding the involvement of neurotransmitters in mediating the adverse behavioral effects from Al₂O₃-NPs.     

The in vivo underlying mechanism for recovery response formation in nano-titanium dioxide exposed Caenorhabditis elegans after transfer to the normal condition

So far, we still know little about mechanism for recovery response of engineered nanomaterials (ENMs). Here we used Caenorhabditis elegans to investigate recovery responses of titanium dioxide nanoparticles (TiO₂-NPs) exposed animals and the underlying mechanism. After acute exposure to TiO₂-NPs (100 mg/L), endpoints including defecation and permeable state of intestinal barrier of exposed nematodes returned to control levels; however, after prolonged exposure to TiO₂-NPs (100 μg/L), endpoints of exposed nematodes could not be recovered to control levels under the normal condition. After prolonged exposure to TiO₂-NPs, nematodes exhibited severe deficits in development of intestinal barrier and AVL and DVB neurons controlling defecation; however, after acute exposure to TiO₂-NPs, nematodes had normal developmental state of intestinal barrier and AVL and DVB neurons. Our results imply that developmental states of intestinal barrier and AVL and DVB neurons may serve as a pivotal determinant for recovery response in TiO₂-NPs exposed nematodes.From the Clinical EditorThis basic science study investigates the recovery response to TiO₂ nanoparticles in a nematode model, and concludes that developmental states of the intestinal barrier and AVL and DVB neurons likely serve as determinants for recovery following TiO2-NP exposure.     

Continuous in vitro exposure of intestinal epithelial cells to E171 food additive causes oxidative stress,inducing oxidation of DNA bases but no endoplasmic reticulum stress

The whitening and opacifying properties of titanium dioxide (TiO₂) are commonly exploited when it is used as a food additive (E171). However, the safety of this additive can be questioned as TiO₂ nanoparticles (TiO₂-NPs) have been classed at potentially toxic. This study aimed to shed some light on the mechanisms behind the potential toxicity of E171 on epithelial intestinal cells, using two in vitro models: (i) a monoculture of differentiated Caco-2 cells and (ii) a coculture of Caco-2 with HT29-MTX mucus-secreting cells. Cells were exposed to E171 and two different types of TiO₂-NPs, either acutely (6–48?h) or repeatedly (three times a week for 3 weeks). Our results confirm that E171 damaged these cells, and that the main mechanism of toxicity was oxidation effects. Responses of the two models to E171 were similar, with a moderate, but significant, accumulation of reactive oxygen species, and concomitant downregulation of the expression of the antioxidant enzymes catalase, superoxide dismutase and glutathione reductase. Oxidative damage to DNA was detected in exposed cells, proving that E171 effectively induces oxidative stress; however, no endoplasmic reticulum stress was detected. E171 effects were less intense after acute exposure compared to repeated exposure, which correlated with higher Ti accumulation. The effects were also more intense in cells exposed to E171 than in cells exposed to TiO₂-NPs. Taken together, these data show that E171 induces only moderate toxicity in epithelial intestinal cells, via oxidation.     

Association of oxidative stress with the formation of reproductive toxicity from mercury exposure on hermaphrodite nematode Caenorhabditis elegans

Here we selected HgCl₂ to investigate the mechanism of Hg toxicity on reproduction in hermaphrodite nematodes. Accompanied with decrease of brood size, Hg exposure caused severe deficits in egg number in uterus, egg laying and reproductive structures, including gonad arms and vulva, and formation of protruding phenotype for vulva. Meanwhile, Hg exposure induced severe stress response and oxidative damage in gonad and vulva. Pre-treatment with vitamin E, a potent antioxidant, at the L2-larval stage prevented the oxidative damage and formation of reproductive deficits in Hg exposed nematodes; however, pre-treatment with paraquat, a regent generating superoxide anions, induced more severe reproductive deficits in Hg exposed nematodes. Moreover, Hg exposure increased expression of clk-2 and isp-1 genes, whose mutations decrease ROS production, and decreased expression of mev-1 and gas-1 genes, whose mutations increase ROS production. Thus, oxidative stress may be essential for the induction of reproductive deficits in Hg exposed hermaphrodite nematodes.     

