Polyamine modification by acrolein exclusively produces 1,5-diazacyclooctanes: a previously unrecognized mechanism for acrolein-mediated oxidative stress.

Science.gov (United States)

Tsutsui, Ayumi; Imamaki, Rie; Kitazume, Shinobu; Hanashima, Shinya; Yamaguchi, Yoshiki; Kaneda, Masato; Oishi, Shinya; Fujii, Nobutaka; Kurbangalieva, Almira; Taniguchi, Naoyuki; Tanaka, Katsunori

2014-07-28

Acrolein, a toxic unsaturated aldehyde generated as a result of oxidative stress, readily reacts with a variety of nucleophilic biomolecules. Polyamines, which produced acrolein in the presence of amine oxidase, were then found to react with acrolein to produce 1,5-diazacyclooctane, a previously unrecognized but significant downstream product of oxidative stress. Although diazacyclooctane formation effectively neutralized acrolein toxicity, the diazacyclooctane hydrogel produced through a sequential diazacyclooctane polymerization reaction was highly cytotoxic. This study suggests that diazacyclooctane formation is involved in the mechanism underlying acrolein-mediated oxidative stress.

Destruction of commercial pesticides by cerium redox couple mediated electrochemical oxidation process in continuous feed mode

International Nuclear Information System (INIS)

Balaji, Subramanian; Chung, Sang Joon; Ryu, Jae-Yong; Moon, Il Shik

2009-01-01

Mediated electrochemical oxidation was carried out for the destruction of commercial pesticide formulations using cerium(IV) in nitric acid as the mediator electrolyte solution in a bench scale set up. The mediator oxidant was regenerated in situ using an electrochemical cell. The real application of this sustainable process for toxic organic pollutant destruction lies in its ability for long term continuous operation with continuous organic feeding and oxidant regeneration with feed water removal. In this report we present the results of fully integrated MEO system. The task of operating the continuous feed MEO system for a long time was made possible by continuously removing the feed water using an evaporator set up. The rate of Ce(IV) regeneration in the electrochemical cell and the consumption for the pesticide destruction was matched based on carbon content of the pesticides. It was found that under the optimized experimental conditions for Ce(III) oxidation, organic addition and water removal destruction efficiency of ca. 99% was obtained for all pesticides studied. It was observed that the Ce(IV) concentration was maintained nearly the same throughout the experiment. The stable operation for 6 h proved that the process can be used for real applications and for possible scale up for the destruction of larger volumes of toxic organic wastes.

Mediator oxidation systems in organic electrosynthesis

International Nuclear Information System (INIS)

Ogibin, Yurii N; Elinson, Michail N; Nikishin, Gennady I

2009-01-01

The data on the use of mediator oxidation systems activated by electric current (anodic or parallel anodic and cathodic) in organic electrosynthesis are considered and generalised. Electrochemical activation of these systems permits successful application of catalytic versions and easy scaling of mediator-promoted processes. Chemical and environmental advantages of electrochemical processes catalysed by mediator oxidation systems are demonstrated. Examples of the application of organic and inorganic mediators for the oxidation of various classes of organic compounds under conditions of electrolysis are given.

Glial activation in nitrous oxide toxicity is related to oxidative stress and glutamate excitotoxicity

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Sandeep Kumar Singh

2017-12-01

Full Text Available Myelin disorders can be due to diverse mechanisms such as autoimmune, parainfectious, metabolic or toxic. The prototype of immune mediated demyelination is multiple sclerosis. To understand the underlying mechanism of cell damage in vitamin b12 deficiency, a number of animal models have been used which include total gastrectomy (TGX, cobalamine deficient diet and N2O exposure (Tredici G, et al., 1998;Scalabrino G, 2001. Six adult wistar male rats were exposed to N2O oxygen mixture in 1:1 ratio at a rate of 2 L/min for 120 min for 60 days. The control rats received only oxygen and room air. At the end of exposure, spontaneous locomotor activity (total distance travelled, time resting, time moving, number of rearing, stereotypic count and grip strength. Plasma glutathione (GSH, total antioxidant capacity (TAC and serum malonodialdehyde (MDA and serum homocysteine (Hcy were measured by spectrophotometer. Glutamate in the cerebral cortex and cerebellum was measured by colorimetry. Immunohistochemistry for GFAP expression in brain and spinal cord was done and quantified using image J software. The N2O exposed rats had significant reduction in total distance travelled, time moving, number of rearing and increased time resting compared to the controls. Hcy, glutamate and MDA levels were increased, and GSH and TAC decreased in N2O exposed group compared to the controls. GFAP was more expressed in N2O exposed group, and its expression was higher in spinal cord compared to brain. The GFAP expression correlated with neurobehavioral changes, oxidative stress and glutamate level.N2O toxicity results in GFAP expression suggesting astrocytic reaction, which is mediated by oxidative stress and excitotoxicity.

Ceriodaphnia dubia as a potential bio-indicator for assessing acute aluminum oxide nanoparticle toxicity in fresh water environment.

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Sunandan Pakrashi

Full Text Available Growing nanomaterials based consumer applications have raised concerns about their potential release into the aquatic ecosystems and the consequent toxicological impacts. So environmental monitoring of the nanomaterials in aqueous systems becomes imperative. The current study reveals the potential of Ceriodaphnia dubia (C. dubia as a bio-indicator for aluminum oxide nanoparticles in a fresh water aquatic ecosystem where it occupies an important ecological niche as a primary consumer. This study aims to investigate the aluminium oxide nanoparticle induced acute toxicity on Ceriodaphnia dubia in a freshwater system. The bioavailability of the aluminum oxide nanoparticles has been studied with respect to their aggregation behavior in the system and correlated with the toxicity endpoints. The oxidative stress generated by the particles contributed greatly toward their toxicity. The crucial role of leached aluminium ion mediated toxicity in the later phases (48 h and 72 h in conjunction with the effects from the nano-sized particles in the initial phases (24 h puts forth the dynamics of nanotoxicity in the test system. The internalization of nanoparticles (both gross and systemic uptake as substantiated through the transmission electron microscopy (TEM and inductively coupled plasma optical emission spectral (ICP-OES analysis was another major contributor toward acute toxicity. Concluding the present study, Ceriodaphnia dubia can be a promising candidate for bio-monitoring the aluminium oxide nanoparticles in a fresh water system.

Potential hepatic toxicity of buprofezin at sublethal concentrations: ROS-mediated conversion of energy metabolism.

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Ji, Xiaotong; Ku, Tingting; Zhu, Na; Ning, Xia; Wei, Wei; Li, Guangke; Sang, Nan

2016-12-15

Buprofezin is known for its broad-spectrum action and environmental safety. The popularity of buprofezin has raised concerns about its potentially adverse effects on human health and risk to the environment. In this study, we first identified the liver as one of the major organs in which buprofezin accumulated, and we detected a severe oxidative stress response. Next, we demonstrated that sublethal concentrations of buprofezin promoted the conversion of energy metabolism from the aerobic tricarboxylic acid (TCA) cycle and oxidative phosphorylation to anaerobic glycolysis. Importantly, reactive oxygen species (ROS) generation partially accounted for the shunting of the energy metabolism through the buprofezin-mediated inhibition of cytochrome c oxidase activity. ROS directly perturbed the activities of several key TCA cycle enzymes, stimulated glycolysis, and indirectly disturbed the activity of the respiratory chain complex by altering mitochondrial DNA (mtDNA). These findings clarify the potential mechanisms of buprofezin toxicity and provide biomarkers for buprofezin-mediated hepatotoxicity at sublethal concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Toxicity Evaluation of Graphene Oxide in Kidneys of Sprague-Dawley Rats

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Anita K. Patlolla

2016-03-01

Full Text Available Recently, graphene and graphene-related materials have attracted a great deal of attention due their unique physical, chemical, and biocompatibility properties and to their applications in biotechnology and medicine. However, the reports on the potential toxicity of graphene oxide (GO in biological systems are very few. The present study investigated the response of kidneys in male Sprague-Dawley rats following exposure to 0, 10, 20 and 40 mg/Kg GO for five days. The results showed that administration of GOs significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent manner in the kidneys compared with control group. Serum creatinine and blood urea nitrogen levels were also significantly increased in rats intoxicated with GO compared with the control group. There was a significant elevation in the levels of hydrogen peroxide and lipid hydro peroxide in GOs-treated rats compared to control animals. Histopathological evaluation showed significant morphological alterations of kidneys in GO-treated rats compared to controls. Taken together, the results of this study demonstrate that GO is nephrotoxic and its toxicity may be mediated through oxidative stress. In the present work, however, we only provided preliminary information on toxicity of GO in rats; further experimental verification and mechanistic elucidation are required before GO widely used for biomedical applications.

Supplementation of Nigella sativa fixed and essential oil mediates potassium bromate induced oxidative stress and multiple organ toxicity.

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Sultan, Muhammad Tauseef; Butt, Masood Sadiq; Ahmad, Rabia Shabeer; Pasha, Imran; Ahmad, Atif Nisar; Qayyum, Mir Muhammad Nasir

2012-01-01

The plants and their functional ingredients hold potential to cure various maladies and number of plants hold therapeutic potential. The present research was designed study the health promoting potential of black cumin (Nigella sativa) fixed oil (BCFO) and essential oil (BCEO) against oxidative stress with special reference to multiple organ toxicity. For the purpose, thirty rats (Strain: Sprague Dawley) were procured and divided into three groups (10 rats/group). The groups were fed on their respective diets i.e. D1 (control), D2 (BCFO @ 4.0%) and D3 (BCEO @ 0.30%) for a period of 56 days. Mild oxidative stress was induced with the help of potassium bromate injection @ 45 mg/Kg body weight. Furthermore, the levels of cardiac and liver enzymes were assayed. The results indicated that oxidative stress increased the activities of cardiac and liver enzymes. However, supplementation of BCFO and BCEO was effective in reducing the abnormal values of enzymes. Elevated levels of lactate dehydrogenase (LDH), CPK and CPK-MB were reduced from 456 to 231, 176 to 122 and 45 to 36mg/dL, respectively. Similarly, liver enzymes were also reduced. However, the results revealed that BCEO supplementation @ 0.30% is more effectual in ameliorating the multiple organ toxicity in oxidative stressed animal modelling. In the nutshell, it can be assumed that black cumin essential oil is more effective in reducing the extent of potassium bromate induced multiple organ toxicity (cardiac and liver enzymes imbalance) that will ultimately helpful in reducing the extent of myocardial and liver necrosis.

Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells

International Nuclear Information System (INIS)

Passagne, Isabelle; Morille, Marie; Rousset, Marine; Pujalté, Igor; L’Azou, Béatrice

2012-01-01

Silica nanoparticles (nano-SiO 2 ) are one of the most popular nanomaterials used in industrial manufacturing, synthesis, engineering and medicine. While inhalation of nanoparticles causes pulmonary damage, nano-SiO 2 can be transported into the blood and deposit in target organs where they exert potential toxic effects. Kidney is considered as such a secondary target organ. However, toxicological information of their effect on renal cells and the mechanisms involved remain sparse. In the present study, the cytotoxicity of nano-SiO 2 of different sizes was investigated on two renal proximal tubular cell lines (human HK-2 and porcine LLC-PK 1 ). The molecular pathways involved were studied with a focus on the involvement of oxidative stress. Nanoparticle characterization was performed (primary nanoparticle size, surface area, dispersion) in order to investigate a potential relationship between their physical properties and their toxic effects. Firstly, evidence of particle internalization was obtained by transmission electron microscopy and conventional flux cytometry techniques. The use of specific inhibitors of endocytosis pathways showed an internalization process by macropinocytosis and clathrin-mediated endocytosis for 100 nm nano-SiO 2 nanoparticles. These nanoparticles were localized in vesicles. Toxicity was size- and time-dependent (24 h, 48 h, 72 h). Indeed, it increased as nanoparticles became smaller. Secondly, analysis of oxidative stress based on the assessment of ROS (reactive oxygen species) production (DHE, dihydroethidium) or lipid peroxidation (MDA, malondialdehyde) clearly demonstrated the involvement of oxidative stress in the toxicity of 20 nm nano-SiO 2 . The induction of antioxidant enzymes (catalase, GSTpi, thioredoxin reductase) could explain their lesser toxicity with 100 nm nano-SiO 2 .

Free radicals quenching potential, protective properties against oxidative mediated ion toxicity and HPLC phenolic profile of a Cameroonian spice: Piper guineensis.

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Moukette Moukette, Bruno; Constant Anatole, Pieme; Nya Biapa, Cabral Prosper; Njimou, Jacques Romain; Ngogang, Jeanne Yonkeu

2015-01-01

Considerations on antioxidants derived from plants have continuously increased during this decade because of their beneficial effects on human health. In the present study we investigated the free radical scavenging properties of extracts from Piper guineense ( P. guineense ) and their inhibitory potentials against oxidative mediated ion toxicity. The free radical quenching properties of the extracts against [1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS•), hydroxyl radical (HO•), nitric oxide (NO•)] radical and their antioxidant potentials by FRAP and phosphomolybdenum were determined as well as their protective properties on liver enzymes. The phenolic profile was also investigated by HPLC. The results obtained, revealed that the extracts significantly inhibited the DPPH, NO, HO and ABTS radicals in a concentration depending manner. They also showed a significant ferrous ion chelating ability through FRAP and phosphomolybdenum antioxidant potential. Their polyphenol contents varied depending on the type of extracts and the solvent used. The hydroethanolic extracts (FFH) and the ethanolic extracts (FFE) of P. guineense leaves showed the higher level of phenolic compounds respectively of 21.62 ± 0.06 mg caffeic acid/g dried extract (CAE/g DE) and 19.01 ± 0.03 CAE/g DE. The HPLC phenolic compounds profile revealed a higher quantity of Eugenol, quercetin, rutin and catechin in the stem than in the leaves. The presence of these molecules could be responsible of the protective potentials of P. guineense extracts against lipid peroxidation and SOD, catalase and peroxidase. In conclusion, P. guineense extracts demonstrated significant antioxidant property and may be used as a prospective protector against metal related toxicity.

Time-dependent effect of p-Aminophenol (PAP) toxicity in renal slices and development of oxidative stress

International Nuclear Information System (INIS)

Harmon, R. Christopher; Terneus, Marcus V.; Kiningham, Kinsley K.; Valentovic, Monica

2005-01-01

p-Aminophenol (PAP), a metabolite of acetaminophen, is nephrotoxic. This study investigated PAP-mediated changes as a function of time that occur prior to loss of membrane integrity. Experiments further evaluated the development of oxidative stress by PAP. Renal slices from male Fischer 344 (F344) rats (N = 4-6) were exposed to 0.1, 0.25, and 0.5 mM PAP for 15-120 min under oxygen and constant shaking at 37 o C. Pyruvate-stimulated gluconeogenesis, adenine nucleotide levels, and total glutathione (GSH) levels were diminished in a concentration- and time-dependent manner prior to detection of a rise in lactate dehydrogenase (LDH) leakage. Glutathione disulfide (GSSG) levels were increased by PAP suggesting the induction of oxidative stress. Western blot analysis confirmed a rise in 4-hydroxynonenal (4-HNE)-adducted proteins in tissues exposed to 0.1 and 0.25 mM PAP for 90 min. The appearance of 4-HNE-adducted proteins at the 0.1 mM concentration of PAP occurred prior to development of increased LDH leakage. Pretreatment with 1 mM glutathione (GSH) for 30 min only partially reduced PAP toxicity as LDH values were less severely depleted relative to tissues not pretreated with GSH. In contrast, pretreatment for 15 min with 2 mM ascorbic acid completely protected against PAP toxicity. Further studies showed that ascorbic acid pretreatment prevented PAP-mediated depletion of GSH. In summary, PAP rapidly depletes GSH and adenine nucleotides and inhibits gluconeogenesis prior to a rise in LDH leakage. PAP induces oxidative stress as indicated by an increase in GSSG and 4-HNE-adducted proteins. Ascorbic acid pretreatment prevents PAP toxicity by maintaining GSH status

Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

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Giovanna Romano

Full Text Available Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms.

Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells.

Science.gov (United States)

Passagne, Isabelle; Morille, Marie; Rousset, Marine; Pujalté, Igor; L'azou, Béatrice

2012-09-28

Silica nanoparticles (nano-SiO(2)) are one of the most popular nanomaterials used in industrial manufacturing, synthesis, engineering and medicine. While inhalation of nanoparticles causes pulmonary damage, nano-SiO(2) can be transported into the blood and deposit in target organs where they exert potential toxic effects. Kidney is considered as such a secondary target organ. However, toxicological information of their effect on renal cells and the mechanisms involved remain sparse. In the present study, the cytotoxicity of nano-SiO(2) of different sizes was investigated on two renal proximal tubular cell lines (human HK-2 and porcine LLC-PK(1)). The molecular pathways involved were studied with a focus on the involvement of oxidative stress. Nanoparticle characterization was performed (primary nanoparticle size, surface area, dispersion) in order to investigate a potential relationship between their physical properties and their toxic effects. Firstly, evidence of particle internalization was obtained by transmission electron microscopy and conventional flux cytometry techniques. The use of specific inhibitors of endocytosis pathways showed an internalization process by macropinocytosis and clathrin-mediated endocytosis for 100 nm nano-SiO(2) nanoparticles. These nanoparticles were localized in vesicles. Toxicity was size- and time-dependent (24h, 48 h, 72 h). Indeed, it increased as nanoparticles became smaller. Secondly, analysis of oxidative stress based on the assessment of ROS (reactive oxygen species) production (DHE, dihydroethidium) or lipid peroxidation (MDA, malondialdehyde) clearly demonstrated the involvement of oxidative stress in the toxicity of 20 nm nano-SiO(2). The induction of antioxidant enzymes (catalase, GSTpi, thioredoxin reductase) could explain their lesser toxicity with 100 nm nano-SiO(2). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

International Nuclear Information System (INIS)

Liu Jing; Gupta, Ramesh C.; Goad, John T.; Karanth, Subramanya; Pope, Carey

2007-01-01

Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation

TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity

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Yun Wang

2017-01-01

Full Text Available Methamphetamine (MA leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS. The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA, and MA plus TBHQ-treated group (MA + TBHQ. Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity.

Mediating toxic emotions in the workplace--the impact of abusive supervision.

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Chu, Li-Chuan

2014-11-01

This study explores whether abusive supervision can effectively predict employees' counterproductive work behaviour (CWB) and organisational citizenship behaviour (OCB) and the role of toxic emotions at work as a potential mediator of these relationships in nursing settings. Workplace bullying is widespread in nursing. Despite the growing literature on abusive supervision and employees' counterproductive work behaviour and organisational citizenship behaviour, few studies have examined the relationships between abusive supervision and these work behaviours from the viewpoint of the victimed employee's emotion process. This study adopted a two-stage survey of 212 nurses, all of whom were employed by hospitals in Taiwan. Hypotheses were tested through the use of hierarchical multiple regression. The results showed that abusive supervision was positively associated with toxic emotions. Moreover, toxic emotions could effectively predict nurses' counterproductive work behaviour and organisational citizenship behaviour. Finally, it was found that toxic emotions partially mediated the negative effects of abusive supervision on both work behaviours. Toxic emotions at work are a critical mediating variable between abusive supervision and both counterproductive work behaviour and organisational citizenship behaviour. Hospital administrators can implement policies designed to manage events effectively that can spark toxic emotions in their employees. Work empowerment may be an effective way to reduce counterproductive work behaviour and to enhance organisational citizenship behaviour among nurses when supervisors do not promote a healthy work environment for them. © 2013 John Wiley & Sons Ltd.

Quinone-induced protein handling changes: Implications for major protein handling systems in quinone-mediated toxicity

International Nuclear Information System (INIS)

Xiong, Rui; Siegel, David; Ross, David

2014-01-01

Para-quinones such as 1,4-Benzoquinone (BQ) and menadione (MD) and ortho-quinones including the oxidation products of catecholamines, are derived from xenobiotics as well as endogenous molecules. The effects of quinones on major protein handling systems in cells; the 20/26S proteasome, the ER stress response, autophagy, chaperone proteins and aggresome formation, have not been investigated in a systematic manner. Both BQ and aminochrome (AC) inhibited proteasomal activity and activated the ER stress response and autophagy in rat dopaminergic N27 cells. AC also induced aggresome formation while MD had little effect on any protein handling systems in N27 cells. The effect of NQO1 on quinone induced protein handling changes and toxicity was examined using N27 cells stably transfected with NQO1 to generate an isogenic NQO1-overexpressing line. NQO1 protected against BQ–induced apoptosis but led to a potentiation of AC- and MD-induced apoptosis. Modulation of quinone-induced apoptosis in N27 and NQO1-overexpressing cells correlated only with changes in the ER stress response and not with changes in other protein handling systems. These data suggested that NQO1 modulated the ER stress response to potentiate toxicity of AC and MD, but protected against BQ toxicity. We further demonstrated that NQO1 mediated reduction to unstable hydroquinones and subsequent redox cycling was important for the activation of the ER stress response and toxicity for both AC and MD. In summary, our data demonstrate that quinone-specific changes in protein handling are evident in N27 cells and the induction of the ER stress response is associated with quinone-mediated toxicity. - Highlights: • Unstable hydroquinones contributed to quinone-induced ER stress and toxicity

Quinone-induced protein handling changes: Implications for major protein handling systems in quinone-mediated toxicity

Energy Technology Data Exchange (ETDEWEB)

Xiong, Rui; Siegel, David; Ross, David, E-mail: david.ross@ucdenver.edu

2014-10-15

Para-quinones such as 1,4-Benzoquinone (BQ) and menadione (MD) and ortho-quinones including the oxidation products of catecholamines, are derived from xenobiotics as well as endogenous molecules. The effects of quinones on major protein handling systems in cells; the 20/26S proteasome, the ER stress response, autophagy, chaperone proteins and aggresome formation, have not been investigated in a systematic manner. Both BQ and aminochrome (AC) inhibited proteasomal activity and activated the ER stress response and autophagy in rat dopaminergic N27 cells. AC also induced aggresome formation while MD had little effect on any protein handling systems in N27 cells. The effect of NQO1 on quinone induced protein handling changes and toxicity was examined using N27 cells stably transfected with NQO1 to generate an isogenic NQO1-overexpressing line. NQO1 protected against BQ–induced apoptosis but led to a potentiation of AC- and MD-induced apoptosis. Modulation of quinone-induced apoptosis in N27 and NQO1-overexpressing cells correlated only with changes in the ER stress response and not with changes in other protein handling systems. These data suggested that NQO1 modulated the ER stress response to potentiate toxicity of AC and MD, but protected against BQ toxicity. We further demonstrated that NQO1 mediated reduction to unstable hydroquinones and subsequent redox cycling was important for the activation of the ER stress response and toxicity for both AC and MD. In summary, our data demonstrate that quinone-specific changes in protein handling are evident in N27 cells and the induction of the ER stress response is associated with quinone-mediated toxicity. - Highlights: • Unstable hydroquinones contributed to quinone-induced ER stress and toxicity.

Comparative metal oxide nanoparticle toxicity using embryonic zebrafish

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Leah C. Wehmas

2015-01-01

Full Text Available Engineered metal oxide nanoparticles (MO NPs are finding increasing utility in the medical field as anticancer agents. Before validation of in vivo anticancer efficacy can occur, a better understanding of whole-animal toxicity is required. We compared the toxicity of seven widely used semiconductor MO NPs made from zinc oxide (ZnO, titanium dioxide, cerium dioxide and tin dioxide prepared in pure water and in synthetic seawater using a five-day embryonic zebrafish assay. We hypothesized that the toxicity of these engineered MO NPs would depend on physicochemical properties. Significant agglomeration of MO NPs in aqueous solutions is common making it challenging to associate NP characteristics such as size and charge with toxicity. However, data from our agglomerated MO NPs suggests that the elemental composition and dissolution potential are major drivers of toxicity. Only ZnO caused significant adverse effects of all MO particles tested, and only when prepared in pure water (point estimate median lethal concentration = 3.5–9.1 mg/L. This toxicity was life stage dependent. The 24 h toxicity increased greatly (∼22.7 fold when zebrafish exposures started at the larval life stage compared to the 24 h toxicity following embryonic exposure. Investigation into whether dissolution could account for ZnO toxicity revealed high levels of zinc ion (40–89% of total sample were generated. Exposure to zinc ion equivalents revealed dissolved Zn2+ may be a major contributor to ZnO toxicity.

The toxic effects of chlorophenols and associated mechanisms in fish

International Nuclear Information System (INIS)

Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun

2017-01-01

Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

The toxic effects of chlorophenols and associated mechanisms in fish

Energy Technology Data Exchange (ETDEWEB)

Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun, E-mail: huangdj@lzu.edu.cn

2017-03-15

Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

Proteome Profiling of BEAS-2B Cells Treated with Titanium Dioxide Reveals Potential Toxicity of and Detoxification Pathways for Nanomaterial

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Oxidative stress is known to play important roles in nanomaterial-induced toxicities. However, the proteins and signaling pathways associated with nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify oxidative stress-responding toxicity pathways an...

In vivo toxic effects of 4-methoxy-5-hydroxy-canthin-6-one in zebrafish embryos via copper dyshomeostasis and oxidative stress.

Science.gov (United States)

Gong, Guiyi; Jiang, Lingling; Lin, Qinghua; Liu, Wenyuan; He, Ming-Fang; Zhang, Jie; Feng, Feng; Qu, Wei; Xie, Ning

2018-01-01

Dysfunction of copper homeostasis can lead to a host of disorders, which might be toxic sometimes. 4-Methoxy-5-hydroxy-canthin-6-one (CAN) is one of the major constituents from Picrasma quassioides and responsible for its therapeutic effects. In this work, we evaluated the toxic effect of CAN (7.5μM) on zebrafish embryos. CAN treatment decreased survival, delayed hatching time and induced malformations (loss of pigmentation, pericardial edema, as well as hematologic and neurologic abnormalities). Besides, exogenous copper supplementation rescued the pigmentation and cardiovascular defects in CAN-treated embryos. Further spectroscopic studies revealed a copper-chelating activity of CAN. Then its regulation on the expressions of copper homeostasis related genes also be analyzed. In addition, CAN lowered the total activity of SOD, elevated the ROS production and altered the oxidative related genes transcriptions, which led to oxidative stress. In conclusion, we demonstrated that CAN (7.5μM) might exert its toxic effects in zebrafish embryos by causing copper dyshomeostasis and oxidative stress. It will give insight into the risk assessment and prevention of CAN-mediated toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxicity of Graphene Shells, Graphene Oxide, and Graphene Oxide Paper Evaluated with Escherichia coli Biotests.

Science.gov (United States)

Efremova, Ludmila V; Vasilchenko, Alexey S; Rakov, Eduard G; Deryabin, Dmitry G

2015-01-01

The plate-like graphene shells (GS) produced by an original methane pyrolysis method and their derivatives graphene oxide (GO) and graphene oxide paper (GO-P) were evaluated with luminescent Escherichia coli biotests and additional bacterial-based assays which together revealed the graphene-family nanomaterials' toxicity and bioactivity mechanisms. Bioluminescence inhibition assay, fluorescent two-component staining to evaluate cell membrane permeability, and atomic force microscopy data showed GO expressed bioactivity in aqueous suspension, whereas GS suspensions and the GO-P surface were assessed as nontoxic materials. The mechanism of toxicity of GO was shown not to be associated with oxidative stress in the targeted soxS::lux and katG::lux reporter cells; also, GO did not lead to significant mechanical disruption of treated bacteria with the release of intracellular DNA contents into the environment. The well-coordinated time- and dose-dependent surface charge neutralization and transport and energetic disorders in the Escherichia coli cells suggest direct membrane interaction, internalization, and perturbation (i.e., "membrane stress") as a clue to graphene oxide's mechanism of toxicity.

Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Titanium Dioxide Nanoparticles

Science.gov (United States)

Oxidative stress is known to play important roles in engineered nanomaterial induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial mediated oxidative stress and toxicity are largely unknown. To identify these toxicity ...

Synaptic contacts impaired by styrene-7,8-oxide toxicity

International Nuclear Information System (INIS)

Corsi, P.; D'Aprile, A.; Nico, B.; Costa, G.L.; Assennato, G.

2007-01-01

Styrene-7,8-oxide (SO), a chemical compound widely used in industrial applications, is a potential hazard for humans, particularly in occupational settings. Neurobehavioral changes are consistently observed in occupationally exposed individuals and alterations of neurotransmitters associated with neuronal loss have been reported in animal models. Although the toxic effects of styrene have been extensively documented, the molecular mechanisms responsible for SO-induced neurotoxicity are still unclear. A possible dopamine-mediated effect of styrene neurotoxicity has been previously demonstrated, since styrene oxide alters dopamine neurotransmission in the brain. Thus, the present study hypothesizes that styrene neurotoxicity may involve synaptic contacts. Primary striatal neurons were exposed to styrene oxide at different concentrations (0.1-1 mM) for different time periods (8, 16, and 24 h) to evaluate the dose able to induce synaptic impairments. The expression of proteins crucial for synaptic transmission such as Synapsin, Synaptophysin, and RAC-1 were considered. The levels of Synaptophysin and RAC-1 decreased in a dose-dependent manner. Accordingly, morphological alterations, observed at the ultrastructural level, primarily involved the pre-synaptic compartment. In SO-exposed cultures, the biochemical cascade of caspases was activated affecting the cytoskeleton components as their target. Thus the impairments in synaptic contacts observed in SO-exposed cultures might reflect a primarily morphological alteration of neuronal cytoskeleton. In addition, our data support the hypothesis developed by previous authors of reactive oxygen species (ROS) initiating events of SO cytotoxicity

Anaerobic ammonium oxidation mediated by Mn-oxides: from sediment to strain level.

Science.gov (United States)

Javanaud, Cedric; Michotey, Valerie; Guasco, Sophie; Garcia, Nicole; Anschutz, Pierre; Canton, Mathieu; Bonin, Patricia

2011-11-01

Nitrite and (29)N(2) productions in slurry incubations of anaerobically sediment after (15)NO(3) or (15)NH(4) labelling in the presence of Mn-oxides suggested that anaerobic Mn-oxides mediated nitrification coupled with denitrification in muddy intertidal sediments of Arcachon Bay (SW Atlantic French coast). From this sediment, bacterial strains were isolated and physiologically characterized in terms of Mn-oxides and nitrate reduction as well as potential anaerobic nitrification. One of the isolated strain, identified as Marinobacter daepoensis strain M4AY14, was a denitrifier. Nitrous oxide production by this strain was demonstrated in the absence of nitrate and with Mn-oxides and NH(4) amendment, giving indirect proof of anaerobic nitrate or nitrite production. Anaerobic Mn-oxide-mediated nitrification was confirmed by (29)N(2) production in the presence of (15)NO(3) and (14)NH(4) under denitrifying conditions. Anaerobic nitrification by M4AY14 seemed to occur only in the absence of nitrate, or at nitrate levels lower than that of Mn-oxides. Most of the other isolates were affiliated with the Shewanella genus and were able to use both nitrate and Mn-oxides as electron acceptors. When both electron acceptors were present, whatever their concentrations, nitrate and Mn-oxide reduction co-occurred. These data indicate that bacterial Mn-oxide reduction could be an important process in marine sediments with low oxygen concentrations, and demonstrate for the first time the role of bacteria in anaerobic Mn-mediated nitrification. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

An integrated (electro- and bio-oxidation) approach for remediation of industrial wastewater containing azo-dyes: Understanding the degradation mechanism and toxicity assessment.

Science.gov (United States)

Aravind, Priyadharshini; Selvaraj, Hosimin; Ferro, Sergio; Sundaram, Maruthamuthu

2016-11-15

A hybrid approach for the remediation of recalcitrant dye wastewater is proposed. The chlorine-mediated electrochemical oxidation of real textile effluents and synthetic samples (using Ti/IrO2-RuO2-TiO2 anodes), lead to discoloration by 92% and 89%, respectively, in 100min, without significant mineralization. The remediation was obtained through biodegradation, after removing the residual bio-toxic active chlorine species via sunlight exposition. Results show that the electrochemical discoloration enhances the effluent biodegradability with about 90% COD removal employing acclimatized naphthalene-degrading bacterial consortia, within 144h. Based on results obtained through FT-IR and GC-MS, it is likely that azo group stripping and oxidative cleavage of dyes occur due to the nucleophilic attack of active chlorine species during electro-oxidation. This leads to generation of aromatic intermediates which are further desulfonated, deaminated or oxidized only at their functional groups. These aromatic intermediates were mineralized into simpler organic acids and aldehydes by bacterial consortia. Phyto-toxicity trials on Vigna radiata confirmed the toxic nature of the untreated dye solutions. An increase in root and shoot development was observed with the electrochemically treated solutions, the same was higher in case of bio-treated solutions. Overall, obtained results confirm the capability of the proposed hybrid oxidation scheme for the remediation of textile wastewater. Copyright © 2016 Elsevier B.V. All rights reserved.

Toxicity of Graphene Shells, Graphene Oxide, and Graphene Oxide Paper Evaluated with Escherichia coli Biotests

Directory of Open Access Journals (Sweden)

Ludmila V. Efremova

2015-01-01

Full Text Available The plate-like graphene shells (GS produced by an original methane pyrolysis method and their derivatives graphene oxide (GO and graphene oxide paper (GO-P were evaluated with luminescent Escherichia coli biotests and additional bacterial-based assays which together revealed the graphene-family nanomaterials’ toxicity and bioactivity mechanisms. Bioluminescence inhibition assay, fluorescent two-component staining to evaluate cell membrane permeability, and atomic force microscopy data showed GO expressed bioactivity in aqueous suspension, whereas GS suspensions and the GO-P surface were assessed as nontoxic materials. The mechanism of toxicity of GO was shown not to be associated with oxidative stress in the targeted soxS::lux and katG::lux reporter cells; also, GO did not lead to significant mechanical disruption of treated bacteria with the release of intracellular DNA contents into the environment. The well-coordinated time- and dose-dependent surface charge neutralization and transport and energetic disorders in the Escherichia coli cells suggest direct membrane interaction, internalization, and perturbation (i.e., “membrane stress” as a clue to graphene oxide’s mechanism of toxicity.

Epigenetic Regulation in Particulate Matter-Mediated Cardiopulmonary Toxicities: A Systems Biology Perspective.

Science.gov (United States)

Wang, Ting; Garcia, Joe Gn; Zhang, Wei

2012-12-01

Particulate matter (PM) air pollution exerts significant adverse health effects in global populations, particularly in developing countries with extensive air pollution. Understanding of the mechanisms of PM-induced health effects including the risk for cardiovascular diseases remains limited. In addition to the direct cellular physiological responses such as mitochondrial dysfunction and oxidative stress, PM mediates remarkable dysregulation of gene expression, especially in cardiovascular tissues. The PM-mediated gene dysregulation is likely to be a complex mechanism affected by various genetic and non-genetic factors. Notably, PM is known to alter epigenetic markers (e.g., DNA methylation and histone modifications), which may contribute to air pollution-mediated health consequences including the risk for cardiovascular diseases. Notably, epigenetic changes induced by ambient PM exposure have emerged to play a critical role in gene regulation. Though the underlying mechanism(s) are not completely clear, the available evidence suggests that the modulated activities of DNA methyltransferase (DNMT), histone acetylase (HAT) and histone deacetylase (HDAC) may contribute to the epigenetic changes induced by PM or PM-related chemicals. By employing genome-wide epigenomic and systems biology approaches, PM toxicogenomics could conceivably progress greatly with the potential identification of individual epigenetic loci associated with dysregulated gene expression after PM exposure, as well the interactions between epigenetic pathways and PM. Furthermore, novel therapeutic targets based on epigenetic markers could be identified through future epigenomic studies on PM-mediated cardiopulmonary toxicities. These considerations collectively inform the future population health applications of genomics in developing countries while benefiting global personalized medicine at the same time.

The benzoquinone-mediated electrochemical microbial biosensor for water biotoxicity assay

International Nuclear Information System (INIS)

Li, Jiuming; Yu, Yuan; Wang, Yuning; Qian, Jun; Zhi, Jinfang

2013-01-01

Graphical abstract: The mediator can participate in microorganism respiration, accept the electrons from respiratory chains, and therefore be reduced by microorganism. The re-oxidization currents of mediators on electrode can reflect the microbial activity, and when respiration is suppressed by toxicants, it can be detected by the resulting change of currents. Unlike other biotoxicity tests, which record the toxic effect after a fixed time for incubation of biocomponents and toxicants, this mediated whole cell biosensor can provide a real-time monitor of the microbial activity during the measurement. -- Abstract: A simple mediated microbial biosensor providing real-time monitoring of water quality and evaluation of biotoxicity was fabricated by entrapping Escherichia coli (E. coli) cells in gelatin on glassy carbon electrode with benzoquinone as the redox mediator. The biotoxicity assay was based on the respiratory activity of E. coli cells estimated by the oxidation current of microbially reduced benzoquinone. The neutrality and lipophilicity rendered benzoquinone better efficiency than ferricyanide in mediated microbial reactions. After the optimization of preparation conditions, the prepared microbial biosensors have measured several common toxicants with different concentrations. In addition, the biotoxicity of binary mixtures of heavy metals and wastewater were investigated. The fabricated biosensor exhibited good repeatability and stability in the biotoxicity measurements

Toxicity, toxicokinetics and biodistribution of dextran stabilized Iron oxide Nanoparticles for biomedical applications.

Science.gov (United States)

Remya, N S; Syama, S; Sabareeswaran, A; Mohanan, P V

2016-09-10

Advancement in the field of nanoscience and technology has alarmingly raised the call for comprehending the potential health effects caused by deliberate or unintentional exposure to nanoparticles. Iron oxide magnetic nanoparticles have an increasing number of biomedical applications and hence a complete toxicological profile of the nanomaterial is therefore a mandatory requirement prior to its intended usage to ensure safety and to minimize potential health hazards upon its exposure. The present study elucidates the toxicity of in house synthesized Dextran stabilized iron oxide nanoparticles (DINP) in a regulatory perspective through various routes of exposure, its associated molecular, immune, genotoxic, carcinogenic effects and bio distribution profile. Synthesized ferrite nanomaterials were successfully coated with dextran (dextran helps in improvising particle stability in biological environments. The nanoparticles do not seem to induce oxidative stress mediated toxicological effects, nor altered physiological process or behavior changes or visible pathological lesions. Furthermore no anticipated health hazards are likely to be associated with the use of DINP and could be concluded that the synthesized DINP is nontoxic/safe to be used for biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Toxicity of Transition Metal Oxide Nanoparticles: Recent Insights from in vitro Studies

Directory of Open Access Journals (Sweden)

Robert S. Aronstam

2010-10-01

Full Text Available Nanotechnology has evolved to play a prominent role in our economy. Increased use of nanomaterials poses potential human health risk. It is therefore critical to understand the nature and origin of the toxicity imposed by nanomaterials (nanotoxicity. In this article we review the toxicity of the transition metal oxides in the 4th period that are widely used in industry and biotechnology. Nanoparticle toxicity is compellingly related to oxidative stress and alteration of calcium homeostasis, gene expression, pro-inflammatory responses, and cellular signaling events. The precise physicochemical properties that dictate the toxicity of nanoparticles have yet to be defined, but may include element-specific surface catalytic activity (e.g., metallic, semiconducting properties, nanoparticle uptake, or nanoparticle dissolution. These in vitro studies substantially advance our understanding in mechanisms of toxicity, which may lead to safer design of nanomaterials.

A novel approach for rapidly and cost-effectively assessing toxicity of toxic metals in acidic water using an acidophilic iron-oxidizing biosensor.

Science.gov (United States)

Yang, Shih-Hung; Cheng, Kuo-Chih; Liao, Vivian Hsiu-Chuan

2017-11-01

Contamination by heavy metals and metalloids is a serious environmental and health concern. Acidic wastewaters are often associated with toxic metals which may enter and spread into agricultural soils. Several biological assays have been developed to detect toxic metals; however, most of them can only detect toxic metals in a neutral pH, not in an acidic environment. In this study, an acidophilic iron-oxidizing bacterium (IOB) Strain Y10 was isolated, characterized, and used to detect toxic metals toxicity in acidic water at pH 2.5. The colorimetric acidophilic IOB biosensor was based on the inhibition of the iron oxidizing ability of Strain Y10, an acidophilic iron-oxidizing bacterium, by metals toxicity. Our results showed that Strain Y10 is acidophilic iron-oxidizing bacterium. Thiobacillus caldus medium (TCM) (pH 2.5) supplied with both S 4 O 6 2- and glucose was the optimum growth medium for Strain Y10. The optimum temperature and pH for the growth of Strain Y10 was 45 °C and pH 2.5, respectively. Our study demonstrates that the color-based acidophilic IOB biosensor can be semi-quantitatively observed by eye or quantitatively measured by spectrometer to detect toxicity from multiple toxic metals at pH 2.5 within 45 min. Our study shows that monitoring toxic metals in acidic water is possible by using the acidophilic IOB biosensor. Our study thus provides a novel approach for rapid and cost-effective detection of toxic metals in acidic conditions that can otherwise compromise current methods of chemical analysis. This method also allows for increased efficiency when screening large numbers of environmental samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of oxidative stress in cadmium toxicity and carcinogenesis

International Nuclear Information System (INIS)

Liu Jie; Qu Wei; Kadiiska, Maria B.

2009-01-01

Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superoxide anion, hydrogen peroxide, and hydroxyl radicals in vivo have been detected by the electron spin resonance spectra, which are often accompanied by activation of redox sensitive transcription factors (e.g., NF-κB, AP-1 and Nrf2) and alteration of ROS-related gene expression. It is generally agreed upon that oxidative stress plays important roles in acute Cd poisoning. However, following long-term Cd exposure at environmentally-relevant low levels, direct evidence for oxidative stress is often obscure. Alterations in ROS-related gene expression during chronic exposures are also less significant compared to acute Cd poisoning. This is probably due to induced adaptation mechanisms (e.g., metallothionein and glutathione) following chronic Cd exposures, which in turn diminish Cd-induced oxidative stress. In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis. Thus, ROS are generated following acute Cd overload and play important roles in tissue damage. Adaptation to chronic Cd exposure reduces ROS production, but acquired Cd tolerance with aberrant gene expression plays important roles in chronic Cd toxicity and carcinogenesis.

Vitamin E and Lycopene Reduce Coal Burning Fluorosis-induced Spermatogenic Cell Apoptosis via Oxidative Stress-mediated JNK and ERK Signaling Pathways.

Science.gov (United States)

Tian, Yuan; Xiao, Yuehai; Wang, Bolin; Sun, Chao; Tang, Kaifa; Sun, Fa

2017-12-22

Although fluoride has been widely used in toothpaste, mouthwash, and drinking water to prevent dental caries, the excessive intake of fluoride can cause fluorosis which is associated with dental, skeletal, and soft tissue fluorosis. Recent evidences have drawn the attention to its adverse effects on male reproductive system that include spermatogenesis defect, sperm count loss, and sperm maturation impairment. Fluoride induces oxidative stress through the activation of mitogen activated protein kinase (MAPK) cascade which can lead to cell apoptosis. Vitamin E (VE) and lycopene are two common anti-oxidants, being protective to reactive oxygen species (ROS)-induced toxic effects. However, whether and how these two anti-oxidants prevent fluoride-induced spermatogenic cell apoptosis are largely unknown. In the present study, a male rat model for coal burning fluorosis was established and the histological lesions and spermatogenic cell apoptosis in rat testes were observed. The decreased expression of clusterin, a heterodimeric glycoprotein reported to regulate spermatogenic cell apoptosis, is detected in fluoride-treated rat testes. Interestingly, the co-administration with VE or lycopene reduced fluorosis-mediated testicular toxicity and rescued clusterin expression. Further, fluoride caused the enhanced Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) phosphorylation, which was reduced by VE or lycopene. Thus, VE and lycopene prevent coal burning fluorosis-induced spermatogenic cell apoptosis through the suppression of oxidative stress-mediated JNK and ERK signaling pathway, which could be an alternative therapeutic strategy for the treatment of fluorosis. ©2017 The Author(s).

Oxidation of ciprofloxacin and enrofloxacin by ferrate(VI): Products identification, and toxicity evaluation

International Nuclear Information System (INIS)

Yang, Bin; Kookana, Rai S.; Williams, Mike; Ying, Guang-Guo; Du, Jun; Doan, Hai; Kumar, Anupama

2016-01-01

Ferrate(VI) (Fe(VI)) has been known to react with emerging organic contaminants containing electron-rich organic moieties, such as phenols, anilines, olefins, reduced sulfur and deprotonated amines. Oxidation of fluoroquinolone antibiotics, ciprofloxacin (CIP) and enrofloxacin (ENR), by Fe(VI) were investigated for their reaction products and toxicity changes as well as biodegradability of these products. Ten products were identified for both CIP and ENR reactions with Fe(VI) using a high-resolution accurate-mass Orbitrap mass analyzer. Structural changes to the CIP and ENR molecule included dealkylation, formation of alcohols and amides in piperazine ring and oxygen transfer to the double bond in quinolone structure. An enamine formation mechanism was tentatively proposed to facilitate the interpretation of CIP and ENR oxidation pathways. Toxicity evaluation using Microbial Assay for toxicity Risk Assessment (MARA) bioassay indicated that Fe(VI) oxidation products of CIP and ENR contributed negligible antibacterial potency and Fe(VI) oxidation treatment can remove the residual toxicity of CIP and ENR impacted source waters. The Fe(VI) oxidation treatment resulted in formation of relatively more biodegradable products (based on in silico assessment) than their corresponding parent compounds. The results showed that Fe(VI) has a good potential to degrade fluoroquinolone antibiotics and their antimicrobial potency in natural waters.

Oxidation of ciprofloxacin and enrofloxacin by ferrate(VI): Products identification, and toxicity evaluation

Energy Technology Data Exchange (ETDEWEB)

Yang, Bin, E-mail: Bin.Yang@csiro.au [CSIRO Land and Water, Waite Campus, PMB 2, Glen Osmond, South Australia 5064 (Australia); Kookana, Rai S.; Williams, Mike [CSIRO Land and Water, Waite Campus, PMB 2, Glen Osmond, South Australia 5064 (Australia); Ying, Guang-Guo [State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Du, Jun; Doan, Hai; Kumar, Anupama [CSIRO Land and Water, Waite Campus, PMB 2, Glen Osmond, South Australia 5064 (Australia)

2016-12-15

Ferrate(VI) (Fe(VI)) has been known to react with emerging organic contaminants containing electron-rich organic moieties, such as phenols, anilines, olefins, reduced sulfur and deprotonated amines. Oxidation of fluoroquinolone antibiotics, ciprofloxacin (CIP) and enrofloxacin (ENR), by Fe(VI) were investigated for their reaction products and toxicity changes as well as biodegradability of these products. Ten products were identified for both CIP and ENR reactions with Fe(VI) using a high-resolution accurate-mass Orbitrap mass analyzer. Structural changes to the CIP and ENR molecule included dealkylation, formation of alcohols and amides in piperazine ring and oxygen transfer to the double bond in quinolone structure. An enamine formation mechanism was tentatively proposed to facilitate the interpretation of CIP and ENR oxidation pathways. Toxicity evaluation using Microbial Assay for toxicity Risk Assessment (MARA) bioassay indicated that Fe(VI) oxidation products of CIP and ENR contributed negligible antibacterial potency and Fe(VI) oxidation treatment can remove the residual toxicity of CIP and ENR impacted source waters. The Fe(VI) oxidation treatment resulted in formation of relatively more biodegradable products (based on in silico assessment) than their corresponding parent compounds. The results showed that Fe(VI) has a good potential to degrade fluoroquinolone antibiotics and their antimicrobial potency in natural waters.

Metal Oxide Nanomaterial QNAR Models: Available Structural Descriptors and Understanding of Toxicity Mechanisms

Directory of Open Access Journals (Sweden)

Jiali Ying

2015-10-01

Full Text Available Metal oxide nanomaterials are widely used in various areas; however, the divergent published toxicology data makes it difficult to determine whether there is a risk associated with exposure to metal oxide nanomaterials. The application of quantitative structure activity relationship (QSAR modeling in metal oxide nanomaterials toxicity studies can reduce the need for time-consuming and resource-intensive nanotoxicity tests. The nanostructure and inorganic composition of metal oxide nanomaterials makes this approach different from classical QSAR study; this review lists and classifies some structural descriptors, such as size, cation charge, and band gap energy, in recent metal oxide nanomaterials quantitative nanostructure activity relationship (QNAR studies and discusses the mechanism of metal oxide nanomaterials toxicity based on these descriptors and traditional nanotoxicity tests.

Surface interactions affect the toxicity of engineered metal oxide nanoparticles toward Paramecium.

Science.gov (United States)

Li, Kungang; Chen, Ying; Zhang, Wen; Pu, Zhichao; Jiang, Lin; Chen, Yongsheng

2012-08-20

To better understand the potential impacts of engineered metal oxide nanoparticles (NPs) in the ecosystem, we investigated the acute toxicity of seven different types of engineered metal oxide NPs against Paramecium multimicronucleatum, a ciliated protozoan, using the 48 h LC(50) (lethal concentration, 50%) test. Our results showed that the 48 h LC(50) values of these NPs to Paramecium ranged from 0.81 (Fe(2)O(3) NPs) to 9269 mg/L (Al(2)O(3) NPs); their toxicity to Paramecium increased as follows: Al(2)O(3) Paramecium; this implies that metal oxide NPs with strong association with the cell surface might induce more severe cytotoxicity in unicellular organisms.

Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

International Nuclear Information System (INIS)

Balmuri, Sricharani Rao; Selvaraj, Uthra; Kumar, Vadivel Vinod; Anthony, Savarimuthu Philip; Tsatsakis, Aristides Michael; Golokhvast, Kirill Sergeevich; Raman, Thiagarajan

2017-01-01

Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH) 2 without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd 2+ ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd 2+ ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd 2+ from sources such as cigarette smoke. - Highlights: • Toxicity of Cd

Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

Energy Technology Data Exchange (ETDEWEB)

Balmuri, Sricharani Rao [Department of Bioengineering, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Selvaraj, Uthra [Department of Biotechnology, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Kumar, Vadivel Vinod [Department of Chemistry, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Anthony, Savarimuthu Philip, E-mail: philip@biotech.sastra.edu [Department of Chemistry, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Tsatsakis, Aristides Michael [Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Heraklion 71003 (Greece); Scientific Educational Center of Nanotechnology, Far Eastern Federal University, Vladivostok 690990 (Russian Federation); Golokhvast, Kirill Sergeevich [Scientific Educational Center of Nanotechnology, Far Eastern Federal University, Vladivostok 690990 (Russian Federation); Raman, Thiagarajan, E-mail: raman@biotech.sastra.edu [Department of Bioengineering, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Centre for Research in Infectious Diseases (CRID), School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India)

2017-01-15

Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH){sub 2} without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd{sup 2+} ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd{sup 2+} ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd{sup 2+} from sources such as cigarette smoke. - Highlights: �

Ferroxidase-Mediated Iron Oxide Biomineralization

DEFF Research Database (Denmark)

Zeth, Kornelius; Hoiczyk, Egbert; Okuda, Mitsuhiro

2016-01-01

Iron oxide biomineralization occurs in all living organisms and typically involves protein compartments ranging from 5 to 100nm in size. The smallest iron-oxo particles are formed inside dodecameric Dps protein cages, while the structurally related ferritin compartments consist of twice as many......, translocation, oxidation, nucleation, and storage, that are mediated by ferroxidase centers. Thus, compartmentalized iron oxide biomineralization yields uniform nanoparticles strictly determined by the sizes of the compartments, allowing customization for highly diverse nanotechnological applications....... identical protein subunits. The largest known compartments are encapsulins, icosahedra made of up to 180 protein subunits that harbor additional ferritin-like proteins in their interior. The formation of iron-oxo particles in all these compartments requires a series of steps including recruitment of iron...

Comparative toxicity of tetra ethyl lead and lead oxide to earthworms, Eisenia fetida (Savigny)

International Nuclear Information System (INIS)

Venkateswara Rao, J.; Kavitha, P.; Padmanabha Rao, A.

2003-01-01

Leaded gasoline contains tetra ethyl lead (TEL) as an antiknocking agent, which produces major amounts of lead oxide in automobile exhaust along with traces of TEL. To minimize the lead contamination, methyl tertiary butyl ether (MTBE) is used as a substitute for producing unleaded gasoline. It has become increasingly apparent that young children are highly susceptible to the harmful effects of lead. Hence, a study was carried out to monitor lead toxicity in soil, using adult earthworms (Eisenia fetida, Savigny). Leaded gasoline (TEL) and lead oxide are 383- and 211-fold more toxic than unleaded gasoline (MTBE) in 7 days of exposure and 627- and 290-fold more toxic in 14 days, respectively. Results indicate that the presence of TEL in leaded gasoline and lead oxide has a significant effect on behavior, morphology, and histopathology of earthworms. Absorption of TEL into the tissues is comparatively less than that of lead oxide but toxic effects were severe. Rupture of the cuticle, extrusion of coelomic fluid and inflexible metameric segmentation were observed, causing desensitization of the posterior region leading to fragmentation in earthworms

Intracellular haemolytic agents of Heterocapsa circularisquama exhibit toxic effects on H. circularisquama cells themselves and suppress both cell-mediated haemolytic activity and toxicity to rotifers (Brachionus plicatilis).

Science.gov (United States)

Nishiguchi, Tomoki; Cho, Kichul; Yasutomi, Masumi; Ueno, Mikinori; Yamaguchi, Kenichi; Basti, Leila; Yamasaki, Yasuhiro; Takeshita, Satoshi; Kim, Daekyung; Oda, Tatsuya

2016-10-01

A harmful dinoflagellate, Heterocapsa circularisquama, is highly toxic to shellfish and the zooplankton rotifer Brachionus plicatilis. A previous study found that H. circularisquama has both light-dependent and -independent haemolytic agents, which might be responsible for its toxicity. Detailed analysis of the haemolytic activity of H. circularisquama suggested that light-independent haemolytic activity was mediated mainly through intact cells, whereas light-dependent haemolytic activity was mediated by intracellular agents which can be discharged from ruptured cells. Because H. circularisquama showed similar toxicity to rotifers regardless of the light conditions, and because ultrasonic ruptured H. circularisquama cells showed no significant toxicity to rotifers, it was suggested that live cell-mediated light-independent haemolytic activity is a major factor responsible for the observed toxicity to rotifers. Interestingly, the ultrasonic-ruptured cells of H. circularisquama suppressed their own lethal effect on the rotifers. Analysis of samples of the cell contents (supernatant) and cell fragments (precipitate) prepared from the ruptured H. circularisquama cells indicated that the cell contents contain inhibitors for the light-independent cell-mediated haemolytic activity, toxins affecting H. circularisquama cells themselves, as well as light-dependent haemolytic agents. Ethanol extract prepared from H. circularisquama, which is supposed to contain a porphyrin derivative that displays photosensitising haemolytic activity, showed potent toxicity to Chattonella marina, Chattonella antiqua, and Karenia mikimotoi, as well as to H. circularisquama at the concentration range at which no significant toxicity to rotifers was observed. Analysis on a column of Sephadex LH-20 revealed that light-dependent haemolytic activity and inhibitory activity on cell-mediated light-independent haemolytic activity existed in two separate fractions (f-2 and f-3), suggesting that both

Extremely radioresistant microbe Deinococcus radiodurans does not survive tellurite-mediated oxidative stress: revelation of molecular basis

International Nuclear Information System (INIS)

Apte, Shree Kumar; Narasimha, Anaganti; Basu, Bhakti

2014-01-01

Deinococcus radiodurans exhibits extraordinary resistance to gamma radiation as well as oxidative stress. Comparison of tellurite stress with gamma irradiation, both of which impart severe oxidative stress, revealed that tellurite induced less ROS and caused less oxidative damage to proteins, but was much more lethal to D. radiodurans than gamma irradiation. The proteomic changes induced by tellurite exposure were mapped by two dimensional protein electrophoresis followed by mass spectrometry. Seventy proteins belonging to major functional categories of oxidative stress alleviation, protein translation/folding and metabolism were identified. Tellurite responsive proteome dynamics displayed (i) up-regulation of proteins involved in tellurite stress resistance and oxidative stress alleviation, dehydrogenases involved in generation of reducing potential, and chaperones (such DnaK), and (ii) down regulation of key glycolysis and TCA cycle enzymes, proteins involved in protein translation/folding and energy production. Tellurite stress also resulted in nearly 50% loss in the cellular reducing potential within 1h of exposure while gamma irradiation had no such effect. The findings provide a better insight into the mechanism of tellurite toxicity, beyond metal mediated oxidative stress, in this extremophile. (author)

Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro.

Science.gov (United States)

Wang, Xu; Wu, Qinghua; Liu, Aimei; Anadón, Arturo; Rodríguez, José-Luis; Martínez-Larrañaga, María-Rosa; Yuan, Zonghui; Martínez, María-Aránzazu

2017-11-01

Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.

Oxidation of indometacin by ferrate (VI): kinetics, degradation pathways, and toxicity assessment.

Science.gov (United States)

Huang, Junlei; Wang, Yahui; Liu, Guoguang; Chen, Ping; Wang, Fengliang; Ma, Jingshuai; Li, Fuhua; Liu, Haijin; Lv, Wenying

2017-04-01

The oxidation of indometacin (IDM) by ferrate(VI) (Fe(VI)) was investigated to determine the reaction kinetics, transformation products, and changes in toxicity. The reaction between IDM and Fe(VI) followed first-order kinetics with respect to each reactant. The apparent second-order rate constants (k app ) decreased from 9.35 to 6.52 M -1  s -1 , as the pH of the solution increased from 7.0 to 10.0. The pH dependence of k app might be well explained by considering the species-specific rate constants of the reactions of IDM with Fe(VI). Detailed product studies using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the oxidation products were primarily derived from the hydrolysis of amide linkages, the addition of hydroxyl groups, and electrophilic oxidation. The toxicity of the oxidation products was evaluated using the Microtox test, which indicated that transformation products exhibited less toxicity to the Vibrio fischeri bacteria. Quantitative structure-activity relationship (QSAR) analysis calculated by the ecological structure activity relationship (ECOSAR) revealed that all of the identified products exhibited lower acute and chronic toxicity than the parent pharmaceutical for fish, daphnid, and green algae. Furthermore, Fe(VI) was effective in the degradation IDM in water containing carbonate ions or fulvic acid (FA), and in lake water samples; however, higher Fe(VI) dosages would be required to completely remove IDM in lake water in contrast to deionized water.