Genotoxicity and cytotoxicity of ZnO and Al2O3 nanoparticles

Abstract

Objectives: Metal oxide nanoparticles (ZnO-NPs and Al₂O₃-NPs) are used in many fields, including consumer products and biomedical applications. As a result, exposure to these NPs is highly frequent, however, no conclusive information on their potential cytotoxicity and genotoxicity mechanisms are available. For this reason, we studied cytotoxic and genotoxic effects of ZnO-NPs and Al₂O₃-NPs on human peripheral blood lymphocytes.

Materials and methods: We obtained our goals by using MTT assay, Annexin V-FITC flow cytometry, and alkaline, neural and pH 12.1 versions of comet assay.

Results: Exposure of lymphocytes to both NPs for 24?h slightly decreased viability of lymphocytes at ≥0.5?mM. For the first time, we revealed using the comet assays that both ZnO-NPs and Al₂O₃-NPs caused a concentration-dependent increase of DNA single-strand breaks, but not alkali-labile sites. Treatment with DNA glycosylases showed that the NPs induced oxidative DNA damage. DNA damage caused by both nanoparticles at 0.05?mM was removed within 120?min, however lymphocytes did not repair DNA damage induced by 0.5?mM NPs. Studied nanoparticles did not induce apoptosis in lymphocytes.

Conclusion: Our results suggest that ZnO-NPs and Al₂O₃-NPs at concentration up to 0.5?mM did not exhibit cytotoxic effect but may exert genotoxic effect on lymphocytes, at least partially by the generation of oxidative DNA damage and strand breaks.     

Long-term exposure of A549 cells to titanium dioxide nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents

Titanium dioxide nanoparticles (TiO₂-NPs) are one of the most produced NPs in the world. Their toxicity has been studied for a decade using acute exposure scenarios, i.e. high exposure concentrations and short exposure times. In the present study, we evaluated their genotoxic impact using long-term and low concentration exposure conditions. A549 alveolar epithelial cells were continuously exposed to 1–50?μg/mL TiO₂-NPs, 86% anatase/14% rutile, 24?±?6?nm average primary diameter, for up to two months. Their cytotoxicity, oxidative potential and intracellular accumulation were evaluated using MTT assay and reactive oxygen species measurement, transmission electron microscopy observation, micro-particle-induced X-ray emission and inductively-coupled plasma mass spectroscopy. Genotoxic impact was assessed using alkaline and Fpg-modified comet assay, immunostaining of 53BP1 foci and the cytokinesis-blocked micronucleus assay. Finally, we evaluated the impact of a subsequent exposure of these cells to the alkylating agent methyl methanesulfonate. We demonstrate that long-term exposure to TiO₂-NPs does not affect cell viability but causes DNA damage, particularly oxidative damage to DNA and increased 53BP1 foci counts, correlated with increased intracellular accumulation of NPs. In addition, exposure over 2 months causes cellular responses suggestive of adaptation, characterized by decreased proliferation rate and stabilization of TiO₂-NP intracellular accumulation, as well as sensitization to MMS. Taken together, these data underline the genotoxic impact and sensitization effect of long-term exposure of lung alveolar epithelial cells to low levels of TiO₂-NPs.     

Oxidative stress and genotoxicity in Rhinella arenarum (Anura: Bufonidae) tadpoles after acute exposure to Ni-Al nanoceramics