Nutritionally Mediated Oxidative Stress and Inflammation

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Alexandra Muñoz

2013-01-01

Full Text Available There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NFκB. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF-α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CXCL2/MIP-2α, and CXCL3/MIP-2β is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNFα, IL-1β, and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.

Characteristics of MOX dissolution with silver mediated electrolytic oxidation method

Energy Technology Data Exchange (ETDEWEB)

Umeda, Miki; Nakazaki, Masato; Kida, Takashi; Sato, Kenji; Kato, Tadahito; Kihara, Takehiro; Sugikawa, Susumu [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

2003-03-01

MOX dissolution with silver mediated electrolytic oxidation method is to be applied to the preparation of plutonium nitrate solution to be used for criticality safety experiments at Nuclear Fuel Cycle Safety Engineering Research Facility (NUCEF). Silver mediated electrolytic oxidation method uses the strong oxidisation ability of Ag(II) ion. This method is though to be effective for the dissolution of MOX, which is difficult to be dissolved with nitric acid. In this paper, the results of experiments on dissolution with 100 g of MOX are described. It was confirmed from the results that the MOX powder to be used at NUCEF was completely dissolved by silver mediated electrolytic oxidation method and that Pu(VI) ion in the obtained solution was reduced to tetravalent by means of NO{sub 2} purging. (author)

Role of Zn doping in oxidative stress mediated cytotoxicity of TiO2 nanoparticles in human breast cancer MCF-7 cells

Science.gov (United States)

Ahamed, Maqusood; Khan, M. A. Majeed; Akhtar, Mohd Javed; Alhadlaq, Hisham A.; Alshamsan, Aws

2016-07-01

We investigated the effect of Zn-doping on structural and optical properties as well as cellular response of TiO2 nanoparticles (NPs) in human breast cancer MCF-7 cells. A library of Zn-doped (1-10 at wt%) TiO2 NPs was prepared. Characterization data indicated that dopant Zn was incorporated into the lattice of host TiO2. The average particle size of TiO2 NPs was decreases (38 to 28 nm) while the band gap energy was increases (3.35 eV-3.85 eV) with increasing the amount of Zn-doping. Cellular data demonstrated that Zn-doped TiO2 NPs induced cytotoxicity (cell viability reduction, membrane damage and cell cycle arrest) and oxidative stress (reactive oxygen species generation & glutathione depletion) in MCF-7 cells and toxic intensity was increases with increasing the concentration of Zn-doping. Molecular data revealed that Zn-doped TiO2 NPs induced the down-regulation of super oxide dismutase gene while the up-regulation of heme oxygenase-1 gene in MCF-7 cells. Cytotoxicity induced by Zn-doped TiO2 NPs was efficiently prevented by N-acetyl-cysteine suggesting that oxidative stress might be the primarily cause of toxicity. In conclusion, our data indicated that Zn-doping decreases the particle size and increases the band gap energy as well the oxidative stress-mediated toxicity of TiO2 NPs in MCF-7 cells.

Mechanism of oxidative stress involved in the toxicity of ZnO nanoparticles against eukaryotic cells

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M. Saliani

2016-01-01

Full Text Available ZnO NPs (zinc oxide nanoparticles has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.

Toxicity of multi-walled carbon nanotubes, graphene oxide, and reduced graphene oxide to zebrafish embryos.

Science.gov (United States)

Liu, Xiao Tong; Mu, Xi Yan; Wu, Xiao Li; Meng, Li Xuan; Guan, Wen Bi; Ma, Yong Qiang; Sun, Hua; Wang, Cheng Ju; Li, Xue Feng

2014-09-01

This study was aimed to investigate the toxic effects of 3 nanomaterials, i.e. multi-walled carbon nanotubes (MWCNTs), graphene oxide (GO), and reduced graphene oxide (RGO), on zebrafish embryos. The 2-h post-fertilization (hpf) zebrafish embryos were exposed to MWCNTs, GO, and RGO at different concentrations (1, 5, 10, 50, 100 mg/L) for 96 h. Afterwards, the effects of the 3 nanomateria on spontaneous movement, heart rate, hatching rate, length of larvae, mortality, and malformations ls were evaluated. Statistical analysis indicated that RGO significantly inhibited the hatching of zebrafish embryos. Furthermore, RGO and MWCNTs decreased the length of the hatched larvae at 96 hpf. No obvious morphological malformation or mortality was observed in the zebrafish embryos after exposure to the three nanomaterials. MWCNTs, GO, and RGO were all toxic to zebrafish embryos to influence embryos hatching and larvae length. Although no obvious morphological malformation and mortality were observed in exposed zebrafish embryos, further studies on the toxicity of the three nanomaterials are still needed. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer.

Science.gov (United States)

Kovacic, Peter

2005-01-01

Cocaine is one of the principal drugs of abuse. Although impressive advances have been made, unanswered questions remain concerning mechanism of toxicity and addiction. Discussion of action mode usually centers on receptor binding and enzyme inhibition, with limited attention to events at the molecular level. This review provides extensive evidence in support of the hypothesis that oxidative metabolites play important roles comprising oxidative stress (OS), reactive oxygen species (ROS), and electron transfer (ET). The metabolites include norcocaine and norcocaine derivatives: nitroxide radical, N-hydroxy, nitrosonium, plus cocaine iminium and formaldehyde. Observed formation of ROS is rationalized by redox cycling involving several possible ET agents. Three potential ones are present in the form of oxidative metabolites, namely, nitroxide, nitrosonium, and iminium. Most attention has been devoted to the nitroxide-hydroxylamine couple which has been designated by various investigators as the principal source of ROS. The proximate ester substituent is deemed important for intramolecular stabilization of reactive intermediates. Reduction potential of nitroxide is in accord with plausibility of ET in the biological milieu. Toxicity by cocaine, with evidence for participation of OS, is demonstrated for many body components, including liver, central nervous system, cardiovascular system, reproductive system, kidney, mitochondria, urine, and immune system. Other adverse effects associated with ROS comprise teratogenesis and apoptosis. Examples of ROS generated are lipid peroxides and hydroxyl radical. Often observed were depletion of antioxidant defenses, and protection by added antioxidants, such as, thiol, salicylate, and deferoxamine. Considerable evidence supports the contention that oxidative ET metabolites of cocaine are responsible for much of the observed OS. Quite significantly, the pro-oxidant, toxic effects, including generation of superoxide and lipid peroxyl

From basic physics to mechanisms of toxicity: the ``liquid drop'' approach applied to develop predictive classification models for toxicity of metal oxide nanoparticles

Science.gov (United States)

Sizochenko, Natalia; Rasulev, Bakhtiyor; Gajewicz, Agnieszka; Kuz'min, Victor; Puzyn, Tomasz; Leszczynski, Jerzy

2014-10-01

Many metal oxide nanoparticles are able to cause persistent stress to live organisms, including humans, when discharged to the environment. To understand the mechanism of metal oxide nanoparticles' toxicity and reduce the number of experiments, the development of predictive toxicity models is important. In this study, performed on a series of nanoparticles, the comparative quantitative-structure activity relationship (nano-QSAR) analyses of their toxicity towards E. coli and HaCaT cells were established. A new approach for representation of nanoparticles' structure is presented. For description of the supramolecular structure of nanoparticles the ``liquid drop'' model was applied. It is expected that a novel, proposed approach could be of general use for predictions related to nanomaterials. In addition, in our study fragmental simplex descriptors and several ligand-metal binding characteristics were calculated. The developed nano-QSAR models were validated and reliably predict the toxicity of all studied metal oxide nanoparticles. Based on the comparative analysis of contributed properties in both models the LDM-based descriptors were revealed to have an almost similar level of contribution to toxicity in both cases, while other parameters (van der Waals interactions, electronegativity and metal-ligand binding characteristics) have unequal contribution levels. In addition, the models developed here suggest different mechanisms of nanotoxicity for these two types of cells.Many metal oxide nanoparticles are able to cause persistent stress to live organisms, including humans, when discharged to the environment. To understand the mechanism of metal oxide nanoparticles' toxicity and reduce the number of experiments, the development of predictive toxicity models is important. In this study, performed on a series of nanoparticles, the comparative quantitative-structure activity relationship (nano-QSAR) analyses of their toxicity towards E. coli and HaCaT cells were

Nitric oxide donors prevent while the nitric oxide synthase inhibitor L-NAME increases arachidonic acid plus CYP2E1-dependent toxicity

International Nuclear Information System (INIS)

Wu Defeng; Cederbaum, Arthur

2006-01-01

Polyunsaturated fatty acids such as arachidonic acid (AA) play an important role in alcohol-induced liver injury. AA promotes toxicity in rat hepatocytes with high levels of cytochrome P4502E1 and in HepG2 E47 cells which express CYP2E1. Nitric oxide (NO) participates in the regulation of various cell activities as well as in cytotoxic events. NO may act as a protectant against cytotoxic stress or may enhance cytotoxicity when produced at elevated concentrations. The goal of the current study was to evaluate the effect of endogenously or exogenously produced NO on AA toxicity in liver cells with high expression of CYP2E1 and assess possible mechanisms for its actions. Pyrazole-induced rat hepatocytes or HepG2 cells expressing CYP2E1 were treated with AA in the presence or absence of an inhibitor of nitric oxide synthase L-N G -Nitroarginine Methylester (L-NAME) or the NO donors S-nitroso-N-acetylpenicillamine (SNAP), and (Z)-1-[-(2-aminoethyl)-N-(2-aminoethyl)]diazen-1-ium-1,2-diolate (DETA-NONO). AA decreased cell viability from 100% to 48 ± 6% after treatment for 48 h. In the presence of L-NAME, viability was further lowered to 23 ± 5%, while, SNAP or DETA-NONO increased viability to 66 ± 8 or 71 ± 6%. The L-NAME potentiated toxicity was primarily necrotic in nature. L-NAME did not affect CYP2E1 activity or CYP2E1 content. SNAP significantly lowered CYP2E1 activity but not protein. AA treatment increased lipid peroxidation and lowered GSH levels. L-NAME potentiated while SNAP prevented these changes. Thus, L-NAME increased, while NO donors decreased AA-induced oxidative stress. Antioxidants prevented the L-NAME potentiation of AA toxicity. Damage to mitochondria by AA was shown by a decline in the mitochondrial membrane potential (MMP). L-NAME potentiated this decline in MMP in association with its increase in AA-induced oxidative stress and toxicity. NO donors decreased this decline in MMP in association with their decrease in AA-induced oxidative stress and

Zinc oxide nanoparticles mediated cytotoxicity, mitochondrial membrane potential and level of antioxidants in presence of melatonin.

Science.gov (United States)

Sruthi, S; Millot, N; Mohanan, P V

2017-10-01

Zinc oxide nanoparticles (ZnO NPs) are widely used in a variety of products and are currently being investigated for biomedical applications. However, they have the potential to interact with macromolecules like proteins, lipids and DNA within the cells which makes the safe biomedical application difficult. The toxicity of the ZnO NP is mainly attributed reactive oxygen species (ROS) generation. Different strategies like iron doping, polymer coating and external supply of antioxidants have been evaluated to minimize the toxic potential of ZnO NPs. Melatonin is a hormone secreted by the pineal gland with great antioxidant properties. The melatonin is known to protect cells from ROS inducing external agents like lipopolysaccharides. In the present study, the protective effect of melatonin on ZnO NPs mediated toxicity was evaluated using C6 glial cells. The Cytotoxicity, mitochondrial membrane potential and free radical formation were measured to study the effect of melatonin. Antioxidant assays were done on mice brain slices, incubated with melatonin and ZnO NPs. The results of the study reveal that, instead of imparting a protective effect, the melatonin pre-treatment enhanced the toxicity of ZnO NPs. Melatonin increased antioxidant enzymes in brain slices. Copyright © 2017 Elsevier B.V. All rights reserved.

Mediated electrochemical hazardous waste destruction

International Nuclear Information System (INIS)

Hickman, R.G.; Farmer, J.C.; Wang, F.T.

1992-03-01

There are few permitted processes for mixed waste (radioactive plus chemically hazardous) treatment. We are developing an electrochemical process, based upon mediated electrochemical oxidation (MEO), that converts toxic organic components of mixed waste to water, carbon dioxide, and chloride or chloride precipitates. Aggressive oxidizer ions such as Ag 2+ , Co 3+ , or Fe 3+ are produced at an anode. These can attack organic molecules directly, and may also produce hydroxyl free radicals that promote destruction. Solid and liquid radioactive waste streams containing only inorganic radionuclide forms may be treated with existing technology and prepared for final disposal. The coulombic efficiency of the process has been determined, as well as the destruction efficiency for ethylene glycol, a surrogate waste. In addition, hazardous organic materials are becoming very expensive to dispose of and when they are combined with transuranic radioactive elements no processes are presently permitted. Mediated electrochemical oxidation is an ambient- temperature aqueous-phase process that can be used to oxidize organic components of mixed wastes. Problems associated with incineration, such as high-temperature volatilization of radionuclides, are avoided. Historically, Ag(II) has been used as a mediator in this process. Fe(III) and Co(III) are attractive alternatives to Ag(II) since they form soluble chlorides during the destruction of chlorinated solvents. Furthermore, silver itself is toxic heavy metal. Quantitative data have been obtained for the complete oxidation of ethylene glycol by Fe(III) and Co(III). Though ethylene glycol is a nonhalogenated organic, these data have enabled us to make direct comparisons of activities of Fe(III) and Co(III) with Ag(II). Very good quantitative data for the oxidation of ethylene glycol by Ag(II) had already been collected

Cerium oxide and platinum nanoparticles protect cells from oxidant-mediated apoptosis

International Nuclear Information System (INIS)

Clark, Andrea; Zhu Aiping; Sun Kai; Petty, Howard R.

2011-01-01

Catalytic nanoparticles represent a potential clinical approach to replace or correct aberrant enzymatic activities in patients. Several diseases, including many blinding eye diseases, are promoted by excessive oxidant stress due to reactive oxygen species (ROS). Cerium oxide and platinum nanoparticles represent two potentially therapeutic nanoparticles that de-toxify ROS. In the present study, we directly compare these two classes of catalytic nanoparticles. Cerium oxide and platinum nanoparticles were found to be 16 ± 2.4 and 1.9 ± 0.2 nm in diameter, respectively. Using surface plasmon-enhanced microscopy, we find that these nanoparticles associate with cells. Furthermore, cerium oxide and platinum nanoparticles demonstrated superoxide dismutase catalytic activity, but did not promote hemolytic or cytolytic pathways in living cells. Importantly, both cerium oxide and platinum nanoparticles reduce oxidant-mediated apoptosis in target cells as judged by the activation of caspase 3. The ability to diminish apoptosis may contribute to maintaining healthy tissues.

Exiguobacterium mediated arsenic removal and its protective effect against arsenic induced toxicity and oxidative damage in freshwater fish, Channa striata

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Neha Pandey

2015-01-01

Full Text Available Arsenic is a toxic metalloid existing widely in the environment, and its removal from contaminated water has become a global challenge. The use of bacteria in this regard finds a promising solution. In the present study, Exiguobacterium sp. As-9, which is an arsenic resistant bacterium, was selected with respect to its arsenic removal efficiency. Quantification of arsenic in the water treated with bacterium showed that Exiguobacterium efficiently removed up to 99% of arsenic in less than 20 h. In order to reveal the possible effect of this bacterium in removal of arsenic from water and protecting fishes from the detrimental effects of arsenic, we initiated a range of studies on fresh water fish, Channa striata. It was observed that the fishes introduced into bacteria treated water displayed no symptoms of arsenic toxicity which was marked by a decreased oxidative damage, whereas the fishes exposed to arsenic revealed a significant (p < 0.05 increase in the oxidative stress together with the elevated levels of malondialdehyde. Determination of the bioaccumulation of arsenic in the liver tissues of C. striata using hydride generation atomic absorption spectrophotometry (HG-AAS revealed an increased As(III accumulation in the fishes exposed to arsenic whereas the arsenic level in the control and bacteria treated fishes were found below the detectable limit. In conclusion, this study presents the strategies of bacterial arsenic removal with possible directions for future research.

Oxidative stress in MeHg-induced neurotoxicity

Energy Technology Data Exchange (ETDEWEB)

Farina, Marcelo, E-mail: farina@ccb.ufsc.br [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Aschner, Michael [Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (United States); Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN (United States); Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

2011-11-15

Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically

Peroxometal-mediated oxidation of bromine leading to ...

Indian Academy of Sciences (India)

Administrator

Peroxometal-mediated oxidation of bromine leading to environmentally favourable protocol for selective bromination of organic substrates: Implications for vanadium bromo peroxidase (VBrPO). SIDDHARTHA D DHAR and MIHIR K CHAUDHURI. Department of Chemistry, Indian Institute of Technology,. Guwahati 781 001 ...

Cleavage of olefinic double bonds by mediated anodic oxidation

International Nuclear Information System (INIS)

Baeumer, U.-St.; Schaefer, H.J.

2003-01-01

Seven alkenes, e.g. 1-decene, methyl oleate, cyclododecene, norbornene, are cleaved by indirect anodic oxidation with IO 4 - /RuCl 3 as mediator to carboxylic acids. The best performance was achieved with two alternative ex cell-methods. Periodate is regenerated from iodate in a divided cell at a PbO 2 /Ti-anode. In the chemical reactor alkene and the produced carboxylic acid are immobilized in a chromatography column on Chromosorb W and oxidized with IO 4 - /RuO 4 in CH 3 CN/water. In the alternative version the alkene is oxidized in an emulsion generated by sonication and the organic phase is retained in the reactor by a separator. Acids and diacids are obtained in 61-91% chemical yield and good current yields. The amount of consumed periodate can be reduced to less than 5% of the amount needed for the chemical oxidation. The mediated anodic cleavage of alkenes is altogether an interesting alternative to ozonolysis

Genetic responses against nitric oxide toxicity

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B. Demple

1999-11-01

Full Text Available The threat of free radical damage is opposed by coordinated responses that modulate expression of sets of gene products. In mammalian cells, 12 proteins are induced by exposure to nitric oxide (NO levels that are sub-toxic but exceed the level needed to activate guanylate cyclase. Heme oxygenase 1 (HO-1 synthesis increases substantially, due to a 30- to 70-fold increase in the level of HO-1 mRNA. HO-1 induction is cGMP-independent and occurs mainly through increased mRNA stability, which therefore indicates a new NO-signaling pathway. HO-1 induction contributes to dramatically increased NO resistance and, together with the other inducible functions, constitutes an adaptive resistance pathway that also defends against oxidants such as H2O2. In E. coli, an oxidative stress response, the soxRS regulon, is activated by direct exposure of E. coli to NO, or by NO generated in murine macrophages after phagocytosis of the bacteria. This response is governed by the SoxR protein, a homodimeric transcription factor (17-kDa subunits containing [2Fe-2S] clusters essential for its activity. SoxR responds to superoxide stress through one-electron oxidation of the iron-sulfur centers, but such oxidation is not observed in reactions of NO with SoxR. Instead, NO nitrosylates the iron-sulfur centers of SoxR both in vitro and in intact cells, which yields a form of the protein with maximal transcriptional activity. Although nitrosylated SoxR is very stable in purified form, the spectroscopic signals for the nitrosylated iron-sulfur centers disappear rapidly in vivo, indicating an active process to reverse or eliminate them.

Benzyl Alcohol-Mediated Versatile Method to Fabricate Nonstoichiometric Metal Oxide Nanostructures.

Science.gov (United States)

Qamar, Mohammad; Adam, Alaaldin; Azad, Abdul-Majeed; Kim, Yong-Wah

2017-11-22

Nanostructured metal oxides with cationic or anionic deficiency find applications in a wide range of technological areas including the energy sector and environment. However, a facile route to prepare such materials in bulk with acceptable reproducibility is still lacking; many synthesis techniques are still only bench-top and cannot be easily scaled-up. Here, we report that the benzyl alcohol (BA)-mediated method is capable of producing a host of nanostructured metal oxides (MO x , where M = Ti, Zn, Ce, Sn, In, Ga, or Fe) with inherent nonstoichiometry. It employs multifunctional BA as a solvent, a reducing agent, and a structure-directing agent. Depending on the oxidation states of metal, elemental or nonstoichiometric oxide forms are obtained. Augmented photoelectrochemical oxidation of water under visible light by some of these nonstoichiometric oxides highlights the versatility of the BA-mediated synthesis protocol.

Mediated electrochemical hazardous waste destruction

International Nuclear Information System (INIS)

Hickman, R.G.; Farmer, J.C.; Wang, F.T.

1991-08-01

There are few permitted processes for mixed waste (radioactive plus chemically hazardous) treatment. We are developing electrochemical processes that convert the toxic organic components of mixed waste to water, carbon dioxide, an innocuous anions such as chloride. Aggressive oxidizer ions such as Ag 2+ or Ce +4 are produced at an anode. These can attack the organic molecules directly. They can also attack water which yields hydroxyl free radicals that in turn attack the organic molecules. The condensed (i.e., solid and/or liquid) effluent streams contain the inorganic radionuclide forms. These may be treated with existing technology and prepared for final disposal. Kinetics and the extent of destruction of some toxic organics have been measured. Depending on how the process is operated, coulombic efficiency can be nearly 100%. In addition, hazardous organic materials are becoming very expensive to dispose of and when they are combined with transuranic radioactive elements no processes are presently permitted. Mediated electrochemical oxidation is an ambient-temperature aqueous-phase process that can be used to oxidize organic components of mixed wastes. Problems associated with incineration, such as high-temperature volatilization of radionuclides, are avoided. Historically, Ag (2) has been used as a mediator in this process. Fe(6) and Co(3) are attractive alternatives to Ag(2) since they form soluble chlorides during the destruction of chlorinated solvents. Furthermore, silver itself is a toxic heavy metal. Quantitative data has been obtained for the complete oxidation of ethylene glycol by Fe(6) and Co(3). Though ethylene glycol is a nonhalogenated organic, this data has enabled us to make direct comparisons of activities of Fe(6) and Co(3) with Ag(2). Very good quantitative data for the oxidation of ethylene glycol by Ag(2) had already been collected. 4 refs., 6 figs

Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

Directory of Open Access Journals (Sweden)

Verónica Pérez-De La Cruz

2012-01-01

Full Text Available Quinolinic acid (QUIN, an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca 2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity.

Reproductive toxicity of chromium in adult bonnet monkeys (Macaca radiata Geoffrey). Reversible oxidative stress in the semen

International Nuclear Information System (INIS)

Subramanian, Senthivinayagam; Rajendiran, Gopalakrishnan; Sekhar, Pasupathi; Gowri, Chandrahasan; Govindarajulu, Pera; Aruldhas, Mariajoseph Michael

2006-01-01

The present study was designed to test the hypothesis that oxidative stress mediates chromium-induced reproductive toxicity. Monthly semen samples were collected from adult monkeys (Macaca radiata), which were exposed to varying doses (50, 100, 200 and 400 ppm) of chromium (as potassium dichromate) for 6 months through drinking water. Chromium treatment decreased sperm count, sperm forward motility and the specific activities of antioxidant enzymes, superoxide dismutase and catalase, and the concentration of reduced glutathione in both seminal plasma and sperm in a dose- and duration-dependent manner. On the other hand, the quantum of hydrogen peroxide in the seminal plasma/sperm from monkeys exposed to chromium increased with increasing dose and duration of chromium exposure. All these changes were reversed after 6 months of chromium-free exposure period. Simultaneous supplementation of vitamin C (0.5 g/L; 1.0 g/L; 2.0 g/L) prevented the development of chromium-induced oxidative stress. Data support the hypothesis and show that chronic chromium exposure induces a reversible oxidative stress in the seminal plasma and sperm by creating an imbalance between reactive oxygen species and antioxidant system, leading to sperm death and reduced motility of live sperm

Reaction mechanisms of ruthenium tetroxide mediated oxidations of organic compounds

Energy Technology Data Exchange (ETDEWEB)

Froehaug, Astrid Elisabeth

1995-12-31

This thesis reports a study of the mechanism of ruthenium tetroxide mediated oxidations of saturated hydrocarbons, ethers, alkenes and alcohols. Several methods were used. The RuO{sub 4}-mediated oxidations of adamantane and cis-decalin were studied in CCl{sub 4}-CH{sub 3}CN-H{sub 2}O and in acetone-water. The rate of reaction was found to be moderately influenced by the polarity of the solvent. Solvent properties other than the polarity were also found to influence the reaction rates. From the oxidations of adamantane and adamantane-1,3,5,7-d{sub 4} two primary kinetic deuterium isotope effects were found. These were comparable with the deuterium isotope effects found for the analogous oxidations of cis-decalin and cis-decalin-d{sub 18}. The results seem to exclude both a one step hydride abstraction reaction mechanism and a one step concerted mechanism, as well as a scheme where two such mechanisms compete. The observations may be explained by a two step reaction mechanism consisting of a pre-equilibrium with formation of a substrate-RuO{sub 4} complex followed by a concerted rate determining reaction. The RuO{sub 4}-mediated oxidation of ethers was of kinetic second order with a small enthalpy of activation and a large negative entropy of activation. Oxidation of cyclopropylmethyl methyl ether gave methyl cyclopropanecarboxylate, no rearranged products were observed. On RuO{sub 4} oxidations in CCl{sub 4} with NaIO{sub 4} as stoichiometric oxidant, no chlorinated products were observed. Several observations not in agreement with a hydride or a hydrogen abstraction mechanism may be explained by assuming that the reaction proceeds by either a concerted reaction or by a reversible oxidative addition of the ether to RuO{sub 4} followed by a slow concerted step. 228 refs., 9 figs., 27 tabs.

Cooperative electrocatalytic alcohol oxidation with electron-proton-transfer mediators

Science.gov (United States)

Badalyan, Artavazd; Stahl, Shannon S.

2016-07-01

The electrochemical oxidation of alcohols is a major focus of energy and chemical conversion efforts, with potential applications ranging from fuel cells to biomass utilization and fine-chemical synthesis. Small-molecule electrocatalysts for processes of this type are promising targets for further development, as demonstrated by recent advances in nickel catalysts for electrochemical production and oxidation of hydrogen. Complexes with tethered amines that resemble the active site of hydrogenases have been shown both to catalyse hydrogen production (from protons and electrons) with rates far exceeding those of such enzymes and to mediate reversible electrocatalytic hydrogen production and oxidation with enzyme-like performance. Progress in electrocatalytic alcohol oxidation has been more modest. Nickel complexes similar to those used for hydrogen oxidation have been shown to mediate efficient electrochemical oxidation of benzyl alcohol, with a turnover frequency of 2.1 per second. These compounds exhibit poor reactivity with ethanol and methanol, however. Organic nitroxyls, such as TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl), are the most widely studied electrocatalysts for alcohol oxidation. These catalysts exhibit good activity (1-2 turnovers per second) with a wide range of alcohols and have great promise for electro-organic synthesis. Their use in energy-conversion applications, however, is limited by the high electrode potentials required to generate the reactive oxoammonium species. Here we report (2,2‧-bipyridine)Cu/nitroxyl co-catalyst systems for electrochemical alcohol oxidation that proceed with much faster rates, while operating at an electrode potential a half-volt lower than that used for the TEMPO-only process. The (2,2‧-bipyridine)Cu(II) and TEMPO redox partners exhibit cooperative reactivity and exploit the low-potential, proton-coupled TEMPO/TEMPOH redox process rather than the high-potential TEMPO/TEMPO+ process. The results show how

Novel approaches to mitigating parathion toxicity: targeting cytochrome P450-mediated metabolism with menadione.

Science.gov (United States)

Jan, Yi-Hua; Richardson, Jason R; Baker, Angela A; Mishin, Vladimir; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

2016-08-01

Accidental or intentional exposures to parathion, an organophosphorus (OP) pesticide, can cause severe poisoning in humans. Parathion toxicity is dependent on its metabolism by the cytochrome P450 (CYP) system to paraoxon (diethyl 4-nitrophenyl phosphate), a highly poisonous nerve agent and potent inhibitor of acetylcholinesterase. We have been investigating inhibitors of CYP-mediated bioactivation of OPs as a method of preventing or reversing progressive parathion toxicity. It is well recognized that NADPH-cytochrome P450 reductase, an enzyme required for the transfer of electrons to CYPs, mediates chemical redox cycling. In this process, the enzyme diverts electrons from CYPs to support chemical redox cycling, which results in inhibition of CYP-mediated biotransformation. Using menadione as the redox-cycling chemical, we discovered that this enzymatic reaction blocks metabolic activation of parathion in rat and human liver microsomes and in recombinant CYPs important to parathion metabolism, including CYP1A2, CYP2B6, and CYP3A4. Administration of menadione to rats reduces metabolism of parathion, as well as parathion-induced inhibition of brain cholinesterase activity. This resulted in inhibition of parathion neurotoxicity. Menadione has relatively low toxicity and is approved by the Food and Drug Administration for other indications. Its ability to block parathion metabolism makes it an attractive therapeutic candidate to mitigate parathion-induced neurotoxicity. © 2016 New York Academy of Sciences.

A marine microbial consortium apparently mediating anaerobic oxidation of methane

DEFF Research Database (Denmark)

Boetius, A.; Ravenschlag, K.; Schubert, CJ

2000-01-01

microorganisms mediating this reaction have not yet been isolated, and the pathway of anaerobic oxidation of methane is insufficiently understood. Recent data suggest that certain archaea reverse the process of methanogenesis by interaction with sulphate-reducing bacteria(5-7). Here we provide microscopic...... cells and are surrounded by sulphate-reducing bacteria. These aggregates were abundant in gas-hydrate-rich sediments with extremely high rates of methane-based sulphate reduction, and apparently mediate anaerobic oxidation of methane.......A large fraction of globally produced methane is converted to CO2 by anaerobic oxidation in marine sediments(1). Strong geochemical evidence for net methane consumption in anoxic sediments is based on methane profiles(2), radiotracer experiments(3) and stable carbon isotope data(4). But the elusive...

Induction of the nuclear factor HIF-1α in acetaminophen toxicity: Evidence for oxidative stress

International Nuclear Information System (INIS)

James, Laura P.; Donahower, Brian; Burke, Angela S.; McCullough, Sandra; Hinson, Jack A.

2006-01-01

Hypoxia inducible factor (HIF) controls the transcription of genes involved in angiogenesis, erythropoiesis, glycolysis, and cell survival. HIF-1α levels are a critical determinant of HIF activity. The induction of HIF-1α was examined in the livers of mice treated with a toxic dose of APAP (300 mg/kg IP) and sacrificed at 1, 2, 4, 8, and 12 h. HIF-1α was induced at 1-12 h and induction occurred prior to the onset of toxicity. Pre-treatment of mice with N-acetylcysteine (1200 mg/kg IP) prevented toxicity and HIF-1α induction. In further studies, hepatocyte suspensions were incubated with APAP (1 mM) in the presence of an oxygen atmosphere. HIF-1α was induced at 1 h, prior to the onset of toxicity. Inclusion of cyclosporine A (10 μM), an inhibitor of mitochondrial permeability transition, oxidative stress, and toxicity, prevented the induction of HIF-1α. Thus, HIF-1α is induced before APAP toxicity and can occur under non-hypoxic conditions. The data suggest a role for oxidative stress in the induction of HIF-1α in APAP toxicity

A review of reproductive toxicity of microcystins

International Nuclear Information System (INIS)

Chen, Liang; Chen, Jun; Zhang, Xuezhen; Xie, Ping

2016-01-01

Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

A review of reproductive toxicity of microcystins

Energy Technology Data Exchange (ETDEWEB)

Chen, Liang, E-mail: chan91@yeah.net [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Chen, Jun, E-mail: chenjun@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Zhang, Xuezhen, E-mail: xuezhen@mail.hzau.edu.cn [College of Fisheries, Huazhong Agricultural University, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070 (China); Xie, Ping, E-mail: xieping@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China)

2016-01-15

Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity

Energy Technology Data Exchange (ETDEWEB)

Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng, E-mail: quanshengzhou@yahoo.com; Cao, Zhifei, E-mail: hunancao@163.com

2015-09-01

Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. - Highlights: • Dehydroeffusol markedly inhibits gastric cancer cell-mediated vasculogenic mimicry. • Dehydroeffusol suppresses the expression of vasculogenic mimicry key gene VE-cadherin. • Dehydroeffusol decreases the MMP2 expression and activity in gastric cancer cells. • Dehydroeffusol is a potential anti-cancer drug candidate with very low toxicity.

Comparative proteomic analysis of the molecular responses of mouse macrophages to titanium dioxide and copper oxide nanoparticles unravels some toxic mechanisms for copper oxide nanoparticles in macrophages.

Directory of Open Access Journals (Sweden)

Sarah Triboulet

Full Text Available Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide or of their biocidal properties (copper oxide, increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at sub toxic doses. Besides titanium dioxide and copper oxide nanoparticles, copper ions were used as controls. We also showed that the overall copper release in the cell does not explain per se the toxicity observed with copper oxide nanoparticles. In addition, both copper ion and copper oxide nanoparticles, but not titanium oxide, induced DNA strands breaks in macrophages. As to functional responses, the phagocytic capacity was not hampered by any of the treatments at non-toxic doses, while copper ion decreased the lipopolysaccharide-induced cytokine and nitric oxide productions. The proteomic analyses highlighted very few changes induced by titanium dioxide nanoparticles, but an induction of heme oxygenase, an increase of glutathione synthesis and a decrease of tetrahydrobiopterin in response to copper oxide nanoparticles. Subsequent targeted analyses demonstrated that the increase in glutathione biosynthesis and the induction of heme oxygenase (e.g. by lovastatin/monacolin K are critical for macrophages to survive a copper challenge, and that the intermediates of the catecholamine pathway induce a strong cross toxicity with copper oxide nanoparticles and copper ions.

Comparative proteomic analysis of the molecular responses of mouse macrophages to titanium dioxide and copper oxide nanoparticles unravels some toxic mechanisms for copper oxide nanoparticles in macrophages.

Science.gov (United States)

Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Collin-Faure, Véronique; Chevallet, Mireille; Diemer, Hélène; Gerdil, Adèle; Proamer, Fabienne; Strub, Jean-Marc; Habert, Aurélie; Herlin, Nathalie; Van Dorsselaer, Alain; Carrière, Marie; Rabilloud, Thierry

2015-01-01

Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide) or of their biocidal properties (copper oxide), increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at sub toxic doses. Besides titanium dioxide and copper oxide nanoparticles, copper ions were used as controls. We also showed that the overall copper release in the cell does not explain per se the toxicity observed with copper oxide nanoparticles. In addition, both copper ion and copper oxide nanoparticles, but not titanium oxide, induced DNA strands breaks in macrophages. As to functional responses, the phagocytic capacity was not hampered by any of the treatments at non-toxic doses, while copper ion decreased the lipopolysaccharide-induced cytokine and nitric oxide productions. The proteomic analyses highlighted very few changes induced by titanium dioxide nanoparticles, but an induction of heme oxygenase, an increase of glutathione synthesis and a decrease of tetrahydrobiopterin in response to copper oxide nanoparticles. Subsequent targeted analyses demonstrated that the increase in glutathione biosynthesis and the induction of heme oxygenase (e.g. by lovastatin/monacolin K) are critical for macrophages to survive a copper challenge, and that the intermediates of the catecholamine pathway induce a strong cross toxicity with copper oxide nanoparticles and copper ions.

Effect of advanced oxidation processes (AOP's) on the toxicity of municipal landfill leachates

Energy Technology Data Exchange (ETDEWEB)

Slomczynska, B.; Slomczynski, T. [Inst. of Environmental Engineering Systems, Warsaw Univ. of Technology, Warsaw (Poland); Wasowski, J. [Inst. of Water Supply and Hydraulic Construction, Warsaw Univ. of Technology, Warsaw (Poland)

2003-07-01

The aim of present study was to assess the effect of AOP's (oxidation ozone and peroxide/ozone) on the toxicity of leachates from municipal landfill for Warsaw, Poland, using battery of tests. Advanced oxidation processes used to pre-treat leachates were carried out in laboratory conditions after their coagulation with the use of FeCl{sub 3}. The effects of the pre-treatment of leachates using the method of coagulation with FeCl{sub 3} depended on the concentration of organic compounds and with optimal conditions of the process ranged from 40 to 70%. Further pre-treatment of the leachates after coagulation, involving the use of oxidation with O{sub 3} and H{sub 2}O{sub 2}/O{sub 3}, did not caused significant decrease of leachate toxicity. The data of this study demonstrated the usefulness of the battery of tests using Daphnia magna, Artemia franciscana, Scenedesmus quadricauda and Vibrio fischeri for the toxicity evaluation of raw and pre-treated leachates. (orig.)

Involvement of oxidative stress in 4-vinylcyclohexene-induced toxicity in Drosophila melanogaster.

Science.gov (United States)

Abolaji, Amos Olalekan; Kamdem, Jean Paul; Lugokenski, Thiago Henrique; Nascimento, Thallita Kalar; Waczuk, Emily Pansera; Farombi, Ebenezer Olatunde; Loreto, Élgion Lúcio da Silva; Rocha, João Batista Teixeira

2014-06-01

4-Vinylcyclohexene (VCH) is a dimer of 1,3-butadiene produced as a by-product of pesticides, plastic, rubber, flame retardants, and tire production. Although, several studies have reported the ovotoxicity of VCH, information on a possible involvement of oxidative stress in the toxicity of this occupational chemical is scarce. Hence, this study was carried out to investigate further possible mechanisms of toxicity of VCH with a specific emphasis on oxidative stress using a Drosophila melanogaster model. D. melanogaster (both genders) of 1 to 3 days old were exposed to different concentrations of VCH (10 µM-1 mM) in the diet for 5 days. Subsequently, the survival and negative geotaxis assays and the quantification of reactive oxygen species (ROS) generation were determined. In addition, we evaluated RT-PCR expressions of selected oxidative stress and antioxidant mRNA genes (HSP27, 70, and 83, SOD, Nrf-2, MAPK2, and catalase). Furthermore, catalase, glutathione-S-transferase (GST), delta aminolevulinic acid dehydratase (δ-ALA-D), and acetylcholinesterase (AChE) activities were determined. VCH exposure impaired negative geotaxic behavior and induced the mRNA of SOD, Nrf-2, and MAPK2 genes expressions. There were increases in catalase and ROS production, as well as inhibitions of GST, δ-ALA-D, and AChE activities (Pbalance, and possible neurotoxic consequences due to decreased AChE activity, and impairments in negative geotaxic behavior. Thus, we conclude that D. melanogaster is a useful model for investigating the toxicity of VCH exposure, and here, we have provided further insights on the mechanism of VCH-induced toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Sub-Acute Toxicity Study of Graphene Oxide in the Sprague-Dawley Rat

Directory of Open Access Journals (Sweden)

Yingbo Li

2016-11-01

Full Text Available Graphene oxide (GO is an oxidized derivative of graphene used in biotechnology and medicine. The safety of GO is uncertain, so we evaluated its toxicity in male rats. Rat tail veins were injected with 2.5, 5, or 10 mg/kg GO for seven days and behavioral patterns, pathology, and tissue morphology were assessed. Data show that behaviors were not altered according to an open field test and a functional observational battery test, but histopathological analysis indicated that GO caused inflammation of the lung, liver, and spleen. GO also reduced cholesterol, high density lipoprotein (HDL, and low density lipoprotein (LDL. No other organs were modified. Thus, high concentrations of GO are toxic for the lung, liver, and spleen, but the mechanism by which this occurs requires more study.

Impaired fatty acid oxidation as a cause for lipotoxicity in cardiomyocytes

Energy Technology Data Exchange (ETDEWEB)

Haffar, T. [Université de Montreal (Canada); Montreal Heart Institute (Canada); Bérubé-Simard, F. [Montreal Heart Institute (Canada); Bousette, N., E-mail: nicolas.bousette@umontreal.ca [Université de Montreal (Canada); Montreal Heart Institute (Canada)

2015-12-04

A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring {sup 14}C–CO{sub 2} production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative and qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. - Highlights: • Palmitate had a slower clearance rate from NCMs than oleate. • Palmitate caused a significant decrease in fatty acid oxidation in cardiomyocytes. • Impaired FAO was not due to loss of Cpt1b protein or mitochondrial integrity. • Enhancing FAO

Impaired fatty acid oxidation as a cause for lipotoxicity in cardiomyocytes

International Nuclear Information System (INIS)

Haffar, T.; Bérubé-Simard, F.; Bousette, N.

2015-01-01

A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring "1"4C–CO_2 production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative and qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. - Highlights: • Palmitate had a slower clearance rate from NCMs than oleate. • Palmitate caused a significant decrease in fatty acid oxidation in cardiomyocytes. • Impaired FAO was not due to loss of Cpt1b protein or mitochondrial integrity. • Enhancing FAO attenuated

Toxicity assessment of simulated urban runoff containing polycyclic musks and cadmium in Carassius auratus using oxidative stress biomarkers

International Nuclear Information System (INIS)

Chen Fang; Gao Jie; Zhou Qixing

2012-01-01

The objective of this study was to assess potential toxic effects of simulated urban runoff on Carassius auratus using oxidative stress biomarkers. The activity of antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and the content of malondialdehyde (MDA) in the liver of C. auratus were analyzed after a 7-, 14- and 21-day exposure to simulated urban runoff containing galaxolide (HHCB) and cadmium (Cd). The results showed that the activity of antioxidant enzymes and the content of MDA increased significantly exposed to the simulated urban runoff containing HHCB alone or mixture of HHCB and Cd. The activity of the investigated enzymes and the content of MDA then returned to the blank level over a longer period of exposure. The oxidative stress could be obviously caused in the liver of C. auratus under the experimental conditions. This could provide useful information for toxic risk assessment of urban runoff. - Highlights: ► We assessed potential toxicity of urban runoff containing HHCB and Cd. ► Exposure of simulated urban runoff can caused oxidative stress in C. auratus liver. ► SOD and CAT are more sensitive than POD and more suitable for indicating the toxicity of urban runoff. ► The present study using oxidative stress biomarkers could provide useful information for toxic risk assessment of urban runoff. - Simulated urban runoff containing HHCB and Cd could cause oxidative stress on the liver of Carassius auratus, which could provide useful information for toxic risk assessment of urban runoff.

Oxidative stress and toxicity of gold nanoparticles in Mytilus edulis

International Nuclear Information System (INIS)

Tedesco, Sara; Doyle, Hugh; Blasco, Julian; Redmond, Gareth; Sheehan, David

2010-01-01

Gold nanoparticles (AuNP) have potential applications in drug delivery, cancer diagnosis and therapy, food industry and environment remediation. However, little is known about their potential toxicity or fate in the environment. Mytilus edulis was exposed in tanks to750 ppb AuNP (average diameter 5.3 ± 1 nm) for 24 h to study in vivo biological effects of nanoparticles. Traditional biomarkers and an affinity procedure selective for thiol-containing proteins followed by two-dimensional electrophoresis (2DE) separations were used to study toxicity and oxidative stress responses. Results were compared to those obtained for treatment with cadmium chloride, a well known pro-oxidant. M. edulis mainly accumulated AuNP in digestive gland which also showed higher lipid peroxidation. One-dimensional SDS/PAGE (1DE) and 2DE analysis of digestive gland samples revealed decreased thiol-containing proteins for AuNP. Lysosomal membrane stability measured in haemolymph gave lower values for neutral red retention time (NRRT) in both treatments but was greater in AuNP. Oxidative stress occurred within 24 h of AuNP exposure in M. edulis. Previously we showed that larger diameter AuNP caused modest effects, indicating that nanoparticle size is a key factor in biological responses to nanoparticles. This study suggests that M. edulis is a suitable model animal for environmental toxicology studies of nanoparticles.

A Broad Spectrum Catalytic System for Removal of Toxic Organics from Water by Deep Oxidation - Final Report

Energy Technology Data Exchange (ETDEWEB)

Sen, Ayusman

2000-12-01

A most pressing need for the DOE environmental management program is the removal of toxic organic compounds present in groundwater and soil at specific DOE sites. While several remediation procedures have been proposed, they suffer from one or more drawbacks. The objective of the present research was to develop new catalytic procedures for the removal of toxic organic compounds from the environment through their deep oxidation to harmless products. In water, metallic palladium was found to catalyze the deep oxidation of a wide variety of toxic organic compounds by dioxygen at 80-90 C in the presence of carbon monoxide or dihydrogen. Several classes of organic compounds were examined: benzene, phenol and substituted phenols, nitro and halo organics, organophosphorus, and organosulfur compounds. In every case, deep oxidation to carbon monoxide, carbon dioxide, and water occurred in high yields, resulting in up to several hundred turnovers over a 24 hour period. For substrates susceptible to hydrogenation, the conversions were generally high with dihydrogen than with carbon monoxide. It is clear from the results obtained that we have discovered an exceptionally versatile catalytic system for the deep oxidation of toxic organic compounds in water. This system possesses several attractive features not found simultaneously in other reported systems. These are (a) the ability to directly utilize dioxygen as the oxidant, (b) the ability to carry out the deep oxidation of a particularly wide range of functional organics, and (c) the ease of recovery of the catalyst by simple filtration.

Is Oxidized Thioredoxin a Major Trigger for Cysteine Oxidation? Clues from a Redox Proteomics Approach

OpenAIRE

García-Santamarina, Sarela; Boronat, Susanna; Calvo, Isabel A.; Rodríguez-Gabriel, Miguel; Ayté, José; Molina, Henrik; Hidalgo, Elena

2013-01-01

This is a copy of an article published in the Antioxidants & Redox Signaling © Mary Ann Liebert, Inc. Antioxidants & Redox Signaling is available online at http://online.liebertpub.com Cysteine oxidation mediates oxidative stress toxicity and signaling. It has been long proposed that the thioredoxin (Trx) system, which consists of Trx and thioredoxin reductase (Trr), is not only involved in recycling classical Trx substrates, such as ribonucleotide reductase, but it also regulates g...

Nitric oxide mediates insect cellular immunity via phospholipase A2 activation

Science.gov (United States)

After infection or invasion is recognized, biochemical mediators act in signaling insect immune functions. These include biogenic amines, insect cytokines, eicosanoids and nitric oxide (NO). Treating insects or isolated hemocyte populations with different mediators often leads to similar results. Se...

An update on oxidative stress-mediated organ pathophysiology.

Science.gov (United States)

Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

2013-12-01

Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biochemistry and pathology of radical-mediated protein oxidation

DEFF Research Database (Denmark)

Dean, R T; Fu, S; Stocker, R

1997-01-01

Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several catego...

Toxicity assessment of silica coated iron oxide nanoparticles and biocompatibility improvement by surface engineering.

Directory of Open Access Journals (Sweden)

Maria Ada Malvindi

Full Text Available We have studied in vitro toxicity of iron oxide nanoparticles (NPs coated with a thin silica shell (Fe3O4/SiO2 NPs on A549 and HeLa cells. We compared bare and surface passivated Fe3O4/SiO2 NPs to evaluate the effects of the coating on the particle stability and toxicity. NPs cytotoxicity was investigated by cell viability, membrane integrity, mitochondrial membrane potential (MMP, reactive oxygen species (ROS assays, and their genotoxicity by comet assay. Our results show that NPs surface passivation reduces the oxidative stress and alteration of iron homeostasis and, consequently, the overall toxicity, despite bare and passivated NPs show similar cell internalization efficiency. We found that the higher toxicity of bare NPs is due to their stronger in-situ degradation, with larger intracellular release of iron ions, as compared to surface passivated NPs. Our results indicate that surface engineering of Fe3O4/SiO2 NPs plays a key role in improving particles stability in biological environments reducing both cytotoxic and genotoxic effects.

Novel approaches to mitigating parathion toxicity: targeting cytochrome P450–mediated metabolism with menadione

Science.gov (United States)

Jan, Yi-Hua; Richardson, Jason R.; Baker, Angela A.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

2016-01-01

Accidental or intentional exposures to parathion, an organophosphorus (OP) pesticide, can cause severe poisoning in humans. Parathion toxicity is dependent on its metabolism by the cytochrome P450 (CYP) system to paraoxon (diethyl 4-nitrophenyl phosphate), a highly poisonous nerve agent and potent inhibitor of acetylcholinesterase (AChE). We have been investigating inhibitors of CYP-mediated bioactivation of OPs as a method of preventing or reversing progressive parathion toxicity. It is well recognized that NADPH–cytochrome P450 reductase, an enzyme required for the transfer of electrons to CYPs, mediates chemical redox cycling. In this process, the enzyme diverts electrons from CYPs to support chemical redox cycling, which results in inhibition of CYP-mediated biotransformation. Using menadione as the redox-cycling chemical, we discovered that this enzymatic reaction blocks metabolic activation of parathion in rat and human liver microsomes and in recombinant CYPs important to parathion metabolism, including CYP1A2, CYP2B6, and CYP3A4. Administration of menadione to rats reduces metabolism of parathion, as well as parathion-induced inhibition of brain cholinesterase activity. This resulted in inhibition of parathion neurotoxicity. Menadione has relatively low toxicity and is approved by the FDA for other indications. Its ability to block parathion metabolism makes it an attractive therapeutic candidate to mitigate parathion-induced neurotoxicity. PMID:27441453

High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.

Science.gov (United States)

Bowen, T Scott; Eisenkolb, Sophia; Drobner, Juliane; Fischer, Tina; Werner, Sarah; Linke, Axel; Mangner, Norman; Schuler, Gerhard; Adams, Volker

2017-01-01

Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice. © FASEB.

Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons

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Shan Liu

2014-01-01

Full Text Available Tumor necrosis factor-α (TNF-α is a critical proinflammatory cytokine regulating neuroinflammation. Elevated levels of TNF-α have been associated with various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, the signaling events that lead to TNF-α-initiated neurotoxicity are still unclear. Here, we report that RIP3-mediated necroptosis, a form of regulated necrosis, is activated in the mouse hippocampus after intracerebroventricular injection of TNF-α. RIP3 deficiency attenuates TNF-α-initiated loss of hippocampal neurons. Furthermore, we characterized the molecular mechanism of TNF-α-induced neurotoxicity in HT-22 hippocampal neuronal cells. HT-22 cells are sensitive to TNF-α only upon caspase blockage and subsequently undergo necrosis. The cell death is suppressed by knockdown of CYLD or RIP1 or RIP3 or MLKL, suggesting that this necrosis is necroptosis and mediated by CYLD-RIP1-RIP3-MLKL signaling pathway. TNF-α-induced necroptosis of HT-22 cells is largely independent of both ROS accumulation and calcium influx although these events have been shown to be critical for necroptosis in certain cell lines. Taken together, these data not only provide the first in vivo evidence for a role of RIP3 in TNF-α-induced toxicity of hippocampal neurons, but also demonstrate that TNF-α promotes CYLD-RIP1-RIP3-MLKL-mediated necroptosis of hippocampal neurons largely bypassing ROS accumulation and calcium influx.

Laccase/mediator assisted degradation of triarylmethane dyes in a continuous membrane reactor.

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Chhabra, Meenu; Mishra, Saroj; Sreekrishnan, Trichur Ramaswamy

2009-08-10

Laccase/mediator systems are important bioremediation agents as the rates of reactions can be enhanced in the presence of the mediators. The decolorization mechanism of two triarylmethane dyes, namely, Basic Green 4 and Acid Violet 17 is reported using Cyathus bulleri laccase. Basic Green 4 was decolorized through N-demethylation by laccase alone, while in mediator assisted reactions, dye breakdown was initiated from oxidation of carbinol form of the dye. Benzaldehyde and N,N-dimethyl aniline were the major end products. With Acid Violet 17, laccase carried out N-deethylation and in mediator assisted reactions, oxidation of the carbinol form of the dye occurred resulting in formation of formyl benzene sulfonic acid, carboxy benzene sulfonic acid and benzene sulfonic acid. Toxicity analysis revealed that Basic Green 4 was toxic and treatment with laccase/mediators resulted in 80-100% detoxification. The treatment of the textile dye solution using laccase and 2,2'-azino-di-(-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was demonstrated in an enzyme membrane reactor. At a hydraulic retention time of 6h, the process was operated for a period of 15 days with nearly 95% decolorization, 10% reduction in flux and 70% recovery of active ABTS.

Troxerutin protects against 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD⁺-depletion.

Science.gov (United States)

Zhang, Zi-Feng; Zhang, Yan-Qiu; Fan, Shao-Hua; Zhuang, Juan; Zheng, Yuan-Lin; Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin

2015-01-01

Emerging evidence indicates that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD(+)-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD(+)-depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity. Copyright © 2014 Elsevier B.V. All rights reserved.

Acrolein toxicity involves oxidative stress caused by glutathione depletion in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Kwolek-Mirek, M; Bednarska, S; Bartosz, G; Biliński, T

2009-08-01

Exposure of yeast cells to allyl alcohol results in intracellular production of acrolein. The toxicity of so formed acrolein involves oxidative stress, as (1) strains deficient in antioxidant defense are hypersensitive to allyl alcohol, (2) exposure to allyl alcohol increases the level of thiobarbituric-acid-reactive substances and decreases glutathione level in the cells, (3) hypoxic and anoxic atmosphere and antioxidants protect against allyl alcohol toxicity, and (4) allyl alcohol causes activation of Yap1p. No increased formation of reactive oxygen species was detected in cells exposed to allyl alcohol, so oxidative stress is due to depletion of cellular thiols and thus alteration in the redox state of yeast cells.

Copper-mediated oxidative degradation of catecholamines and oxidative damage of protein

Energy Technology Data Exchange (ETDEWEB)

Goncalves, P.R.; Harria, M.I.N.; Felix, J.M.; Hoffmann, M.E. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Biologia

1997-12-31

Full text. Degradative oxidation of catecholamines has been a matter of large interest in recent years due to the evidences associating their autoxidation with the etiology of neurotoxic and cardiotoxic processes. In this work we present data on the degradative oxidation of catecholamines of physiological importance: isoproterenol (IP), epinephrine (EP), norepinephrine (NEP), deoxyepinephrine (DEP) and dopamine (DA). The degradative oxidation of the catecholamines was followed by measurement of spectral changes and oxygen consumption by neutral aqueous solutions. The data show that Cu{sup 2+} strongly accelerated the rate of catecholamine oxidation, following the decreasing order; EP>DEP>IP>NEP>DA. The production of superoxide anion radical during catecholamine oxidation was very slow, even in the presence of Cu{sup 2+}. The ability of IP to induce damages on bovine serum albumin (BSA) was determined by measuring the formation of carbonyl-groups in the protein, detected by reduction with tritiated Na BH{sub 4}. The incubation of BSA with IP (50-500{mu}M), in the presence of 100{mu}M Cu{sup 2+} leaded to an increased and dose dependent {sup 3} H-incorporation by the oxidized protein. The production of oxidative damage by IP/Cu{sup 2+} was accompanied by marked BSA fragmentation, detected by SDS-polyacrylamide gel dependent (25-400{mu}M IP) des appearance of the original BSA band and appearance of smaller fragments spread in the gel, when incubation has been done in the presence of 100{mu}M Cu{sup 2+}. These results suggest that copper-catalysed oxidative degradation of proteins induced by catecholamines might be critically involved in the toxic action of these molecules

Waste treatment in NUCEF facility with silver mediated electrochemical oxidation technique

International Nuclear Information System (INIS)

Umeda, M.; Sugikawa, S.

2000-01-01

Silver mediated electrochemical oxidation technique has been considered one of promising candidates for alpha-bearing waste treatment. Destruction tests of organic compounds, such as insoluble tannin, TBP and dodecane, were carried out by this technique and the experimental data such as destruction rates, current efficiencies and intermediates were obtained. These compounds could be completely mineralized without the formation of reactive organic nitrate associated to safety hazards. On the basis of these results, the applicability of silver mediated electrochemical oxidation technique to waste treatment in NUCEF was evaluated. (authors)

TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity

DEFF Research Database (Denmark)

Decressac, Mickael; Mattsson, Bengt; Weikop, Pia

2013-01-01

that the PD-like neurodegenerative changes induced by excess cellular levels of α-synuclein in nigral dopamine neurons are closely linked to a progressive decline in markers of lysosome function, accompanied by cytoplasmic retention of transcription factor EB (TFEB), a major transcriptional regulator...... in both A9 and A10 dopamine neurons. Delayed activation of TFEB function through inhibition of mammalian target of rapamycin blocked α-synuclein induced neurodegeneration and further disease progression. The results provide a mechanistic link between α-synuclein toxicity and impaired TFEB function......The aggregation of α-synuclein plays a major role in Parkinson disease (PD) pathogenesis. Recent evidence suggests that defects in the autophagy-mediated clearance of α-synuclein contribute to the progressive loss of nigral dopamine neurons. Using an in vivo model of α-synuclein toxicity, we show...

Resveratrol prevents ammonia toxicity in astroglial cells.

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Larissa Daniele Bobermin

Full Text Available Ammonia is implicated as a neurotoxin in brain metabolic disorders associated with hyperammonemia. Acute ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and nitric oxide (NO production. Astrocytes interact with neurons, providing metabolic support and protecting against oxidative stress and excitotoxicity. Astrocytes also convert excess ammonia and glutamate into glutamine via glutamine synthetase (GS. Resveratrol, a polyphenol found in grapes and red wines, exhibits antioxidant and anti-inflammatory properties and modulates glial functions, such as glutamate metabolism. We investigated the effect of resveratrol on the production of reactive oxygen species (ROS, GS activity, S100B secretion, TNF-α, IL-1β and IL-6 levels in astroglial cells exposed to ammonia. Ammonia induced oxidative stress, decreased GS activity and increased cytokines release, probably by a mechanism dependent on protein kinase A (PKA and extracellular signal-regulated kinase (ERK pathways. Resveratrol prevented ammonia toxicity by modulating oxidative stress, glial and inflammatory responses. The ERK and nuclear factor-κB (NF-κB are involved in the protective effect of resveratrol on cytokines proinflammatory release. In contrast, other antioxidants (e.g., ascorbic acid and trolox were not effective against hyperammonemia. Thus, resveratrol could be used to protect against ammonia-induced neurotoxicity.

Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

Science.gov (United States)

Guerra, Maria Cristina; Leite, Marina Concli; Souza, Diogo Onofre; Gonçalves, Carlos-Alberto; Gottfried, Carmem

2012-01-01

Ammonia is implicated as a neurotoxin in brain metabolic disorders associated with hyperammonemia. Acute ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and nitric oxide (NO) production. Astrocytes interact with neurons, providing metabolic support and protecting against oxidative stress and excitotoxicity. Astrocytes also convert excess ammonia and glutamate into glutamine via glutamine synthetase (GS). Resveratrol, a polyphenol found in grapes and red wines, exhibits antioxidant and anti-inflammatory properties and modulates glial functions, such as glutamate metabolism. We investigated the effect of resveratrol on the production of reactive oxygen species (ROS), GS activity, S100B secretion, TNF-α, IL-1β and IL-6 levels in astroglial cells exposed to ammonia. Ammonia induced oxidative stress, decreased GS activity and increased cytokines release, probably by a mechanism dependent on protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways. Resveratrol prevented ammonia toxicity by modulating oxidative stress, glial and inflammatory responses. The ERK and nuclear factor-κB (NF-κB) are involved in the protective effect of resveratrol on cytokines proinflammatory release. In contrast, other antioxidants (e.g., ascorbic acid and trolox) were not effective against hyperammonemia. Thus, resveratrol could be used to protect against ammonia-induced neurotoxicity. PMID:23284918

Oral Chromium Exposure and Toxicity

Science.gov (United States)

Sun, Hong; Brocato, Jason

2015-01-01

Hexavalent chromium [Cr(VI)] is a known carcinogen when inhaled. However, inhalational exposure to Cr(VI) affects only a small portion of the population, mainly by occupational exposures. In contrast, oral exposure to Cr(VI) is widespread and affects many people throughout the globe. In 2008, the National Toxicology Program (NTP) released a 2-year study demonstrating that ingested Cr(VI) was carcinogenic in rats and mice. The effects of Cr(VI) oral exposure is mitigated by reduction in the gut, however a portion evades the reductive detoxification and reaches target tissues. Once Cr(VI) enters the cell, it ultimately gets reduced to Cr(III), which mediates its toxicity via induction of oxidative stress during the reduction while Cr intermediates react with protein and DNA. Cr(III) can form adducts with DNA that may lead to mutations. This review will discuss the potential adverse effects of oral exposure to Cr(VI) by presenting up-to-date human and animal studies, examining the underlying mechanisms that mediate Cr(VI) toxicity, as well as highlighting opportunities for future research. PMID:26231506

Involvement of inositol biosynthesis and nitric oxide in the mediation of UV-B induced oxidative stress

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Dmytro I Lytvyn

2016-04-01

Full Text Available The involvement of NO-signaling in ultraviolet B (UV-B induced oxidative stress in plants is an open question. Inositol biosynthesis contributes to numerous cellular functions, including the regulation of plants tolerance to stress. This work reveals the involvement of inositol-3-phosphate synthase 1 (IPS1, a key enzyme for biosynthesis of myo-inositol and its derivatives, in the response to NO-dependent oxidative stress in Arabidopsis. Homozygous mutants deficient for IPS1 (atips1 and wild-type plants were transformed with a reduction-oxidation-sensitive green fluorescent protein 2 (grx1-rogfp2 and used for the dynamic measurement of UV-B-induced and SNP (sodium nitroprusside-mediated oxidative stresses by confocal microscopy. atips1 mutants displayed greater tissue-specific resistance to the action of UV-B than the wild type. SNP can act both as an oxidant or repairer depending on the applied concentration, but mutant plants were more tolerant than the wild type to nitrosative effects of high concentration of SNP. Additionally, pretreatment with low concentrations of SNP (10, 100 μM before UV-B irradiation resulted in a tissue-specific protective effect that was enhanced in atips1. We conclude that the interplay between nitric oxide and inositol signaling can be involved in the mediation of UV-B-initiated oxidative stress in the plant cell.

Molten salt oxidation of ion-exchange resins doped with toxic metals and radioactive metal surrogates

International Nuclear Information System (INIS)

Yang, Hee-Chul; Cho, Yong-Jun; Yoo, Jae-Hyung; Kim, Joon-Hyung; Eun, Hee-Chul

2005-01-01

Ion-exchange resins doped with toxic metals and radioactive metal surrogates were test-burned in a bench-scale molten salt oxidation (MSO) reactor system. The purposes of this study are to confirm the destruction performance of the two-stage MSO reactor system for the organic ion-exchange resin and to obtain an understanding of the behavior of the fixed toxic metals and the sulfur in the cationic exchange resins. The destruction of the organics is very efficient in the primary reactor. The primarily destroyed products such as carbon monoxide are completely oxidized in the secondary MSO reactor. The overall collection of the sulfur and metals in the two-stage MSO reactor system appeared to be very efficient. Over 99.5% of all the fixed toxic metals (lead and cadmium) and radioactive metal surrogates (cesium, cobalt, strontium) remained in the MSO reactor bottom. Thermodynamic equilibrium calculations and the XRD patterns of the spent salt samples revealed that the collected metals existed in the form of each of their carbonates or oxides, which are non-volatile species at the MSO system operating conditions. (author)

Hypervalent iodine/TEMPO-mediated oxidation in flow systems: a fast and efficient protocol for alcohol oxidation

Directory of Open Access Journals (Sweden)

Nida Ambreen

2013-07-01

Full Text Available Hypervalent iodine(III/TEMPO-mediated oxidation of various aliphatic, aromatic and allylic alcohols to their corresponding carbonyl compounds was successfully achieved by using microreactor technology. This method can be used as an alternative for the oxidation of various alcohols achieving excellent yields and selectivities in significantly shortened reaction times.

Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

Energy Technology Data Exchange (ETDEWEB)

Wang, Cheng; Nie, Xiaoke; Zhang, Yan [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Li, Ting; Mao, Jiamin [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Liu, Xinhang [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Gu, Yiyang; Shi, Jiyun [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Xiao, Jing [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wan, Chunhua [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wu, Qiyun, E-mail: wqy@ntu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)

2015-10-15

Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

International Nuclear Information System (INIS)

Wang, Cheng; Nie, Xiaoke; Zhang, Yan; Li, Ting; Mao, Jiamin; Liu, Xinhang; Gu, Yiyang; Shi, Jiyun; Xiao, Jing; Wan, Chunhua; Wu, Qiyun

2015-01-01

Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

Salinity mediates the toxic effect of nano-TiO2 on the juvenile olive flounder Paralichthys olivaceus.

Science.gov (United States)

Huang, Xizhi; Lan, Yawen; Liu, Zekang; Huang, Wei; Guo, Qindan; Liu, Liping; Hu, Menghong; Sui, Yanming; Wu, Fangli; Lu, Weiqun; Wang, Youji

2018-06-04

Increased production of engineered nanoparticles has raised extensive concern about the potential toxic effects on marine organisms living in estuarine and coastal environments. Meanwhile, salinity is one of the key environmental factors that may influence the physiological activities in flatfish species inhabiting in those waters due to fluctuations caused by freshwater input or rainfall. In this study, we investigated the oxidative stress and histopathological alteration of the juvenile Paralichthys olivaceus exposed to nano-TiO 2 (1 and 10 mg L -1 ) under salinities of 10 and 30 psu for 4 days. In the gills, Na + -K + -ATPase activity significantly deceased after 4 days 10 psu exposure without nano-TiO 2 compared with 1 day of acclimating the salinity from the normal salinity (30 psu) to 10 psu. Under this coastal salinity, low concentration (1 mg L -1 ) of nano-TiO 2 exerted significant impacts. In the liver, the activities of superoxide dismutase, catalase, the levels of lipid peroxide and malondialdehyde increased with nano-TiO 2 exposed under 30 psu. Such increase indicated an oxidative stress response. The result of the integrated biomarker responses showed that P. olivaceus can be adversely affected by high salinity and high concentration of nano-TiO 2 for a short-term (4 days) exposure. The histological analysis revealed the accompanying severe damages for the gill filaments. Principal component analysis further showed that the oxidative stress was associated with the nano-TiO 2 effect at normal salinity. These findings indicated that nano-TiO 2 and normal salinity exert synergistic effects on juvenile P. olivaceus, and low salinity plays a protective role in its physiological state upon short-term exposure to nano-TiO 2 . The mechanism of salinity mediating the toxic effects of NPs on estuarine fish should be further considered. Copyright © 2018 Elsevier B.V. All rights reserved.

Protection of methamphetamine nigrostriatal toxicity by dietary selenium.

Science.gov (United States)

Kim, H C; Jhoo, W K; Choi, D Y; Im, D H; Shin, E J; Suh, J H; Floyd, R A; Bing, G

1999-12-18

Multiple dose administration of methamphetamine (MA) results in long-lasting toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased production of hydrogen peroxide or other reactive oxygen species in the dopaminergic system. The present study was designed to determine the protective effects of dietary antioxidant selenium on MA-induced neurotoxicity in the nigrostriatal dopaminergic system. Male C57BL/6J mice were fed either selenium-deficient (methamphetamine neurotoxicity and that this protection involves GPx-mediated antioxidant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is not yet clear.

Ethylene- and diethylene glycol metabolism, toxicity and treatment

International Nuclear Information System (INIS)

Wiener, H.L.

1986-01-01

Each year numerous men and domestic animals suffer from ethylene glycol (EG) poisoning. The present approach to treating EG poisoning by administering ethanol is aimed at preventing the oxidation of EG to glycolate, the toxic mediator. When treatment is delayed or the amount of EG consumed is large, successful treatment is rarely obtained, since the concentration of glycolate becomes excessive. In an effort to develop a better approach to treating EG poisoning, studies were conducted to determine the feasibility of using pig liver glycolic acid oxidase (GAO) as a means of enzyme therapy in male rats receiving EG. Pig liver GAO was active in vitro in rat blood, oxidizing glycolate to glyoxylate. When injected intravenously into male rats, GAO had an approximate half-life of twenty five minutes and its elimination followed first order kinetics. Despite activity in vitro, native pig liver GAO did not display detectable activity in vivo. Diethylene glycol (DEG) when ingested also results in toxicity. The metabolism and toxicity of DEG was investigated in male Wistar rats using [ 14 C]-DEG synthesized from [U- 14 C]-EG and ethylene oxide and purified by high performance liquid chromatography. (2-Hydroxyethoxy)acetic acid (HEAA) was identified as the major product of DEG oxidation. These results suggest that the treatment of DEG poisoning should follow the same regimen as treatment for EG poisoning

Cytosolic PrP Can Participate in Prion-Mediated Toxicity

Science.gov (United States)

Thackray, Alana M.; Zhang, Chang; Arndt, Tina

2014-01-01

ABSTRACT Prion diseases are characterized by a conformational change in the normal host protein PrPC. While the majority of mature PrPC is tethered to the plasma membrane by a glycosylphosphatidylinositol anchor, topological variants of this protein can arise during its biosynthesis. Here we have generated Drosophila transgenic for cytosolic ovine PrP in order to investigate its toxic potential in flies in the absence or presence of exogenous ovine prions. While cytosolic ovine PrP expressed in Drosophila was predominantly detergent insoluble and showed resistance to low concentrations of proteinase K, it was not overtly detrimental to the flies. However, Drosophila transgenic for cytosolic PrP expression exposed to classical or atypical scrapie prion inocula showed a faster decrease in locomotor activity than similar flies exposed to scrapie-free material. The susceptibility to classical scrapie inocula could be assessed in Drosophila transgenic for panneuronal expression of cytosolic PrP, whereas susceptibility to atypical scrapie required ubiquitous PrP expression. Significantly, the toxic phenotype induced by ovine scrapie in cytosolic PrP transgenic Drosophila was transmissible to recipient PrP transgenic flies. These data show that while cytosolic PrP expression does not adversely affect Drosophila, this topological PrP variant can participate in the generation of transmissible scrapie-induced toxicity. These observations also show that PrP transgenic Drosophila are susceptible to classical and atypical scrapie prion strains and highlight the utility of this invertebrate host as a model of mammalian prion disease. IMPORTANCE During prion diseases, the host protein PrPC converts into an abnormal conformer, PrPSc, a process coupled to the generation of transmissible prions and neurotoxicity. While PrPC is principally a glycosylphosphatidylinositol-anchored membrane protein, the role of topological variants, such as cytosolic PrP, in prion-mediated toxicity and

Cissus quadrangularis mediated ecofriendly synthesis of copper oxide nanoparticles and its antifungal studies against Aspergillus niger, Aspergillus flavus.

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Devipriya, Duraipandi; Roopan, Selvaraj Mohana

2017-11-01

Recently, non-toxic source mediated synthesis of metal and a metal oxide nanoparticle attains more attention due to key applicational responsibilities. This present report stated that the eco-friendly synthesis of copper oxide nanoparticles (CuO NPs) using Cissus quadrangularis (C. quadrangularis) plant extract. Further the eco-friendly synthesized CuO NPs were characterized using a number of analytical techniques. The observed results stated that the synthesized CuO NPs were spherical in shape with 30±2nm. Then the eco-friendly synthesized CuO NPs were subjected for anti-fungal against two strains namely Aspergillus niger (A. niger) resulted in 83% at 500ppm, 86% of inhibition at 1000ppm and Aspergillus flavus (A. flavus) resulted in 81% at 500ppm, 85% of inhibition at 1000ppm respectively. Despite the fact that compared to standard Carbendazim, eco-friendly synthesized CuO NPs exhibits better results were discussed in this manuscript. Copyright © 2017 Elsevier B.V. All rights reserved.

Mediated electrochemical oxidation of organic wastes using a Co(III) mediator in a neutral electrolyte

International Nuclear Information System (INIS)

Balazs, G.B.; Lewis, P.R.

1999-01-01

An electrochemical cell with a Co(III) mediator and neutral pH anolyte provides efficient destruction of organic and mixed wastes. The organic waste is concentrated in the anolyte reservoir, where the cobalt mediator oxidizes the organics and insoluble radioactive species and is regenerated at the anode until all organics are converted to carbon dioxide and destroyed. The neutral electrolyte is non-corrosive, and thus extends the lifetime of the cell and its components. 2 figs

Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice.

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Sundarraj, Kiruthika; Manickam, Vijayprakash; Raghunath, Azhwar; Periyasamy, Madhivadhani; Viswanathan, Mangala Priya; Perumal, Ekambaram

2017-02-01

The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe 2 O 3 -NPs) could be toxic to mice testis. Fe 2 O 3 -NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe 2 O 3 -NPs have the ability to cross the blood-testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe 2 O 3 -NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe 2 O 3 -NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants-superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved-caspase-3, and cleaved-PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe 2 O 3 -NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe 2 O 3 -NPs treatment. The data from our study entailed that testicular toxicity caused by Fe 2 O 3 -NPs exposure may be associated with Fe 2 O 3 -NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe 2 O 3 -NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe 2 O 3 -NPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594-608, 2017. © 2016 Wiley Periodicals, Inc.

MnSOD and catalase transgenes demonstrate that protection of islets from oxidative stress does not alter cytokine toxicity.

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Chen, Hainan; Li, Xiaoyan; Epstein, Paul N

2005-05-01

Reactive oxygen species (ROS) and nitric oxide (NO) are proposed mediators of cytokine-induced beta-cell destruction in type 1 diabetes. We produced transgenic mice with increased beta-cell expression of manganese superoxide dismutase (MnSOD) and catalase. Expression of these antioxidants increased beta-cell ROS scavenging and improved beta-cell survival after treatment with different sources of ROS. MnSOD or catalase conferred protection against streptozotocin (STZ)-induced beta-cell injury. Coexpression of MnSOD and catalase provided synergistic protection against peroxynitrite and STZ. To determine the potential effect of these antioxidants on cytokine-induced toxicity, we exposed isolated islets to a cytokine mixture, including interleukin-1beta and interferon-gamma. Cytokine toxicity was measured as reduced metabolic activity after 6 days and reduced insulin secretion after 1 day. Cytokines increased ROS production, and both antioxidants were effective in reducing cytokine-induced ROS. However, MnSOD and/or catalase provided no protection against cytokine-induced injury. To understand this, the nuclear factor-kappaB (NF-kappaB) signaling cascade was investigated. Antioxidants reduced NF-kappaB activation by ROS, but none of the antioxidants altered activation by cytokines, as measured by inhibitor of kappaB phosphorylation, NF-kappaB translocation, inducible NO synthase activation, and NO production. Our data agree with previous reports that antioxidants benefit beta-cell survival against ROS damage, but they are not consistent with reports that antioxidants reduce cytokine toxicity. ROS appear to have no role in cytokine toxicity in primary beta-cells.

Structural mediation on polycation nanoparticles by sulfadiazine to enhance DNA transfection efficiency and reduce toxicity.

Science.gov (United States)

Long, Xingwen; Zhang, Zhihui; Han, Shangcong; Tang, Minjie; Zhou, Junhui; Zhang, Jianhua; Xue, Zhenyi; Li, Yan; Zhang, Rongxin; Deng, Liandong; Dong, Anjie

2015-04-15

Reducing the toxicity while maintaining high transfection efficiency is an important issue for cationic polymers as gene carriers in clinical application. In this paper, a new zwitterionic copolymer, polycaprolactone-g-poly(dimethylaminoethyl methyacrylate-co-sulfadiazine methacrylate) (PC-SDZ) with unique pH-sensitivity, was designed and prepared. The incorporation of sulfadiazine into poly(dimethylaminoethyl methacrylate) (PDMAEMA) chains successfully mediates the surface properties including compacter shell structure, lower density of positive charges, stronger proton buffer capability, and enhanced hydrophobicity, which lead to reduction in toxicity and enhancements in stability, cellular uptake, endosome escape, and transfection efficiency for the PC-SDZ2 nanoparticles (NPs)/DNA complexes. Excellent transfection efficiency at the optimal N/P ratio of 10 was observed for PC-SDZ2 NPs/DNA complexes, which was higher than that of the commercial reagent-branched polyethylenimine (PEI). The cytotoxicity was evaluated by CCK8 measurement, and the results showed significant reduction in cytotoxicity even at high concentration of complexes after sulfadiazine modification. Therefore, this work may demonstrate a new way of structural mediation of cationic polymer carriers for gene delivery with high efficiency and low toxicity.

Acetaminophen hepatotoxicity and HIF-1α induction in acetaminophen toxicity in mice occurs without hypoxia

International Nuclear Information System (INIS)

Chaudhuri, Shubhra; McCullough, Sandra S.; Hennings, Leah; Letzig, Lynda; Simpson, Pippa M.; Hinson, Jack A.; James, Laura P.

2011-01-01

HIF-1α is a nuclear factor important in the transcription of genes controlling angiogenesis including vascular endothelial growth factor (VEGF). Both hypoxia and oxidative stress are known mechanisms for the induction of HIF-1α. Oxidative stress and mitochondrial permeability transition (MPT) are mechanistically important in acetaminophen (APAP) toxicity in the mouse. MPT may occur as a result of oxidative stress and leads to a large increase in oxidative stress. We previously reported the induction of HIF-1α in mice with APAP toxicity and have shown that VEGF is important in hepatocyte regeneration following APAP toxicity. The following study was performed to examine the relative contribution of hypoxia versus oxidative stress to the induction of HIF-1α in APAP toxicity in the mouse. Time course studies using the hypoxia marker pimonidazole showed no staining for pimonidazole at 1 or 2 h in B6C3F1 mice treated with APAP. Staining for pimonidazole was present in the midzonal to periportal regions at 4, 8, 24 and 48 h and no staining was observed in centrilobular hepatocytes, the sites of the toxicity. Subsequent studies with the MPT inhibitor cyclosporine A showed that cyclosporine A (CYC; 10 mg/kg) reduced HIF-1α induction in APAP treated mice at 1 and 4 h and did not inhibit the metabolism of APAP (depletion of hepatic non-protein sulfhydryls and hepatic protein adduct levels). The data suggest that HIF-1α induction in the early stages of APAP toxicity is secondary to oxidative stress via a mechanism involving MPT. In addition, APAP toxicity is not mediated by a hypoxia mechanism.

Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION

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Neenu Singh

2010-09-01

Full Text Available Superparamagnetic iron oxide nanoparticles (SPION are being widely used for various biomedical applications, for example, magnetic resonance imaging, targeted delivery of drugs or genes, and in hyperthermia. Although, the potential benefits of SPION are considerable, there is a distinct need to identify any potential cellular damage associated with these nanoparticles. Besides focussing on cytotoxicity, the most commonly used determinant of toxicity as a result of exposure to SPION, this review also mentions the importance of studying the subtle cellular alterations in the form of DNA damage and oxidative stress. We review current studies and discuss how SPION, with or without different surface coating, may cause cellular perturbations including modulation of actin cytoskeleton, alteration in gene expression profiles, disturbance in iron homeostasis and altered cellular responses such as activation of signalling pathways and impairment of cell cycle regulation. The importance of protein–SPION interaction and various safety considerations relating to SPION exposure are also addressed.

Haloacetonitriles: metabolism and toxicity.

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Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

2009-01-01

bioactivation process, depending on the particular HAN and the enzyme involved. HANs can inhibit CYP2E1-mediated metabolism, an effect which may be dependent on a covalent interaction with the enzyme. In addition, HAN compounds inhibit GST-mediated conjugation, but this effect is reversible upon dialysis, indicating that the interaction does not represent covalent binding. No subchronic studies of HAN toxicity are available in the literature. However, studies show that HANs produce developmental toxicity in experimental animals. The nature of developmental toxicity is affected by the type of administration vehicle, which renders interpretation of results more difficult. Skin tumors have been found following dermal application of HANs, but oral studies for carcinogenicity are negative. Pulmonary adenomas were increased following oral administration of HANs, but the A/J strain of mice employed has a characteristically high background rate of such tumors. HANs interact with DNA to produce unscheduled DNA repair, SCE and reverse mutations in Salmonella. HANs did not induce micronuclei or cause alterations in sperm head morphology in mice, but did induce micronuclei in newts. Thus, there is concern for the potential carcinogenicity of HANs. It would be valuable to delineate any relationship between the apparent threshold for micronuclei formation in newts and the potential mechanism of toxicity involving HAN-induced oxidative stress. Dose-response studies in rodents may provide useful information on toxicity mechanisms and dose selection for longer term toxicity studies. Additional studies are warranted before drawing firm conclusions on the hazards of HAN exposure. Moreover, additional studies on HAN-DNA and HAN-protein interaction mechanisms, are needed. Such studies can better characterize the role of metabolism in toxicity of individual HANs, and delineate the role of oxidative stress, both of which enhance the capacity to predict risk. Most needed, now, are new subchronic (and

Levofloxacin oxidation by ozone and hydroxyl radicals: kinetic study, transformation products and toxicity.

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Hamdi El Najjar, Nasma; Touffet, Arnaud; Deborde, Marie; Journel, Romain; Leitner, Nathalie Karpel Vel

2013-10-01

This work was carried out to investigate the fate of the antibiotic levofloxacin upon oxidation with ozone and hydroxyl radicals. A kinetic study was conducted at 20 °C for each oxidant. Ozonation experiments were performed using a competitive kinetic method with carbamazepin as competitor. Significant levofloxacin removal was observed during ozonation and a rate constant value of 6.0×10(4) M(-1) s(-1) was obtained at pH 7.2. An H2O2/UV system was used for the formation of hydroxyl radicals HO. The rate constant of HO was determined in the presence of a high H2O2 concentration. The kinetic expressions yielded a [Formula: see text] value of 4.5×10(9) M(-1) s(-1) at pH 6.0 and 5.2×10(9) M(-1) s(-1) at pH 7.2. These results were used to develop a model to predict the efficacy of the ozonation process and pharmaceutical removal was estimated under different ozonation conditions (i.e. oxidant concentrations and contact times). The results showed that levofloxacin was completely degraded by molecular ozone during ozonation of water and that hydroxyl radicals had no effect in real waters conditions. Moreover, LC/MS/MS and toxicity assays using Lumistox test were performed to identify ozonation transformation products. Under these conditions, four transformation products were observed and their chemical structures were proposed. The results showed an increase in toxicity during ozonation, even after degradation of all of the observed transformation products. The formation of other transformation products not identified under our experimental conditions could be responsible for the observed toxicity. These products might be ozone-resistant and more toxic to Vibrio fisheri than levofloxacin. Copyright © 2013 Elsevier Ltd. All rights reserved.

Oxidation and detoxification of trivalent arsenic species

International Nuclear Information System (INIS)

Aposhian, H. Vasken; Zakharyan, Robert A.; Avram, Mihaela D.; Kopplin, Michael J.; Wollenberg, Michael L.

2003-01-01

Arsenic compounds with a +3 oxidation state are more toxic than analogous compounds with a +5 oxidation state, for example, arsenite versus arsenate, monomethylarsonous acid (MMA III ) versus monomethylarsonic acid (MMA V ), and dimethylarsinous acid (DMA III ) versus dimethylarsinic acid (DMA V ). It is no longer believed that the methylation of arsenite is the beginning of a methylation-mediated detoxication pathway. The oxidation of these +3 compounds to their less toxic +5 analogs by hydrogen peroxide needs investigation and consideration as a potential mechanism for detoxification. Xanthine oxidase uses oxygen to oxidize hypoxanthine to xanthine to uric acid. Hydrogen peroxide and reactive oxygen are also products. The oxidation of +3 arsenicals by the hydrogen peroxide produced in the xanthine oxidase reaction was blocked by catalase or allopurinol but not by scavengers of the hydroxy radical, e.g., mannitol or potassium iodide. Melatonin, the singlet oxygen radical scavenger, did not inhibit the oxidation. The production of H 2 O 2 by xanthine oxidase may be an important route for decreasing the toxicity of trivalent arsenic species by oxidizing them to their less toxic pentavalent analogs. In addition, there are many other reactions that produce hydrogen peroxide in the cell. Although chemists have used hydrogen peroxide for the oxidation of arsenite to arsenate to purify water, we are not aware of any published account of its potential importance in the detoxification of trivalent arsenicals in biological systems. At present, this oxidation of the +3 oxidation state arsenicals is based on evidence from in vitro experiments. In vivo experiments are needed to substantiate the role and importance of H 2 O 2 in arsenic detoxication in mammals

Evaluation of nano-specific toxicity of zinc oxide, copper oxide, and silver nanoparticles through toxic ratio

Energy Technology Data Exchange (ETDEWEB)

Zhang, Weicheng; Liu, Xiawei; Bao, Shaopan; Xiao, Bangding; Fang, Tao, E-mail: fangt@ihb.ac.cn [Chinese Academy of Sciences, Institute of Hydrobiology (China)

2016-12-15

For safety and environmental risk assessments of nanomaterials (NMs) and to provide essential toxicity data, nano-specific toxicities, or excess toxicities, of ZnO, CuO, and Ag nanoparticles (NPs) (20, 20, and 30 nm, respectively) to Escherichia coli and Saccharomyces cerevisiae in short-term (6 h) and long-term (48 h) bioassays were quantified based on a toxic ratio. ZnO NPs exhibited no nano-specific toxicities, reflecting similar toxicities as ZnO bulk particles (BPs) (as well as zinc salt). However, CuO and Ag NPs yielded distinctly nano-specific toxicities when compared with their BPs. According to their nano-specific toxicities, the capability of these NPs in eliciting hazardous effects on humans and the environment was as follows: CuO > Ag > ZnO NPs. Moreover, long-term bioassays were more sensitive to nano-specific toxicity than short-term bioassays. Overall, nano-specific toxicity is a meaningful measurement to evaluate the environmental risk of NPs. The log T{sub e}{sup particle} value is a useful parameter for quantifying NP nano-specific toxicity and enabling comparisons of international toxicological data. Furthermore, this value could be used to determine the environmental risk of NPs.

Oxidative stress by layered double hydroxide nanoparticles via an SFK-JNK and p38-NF-κB signaling pathway mediates induction of interleukin-6 and interleukin-8 in human lung epithelial cells

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Choi SJ

2015-04-01

Full Text Available Soo-Jin Choi, Hee-Jeong Paek, Jin YuDepartment of Food Science and Technology, Seoul Women’s University, Seoul, Republic of KoreaAbstract: Anionic nanoclays are layered double hydroxide nanoparticles (LDH-NPs that have been shown to exhibit toxicity by inducing reactive oxidative species and a proinflammatory mediator in human lung epithelial A549 cells. However, the molecular mechanism responsible for this LDH-NP-induced toxicity and the relationship between oxidative stress and inflammatory events remains unclear. In this study, we focused on intracellular signaling pathways and transcription factors induced in response to oxidative stress caused by exposure to LDH-NPs in A549 cells. Mitogen-activated protein kinase (MAPK cascades, such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase (JNK, and p38, were investigated as potential signaling mechanisms responsible for regulation of oxidative stress and cytokine release. Src family kinases (SFKs, which are known to mediate activation of MAPK, together with redox-sensitive transcription factors, including nuclear factor kappa B and nuclear factor-erythroid 2-related factor-2, were also investigated as downstream events of MAPK signaling. The results obtained suggest that LDH-NP exposure causes oxidative stress, leading to expression of antioxidant enzymes, such as catalase, glucose reductase, superoxide dismutase, and heme oxygenase-1, via a SFK-JNK and p38-nuclear factor kappa B signaling pathway. Further, activation of this signaling was also found to regulate release of inflammatory cytokines, including interleukin-6 and interleukin-8, demonstrating the inflammatory potential of LDH-NP.Keywords: layered double hydroxide, mitogen-activated protein kinases, Src family kinases, nuclear factor kappa B, oxidative stress, inflammatory cytokine

Troxerutin protects against 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD+-depletion

International Nuclear Information System (INIS)

Zhang, Zi-Feng; Zhang, Yan-qiu; Fan, Shao-Hua; Zhuang, Juan; Zheng, Yuan-Lin; Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin

2015-01-01

Highlights: • BDE-47 promotes liver inflammation by triggering oxidative stress-induced NAD + depletion. • Troxerutin inhibits BDE-47-induced liver inflammation via its antioxidant properties. • Troxerutin restores NAD + level and consequently abates SirT1 loss. • Troxerutin represses acetylation of NF-κB p65 (K310) and H3K9. • Troxerutin is a candidate for prevention and therapy of BDE-47-induced hepatotoxicity. - Abstract: Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD + -depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD + -depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity

Constraints on superoxide mediated formation of manganese oxides

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Deric R. Learman

2013-09-01

Full Text Available Manganese (Mn oxides are among the most reactive sorbents and oxidants within the environment, where they play a central role in the cycling of nutrients, metals, and carbon. Recent discoveries have identified superoxide (O2- (both of biogenic and abiogenic origin as an effective oxidant of Mn(II leading to the formation of Mn oxides. Here we examined the conditions under which abiotically produced superoxide led to oxidative precipitation of Mn and the solid-phases produced. Oxidized Mn, as both aqueous Mn(III and Mn(III/IV oxides, was only observed in the presence of active catalase, indicating that hydrogen peroxide, a product of the reaction of O2- with Mn(II, inhibits the oxidation process presumably through the reduction of Mn(III. Citrate and pyrophosphate increased the yield of oxidized Mn but decreased the amount of Mn oxide produced via formation of Mn(III-ligand complexes. While complexing ligands played a role in stabilizing Mn(III, they did not eliminate the inhibition of net Mn(III formation by H2O2. The Mn oxides precipitated were highly disordered colloidal hexagonal birnessite, similar to those produced by biotically generated superoxide. Yet, in contrast to the large particulate Mn oxides formed by biogenic superoxide, abiotic Mn oxides did not ripen to larger, more crystalline phases. This suggests that the deposition of crystalline Mn oxides within the environment requires a biological, or at least organic, influence. This work provides the first direct evidence that, under conditions relevant to natural waters, oxidation of Mn(II by superoxide can occur and lead to formation of Mn oxides. For organisms that oxidize Mn(II by producing superoxide, these findings may also point to other microbially mediated processes, in particular enzymatic hydrogen peroxide degradation and/or production of organic ligand metabolites, that allow for Mn oxide formation.