The employ of nanomaterials (NMs) has exponentially grown due to the large number of technological advances in industrial, pharmaceutical and medical areas. That is the case of alumina (Al) nanoparticles which are extensively employed as support in heterogeneous catalysis processes. However, these NMs can cause great toxicity because of their ubiquitous properties, such as extremely small size and high specific surface area. So, it is required to assess the potential deleterious effects of these NMs on living organisms. In the present study, we analyze the oxidative stress and genotoxic potential of a nanoceramic catalyst Ni/<gamma>-Al₂O₃ (NC) and the NMs involved in their synthesis, <gamma>-Al₂O₃ support (SPC) and NiO/<gamma>-Al₂O₃ precursor (PC) on Rhinella arenarum larvae. Biomarkers of oxidative stress and genotoxic damage were measured in tadpoles exposed to 5 and 25 mg/L of each NMs for 96 h. The results indicated an inhibition of catalase activity in tadpoles exposed to both concentrations of PC and to 25 mg/L of SPC and NC. Moreover, both exposure concentrations of PC and NC significantly inhibited superoxide dismutase activity. Exposure to the three NMs caused inhibition of glutathione S-transferase activity, but there were no significant variations in reduced glutathione levels. Oxidative stress damage (lipid peroxidation) was observed in tadpoles treated with 25 mg/L PC, while the other treatments did not produce alterations. The MNs frequency significantly increased in larvae exposed to 25 mg/L PC indicating irreversible genotoxic damage. The results show that these NMs exert genotoxic effects and antioxidant defense system disruption in R. arenarum larvae.     

Susceptible genes regulate the adverse effects of TiO2-NPs at predicted environmental relevant concentrations on nematode Caenorhabditis elegans

Contributions from mutations of susceptible genes to TiO₂-NPs toxicity at environmental relevant concentrations (ERCs) and the underlying mechanism are largely unclear. After prolonged exposure, among the examined 19 mutants associated with oxidative stress or stress response, we show that sod-2, sod-3, mtl-2, and hsp-16.48 were susceptible genes for TiO₂-NPs toxicity on reproduction and locomotion behavior, sod-2, sod-3, and mtl-2 were susceptible genes for TiO₂-NPs toxicity on survival and intestinal development, and mtl-2 was susceptible gene for TiO₂-NPs toxicity on development. Mutations of these susceptible genes, together with sensitive endpoints, could be used to evaluate TiO₂-NPs toxicity at the concentration of 0.0001 μg/L. Our results imply the usefulness of identified susceptible genes in assessing the potential nanotoxicity of engineered nanomaterial (ENM) at ERCs. One important mechanism to explain property of identified susceptible genes for TiO₂-NPs toxicity was that mutations of these susceptible genes enhanced the uptake of TiO₂-NPs into body of nematodes.From the Clinical EditorThis team of authors identified susceptibility genes influencing the uptake and consequential toxicity of TiO₂ nanoparticles in a nematode, highlighting the general importance of investigating genetic influence on nanoparticle delivery.     

Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain

Abstract

Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO₂, ZnO and Al₂O₃ on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500?mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.     

Contribution of oxidative stress in acute intestinal mucositis induced by 5 fluorouracil (5-FU) and its pro-drug capecitabine in rats

This study was designed to examine the contribution of oxidative stress in gastrointestinal disorders after an intraperitoneal administration of 5 fluorouracil (5-FU; 100?mg/kg of body weight (b.w.)) and capecitabine oral administration (500?mg/kg b.w.). The animals were divided into three groups: Group A (NaCl,10?ml/kg of b.w.) considered as control group, group B was intoxicated by 5-FU and group C was the group of animals treated with capecitabine (CAP). To evaluate the secretory and enteropooling effects, we used magnesium sulfate (MgSO₄), 1?ml/100?g of b.w. as a hypersecretion agent . The mucosal gastro-intestinal specimens were scraped and examined for biological markers of oxidative stress and intracellular mediators. These anticancer drugs caused many intestinal damages manifested by an elevation of fluid accumulation and imbalance in electrolytes secretion. The intestinal tissues from treated rats not only showed a significant increase in malondialdehyde (MDA), protein carbonylation and hydrogen peroxide (H₂O₂) production. but also showed a significant depletion of enzymatic and non-enzymatic antioxidant, such as, glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and sulfhydryl groups (-SH). These effects were related with histopathological damage and a perturbation of intracellular mediators. As expected, these disturbances were observed in the group of rats poisoned by the MgSO₄. Data suggest the contribution of oxidative stress in chemotherapy-induced many disorders in intestinal tract.     