Toxicity and transformation of graphene oxide and reduced graphene oxide in bacteria biofilm.

Science.gov (United States)

Guo, Zhiling; Xie, Changjian; Zhang, Peng; Zhang, Junzhe; Wang, Guohua; He, Xiao; Ma, Yuhui; Zhao, Bin; Zhang, Zhiyong

2017-02-15

Impact of graphene based material (GNMs) on bacteria biofilm has not been well understood yet. In this study, we compared the impact of graphene oxide (GO) and reduced graphene oxide (rGO) on biofilm formation and development in Luria-Bertani (LB) medium using Escherichia coli and Staphylococcus aureus as models. GO significantly enhanced the cell growth, biofilm formation, and biofilm development even up to a concentration of 500mg/L. In contrast, rGO (≥50mg/L) strongly inhibited cell growth and biofilm formation. However, the inhibitory effects of rGO (50mg/L and 100mg/L) were attenuated in the mature phase (>24h) and eliminated at 48h. GO at 250mg/L decreased the reactive oxygen species (ROS) levels in biofilm and extracellular region at mature phase. ROS levels were significantly increased by rGO at early phase, while they returned to the same levels as control at mature phase. These results suggest that oxidative stress contributed to the inhibitory effect of rGO on bacterial biofilm. We further found that supplement of extracellular polymeric substances (EPS) in the growth medium attenuated the inhibitory effect of rGO on the growth of developed biofilm. XPS results showed that rGO were oxidized to GO which can enhance the bacterial growth. We deduced that the elimination of the toxicity of rGO at mature phase was contributed by EPS protection and the oxidation of rGO. This study provides new insights into the interaction of GNMs with bacteria biofilm. Copyright © 2016 Elsevier B.V. All rights reserved.

Toxicity of isoproturon on Saccharomyces cerevisiae growing in mineral medium depends on glutathione-mediated antioxidant capacity.

OpenAIRE

Candeias, M; Alves-Pereira, I; Ferreira, Rui

2011-01-01

The results revealed an increase of viable cells, after 72 h of culture and an increase of antioxidant power mediated by GSH and GR activity in S. cerevisiae UE-ME3. The adaptive response of UE-ME3 strain to isoproturon, determined in MB, was clearly higher than observed in IGC-3507 strain. So, we presume that the extent of the toxic effect of isoproturon in both yeast strains depends on glutathione-mediated antioxidant capacity.

Fluoroacetate-mediated toxicity of fluorinated ethanes.

Science.gov (United States)

Keller, D A; Roe, D C; Lieder, P H

1996-04-01

A series of 1-(di)halo-2-fluoroethanes reported in the literature to be nontoxic or of low toxicity were found to be highly toxic by the inhalation route. Experiments were performed that showed the compounds, 1,2-difluoroethane, 1-chloro-2-fluoroethane, 1-chloro-1,2-difluoroethane, and 1-bromo-2-fluoroethane to be highly toxic to rats upon inhalation for 4 hr. All four compounds had 4-hr approximate lethal concentrations of difluoroethane (commonly referred to as HFC-152a) has very low acute toxicity with a 4-hr LC50 of > 400,000 ppm in rats. Rats exposed to the selected toxic fluoroethanes showed clinical signs of fluoroacetate toxicity (lethargy, hunched posture, convulsions). 1,2-Difluoroethane, 1-chloro-2-fluoroethane, 1-chloro-1,2-difluoroethane, and 1-bromo-2-fluoroethane were shown to increase concentrations of citrate in serum and heart tissue, a hallmark of fluoroacetate intoxication. 19F NMR analysis confirmed that fluoroacetate was present in the urine of rats exposed to each toxic compound. Fluorocitrate, a condensation product of fluoroacetate and oxaloacetate, was identified in the kidney of rats exposed to 1,2-difluoroethane. There was a concentration-related elevation of serum and heart citrate in rats exposed to 0-1000 ppm 1,2-fluoroethane. Serum citrate was increased up to 5-fold and heart citrate was increased up to 11-fold over control citrate levels. Metabolism of 1,2-difluoroethane by cytochrome P450 (most likely CYP2E1) is suspected because pretreatment of rats or mice with SKF-525F, disulfiram, or dimethyl sulfoxide prevented or delayed the toxicity observed in rats not pretreated. Experimental evidence indicates that the metabolism of the toxic fluoroethanes is initiated at the carbon-hydrogen bond, with metabolism to fluoroacetate via an aldehyde or an acyl fluoride. The results of these studies show that 1-(di)halo-2-fluoroethanes are highly toxic to rats and should be considered a hazard to humans unless demonstrated otherwise.

Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse

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Sophie A. Bradley

2016-01-01

Full Text Available Nitric oxide (NO is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS, new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic origin. During normal brain function, both pathways serve as important cellular signalling cascades that modulate a diverse array of physiological processes, including synaptic plasticity, transcriptional activity, and neuronal survival. In contrast, evidence suggests that aging and disease can induce nitrosative stress via excessive NO production. Consequently, uncontrolled S-nitrosylation/3-nitrotyrosination can occur and represent pathological features that contribute to the onset and progression of various neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Huntington’s.

Toxic Effects of Nickel Oxide Bulk and Nanoparticles on the Aquatic Plant Lemna gibba L.

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Abdallah Oukarroum

2015-01-01

Full Text Available The aquatic plant Lemna gibba L. was used to investigate and compare the toxicity induced by 30 nm nickel oxide nanoparticles (NiO-NPs and nickel(II oxide as bulk (NiO-Bulk. Plants were exposed during 24 h to 0–1000 mg/L of NiO-NPs or NiO-Bulk. Analysis of physicochemical characteristics of nanoparticles in solution indicated agglomerations of NiO-NPs in culture medium and a wide size distribution was observed. Both NiO-NPs and NiO-Bulk caused a strong increase in reactive oxygen species (ROS formation, especially at high concentration (1000 mg/L. These results showed a strong evidence of a cellular oxidative stress induction caused by the exposure to NiO. Under this condition, NiO-NPs and NiO-Bulk induced a strong inhibitory effect on the PSII quantum yield, indicating an alteration of the photosynthetic electron transport performance. Under the experimental conditions used, it is clear that the observed toxicity impact was mainly due to NiO particles effect. Therefore, results of this study permitted determining the use of ROS production as an early biomarker of NiO exposure on the aquatic plant model L. gibba used in toxicity testing.

CYP2F2-generated metabolites, not styrene oxide, are a key event mediating the mode of action of styrene-induced mouse lung tumors.

Science.gov (United States)

Cruzan, G; Bus, J; Hotchkiss, J; Harkema, J; Banton, M; Sarang, S

2012-02-01

Styrene induces lung tumors in mice but not in rats. Although metabolism of styrene to 7,8-styrene oxide (SO) by CYP2E1 has been suggested as a mediator of styrene toxicity, lung toxicity is not attenuated in CYP2E1 knockout mice. However, styrene and/or SO metabolism by mouse lung Clara cell-localized CYP2F2 to ring-oxidized cytotoxic metabolite(s) has been postulated as a key metabolic gateway responsible for both lung toxicity and possible tumorigenicity. To test this hypothesis, the lung toxicity of styrene and SO was evaluated in C57BL/6 (WT) and CYP2F2⁻/⁻ knockout mice treated with styrene (400 mg/kg/day, gavage, or 200 or 400 mg/kg/day, ip) or S- or R-SO (200 mg/kg/day, ip) for 5 days. Styrene treated WT mice displayed significant necrosis and exfoliation of Clara cells, and cumulative BrdU-labeling index of S-phase cells was markedly increased in terminal bronchioles of WT mice exposed to styrene or S- or RSO. In contrast, Clara and terminal bronchiole cell toxicity was not observed in CYP2F2⁻/⁻ mice exposed to either styrene or SO. This study clearly demonstrates that the mouse lung toxicity of both styrene and SO is critically dependent on metabolism by CYP2F2. Importantly, the human isoform of CYP2F, CYP2F1, is expressed at much lower levels and likely does not catalyze significant styrene metabolism, supporting the hypothesis that styrene-induced mouse lung tumors may not quantitatively, or possibly qualitatively, predict lung tumor potential in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

The neuronal nitric oxide synthase inhibitor NANT blocks acetaminophen toxicity and protein nitration in freshly isolated hepatocytes.

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Banerjee, Sudip; Melnyk, Stepan B; Krager, Kimberly J; Aykin-Burns, Nukhet; Letzig, Lynda G; James, Laura P; Hinson, Jack A

2015-12-01

3-Nitrotyrosine (3NT) in liver proteins of mice treated with hepatotoxic doses of acetaminophen (APAP) has been postulated to be causative in toxicity. Nitration is by a reactive nitrogen species formed from nitric oxide (NO). The source of the NO is unclear. iNOS knockout mice were previously found to be equally susceptible to APAP toxicity as wildtype mice and iNOS inhibitors did not decrease toxicity in mice or in hepatocytes. In this work we examined the potential role of nNOS in APAP toxicity in hepatocytes using the specific nNOS inhibitor NANT (10 µM)(N-[(4S)-4-amino-5-[(2-aminoethyl)amino]pentyl]-N'-nitroguanidinetris (trifluoroacetate)). Primary hepatocytes (1 million/ml) from male B6C3F1 mice were incubated with APAP (1mM). Cells were removed and assayed spectrofluorometrically for reactive nitrogen and oxygen species using diaminofluorescein (DAF) and Mitosox red, respectively. Cytotoxicity was determined by LDH release into media. Glutathione (GSH, GSSG), 3NT, GSNO, acetaminophen-cysteine adducts, NAD, and NADH were measured by HPLC. APAP significantly increased cytotoxicity at 1.5-3.0 h. The increase was blocked by NANT. NANT did not alter APAP mediated GSH depletion or acetaminophen-cysteine adducts in proteins which indicated that NANT did not inhibit metabolism. APAP significantly increased spectroflurometric evidence of reactive nitrogen and oxygen formation at 0.5 and 1.0 h, respectively, and increased 3NT and GSNO at 1.5-3.0 h. These increases were blocked by NANT. APAP dramatically increased NADH from 0.5-3.0 h and this increase was blocked by NANT. Also, APAP decreased the Oxygen Consumption Rate (OCR), decreased ATP production, and caused a loss of mitochondrial membrane potential, which were all blocked by NANT. Copyright © 2015 Elsevier Inc. All rights reserved.

Troxerutin protects against 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD{sup +}-depletion

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Zhang, Zi-Feng [School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China); Zhang, Yan-qiu [School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Fan, Shao-Hua [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China); Zhuang, Juan [School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zheng, Yuan-Lin, E-mail: ylzheng@jsnu.edu.cn [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China); Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou 221116, Jiangsu Province (China)

2015-02-11

Highlights: • BDE-47 promotes liver inflammation by triggering oxidative stress-induced NAD{sup +} depletion. • Troxerutin inhibits BDE-47-induced liver inflammation via its antioxidant properties. • Troxerutin restores NAD{sup +} level and consequently abates SirT1 loss. • Troxerutin represses acetylation of NF-κB p65 (K310) and H3K9. • Troxerutin is a candidate for prevention and therapy of BDE-47-induced hepatotoxicity. - Abstract: Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD{sup +}-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD{sup +}-depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced

Toxicity Evaluation of Graphene Oxide and Titania Loaded Nafion Membranes in Zebrafish

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Roberta Pecoraro

2018-01-01

Full Text Available The use of nanomaterials in several application fields has received in the last decades a great attention due to their peculiar properties, but also raised many doubts about possible toxicity when these materials are used for some specific applications, such as water purification. Indeed a careful investigation is needed in order to exclude possible harmful side effects related to the use of nanotechnology. Nanoparticles effects on the marine organisms may depend on their chemical composition, size, surface structure, solubility, shape and how the individual nanoparticles aggregate together. In order to make the most of their potential, without polluting the environment, many researchers are trying to trap them into some kind of matrix that keeps them active but avoids their dispersion in the environment. In this study we have tested nanocomposite membranes prepared using Nafion polymer combined with various fillers, such as anatase-type TiO2 nanoparticles and graphene oxide. The non-toxicity of these nanocomposites, already shown to be effective for water purification applications in our previous studies, was recognized by testing the effect of the different materials on zebrafish embryos. Zebrafish was considered an excellent model for ecotoxicological studies and for this motivation zebrafish embryos were exposed to different concentrations of free nanoparticles and to the nanocomposite membranes. As biomarkers of exposure, we evaluated the expression of heme-oxygenase 1 and inducible Nitric Oxide Synthases by immunohistochemistry and gene expression. Embryo toxicity test showed that nor sublethal effects neither mortality were caused by the different nanoparticles and nano-systems tested. Only zebrafish larvae exposed to free nanoparticles have shown a different response to antibodies anti-heme-oxygenase 1 and anti- inducible Nitric Oxide Synthases. The immunolocalization analysis in fact has highlighted an increase in the synthesis of these

Comparative effects of graphene and graphene oxide on copper toxicity to Daphnia magna: Role of surface oxygenic functional groups.

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Liu, Yingying; Fan, Wenhong; Xu, Zhizhen; Peng, Weihua; Luo, Shenglian

2018-05-01

Although the risk of graphene materials to aquatic organisms has drawn wide attention, the combined effects of graphene materials with other contaminants such as toxic metals, which may bring about more serious effects than graphene materials alone, have seldom been explored. Herein, the effects of graphene (GN) and graphene oxide (GO, an important oxidized derivative of graphene) on copper (Cu) toxicity to Daphnia magna were systematically investigated. The results indicated that GN remarkably increased the Cu accumulation in D. magna and enhanced the oxidative stress injury caused by Cu, whereas did not significantly alter D. magna acute mortality within the tested Cu concentrations (0-200 μg L -1 ). On the contrary, GO significantly decreased the Cu accumulation in D. magna and alleviated the oxidative stress injury caused by Cu. Meanwhile, the presence of GO significantly reduced the mortality of D. magna when Cu concentration exceeded 50 μg L -1 . The different effects of GN and GO on Cu toxicity were possibly dependent on the action of surface oxygenic functional group. Because of the introduction of surface oxygenic functional groups, the adsorption ability to metal ions, stability in water and interaction mode with organisms of GO are quite different from that of GN, causing different effects on Cu toxicity. This study provides important information on the bioavailability and toxicity of heavy metals as affected by graphene materials in natural water. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of surface modification in zinc oxide nanoparticles and its toxicity assessment toward human dermal fibroblast cells

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Ramasamy M

2014-08-01

Full Text Available Mohankandhasamy Ramasamy,1 Minakshi Das,1 Seong Soo A An,1 Dong Kee Yi2 1Division of Bionanotechnology, Gachon University, Seongnam, 2Department of Chemistry, Myongji University, Yongin, South Korea Abstract: The wide-scale applications of zinc oxide (ZnO nanoparticles (NPs in ­photocatalysts, gas sensors, and cosmetics may cause toxicity to humans and environments. Therefore, the aim of the present study was to reduce the toxicity of ZnO NPs by coating them with a silica (SiO2 layer, which could be used in human applications, such as cosmetic preparations. The sol–gel method was used to synthesize core ZnO with SiO2-shelled NPs (SiO2/ZnO NPs with varying degrees of coating. Diverse studies were performed to analyze the toxicity of NPs against cells in a dose- and time-dependent manner. To ensure the decreased toxicity of the produced SiO2/ZnO NPs, cytotoxicity in membrane damage and/or intracellular reactive oxygen species (ROS were assessed by employing 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, lactate dehydrogenase, 2',7'-dichlorofluorescin, and lipid peroxide estimations. The cores of ZnO NPs exhibited cytotoxicity over time, regardless of shell thickness. Nevertheless, the thicker SiO2/ZnO NPs revealed reduced enzyme leakage, decreased peroxide production, and less oxidative stress than their bare ZnO NPs or thinner SiO2/ZnO NPs. Therefore, thicker SiO2/ZnO NPs moderated the toxicity of ZnO NPs by restricting free radical formation and the release of zinc ions, and decreasing surface contact with cells. Keywords: zinc oxide, silica coating, photostability, human dermal fibroblast, membrane damage, oxidative stress

Mechanisms of the Testis Toxicity Induced by Chronic Exposure to Mequindox

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Qianying Liu

2017-09-01

Full Text Available Mequindox (MEQ is a synthetic antimicrobial agent widely used in China since the 1980s. Although the toxicity of MEQ is well recognized, its testis toxicity has not been adequately investigated. In the present study, we provide evidence that MEQ triggers oxidative stress, mitochondrion dysfunction and spermatogenesis deficiency in mice after exposure to MEQ (0, 25, 55, and 110 mg/kg in the diet for up to 18 months. The genotoxicity and adrenal toxicity may contribute to sperm abnormalities caused by MEQ. Moreover, using LC/MS-IT-TOF analysis, two metabolites, 3-methyl-2-(1-hydroxyethyl quinoxaline-N4-monoxide (M4 and 3-methyl-2-(1-hydroxyethyl quinoxaline-N1-monoxide (M8, were detected in the serum of mice, which directly confirms the relationship between the N→O group reduction metabolism of MEQ and oxidative stress. Interestingly, only M4 was detected in the testes, suggesting that the higher reproductive toxicity of M4 than M8 might be due to the increased stability of M4-radical (M4-R compared to M8-radical (M8-R. Furthermore, the expression of the blood-testis barrier (BTB-associated junctions such as tight junctions, gap junctions and basal ectoplasmic specializations were also examined. The present study demonstrated for the first time the role of the M4 in testis toxicity, and illustrated that the oxidative stress, mitochondrion dysfunction and interference in spermatogenesis, as well as the altered expression of BTB related junctions, were involved in the reproductive toxicity mediated by MEQ in vivo.

Pulmonary toxicity of manufactured nanoparticles

Science.gov (United States)

Peebles, Brian Christopher

Manufactured nanomaterials have become ubiquitous in science, industry, and medicine. Although electron microscopy and surface probe techniques have improved understanding of the physicochemical properties of nanomaterials, much less is known about what makes nanomaterials toxic. Particulate matter less than 2.5 mum in effective aerodynamic diameter is easily inhaled and taken deep into the lungs. The toxicity of inhaled particulate matter is related to its size and surface chemistry; for instance, the smaller the size of particles, the greater their specific surface area. The chemistry and toxicity of insoluble particles depends on their surface area, since chemical reactions may happen with the environment on the surface. Oxidation and reduction may occur on the surfaces of particles after they are produced. For instance, it is known that carbonaceous particles from vehicle exhaust and industrial emission may interact with reactive species like ozone in their ambient environment, altering the surface chemistry of the particles. Reaction with species in the environment may cause changes in the chemical functionality of the surface and change the toxic properties of the particles when they are inhaled. Furthermore, metals on the surface of inhalable particles can contribute to their toxicity. Much attention has been given to the presence of iron on the surfaces of inhalable particles in the environment. After particle inhalation, particles are endocytosed by alveolar macrophages in the immune response to foreign matter. They are exposed to hydrogen peroxide in the oxidative burst, which can cause the iron-mediated production of hydroxyl free radicals via the Fenton reaction, causing oxidative stress that leads to inflammation and cell death. The toxicity of particles that contain metals depends on the redox activity and bioavailability of the metals, the causes of thich have not yet been adequately explored. In this thesis, electron paramagnetic spectroscopy showed

Toxicity of superparamagnetic iron oxide nanoparticles: Research strategies and implications for nanomedicine

International Nuclear Information System (INIS)

Li Lei; Jiang Ling-Ling; Zeng Yun; Liu Gang

2013-01-01

Superparamagnetic iron oxide nanoparticles (SPIONs) are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs. (topical review - magnetism, magnetic materials, and interdisciplinary research)

The protective effect of dexanabinol (HU-211) on nitric oxide and cysteine protease-mediated neuronal death in focal cerebral ischemia.

Science.gov (United States)

Durmaz, Ramazan; Ozden, Hilmi; Kanbak, Güngör; Aral, Erinç; Arslan, Okan Can; Kartkaya, Kazim; Uzuner, Kubilay

2008-09-01

We hypothesized that dexanabinol can prevent neuronal death by protecting neuronal lysosomes from nitric oxide (NO)-mediated toxicity, and in turn, by suppressing the release of cathepsins during cerebral ischemia. Focal cerebral ischemia was induced in two sets of animals by permanent middle cerebral artery occlusion. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. In post-ischemic brain tissue, NO content and cathepsin B and L activity increased (p 0.05). The number of eosinophilic and apoptotic neurons increased in the post-ischemic cerebral cortex (p agent for the treatment of stroke patients.

Toxicity of Nickel Oxide Nanoparticles on a Freshwater Green Algal Strain of Chlorella vulgaris

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Abdallah Oukarroum

2017-01-01

Full Text Available A freshwater microalga strain of Chlorella vulgaris was used to investigate toxic effects induced by nickel oxide nanoparticles (NiO-NPs in suspension. Algal cells were exposed during 96 h to 0–100 mg L−1 of NiO-NPs and analyzed by flow cytometry. Physicochemical characterization of nanoparticles in tested media showed a soluble fraction (free Ni2+ of only 6.42% for 100 mg L−1 of NiO-NPs, indicating the low solubility capacity of these NPs. Toxicity analysis showed cellular alterations which were related to NiO-NPs concentration, such as inhibition in cell division (relative cell size and granularity, deterioration of the photosynthetic apparatus (chlorophyll synthesis and photochemical reactions of photosynthesis, and oxidative stress (ROS production. The change in cellular viability demonstrated to be a very sensitive biomarker of NiO-NPs toxicity with EC50 of 13.7 mg L−1. Analysis by TEM and X-ray confirmed that NiO-NPs were able to cross biological membranes and to accumulate inside algal cells. Therefore, this study provides a characterization of both physicochemical and toxicological properties of NiO-NPs suspensions in tested media. The use of the freshwater strain of C. vulgaris demonstrated to be a sensitive bioindicator of NiO-NPs toxicity on the viability of green algae.

Effect of Nano-Al₂O₃ on the Toxicity and Oxidative Stress of Copper towards Scenedesmus obliquus.

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Li, Xiaomin; Zhou, Suyang; Fan, Wenhong

2016-06-09

Nano-Al₂O₃ has been widely used in various industries; unfortunately, it can be released into the aquatic environment. Although nano-Al₂O₃ is believed to be of low toxicity, it can interact with other pollutants in water, such as heavy metals. However, the interactions between nano-Al₂O₃ and heavy metals as well as the effect of nano-Al₂O₃ on the toxicity of the metals have been rarely investigated. The current study investigated copper toxicity in the presence of nano-Al₂O₃ towards Scenedesmus obliquus. Superoxide dismutase activity and concentration of glutathione and malondialdehyde in cells were determined in order to quantify oxidative stress in this study. Results showed that the presence of nano-Al₂O₃ reduced the toxicity of Cu towards S. obliquus. The existence of nano-Al₂O₃ decreased the growth inhibition of S. obliquus. The accumulation of copper and the level of oxidative stress in algae were reduced in the presence of nano-Al₂O₃. Furthermore, lower copper accumulation was the main factor that mitigated copper toxicity with the addition of nano-Al₂O₃. The decreased copper uptake could be attributed to the adsorption of copper onto nanoparticles and the subsequent decrease of available copper in water.

IBX-mediated oxidation of unactivated cyclic amines: application in highly diastereoselective oxidative Ugi-type and aza-Friedel-Crafts reactions.

Science.gov (United States)

de Graaff, C; Bensch, L; van Lint, Matthijs J; Ruijter, E; Orru, R V A

2015-10-28

The first o-iodoxybenzoic acid (IBX) mediated oxidation of unactivated amines to imines is described. A range of meso-pyrrolidines were shown to be suitable substrates. The chemical space was further explored with one-pot oxidative Ugi-type and aza-Friedel-Crafts reactions, which proved to be highly diastereoselective.

Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity

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Chi-Huang Chang

2014-01-01

Full Text Available Glutamate is a major excitatory neurotransmitter present in the central nervous system. The glutamate/cystine antiporter system xc– connects the antioxidant defense with neurotransmission and behaviour. Overactivation of ionotropic glutamate receptors induces neuronal death, a pathway called excitotoxicity. Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases including cerebral ischemia, Alzheimer’s and Huntington’s disease. Curcuma has a wide spectrum of biological activities regarding neuroprotection and neurocognition. By reducing the oxidative damage, curcumin attenuates a spinal cord ischemia-reperfusion injury, seizures and hippocampal neuronal loss. The rat pheochromocytoma (PC12 cell line exhibits many characteristics useful for the study of the neuroprotection and neurocognition. This investigation was carried out to determine whether the neuroprotective effects of curcumin can be observed via the glutamate-PC12 cell model. Results indicate that glutamate (20 mM upregulated glutathione peroxidase 1, glutathione disulphide, Ca2+ influx, nitric oxide production, cytochrome c release, Bax/Bcl-2 ratio, caspase-3 activity, lactate dehydrogenase release, reactive oxygen species, H2O2, and malondialdehyde; and downregulated glutathione, glutathione reductase, superoxide dismutase and catalase, resulting in enhanced cell apoptosis. Curcumin alleviates all these adverse effects. Conclusively, curcumin can effectively protect PC12 cells against the glutamate-induced oxidative toxicity. Its mode of action involves two pathways: the glutathione-dependent nitric oxide-reactive oxygen species pathway and the mitochondria-dependent nitric oxide-reactive oxygen species pathway.

The endogenous nitric oxide mediates selenium-induced phytotoxicity by promoting ROS generation in Brassica rapa.

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Yi Chen

Full Text Available Selenium (Se is suggested as an emerging pollutant in agricultural environment because of the increasing anthropogenic release of Se, which in turn results in phytotoxicity. The most common consequence of Se-induced toxicity in plants is oxidative injury, but how Se induces reactive oxygen species (ROS burst remains unclear. In this work, histofluorescent staining was applied to monitor the dynamics of ROS and nitric oxide (NO in the root of Brassica rapa under Se(IV stress. Se(IV-induced faster accumulation of NO than ROS. Both NO and ROS accumulation were positively correlated with Se(IV-induced inhibition of root growth. The NO accumulation was nitrate reductase (NR- and nitric oxide synthase (NOS-dependent while ROS accumulation was NADPH oxidase-dependent. The removal of NO by NR inhibitor, NOS inhibitor, and NO scavenger could alleviate Se(IV-induced expression of Br_Rbohs coding for NADPH oxidase and the following ROS accumulation in roots, which further resulted in the amelioration of Se(IV-induced oxidative injury and growth inhibition. Thus, we proposed that the endogenous NO played a toxic role in B. rapa under Se(IV stress by triggering ROS burst. Such findings can be used to evaluate the toxic effects of Se contamination on crop plants.

Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

Energy Technology Data Exchange (ETDEWEB)

Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina [Department of Forensic Pathology, University of Foggia, Foggia (Italy); Cerretani, Daniela [Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena (Italy); Di Paolo, Marco [Department of Forensic Pathology, University of Pisa, Pisa (Italy); Fiaschi, Anna Ida [Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena (Italy); Frati, Paola [Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome (Italy); Neri, Margherita [Department of Forensic Pathology, University of Foggia, Foggia (Italy); Pedretti, Monica [Department of Forensic Pathology, University of Pisa, Pisa (Italy); Fineschi, Vittorio, E-mail: vfinesc@tin.it [Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome (Italy)

2014-10-01

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney.

Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

International Nuclear Information System (INIS)

Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina; Cerretani, Daniela; Di Paolo, Marco; Fiaschi, Anna Ida; Frati, Paola; Neri, Margherita; Pedretti, Monica; Fineschi, Vittorio

2014-01-01

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney

Sub-acute deltamethrin and fluoride toxicity induced hepatic oxidative stress and biochemical alterations in rats.

Science.gov (United States)

Dubey, Nitin; Khan, Adil Mehraj; Raina, Rajinder

2013-09-01

The current study investigated the effects of deltamethrin, fluoride (F(-)) and their combination on the hepatic oxidative stress and consequent alterations in blood biochemical markers of hepatic damage in rats. Significant hepatic oxidative stress and hepatic damage were observed in the toxicant exposed groups. These changes were higher in the deltamethrin-F(-) co-exposure treatment group, depicting a positive interaction between the two chemicals.

An ethanol extract of Piper betle Linn. mediates its anti-inflammatory activity via down-regulation of nitric oxide.

Science.gov (United States)

Ganguly, Sudipto; Mula, Soumyaditya; Chattopadhyay, Subrata; Chatterjee, Mitali

2007-05-01

The leaves of Piper betle (locally known as Paan) have long been in use in the Indian indigenous system of medicine for the relief of pain; however, the underlying molecular mechanisms of this effect have not been elucidated. The anti-inflammatory and immunomodulatory effects of an ethanolic extract of the leaves of P. betle (100 mg kg(-1); PB) were demonstrated in a complete Freund's adjuvant-induced model of arthritis in rats with dexamethasone (0.1 mg kg(-1)) as the positive control. At non-toxic concentrations of PB (5-25 microg mL(-1)), a dose-dependent decrease in extracellular production of nitric oxide in murine peritoneal macrophages was measured by the Griess assay and corroborated by flow cytometry using the nitric oxide specific probe, 4,5-diaminofluorescein-2 diacetate. This decreased generation of reactive nitrogen species was mediated by PB progressively down-regulating transcription of inducible nitric oxide synthase in macrophages, and concomitantly causing a dose-dependent decrease in the expression of interleukin-12 p40, indicating the ability of PB to down-regulate T-helper 1 pro-inflammatory responses. Taken together, the anti-inflammatory and anti-arthrotic activity of PB is attributable to its ability to down-regulate the generation of reactive nitrogen species, thus meriting further pharmacological investigation.

Treatment of toxic and hazardous organic wastes by wet oxidation process with oxygenated water at low temperature

International Nuclear Information System (INIS)

Piccinno, T.; Salluzzo, A.; Nardi, L.; Gili, M.; Luce, A.; Troiani, F.; Cornacchia, G.

1989-11-01

The wet oxidation process using air or molecular oxygen is a well-known process from long time. It is suitable to oxidize several types of waste refractory to the usual biological, thermal and chemical treatments. The drastic operating conditions (high pressures and temperatures) prevented its industrial development. In the last years a new interest was assigned to the process for the treatment of nuclear wastes (organic resins and exhaust organic wastes); the treatment is carried out at widely reduced operating conditions (atmospheric pressure and boiling temperature) by means of metallic catalysts and hydrogen peroxide. With some limits, the wet oxidation with hydrogen peroxide at low temperature can be applied to conventional waste waters containing toxic organic compounds. In the present report are summarized the activities developed at ENEA Fuel Cycle Department by the task force 'Deox' constituted by laboratory and plant specialists in order to verify the application of the wet oxidation process to the treatment of the toxic wastes. (author)

Protective effects of dietary glycine and glutamic acid toward the toxic effects of oxidized mustard oil in rabbits.

Science.gov (United States)

Zeb, Alam; Rahman, Saleem Ur

2017-01-25

The protective role of glycine and glutamic acid against the toxic effects of oxidized oil was studied for the first time. Mustard seed oil was thermally oxidized and characterized for quality characteristics and polyphenolic composition using reversed phase HPLC-DAD. Significant changes in the quality characteristics occurred with thermal oxidation. Fourteen polyphenolic compounds were identified and quantified in oils. Quercetin-3-glucoside, quercetin-3-feruloylsophoroside, catechin, quercetin-3-rutinoside, quercetin-3,7-diglucoside, sinapic acid and vanillic acid hexoside were the major compounds in the fresh and oxidized oil. Oxidized, un-oxidized mustard oils, glycine and glutamic acid were given to rabbits alone or in combination. The biochemical responses were studied in terms of haematological and biochemical parameters and histopathology. It has been observed that biochemical and haematological parameters were adversely affected by the oxidized oil, while supplementation of both amino acids was beneficial in normalizing these parameters. Both amino acids alone have no significant effects, however, oxidized oil affected the liver by enhancing fat accumulation, causing hepatitis, reactive Kupffer cells and necrosis. The co-administration of oxidized oils with glycine or glutamic acid revealed significant recovery of the liver structure and function. In conclusion, glycine or glutamic acid is beneficial and protective against food toxicity and can be considered as an ameliorative food supplement.

Gibberellic acid alleviates cadmium toxicity by reducing nitric oxide accumulation and expression of IRT1 in Arabidopsis thaliana

International Nuclear Information System (INIS)

Zhu, Xiao Fang; Jiang, Tao; Wang, Zhi Wei; Lei, Gui Jie; Shi, Yuan Zhi; Li, Gui Xin; Zheng, Shao Jian

2012-01-01

Highlights: ► Cd reduces endogenous GA levels in Arabidopsis. ► GA exogenous applied decreases Cd accumulation in plant. ► GA suppresses the Cd-induced accumulation of NO. ► Decreased NO level downregulates the expression of IRT1. ► Suppressed IRT1 expression reduces Cd transport across plasma membrane. - Abstract: Gibberellic acid (GA) is involved in not only plant growth and development but also plant responses to abiotic stresses. Here it was found that treating the plants with GA concentrations from 0.1 to 5 μM for 24 h had no obvious effect on root elongation in the absence of cadmium (Cd), whereas in the presence of Cd 2+ , GA at 5 μM improved root growth, reduced Cd content and lipid peroxidation in the roots, indicating that GA can partially alleviate Cd toxicity. Cd 2+ increased nitric oxide (NO) accumulation in the roots, but GA remarkably reduced it, and suppressed the up-regulation of the expression of IRT1. In contrary, the beneficial effect of GA on alleviating Cd toxicity was not observed in an IRT1 knock-out mutant irt1, suggesting the involvement of IRT1 in Cd 2+ absorption. Furthermore, the GA-induced reduction of NO and Cd content can also be partially reversed by the application of a NO donor (S-nitrosoglutathione [GSNO]). Taken all these together, the results showed that GA-alleviated Cd toxicity is mediated through the reduction of the Cd-dependent NO accumulation and expression of Cd 2+ uptake related gene-IRT1 in Arabidopsis.

Innovative reactor technology for selective oxidation of toxic organic pollutants in wastewater by ozone

NARCIS (Netherlands)

Boncz, M.A.; Bruning, H.; Rulkens, W.H.

2003-01-01

Ozonation can be a suitable technique for the pre-treatment of wastewater containing low concentrations of toxic or non-biodegradable compounds that cannot be treated with satisfactory results when only the traditional, less expensive biological techniques are applied. In this case, the oxidation

Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy

Directory of Open Access Journals (Sweden)

Aparna Areti

2014-01-01

Full Text Available Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.

Electrochemical Water Oxidation and Stereoselective Oxygen Atom Transfer Mediated by a Copper Complex.

Science.gov (United States)

Kafentzi, Maria-Chrysanthi; Papadakis, Raffaello; Gennarini, Federica; Kochem, Amélie; Iranzo, Olga; Le Mest, Yves; Le Poul, Nicolas; Tron, Thierry; Faure, Bruno; Simaan, A Jalila; Réglier, Marius

2018-04-06

Water oxidation by copper-based complexes to form dioxygen has attracted attention in recent years, with the aim of developing efficient and cheap catalysts for chemical energy storage. In addition, high-valent metal-oxo species produced by the oxidation of metal complexes in the presence of water can be used to achieve substrate oxygenation with the use of H 2 O as an oxygen source. To date, this strategy has not been reported for copper complexes. Herein, a copper(II) complex, [(RPY2)Cu(OTf) 2 ] (RPY2=N-substituted bis[2-pyridyl(ethylamine)] ligands; R=indane; OTf=triflate), is used. This complex, which contains an oxidizable substrate moiety (indane), is used as a tool to monitor an intramolecular oxygen atom transfer reaction. Electrochemical properties were investigated and, upon electrolysis at 1.30 V versus a normal hydrogen electrode (NHE), both dioxygen production and oxygenation of the indane moiety were observed. The ligand was oxidized in a highly diastereoselective manner, which indicated that the observed reactivity was mediated by metal-centered reactive species. The pH dependence of the reactivity was monitored and correlated with speciation deduced from different techniques, ranging from potentiometric titrations to spectroscopic studies and DFT calculations. Water oxidation for dioxygen production occurs at neutral pH and is probably mediated by the oxidation of a mononuclear copper(II) precursor. It is achieved with a rather low overpotential (280 mV at pH 7), although with limited efficiency. On the other hand, oxygenation is maximum at pH 8-8.5 and is probably mediated by the electrochemical oxidation of an antiferromagnetically coupled dinuclear bis(μ-hydroxo) copper(II) precursor. This constitutes the first example of copper-centered oxidative water activation for a selective oxygenation reaction. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of selenium toxicity and oxidative stress in aquatic birds

Science.gov (United States)

Hoffman, D.J.

2002-01-01

hepatic GSH peroxidase, depletion of hepatic protein bound thiols and total thiols, but a small increase in GSH. Diving ducks in the San Francisco Bay area exhibited a positive correlation between hepatic Se concentration and GSH peroxidase activity (r=0.63, Pbirds. Further selenium nutritional interaction studies may also help to illucidate the mechanism of selenium induced teratogenesis, by optimizing GSH and other antioxidant defense mechanisms in a manner that would stabilize or raise the cell's threshold for susceptibility to toxic attack from excess selenium. It is concluded that Se-related manifestations of oxidative stress may serve as useful bioindicators of Se exposure and toxicity in wild aquatic birds.

The cathepsin B inhibitor z-FA-CMK induces cell death in leukemic T cells via oxidative stress.

Science.gov (United States)

Liow, K Y; Chow, Sek C

2018-01-01

The cathepsin B inhibitor benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK) was recently found to induce apoptosis at low concentrations in Jurkat T cells, while at higher concentrations, the cells die of necrosis. In the present study, we showed that z-FA-CMK readily depletes intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) generation. The toxicity of z-FA-CMK in Jurkat T cells was completely abrogated by N-acetylcysteine (NAC), suggesting that the toxicity mediated by z-FA-CMK is due to oxidative stress. We found that L-buthionine sulfoximine (BSO) which depletes intracellular GSH through the inhibition of GSH biosynthesis in Jurkat T cells did not promote ROS increase or induce cell death. However, NAC was still able to block z-FA-CMK toxicity in Jurkat T cells in the presence of BSO, indicating that the protective effect of NAC does not involve GSH biosynthesis. This is further corroborated by the protective effect of the non-metabolically active D-cysteine on z-FA-CMK toxicity. Furthermore, in BSO-treated cells, z-FA-CMK-induced ROS increased which remains unchanged, suggesting that the depletion of GSH and increase in ROS generation mediated by z-FA-CMK may be two separate events. Collectively, our results demonstrated that z-FA-CMK toxicity is mediated by oxidative stress through the increase in ROS generation.

Gel entrapment culture of rat hepatocytes for investigation of tetracycline-induced toxicity

International Nuclear Information System (INIS)

Shen Chong; Meng Qin; Schmelzer, Eva; Bader, Augustinus

2009-01-01

This paper aimed to explore three-dimensionally cultured hepatocytes for testing drug-induced nonalcoholic steatohepatitis. Gel entrapped rat hepatocytes were applied for investigation of the tetracycline-induced steatohepatitis, while hepatocyte monolayer was set as a control. The toxic responses of hepatocytes were systematically evaluated by measuring cell viability, liver-specific function, lipid accumulation, oxidative stress, adenosine triphosphate content and mitochondrial membrane potential. The results suggested that gel entrapped hepatocytes showed cell death after 96 h of tetracycline treatment at 25 μM which is equivalent to toxic serum concentration in rats, while hepatocyte monolayer showed cell death at a high dose of 200 μM. The concentration-dependent accumulation of lipid as well as mitochondrial damage were regarded as two early events for tetracycline hepatotoxicity in gel entrapment culture due to their detectability ahead of subsequent increase of oxidative stress and a final cell death. Furthermore, the potent protection of fenofibrate and fructose-1,6-diphosphate were evidenced in only gel entrapment culture with higher expressions on the genes related to β-oxidation than hepatocyte monolayer, suggesting the mediation of lipid metabolism and mitochondrial damage in tetracycline toxicity. Overall, gel entrapped hepatocytes in three-dimension reflected more of the tetracycline toxicity in vivo than hepatocyte monolayer and thus was suggested as a more relevant system for evaluating steatogenic drugs.

Size- and composition-dependent toxicity of synthetic and soil-derived Fe oxide colloids for the nematode Caenorhabditis elegans.

Science.gov (United States)

Höss, Sebastian; Fritzsche, Andreas; Meyer, Carolin; Bosch, Julian; Meckenstock, Rainer U; Totsche, Kai Uwe

2015-01-06

Colloidal iron oxides (FeOx) are increasingly released to the environment due to their use in environmental remediation and biomedical applications, potentially harming living organisms. Size and composition could affect the bioavailability and toxicity of such colloids. Therefore, we investigated the toxicity of selected FeOx with variable aggregate size and variably composed FeOx-associated organic matter (OM) toward the nematode Caenorhabditis elegans. Ferrihydrite colloids containing citrate were taken up by C. elegans with the food and accumulated inside their body. The toxicity of ferrihydrite, goethite, and akaganeite was dependent on aggregate size and specific surface area, with EC50 values for reproduction ranging from 4 to 29 mg Fe L(-1). Experiments with mutant strains lacking mitochondrial superoxide dismutase (sod-2) showed oxidative stress for two FeOx and Fe(3+)-ions, however, revealed that it was not the predominant mechanism of toxicity. The OM composition determined the toxicity of mixed OM-FeOx phases on C. elegans. FeOx associated with humic acids or citrate were less toxic than OM-free FeOx. In contrast, soil-derived ferrihydrite, containing proteins and polysaccharides from mobile OM, was even more toxic than OM-free Fh of similar aggregate size. Consequently, the careful choice of the type of FeOx and the type of associated OM may help in reducing the ecological risks if actively applied to the subsurface.

In vitro studies on oxidative stress-independent, Ag nanoparticles-induced cell toxicity of Candida albicans, an opportunistic pathogen

Directory of Open Access Journals (Sweden)

Radhakrishnan VS

2018-03-01

Full Text Available Venkatraman Srinivasan Radhakrishnan,1 Surya Prakash Dwivedi,2 Mohammed Haris Siddiqui,3 Tulika Prasad1 1Advanced Instrumentation Research Facility (AIRF, Jawaharlal Nehru University, New Delhi, 2School of Biotechnology, IFTM University, Moradabad, 3Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, India Abstract: Silver nanoparticles (AgNps have attracted maximal attention among all metal nanoparticles, and the study of their biological properties has gained impetus for further medical adoption. This study evaluated the cellular and molecular mechanisms associated with the action of AgNps against an opportunistic pathogen, Candida albicans. Spherical, stable AgNp (average size 21.6 nm prepared by a chemical reduction method showed minimum inhibitory concentration (required to inhibit the growth of 90% of organisms at 40 µg/mL. AgNps have been reported to induce oxidative stress-mediated programmed cell death through the accumulation of intracellular reactive oxygen species (ROS. However, this study demonstrated that intracellular levels of AgNp-induced ROS could be reversed by using antioxidant ascorbic acid, but the sensitivity of AgNp-treated Candida cells could not be completely reversed. Moreover, in addition to the generation of ROS, the AgNps were found to affect other cellular targets resulting in altered membrane fluidity, membrane microenvironment, ergosterol content, cellular morphology, and ultrastructure. Thus, the generation of ROS does not seem to be the sole major cause of AgNp-mediated cell toxicity in Candida. Rather, the multitargeted action of AgNps, generation of ROS, alterations in ergosterol content, and membrane fluidity together seem to have potentiated anti-Candida action. Thus, this “nano-based drug therapy” is likely to favor broad-spectrum activity, multiple cellular targets, and minimum host toxicity. AgNps, therefore, appear to have the potential to address the challenges in multidrug

Oxidized/misfolded superoxide dismutase-1: the cause of all amyotrophic lateral sclerosis?

Science.gov (United States)

Kabashi, Edor; Valdmanis, Paul N; Dion, Patrick; Rouleau, Guy A

2007-12-01

The identification in 1993 of superoxide dismutase-1 (SOD1) mutations as the cause of 10 to 20% of familial amyotrophic lateral sclerosis cases, which represents 1 to 2% of all amyotrophic lateral sclerosis (ALS) cases, prompted a substantial amount of research into the mechanisms of SOD1-mediated toxicity. Recent experiments have demonstrated that oxidation of wild-type SOD1 leads to its misfolding, causing it to gain many of the same toxic properties as mutant SOD1. In vitro studies of oxidized/misfolded SOD1 and in vivo studies of misfolded SOD1 have indicated that these protein species are selectively toxic to motor neurons, suggesting that oxidized/misfolded SOD1 could lead to ALS even in individuals who do not carry an SOD1 mutation. It has also been reported that glial cells secrete oxidized/misfolded mutant SOD1 to the extracellular environment, where it can trigger the selective death of motor neurons, offering a possible explanation for the noncell autonomous nature of mutant SOD1 toxicity and the rapid progression of disease once the first symptoms develop. Therefore, considering that sporadic (SALS) and familial ALS (FALS) cases are clinically indistinguishable, the toxic properties of mutated SOD1 are similar to that of oxidized/misfolded wild-type SOD1 (wtSOD1), and secreted/extracellular misfolded SOD1 is selectively toxic to motor neurons, we propose that oxidized/misfolded SOD1 is the cause of most forms of classic ALS and should be a prime target for the design of ALS treatments.

Toxicity of iron oxide nanoparticles against osteoblasts

International Nuclear Information System (INIS)

Shi Sifeng; Jia Jingfu; Guo Xiaokui; Zhao Yaping; Liu Boyu; Chen Desheng; Guo Yongyuan; Zhang Xianlong

2012-01-01

Magnetic nanoparticles have been widely used for tissue repair, magnetic resonance imaging, immunoassays and drug delivery. They are very promising in orthopaedic applications and several magnetic nanoparticles have been exploited for the treatment of orthopaedic disease. Here, we conducted an in vitro study to examine the interaction of magnetic iron oxide nanoparticles with human osteoblasts to evaluate the dose-related toxicity of the nanoparticles on osteoblasts. A transmission electron microscope was used to visualise the internalised magnetic nanoparticles in osteoblasts. The CCK-8 results revealed increased cell viability (107.5 % vitality compared with the control group) when co-cultured at a low concentration (20 μg/mL) and decreased cell viability (59.5 % vitality in a concentration of 300 μg/mL and 25.9 % in 500 μg/mL) when co-cultured in high concentrations. The flow cytometric detection revealed similar results with 5.48 % of apoptosis in a concentration of 20 μg/mL, 23.40 % of apoptosis in a concentration of 300 μg/mL and 28.49 % in a concentration of 500 μg/mL. The disrupted cytoskeleton of osteoblasts was also revealed using a laser scanning confocal microscope. We concluded that use of a low concentration of magnetic iron oxide nanoparticles is important to avoid damage to osteoblasts.

Toxicity of iron oxide nanoparticles against osteoblasts

Energy Technology Data Exchange (ETDEWEB)

Shi Sifeng [Shanghai Jiao Tong University, Department of Orthopaedic Surgery, Shanghai Sixth People' s Hospital (China); Jia Jingfu [Shanghai Jiao Tong University, School of Chemistry and Chemical Technology (China); Guo Xiaokui [Shanghai Jiao Tong University School of Medicine, Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences (China); Zhao Yaping [Shanghai Jiao Tong University, School of Chemistry and Chemical Technology (China); Liu Boyu [Shanghai Jiao Tong University School of Medicine, Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences (China); Chen Desheng; Guo Yongyuan; Zhang Xianlong, E-mail: zhangxianlong20101@163.com [Shanghai Jiao Tong University, Department of Orthopaedic Surgery, Shanghai Sixth People' s Hospital (China)

2012-09-15

Magnetic nanoparticles have been widely used for tissue repair, magnetic resonance imaging, immunoassays and drug delivery. They are very promising in orthopaedic applications and several magnetic nanoparticles have been exploited for the treatment of orthopaedic disease. Here, we conducted an in vitro study to examine the interaction of magnetic iron oxide nanoparticles with human osteoblasts to evaluate the dose-related toxicity of the nanoparticles on osteoblasts. A transmission electron microscope was used to visualise the internalised magnetic nanoparticles in osteoblasts. The CCK-8 results revealed increased cell viability (107.5 % vitality compared with the control group) when co-cultured at a low concentration (20 {mu}g/mL) and decreased cell viability (59.5 % vitality in a concentration of 300 {mu}g/mL and 25.9 % in 500 {mu}g/mL) when co-cultured in high concentrations. The flow cytometric detection revealed similar results with 5.48 % of apoptosis in a concentration of 20 {mu}g/mL, 23.40 % of apoptosis in a concentration of 300 {mu}g/mL and 28.49 % in a concentration of 500 {mu}g/mL. The disrupted cytoskeleton of osteoblasts was also revealed using a laser scanning confocal microscope. We concluded that use of a low concentration of magnetic iron oxide nanoparticles is important to avoid damage to osteoblasts.

Graphene oxide-mediated rapid dechlorination of carbon tetrachloride by green rust

DEFF Research Database (Denmark)

Huang, Li-Zhi; Hansen, Hans Christian B.; Daasbjerg, Kim

2017-01-01

Graphene-based nanomaterials can mediate environmentally relevant abiotic redox reactions of chlorinated aliphatic hydrocarbons. In this study as low amounts as ∼0.007 % of graphene oxide (GO) was found to catalyze the reduction of carbon tetrachloride by layered Fe(II)-Fe(III) hydroxide (Green R....... This study indicates that traces of graphene oxide can affect reaction pathways as well as kinetics for dechlorination processes in anoxic sediments by facilitating a partial dechlorination....

Iron-mediated lipid oxidation in 70% fish oil-in-ater emulsions

DEFF Research Database (Denmark)

Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

2012-01-01

The objective of this study was to investigate the protective effect of five different emulsifiers on iron‐mediated lipid oxidation in 70% fish oil‐in‐water emulsions. The emulsifiers were either based on protein (whey protein isolate and sodium caseinate) or based on phospholipid (soy lecithin...... and two milk phospholipids with different phospholipid contents, MPL20 and MPL75). Lipid oxidation was studied at pH 4.5 and 7.0, and results were compared to lipid oxidation in neat fish oil. Results showed that all emulsions oxidised more than neat oil. Furthermore, emulsions prepared with proteins...

Toxicity of metal oxide nanoparticles in Escherichia coli correlates with conduction band and hydration energies.

Science.gov (United States)

Kaweeteerawat, Chitrada; Ivask, Angela; Liu, Rong; Zhang, Haiyuan; Chang, Chong Hyun; Low-Kam, Cecile; Fischer, Heidi; Ji, Zhaoxia; Pokhrel, Suman; Cohen, Yoram; Telesca, Donatello; Zink, Jeffrey; Mädler, Lutz; Holden, Patricia A; Nel, Andre; Godwin, Hilary

2015-01-20

Metal oxide nanoparticles (MOx NPs) are used for a host of applications, such as electronics, cosmetics, construction, and medicine, and as a result, the safety of these materials to humans and the environment is of considerable interest. A prior study of 24 MOx NPs in mammalian cells revealed that some of these materials show hazard potential. Here, we report the growth inhibitory effects of the same series of MOx NPs in the bacterium Escherichia coli and show that toxicity trends observed in E. coli parallel those seen previously in mammalian cells. Of the 24 materials studied, only ZnO, CuO, CoO, Mn2O3, Co3O4, Ni2O3, and Cr2O3 were found to exert significant growth inhibitory effects; these effects were found to relate to membrane damage and oxidative stress responses in minimal trophic media. A correlation of the toxicological data with physicochemical parameters of MOx NPs revealed that the probability of a MOx NP being toxic increases as the hydration enthalpy becomes less negative and as the conduction band energy approaches those of biological molecules. These observations are consistent with prior results observed in mammalian cells, revealing that mechanisms of toxicity of MOx NPs are consistent across two very different taxa. These results suggest that studying nanotoxicity in E. coli may help to predict toxicity patterns in higher organisms.

Selenium alleviates cadmium toxicity by preventing oxidative stress in sunflower (Helianthus annuus) seedlings.

Science.gov (United States)

Saidi, Issam; Chtourou, Yacine; Djebali, Wahbi

2014-03-01

The present study investigated the possible mediatory role of selenium (Se) in protecting plants from cadmium (Cd) toxicity. The exposure of sunflower seedlings to 20μM Cd inhibited biomass production, decreased chlorophyll and carotenoid concentrations and strongly increased accumulation of Cd in both roots and shoots. Similarly, Cd enhanced hydrogen peroxides content and lipid peroxidation as indicated by malondialdehyde accumulation. Pre-soaking seeds with Se (5, 10 and 20μM) alleviated the negative effect of Cd on growth and led to a decrease in oxidative injuries caused by Cd. Furthermore, Se enhanced the activities of catalase, ascorbate peroxidase and glutathione reductase, but lowered that of superoxide dismutase and guaiacol peroxidase. As important antioxidants, ascorbate and glutathione contents in sunflower leaves exposed to Cd were significantly decreased by Se treatment. The data suggest that the beneficial effect of Se during an earlier growth period could be related to avoidance of cumulative damage upon exposure to Cd, thus reducing the negative consequences of oxidative stress caused by heavy metal toxicity. Copyright © 2013 Elsevier GmbH. All rights reserved.

The Study and Development of Metal Oxide Reactive Adsorbents for the Destruction of Toxic Organic Compounds

National Research Council Canada - National Science Library

Mitchell, Mark B

2008-01-01

... and other toxic organic compounds. The research program that was developed built upon earlier results achieved in the room temperature oxidative decomposition of a chemical warfare agent simulant, dimethyl methylphosphonate (DMMP...

Iron-mediated anaerobic oxidation of methane in brackish coastal sediments.

Science.gov (United States)

Egger, Matthias; Rasigraf, Olivia; Sapart, Célia J; Jilbert, Tom; Jetten, Mike S M; Röckmann, Thomas; van der Veen, Carina; Bândă, Narcisa; Kartal, Boran; Ettwig, Katharina F; Slomp, Caroline P

2015-01-06

Methane is a powerful greenhouse gas and its biological conversion in marine sediments, largely controlled by anaerobic oxidation of methane (AOM), is a crucial part of the global carbon cycle. However, little is known about the role of iron oxides as an oxidant for AOM. Here we provide the first field evidence for iron-dependent AOM in brackish coastal surface sediments and show that methane produced in Bothnian Sea sediments is oxidized in distinct zones of iron- and sulfate-dependent AOM. At our study site, anthropogenic eutrophication over recent decades has led to an upward migration of the sulfate/methane transition zone in the sediment. Abundant iron oxides and high dissolved ferrous iron indicate iron reduction in the methanogenic sediments below the newly established sulfate/methane transition. Laboratory incubation studies of these sediments strongly suggest that the in situ microbial community is capable of linking methane oxidation to iron oxide reduction. Eutrophication of coastal environments may therefore create geochemical conditions favorable for iron-mediated AOM and thus increase the relevance of iron-dependent methane oxidation in the future. Besides its role in mitigating methane emissions, iron-dependent AOM strongly impacts sedimentary iron cycling and related biogeochemical processes through the reduction of large quantities of iron oxides.

Toxicity of graphene oxide on intestinal bacteria and Caco-2 cells.

Science.gov (United States)

Nguyen, Trang H D; Lin, Mengshi; Mustapha, Azlin

2015-05-01

In recent years, novel nanomaterials have received much attention due to their great potential for applications in agriculture, food safety, and food packaging. Among them, graphene and graphene oxide (GO) are emerging as promising nanomaterials that may have a profound impact on food packaging. However, there are some concerns from consumers and the scientific community about the potential toxicity and biocompatibility of nanomaterials. In this study, we investigated the antibacterial properties of GO against human intestinal bacteria. The cytotoxicity of GO was also studied in vitro using the Caco-2 cell line derived from a colon carcinoma. Electron microscopy was used to investigate the morphology of GO and the interaction between GO flakes and Caco-2 cells. GO at different concentrations (10 to 500 μg/ml) exhibited no toxicity against the selected bacteria and a mild cytotoxic action on Caco-2 cells after 24 h of exposure. The results show that weak adsorption of medium nutrients may contribute to GO's low toxicity. This study suggests that GO is biocompatible and has a potential to be used in agriculture and food science, indicating that more studies are needed to exploit its potential applications.