Aluminium oxide nanoparticles induced morphological changes,cytotoxicity and oxidative stress in Chinook salmon (CHSE‐214) cells

Aluminium oxide nanoparticles (Al₂O₃ NPs) are increasingly used in diverse applications that has raised concern about their safety. Recent studies suggested that Al₂O₃ NPs induced oxidative stress may be the cause of toxicity in algae, Ceriodaphnia dubia, Caenorhabditis elegans and Danio rerio. However, there is paucity on the toxicity of Al₂O₃ NPs on fish cell lines. The current study was aimed to investigate Al₂O₃ NPs induced cytotoxicity, oxidative stress and morphological abnormality of Chinnok salmon cells (CHSE‐214). A dose‐dependent decline in cell viability was observed in CHSE‐214 cells exposed to Al₂O₃ NPs. Oxidative stress induced by Al₂O₃ NPs in CHSE‐214 cells has resulted in the significant reduction of superoxide dismutase, catalase and glutathione in a dose‐dependent manner. However, a significant increase in glutathione sulfo‐transferase and lipid peroxidation was observed in CHSE‐214 cells exposed to Al₂O₃ NPs in a dose‐dependent manner. Significant morphological changes in CHSE‐214 cells were observed when exposed to Al₂O₃ NPs at 6, 12 and 24 h. The cells started to detach and appear spherical at 6 h followed by loss of cellular contents resulting in the shrinking of the cells. At 24 h, the cells started to disintegrate and resulted in cell death. Our data demonstrate that Al₂O₃ NPs induce cytotoxicity and oxidative stress in a dose‐dependent manner in CHSE‐214 cells. Thus, our current work may serve as a base‐line study for future evaluation of toxicity studies using CHSE‐214 cells. Copyright © 2015 John Wiley & Sons, Ltd.     

Protective effects of prostaglandin E1 on human umbilical vein endothelial cell injury induced by hydrogen peroxide

Aim:

To investigate the protective effects of prostaglandin E₁ (PGE₁) against H₂O₂-induced oxidative damage on human umbilical vein endothelial cells (HUVECs).

Methods:

HUVECs were pretreated with PGE₁ (0.25, 0.50, and 1.00 μmol/L) for 24 h and exposed to H₂O₂ (200 μmol/L) for 12 h, and cell viability was measured by the MTT assay. LDH, NO, SOD, GSH-Px, MDA, ROS, and apoptotic percentage were determined. eNOS expression was measured by Western blotting and real-time PCR.

Results:

PGE₁ (0.25−1.00 μmol/L) was able to markedly restore the viability of HUVECs under oxidative stress, and scavenged intracellular reactive oxygen species induced by H₂O₂. PGE₁ also suppressed the production of lipid peroxides, such as MDA, restored the activities of endogenous antioxidants including SOD and GSH-Px, and inhibited cell apoptosis. In addition, PGE₁ significantly increased NO content, eNOS protein, and mRNA expression.

Conclusion:

PGE₁ effectively protected endothelial cells against oxidative stress induced by H₂O₂, an activity that might depend on the up-regulation of NO expression.     

Physiological effects of magnetite (Fe3O4) nanoparticles on perennial ryegrass (Lolium perenne L.) and pumpkin (Cucurbita mixta) plants

Abstract

To date, knowledge gaps and associated uncertainties remain unaddressed on the effects of nanoparticles (NPs) on plants. This study was focused on revealing some of the physiological effects of magnetite (Fe₃O₄) NPs on perennial ryegrass (Lolium perenne L.) and pumpkin (Cucurbita mixta cv. white cushaw) plants under hydroponic conditions. This study for the first time reports that Fe₃O₄ NPs often induced more oxidative stress than Fe₃O₄ bulk particles in the ryegrass and pumpkin roots and shoots as indicated by significantly increased: (i) superoxide dismutase and catalase enzyme activities, and (ii) lipid peroxidation. However, tested Fe₃O₄ NPs appear unable to be translocated in the ryegrass and pumpkin plants. This was supported by the following data: (i) No magnetization was detected in the shoots of either plant treated with 30, 100 and 500 mg l^?1 Fe₃O₄ NPs; (ii) Fe K-edge X-ray absorption spectroscopic study confirmed that the coordination environment of Fe in these plant shoots was similar to that of Fe-citrate complexes, but not to that of Fe₃O₄ NPs; and (iii) total Fe content in the ryegrass and pumpkin shoots treated with Fe₃O₄ NPs was not significantly increased compared to that in the control shoots.     

Protection of l-methionine against H2O2-induced oxidative damage in mitochondria

Reactive oxygen species (ROS) is reported to be a critical pathogenic factor and mitochondria is one of the susceptible subcellular organs for oxidative damage. Methionine sulfoxide reductase A (MsrA) is a key anti-oxidant enzyme associated with cytoprotection and previous reports have revealed its importance in mitochondrial function. The anti-oxidation of MsrA is due to Met-centered redox cycle, suggesting that Met-centered redox cycle may play a critical role in mitochondrial protection. l-Methionine (l-Met), a natural amino acid with anti-oxidation activity, can mimic the effect of Met-centered redox cycle. Here, we investigated the protection of l-Met on H₂O₂-induced oxidative damage in mitochondria. Our study demonstrated that l-Met protected H₂O₂-induced injury in CHO cells. Cytoprotections of l-Met at low concentrations (1–5 mM) were abolished by dimethyl sulfoxide (DMSO), a competitive inhibitor of MsrA function, suggesting that these effects may involve the participation of MsrA. Overexpression of MsrA in CHO cells protected mitochondria from H₂O₂-induced downtrend of membrane potential and production of mitochondrial superoxide. Pre-treatment with l-Met (1 mM) produced a similar effect on the mitochondrial protection against H₂O₂. Furthermore, it was observed that topical application of l-Met can prevent 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced oxidative damage in the skin of mice. These results suggest that anti-oxidation activity of l-Met may promise a new strategy for the prevention of oxidative stress-induced damage.     

Markers of lipid oxidative damage in the exhaled breath condensate of nano TiO2 production workers

Nanoscale titanium dioxide (nanoTiO₂) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO₂ is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO₂. This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, 8-isoProstaglandin F2α and aldehydes C₆–C₁₂) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98?×?10⁴ to 2.32?×?10⁴ particles/cm³ with ～80% of the particles?<100?nm in diameter. Mass concentration varied between 0.40 and 0.65?mg/m³. All 11 markers of lipid oxidation were elevated in production workers relative to the controls (p?2 and markers of lipid oxidation in the EBC. These markers were not elevated in the urine samples. Lipid oxidation in the EBC of workers exposed to (nano)TiO₂ complements our earlier findings on DNA and protein damage. These results are consistent with the oxidative stress hypothesis and suggest lung injury at the molecular level. Further studies should focus on clinical markers of potential disease progression. EBC has reemerged as a sensitive technique for noninvasive monitoring of workers exposed to engineered nanoparticles.     

Toxicity of zinc oxide (ZnO) nanoparticles on human bronchial epithelial cells (BEAS-2B) is accentuated by oxidative stress

Although several studies reported that cytotoxic effects of various nanoparticles are partially due to induction of oxidative stress, it is unclear how oxidative state of the cell per se could influence its sensitivity to cytotoxic nanoparticles. This is of clinical significance because certain pathological conditions such as inflammation is associated with elevated oxidative stress and this may alter sensitivity of cells and tissues to cytotoxic nanoparticles. Hence, this study investigated how initial exposure of BEAS-2B human bronchial epithelial cells to oxidative stress influences subsequent response to cytotoxic challenge with zinc oxide (ZnO) nanoparticles (≈10 nm). Oxidative stress was induced by exposing BEAS-2B cells to 5 and 10 μM of H₂O₂ for 45 min in PBS (with Ca²⁺). Subsequently, the H₂O₂ solutions were washed off and the cells were exposed to varying concentrations (5–25 μg/ml) of ZnO nanoparticles in culture media for 24 h, followed by cell viability assessment with the WST-8 assay. The results demonstrated that initial transient exposure of cells to oxidative stress accentuated cytotoxicity of ZnO nanoparticles. In the negative control unexposed to H₂O₂, >99% of cells remained viable up to a ZnO nanoparticle concentration of 10 μg/ml, but displayed a steep decrease in viability above 10 μg/ml ZnO. By contrast, cells that were initially exposed to 5 and 10 μM of H₂O₂, displayed a sharp drop in viability even at concentrations below 10 μg/ml ZnO. At 10 μg/ml ZnO, cells initially exposed to 10 μM H₂O₂ displayed a viability of 40.6 ± 2.0%, which is significantly lower than the corresponding values of 72.8 ± 2.0% and 99.9 ± 1.1% obtained for initial exposure to 5 μM H₂O₂ and the negative control, respectively. Hence, initial exposure of BEAS-2B cells to oxidative stress sensitized their subsequent response to cytotoxic challenge with ZnO nanoparticles.     

Diarylheptanoid 7-(3,4 dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene from Curcuma comosa Roxb. protects retinal pigment epithelial cells against oxidative stress-induced cell death

Chronic exposure to oxidative stress causes damage to retinal pigment epithelial cells which may lead to the development of age-related macular degeneration, the major cause of vision loss in humans. Anti-oxidants provide a natural defense against retinal cell damage. The present study was designed to evaluate the potential anti-oxidant activity and protective effect of two diarylheptanoids isolated from a medicinal herb Curcuma comosa; 7-(3,4 dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound A), and 1,7-diphenyl-4(E),6(E)-heptadien-3-ol (compound B) against oxidative stress (H₂O₂)-induced human retinal pigment epithelial (APRE-19) cell death. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay indicated that the anti-oxidant activity (IC₅₀) of compound A was similar to that of vitamin C. Pre-treatment of ARPE-19 cells with 20 μM compound A for 4 h afforded greater protection against the insult from 500 μM H₂O₂, compared to a similar protection period for compound B. Compound A lowered H₂O₂-induced lipid peroxidation, malondialdehyde formation and intracellular reactive oxygen species. Furthermore, compound A ameliorated the H₂O₂-induced decrease in anti-oxidant enzyme activities and subsequent apoptotic cell death in ARPE-19 cells in a dose and time-dependent manner. These results suggest that compound A protects ARPE-19 cells against oxidative stress, in part, by enhancing several anti-oxidant defense mechanisms. Therefore, compound A may have therapeutic potential for diseases associated with oxidative stress, particularly degenerative retinal diseases.     

Comparison of the effects of MnO2-NPs and MnO2-MPs on mitochondrial complexes in different organs

Today, nanoparticles (NPs) have been widely used in various fields. Manganese oxide nanoparticles have attracted a lot of attention due to many applications. One of the major concerns regarding the widespread use of various NPs is the exposure and accumulation in human organs and finally toxicity. The generation of reactive oxygen species (ROS) by mitochondria is one of the most important mechanisms of toxicity suggested by published studies induced by other NPs. However, limited studies have been conducted on the mechanism of toxicity of MnO₂-NPs and MnO₂-microparticles (MnO₂-MPs). In this study, we compared the accumulation of MnO₂-NPs and MnO₂-MPs in different tissues and evaluated their effects on mitochondrial complexes in isolated mitochondria. Our results showed that intravascular (iv) administration of the MnO₂-NPs in the same dose compared to the MnO₂-MPs resulted in more accumulation in the C57 mouse female tissues. The effect of MnO₂-NPs and MnO₂-MPs in mitochondria showed that complexes I and III play an important role in increasing ROS generation and this effect is related to type of tissue. Also, our results showed that exposure to MnO₂-NPs and MnO₂-MPs reduced the activity of mitochondrial complexes II and IV. Our results suggest that the toxicity of the MnO₂-NPs is higher than that of the MnO₂-MPs and can lead to the depletion of antioxidant status, likely induction of apoptosis, cancer, and neurodegenerative disease.

Abbreviations: NPs: nanoparticles; ROS: reactive oxygen species; SDH: succinate dehydrogenase; DCFH-DA: dichloro-dihydro-fluorescein diacetate; ELISA: enzyme-linked immunosorbent assay; MnO2-NPs: manganese oxide nanoparticles