Low-solubility particles and a Trojan-horse type mechanism of toxicity: the case of cobalt oxide on human lung cells

International Nuclear Information System (INIS)

Ortega, Richard; Roudeau, Stephane; Perrin, Laura; Carmona, Asuncion; Bresson, Carole; Darolles, Carine; Aloin, Valerie; Malard, Veronique; Gautier, Celine; Janin, Myriam; Floriani, Magali

2014-01-01

The mechanisms of toxicity of metal oxide particles towards lung cells are far from being understood. In particular, the relative contribution of intracellular particulate versus solubilized fractions is rarely considered as it is very challenging to assess, especially for low-solubility particles such as cobalt oxide (Co_3O_4). This study was possible owing to two highly sensitive, independent, analytical techniques, based on single-cell analysis, using ion beam microanalysis, and on bulk analysis of cell lysates, using mass spectrometry. Our study shows that cobalt oxide particles, of very low solubility in the culture medium, are readily incorporated by BEAS-2B human lung cells through endocytosis via the clathrin-dependent pathway. They are partially solubilized at low pH within lysosomes, leading to cobalt ions release. Solubilized cobalt was detected within the cytoplasm and the nucleus. As expected from these low-solubility particles, the intracellular solubilized cobalt content is small compared with the intracellular particulate cobalt content, in the parts-per-thousand range or below. However, we were able to demonstrate that this minute fraction of intracellular solubilized cobalt is responsible for the overall toxicity. Cobalt oxide particles are readily internalized by pulmonary cells via the endo-lysosomal pathway and can lead, through a Trojan-horse mechanism, to intracellular release of toxic metal ions over long periods of time, involving specific toxicity. (authors)

Developmental Toxicity of Zinc Oxide Nanoparticles to Zebrafish (Danio rerio: A Transcriptomic Analysis.

Directory of Open Access Journals (Sweden)

Jin Soo Choi

Full Text Available Zinc oxide nanoparticles (ZnO NPs are being utilized in an increasing number of fields and commercial applications. While their general toxicity and associated oxidative stress have been extensively studied, the toxicological pathways that they induce in developmental stages are still largely unknown. In this study, the developmental toxicity of ZnO NPs to embryonic/larval zebrafish was investigated. The transcriptional expression profiles induced by ZnO NPs were also investigated to ascertain novel genomic responses related to their specific toxicity pathway. Zebrafish embryos were exposed to 0.01, 0.1, 1, and 10 mg/L ZnO NPs for 96 h post-fertilization. The toxicity of ZnO NPs, based on their Zn concentration, was quite similar to that in embryonic/larval zebrafish exposed to corresponding ZnSO4 concentrations. Pericardial edema and yolk-sac edema were the principal malformations induced by ZnO NPs. Gene-expression profiling using microarrays demonstrated 689 genes that were differentially regulated (fold change >1.5 following exposure to ZnO NPs (498 upregulated, 191 downregulated. Several genes that were differentially regulated following ZnO NP exposure shared similar biological pathways with those observed with ZnSO4 exposure, but six genes (aicda, cyb5d1, edar, intl2, ogfrl2 and tnfsf13b associated with inflammation and the immune system responded specifically to ZnO NPs (either in the opposite direction or were unchanged in ZnSO4 exposure. Real-time reverse-transcription quantitative polymerase chain reaction confirmed that the responses of these genes to ZnO NPs were significantly different from their response to ZnSO4 exposure. ZnO NPs may affect genes related to inflammation and the immune system, resulting in yolk-sac edema and pericardia edema in embryonic/larval developmental stages. These results will assist in elucidating the mechanisms of toxicity of ZnO NPs during development of zebrafish.

In silico analysis of Pycnoporus cinnabarinus laccase active site with toxic industrial dyes.

Science.gov (United States)

Prasad, Nirmal K; Vindal, Vaibhav; Narayana, Siva Lakshmi; Ramakrishna, V; Kunal, Swaraj Priyaranjan; Srinivas, M

2012-05-01

Laccases belong to multicopper oxidases, a widespread class of enzymes implicated in many oxidative functions in various industrial oxidative processes like production of fine chemicals to bioremediation of contaminated soil and water. In order to understand the mechanisms of substrate binding and interaction between substrates and Pycnoporus cinnabarinus laccase, a homology model was generated. The resulted model was further validated and used for docking studies with toxic industrial dyes- acid blue 74, reactive black 5 and reactive blue 19. Interactions of chemical mediators with the laccase was also examined. The docking analysis showed that the active site always cannot accommodate the dye molecules, due to constricted nature of the active site pocket and steric hindrance of the residues whereas mediators are relatively small and can easily be accommodated into the active site pocket, which, thereafter leads to the productive binding. The binding properties of these compounds along with identification of critical active site residues can be used for further site-directed mutagenesis experiments in order to identify their role in activity and substrate specificity, ultimately leading to improved mutants for degradation of these toxic compounds.

Susceptibility of Iα- and Iβ-Dominated Cellulose to TEMPO-Mediated Oxidation.

Science.gov (United States)

Carlsson, Daniel O; Lindh, Jonas; Strømme, Maria; Mihranyan, Albert

2015-05-11

The susceptibility of Iα- and Iβ-dominated cellulose to TEMPO-mediated oxidation was studied in this work since the cellulose Iα-allomorph is generally considered to be thermodynamically less stable and therefore more reactive than the cellulose Iβ-allomorph. Highly crystalline Cladophora nanocellulose, which is dominated by the Iα-allomorph, was oxidized to various degrees with TEMPO oxidant via bulk electrolysis in the absence of co-oxidants. Further, the Cladophora nanocellulose was thermally annealed in glycerol to produce its Iβ-dominated form and then oxidized. The produced materials were subsequently studied using FTIR, CP/MAS (13)C NMR, XRD, and SEM. The solid-state analyses confirmed that the annealed Cladophora cellulose was successfully transformed from an Iα- to an Iβ-dominated form. The results of the analyses of pristine and annealed TEMPO-oxidized samples suggest that Iα- and Iβ-dominated cellulose do not differ in susceptibility to TEMPO-oxidation. This work hence suggests that cellulose from different sources are not expected to differ in susceptibility to the oxidation due to differences in allomorph composition.

Nitric Oxide Ameliorates Zinc Oxide Nanoparticles Phytotoxicity in Wheat Seedlings: Implication of the Ascorbate–Glutathione Cycle

Science.gov (United States)

Tripathi, Durgesh K.; Mishra, Rohit K.; Singh, Swati; Singh, Samiksha; Vishwakarma, Kanchan; Sharma, Shivesh; Singh, Vijay P.; Singh, Prashant K.; Prasad, Sheo M.; Dubey, Nawal K.; Pandey, Avinash C.; Sahi, Shivendra; Chauhan, Devendra K.

2017-01-01

The present study investigates ameliorative effects of nitric oxide (NO) against zinc oxide nanoparticles (ZnONPs) phytotoxicity in wheat seedlings. ZnONPs exposure hampered growth of wheat seedlings, which coincided with reduced photosynthetic efficiency (Fv/Fm and qP), due to increased accumulation of zinc (Zn) in xylem and phloem saps. However, SNP supplementation partially mitigated the ZnONPs-mediated toxicity through the modulation of photosynthetic activity and Zn accumulation in xylem and phloem saps. Further, the results reveal that ZnONPs treatments enhanced levels of hydrogen peroxide and lipid peroxidation (as malondialdehyde; MDA) due to severely inhibited activities of the following ascorbate–glutatione cycle (AsA–GSH) enzymes: ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase, and its associated metabolites ascorbate and glutathione. In contrast to this, the addition of SNP together with ZnONPs maintained the cellular functioning of the AsA–GSH cycle properly, hence lesser damage was noticed in comparison to ZnONPs treatments alone. The protective effect of SNP against ZnONPs toxicity on fresh weight (growth) can be reversed by 2-(4carboxy-2-phenyl)-4,4,5,5-tetramethyl- imidazoline-1-oxyl-3-oxide, a NO scavenger, and thus suggesting that NO released from SNP ameliorates ZnONPs toxicity. Overall, the results of the present study have shown the role of NO in the reducing of ZnONPs toxicity through the regulation of accumulation of Zn as well as the functioning of the AsA–GSH cycle. PMID:28220127

Gibberellic acid alleviates cadmium toxicity by reducing nitric oxide accumulation and expression of IRT1 in Arabidopsis thaliana

Energy Technology Data Exchange (ETDEWEB)

Zhu, Xiao Fang [State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Jiang, Tao [Key Laboratory of Conservation Biology for Endangered Wildlife of the Ministry of Education, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Wang, Zhi Wei [State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Lei, Gui Jie [Key Laboratory of Conservation Biology for Endangered Wildlife of the Ministry of Education, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Shi, Yuan Zhi [The Key Laboratory of Tea Chemical Engineering, Ministry of Agriculture, Yunqi Road 1, Hangzhou 310008 (China); Li, Gui Xin, E-mail: guixinli@zju.edu.cn [College of Agronomy and Biotechnology, Zhejiang University, Hangzhou 310058 (China); Zheng, Shao Jian [State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Key Laboratory of Conservation Biology for Endangered Wildlife of the Ministry of Education, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China)

2012-11-15

Highlights: Black-Right-Pointing-Pointer Cd reduces endogenous GA levels in Arabidopsis. Black-Right-Pointing-Pointer GA exogenous applied decreases Cd accumulation in plant. Black-Right-Pointing-Pointer GA suppresses the Cd-induced accumulation of NO. Black-Right-Pointing-Pointer Decreased NO level downregulates the expression of IRT1. Black-Right-Pointing-Pointer Suppressed IRT1 expression reduces Cd transport across plasma membrane. - Abstract: Gibberellic acid (GA) is involved in not only plant growth and development but also plant responses to abiotic stresses. Here it was found that treating the plants with GA concentrations from 0.1 to 5 {mu}M for 24 h had no obvious effect on root elongation in the absence of cadmium (Cd), whereas in the presence of Cd{sup 2+}, GA at 5 {mu}M improved root growth, reduced Cd content and lipid peroxidation in the roots, indicating that GA can partially alleviate Cd toxicity. Cd{sup 2+} increased nitric oxide (NO) accumulation in the roots, but GA remarkably reduced it, and suppressed the up-regulation of the expression of IRT1. In contrary, the beneficial effect of GA on alleviating Cd toxicity was not observed in an IRT1 knock-out mutant irt1, suggesting the involvement of IRT1 in Cd{sup 2+} absorption. Furthermore, the GA-induced reduction of NO and Cd content can also be partially reversed by the application of a NO donor (S-nitrosoglutathione [GSNO]). Taken all these together, the results showed that GA-alleviated Cd toxicity is mediated through the reduction of the Cd-dependent NO accumulation and expression of Cd{sup 2+} uptake related gene-IRT1 in Arabidopsis.

Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes

Science.gov (United States)

Hawkins, Simon J.; Crompton, Lucy A.; Sood, Aman; Saunders, Margaret; Boyle, Noreen T.; Buckley, Amy; Minogue, Aedín M.; McComish, Sarah F.; Jiménez-Moreno, Natalia; Cordero-Llana, Oscar; Stathakos, Petros; Gilmore, Catherine E.; Kelly, Stephen; Lane, Jon D.; Case, C. Patrick; Caldwell, Maeve A.

2018-05-01

The potential for maternal nanoparticle (NP) exposures to cause developmental toxicity in the fetus without the direct passage of NPs has previously been shown, but the mechanism remained elusive. We now demonstrate that exposure of cobalt and chromium NPs to BeWo cell barriers, an in vitro model of the human placenta, triggers impairment of the autophagic flux and release of interleukin-6. This contributes to the altered differentiation of human neural progenitor cells and DNA damage in the derived neurons and astrocytes. Crucially, neuronal DNA damage is mediated by astrocytes. Inhibiting the autophagic degradation in the BeWo barrier by overexpression of the dominant-negative human ATG4BC74A significantly reduces the levels of DNA damage in astrocytes. In vivo, indirect NP toxicity in mice results in neurodevelopmental abnormalities with reactive astrogliosis and increased DNA damage in the fetal hippocampus. Our results demonstrate the potential importance of autophagy to elicit NP toxicity and the risk of indirect developmental neurotoxicity after maternal NP exposure.

Sweat gland toxicity induced by bis (tributyltin) oxide: an ultrastructural and X-ray microanalysis study

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, O. [Univ. of Occupational and Environmental Health Japan, Kitakyushu (Japan). Dept. of Dermatology and Occupational Dermatopathology; Doi, Y.; Kudo, H.; Fujimoto, S. [Univ. of Occupational and Environmental Health Japan, Kitakyushu (Japan). Dept. of Anatomy; Yoshizuka, M. [Kurume Univ. (Japan). Dept. of Anatomy

2000-12-01

Acute toxicity of bis (tributyltin) oxide in the sweat glands in the rat footpad was investigated by electron microscopy and an energy-dispersive X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg bis (tributyltin) oxide. After 6-8 h, swelling of mitochondria appeared in the secretory cells of the sweat glands. After 12 h, the secretory cells began to show intracytoplasmic edema. After 16-20 h, secretory cells in some sweat glands showed marked hydropic degeneration with swollen cytoplasm. Using X-ray microanalysis, tin peaks were preferentially obtained from the swollen mitochondria of the affected secretory cells. Mitochondria dysfunction due to the toxic effects of bis (tributyltin) oxide induced changes in the secretory cells of rat sweat glands contained three types of cells: degenerating dark cells, regenerating cells carrying injured mitochondria, and light cells which were morphologically very similar to the cells in the transitional portion of the sweat gland. These light cells appeared to differentiate into active secretory cells after settling down in the secretory portion. Based on these observations, we concluded that the cells in the transitional portion could play an important role at least as reserve cells against secretory cell toxicity. In association with the regenerating process of the damaged secretory portions, increased mitotic activities were seen in different areas of all the dermal sweat ducts. The above-mentioned morphological observations for cell damage and subsequent regeneration and renewal of secretory cells in sweat gland intoxication have not been reported so far. (orig.)

Myeloperoxidase potentiates nitric oxide-mediated nitrosation.

Science.gov (United States)

Lakshmi, Vijaya M; Nauseef, William M; Zenser, Terry V

2005-01-21

Nitrosation is an important reaction elicited by nitric oxide (NO). To better understand how nitrosation occurs in biological systems, we assessed the effect of myeloperoxidase (MPO), a mediator of inflammation, on nitrosation observed during NO autoxidation. Nitrosation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ; 10 mum) to 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N-NO-IQ) was monitored by HPLC. Using the NO donor spermine NONOate at pH 7.4, MPO potentiated N-NO-IQ formation. The minimum effective quantity of necessary components was 8.5 nm MPO, 0.25 mum H(2)O(2)/min, and 0.024 mum NO/min. Autoxidation was only detected at >/=1.2 mum NO/min. MPO potentiation was not affected by a 40-fold excess flux of H(2)O(2) over NO or less than a 2.4-fold excess flux of NO over H(2)O(2). Potentiation was due to an 8.8-fold increased affinity of MPO-derived nitrosating species for IQ. Autoxidation was inhibited by azide, suggesting involvement of the nitrosonium ion, NO(+). MPO potentiation was inhibited by NADH, but not azide, suggesting oxidative nitrosylation with NO(2)(.) or an NO(2)(.)-like species. MPO nonnitrosative oxidation of IQ with 0.3 mm NO(2)(-) at pH 5.5 was inhibited by azide, but not NADH, demonstrating differences between MPO oxidation of IQ with NO compared with NO(2)(-). Using phorbol ester-stimulated human neutrophils, N-NO-IQ formation was increased with superoxide dismutase and inhibited by catalase and NADH, but not NaN(3). This is consistent with nitrosation potentiation by MPO, not peroxynitrite. Increased N-NO-IQ formation was not detected with polymorphonuclear neutrophils from two unrelated MPO-deficient patients. Results suggest that the highly diffusible stable gas NO could initiate nitrosation at sites of neutrophil infiltration.

Experimental Hepatic Carcinogenesis: Oxidative Stress and Natural Antioxidants

Directory of Open Access Journals (Sweden)

Velid Unsal

2017-08-01

Full Text Available Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C. Oxidative stress is becoming recognized as a key factor in the progression of hepatocarcinogenesis. Reactive oxygen species can play a leading role in initiation and promotion of hepatic carcinogenesis. The metabolites of DEN Diethylnitrosamine (DEN mediate the binding of tumour promoters by covalently binding to the DNA with one or two oxidation-providing electrons. 2-AAF is the inducer of DEN, and it is involved in tumour formation in the bladder and liver. Reactive Oxygen species (ROS; carbohydrates, lipids, DNA and enzymes, such as affect all important structures. Additionally, an excessive amount of ROS is highly toxic to cells. Antioxidants are protects against ROS, toxic substances, carcinogens. This review focuses on the literature on studies of Hepatic Carcinogenesis, oxidative stress and antioxidant therapy.

The mechanism of mediated oxidation of carboxylates with ferrocene as redox catalyst in absence of grafting effects. An experimental and theoretical approach

International Nuclear Information System (INIS)

Hernández-Muñoz, Lindsay S.; Galano, Annia; Astudillo-Sánchez, Pablo D.; Abu-Omar, Mahdi M.; González, Felipe J.

2014-01-01

Graphical abstract: - Highlights: • The mechanism of mediated oxidation of carboxylates. • Thermodynamics of the mediated Kolbe and Non-Kolbe mechanisms. • The oxidation of acetate and diphenylacetate ions by using ferrocene as redox catalyst. • Simulation and DFT calculations of the mediated oxidation of carboxylates. • Radical and carbocationic pathways in the carboxylate oxidation in acetonitrile. - Abstract: The oxidation of tetrabutylammonium carboxylates by using ferrocene derivatives as redox mediators has been recently used to perform the covalent grafting of carbon surfaces with organic and organometallic groups. Due to the intervention of this surface process, a partial description of the reaction mechanism has only been stated. Therefore, this article concerns about two features of the oxidation of carboxylates mediated by ferrocene. In the first part, it is discussed that in the oxidation of acetate ions by using ferrocene as redox catalyst, the gap between both oxidation potentials is very high, which means that the homogeneous electron transfer between the acetate ion and the electrochemically generated ferrocenium ion is energetically unfavorable. However, by using density functional theory calculations, it has been shown that the whole set of coupled chemical reactions involved either in a Kolbe or Non-Kolbe pathway drive the overall mechanisms towards a thermodynamically favorable situation. In order to avoid the strong covalent grafting process that occurs during the mediated oxidation of acetate ions, the second part of this work deals with the oxidation of tetrabutylammonium diphenylacetate by using ferrocene as a redox mediator in acetonitrile on glassy carbon electrodes. With this carboxylate, no electrode inhibition process occurs and, therefore cyclic voltammetry simulation was done to propose the electrochemical and chemical steps that are present when a carboxylate oxidation is performed in the presence of ferrocene derivatives

Oxidative Stress and Nano-Toxicity Induced by TiO2 and ZnO on WAG Cell Line.

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Akhilesh Dubey

Full Text Available Metallic nanoparticles are widely used in cosmetics, food products and textile industry. These particles are known to cause respiratory toxicity and epithelial inflammation. They are eventually released to aquatic environment necessitating toxicity studies in cells from respiratory organs of aquatic organisms. Hence, we have developed and characterized a new cell line, WAG, from gill tissue of Wallago attu for toxicity assessment of TiO2 and ZnO nanoparticles. The efficacy of the cell line as an in vitro system for nanoparticles toxicity studies was established using electron microscopy, cytotoxicity assays, genotoxicity assays and oxidative stress biomarkers. Results obtained with MTT assay, neutral red uptake assay and lactate dehydrogenase assay showed acute toxicity to WAG cells with IC50 values of 25.29 ± 0.12, 34.99 ± 0.09 and 35.06 ± 0.09 mg/l for TiO2 and 5.716 ± 0.1, 3.160 ± 0.1 and 5.57 ± 0.12 mg/l for ZnO treatment respectively. The physicochemical properties and size distribution of nanoparticles were characterized using electron microscopy with integrated energy dispersive X-ray spectroscopy and Zetasizer. Dose dependent increase in DNA damage, lipid peroxidation and protein carbonylation along with a significant decrease in activity of Superoxide Dismutase, Catalase, total Glutathione levels and total antioxidant capacity with increasing concentration of exposed nanoparticles indicated that the cells were under oxidative stress. The study established WAG cell line as an in vitro system to study toxicity mechanisms of nanoparticles on aquatic organisms.

Microbially-mediated method for synthesis of non-oxide semiconductor nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Phelps, Tommy J.; Lauf, Robert J.; Moon, Ji-Won; Rondinone, Adam Justin; Love, Lonnie J.; Duty, Chad Edward; Madden, Andrew Stephen; Li, Yiliang; Ivanov, Ilia N.; Rawn, Claudia Jeanette

2017-09-19

The invention is directed to a method for producing non-oxide semiconductor nanoparticles, the method comprising: (a) subjecting a combination of reaction components to conditions conducive to microbially-mediated formation of non-oxide semiconductor nanoparticles, wherein said combination of reaction components comprises i) anaerobic microbes, ii) a culture medium suitable for sustaining said anaerobic microbes, iii) a metal component comprising at least one type of metal ion, iv) a non-metal component comprising at least one non-metal selected from the group consisting of S, Se, Te, and As, and v) one or more electron donors that provide donatable electrons to said anaerobic microbes during consumption of the electron donor by said anaerobic microbes; and (b) isolating said non-oxide semiconductor nanoparticles, which contain at least one of said metal ions and at least one of said non-metals. The invention is also directed to non-oxide semiconductor nanoparticle compositions produced as above and having distinctive properties.

Microbially-mediated method for synthesis of non-oxide semiconductor nanoparticles

Science.gov (United States)

Phelps, Tommy J.; Lauf, Robert J.; Moon, Ji Won; Rondinone, Adam J.; Love, Lonnie J.; Duty, Chad Edward; Madden, Andrew Stephen; Li, Yiliang; Ivanov, Ilia N.; Rawn, Claudia Jeanette

2014-06-24

The invention is directed to a method for producing non-oxide semiconductor nanoparticles, the method comprising: (a) subjecting a combination of reaction components to conditions conducive to microbially-mediated formation of non-oxide semiconductor nanoparticles, wherein said combination of reaction components comprises i) anaerobic microbes, ii) a culture medium suitable for sustaining said anaerobic microbes, iii) a metal component comprising at least one type of metal ion, iv) a non-metal component containing at least one non-metal selected from the group consisting of S, Se, Te, and As, and v) one or more electron donors that provide donatable electrons to said anaerobic microbes during consumption of the electron donor by said anaerobic microbes; and (b) isolating said non-oxide semiconductor nanoparticles, which contain at least one of said metal ions and at least one of said non-metals. The invention is also directed to non-oxide semiconductor nanoparticle compositions produced as above and having distinctive properties.

Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

Science.gov (United States)

Miao, Lu; Holley, Aaron K.; Zhao, Yanming; St. Clair, William H.

2014-01-01

Abstract Significance: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. Recent Advances: Ionizing radiation (IR)–generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. Critical Issues: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. Future Directions: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo- and radio-resistance in tumor cells and toxicity in normal tissues. Antioxid. Redox Signal. 20, 1481–1500. PMID:24093432

Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

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Liye Zhu

2016-12-01

Full Text Available Ochratoxin A (OTA displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD and livers (SOD and GSH. DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model.

Kinetic Study of Hydroxyl and Sulfate Radical-Mediated Oxidation of Pharmaceuticals in Wastewater Effluents.

Science.gov (United States)

Lian, Lushi; Yao, Bo; Hou, Shaodong; Fang, Jingyun; Yan, Shuwen; Song, Weihua

2017-03-07

Advanced oxidation processes (AOPs), such as hydroxyl radical (HO • )- and sulfate radical (SO 4 •- )-mediated oxidation, are alternatives for the attenuation of pharmaceuticals and personal care products (PPCPs) in wastewater effluents. However, the kinetics of these reactions needs to be investigated. In this study, kinetic models for 15 PPCPs were built to predict the degradation of PPCPs in both HO • - and SO 4 •- -mediated oxidation. In the UV/H 2 O 2 process, a simplified kinetic model involving only steady state concentrations of HO • and its biomolecular reaction rate constants is suitable for predicting the removal of PPCPs, indicating the dominant role of HO • in the removal of PPCPs. In the UV/K 2 S 2 O 8 process, the calculated steady state concentrations of CO 3 •- and bromine radicals (Br • , Br 2 •- and BrCl •- ) were 600-fold and 1-2 orders of magnitude higher than the concentrations of SO 4 •- , respectively. The kinetic model, involving both SO 4 •- and CO 3 •- as reactive species, was more accurate for predicting the removal of the 9 PPCPs, except for salbutamol and nitroimidazoles. The steric and ionic effects of organic matter toward SO 4 •- could lead to overestimations of the removal efficiencies of the SO 4 •- -mediated oxidation of nitroimidazoles in wastewater effluents.

Sulfur polymer cement encapsulation of RCRA toxic metals and metal oxides

International Nuclear Information System (INIS)

Calhoun, C.L. Jr.; Nulf, L.E.; Gorin, A.H.

1995-06-01

A study was conducted to determine the suitability of Sulfur Polymer Cement (SPC) encapsulation technology for the stabilization of RCRA toxic metal and metal oxide wastes. In a series of bench-scale experiments, the effects of sodium sulfide additions to the waste mixture, residence time, and temperature profile were evaluated. In addition, an effort was made to ascertain the degree to which SPC affords chemical stabilization as opposed to physical encapsulation. Experimental results have demonstrated that at the 25 wt % loading level, SPC can effectively immobilize Cr, Cr 2 O 3 , Hg, Pb, and Se to levels below regulatory limits. SPC encapsulation also has been shown to significantly reduce the leachability of other toxic compounds including PbO, PbO 2 , As 2 O 3 , BaO, and CdO. In addition, data has confirmed sulfide conversion of Hg, Pb, PbO, PbO 2 , and BaO as the product of their reaction with SPC

Different toxicity mechanisms between bare and polymer-coated copper oxide nanoparticles in Lemna gibba

International Nuclear Information System (INIS)

Perreault, François; Popovic, Radovan; Dewez, David

2014-01-01

In this report, we investigated how the presence of a polymer shell (poly(styrene-co-butyl acrylate) alters the toxicity of CuO NPs in Lemna gibba. Based on total Cu concentration, core–shell CuO NPs were 10 times more toxic than CuO NPs, inducing a 50% decrease of growth rate at 0.4 g l −1 after 48-h of exposure while a concentration of 4.5 g l −1 was required for CuO NPs for a similar effect. Toxicity of CuO NPs was mainly due to NPs solubilization in the media. Based on the accumulated copper content in the plants, core–shell CuO NPs induced 4 times more reactive oxygen species compared to CuO NPs and copper sulfate, indicating that the presence of the polymer shell changed the toxic effect induced in L. gibba. This effect could not be attributed to the polymer alone and reveals that surface modification may change the nature of NPs toxicity. -- Highlights: • Bare and polymer-coated CuO nanoparticles were toxic to Lemna gibba. • Toxicity of bare CuO was mainly due to solubilized soluble copper. • Coated CuO accumulated inside the plants four times more. • Formation of reactive oxygen species was increased by polymer coating. • Coating of nanomaterials modifies mechanisms of action at cellular level. -- Polymer coating increases oxidative stress effect by core–shell CuO nanoparticles

Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein

Energy Technology Data Exchange (ETDEWEB)

Sekine, Shuichi; Ito, Konomi; Watanabe, Haruna; Nakano, Takafumi [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan); Moriya, Kyoji; Shintani, Yoshizumi; Fujie, Hajime; Tsutsumi, Takeya; Miyoshi, Hideyuki; Fujinaga, Hidetake; Shinzawa, Seiko; Koike, Kazuhiko [Department of Internal Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Horie, Toshiharu, E-mail: t.horie@thu.ac.jp [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan)

2015-02-01

Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2 (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron ({sup 59}Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca{sup 2+} uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. - Highlights: • Iron accumulation in the livers of patients with hepatitis C virus (HCV) infection is thought to exacerbate oxidative stress. • The impact of iron overload on mitochondrial damage and ROS production in HCV core protein-expressing cells were examined. • Mitochondrial iron uptake was increased in the livers of HCV core protein-expressing transgenic mice. • Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates

Silver-mediated oxidative C-H difluoromethylation of phenanthridines and 1,10-phenanthrolines.

Science.gov (United States)

Zhu, Sheng-Qing; Xu, Xiu-Hua; Qing, Feng-Ling

2017-10-17

A silver-mediated oxidative difluoromethylation of phenanthridines and 1,10-phenanthrolines with TMSCF 2 H is disclosed. This C-H difluoromethylation of N-containing polycyclic aromatics constitutes an efficient method for the regioselective synthesis of difluoromethylated N-heterocycles.

In vitro toxicity of zinc oxide nanoparticles: a review

International Nuclear Information System (INIS)

Pandurangan, Muthuraman; Kim, Doo Hwan

2015-01-01

The toxic effect of ZnO nanoparticles is due to their solubility. ZnO nanoparticles dissolve in the extracellular region, which in turn increases the intracellular [Zn 2+ ] level. The mechanism for increased intracellular [Zn 2+ ] level and ZnO nanoparticles dissolution in the medium is still unclear. Cytotoxicity, increased oxidative stress, increased intracellular [Ca 2+ ] level, decreased mitochondrial membrane potential, and interleukin-8 productions occur in the BEAS-2B bronchial epithelial cells and A549 alveolar adenocarcinoma cells following the exposure of ZnO nanoparticles. Confluent C2C12 cells are more resistant to ZnO nanoparticles compared to the sparse monolayer. Loss of 3T3-L1 cell viability, membrane leakage, and morphological changes occurs due to exposure of ZnO nanoparticles. ZnO nanoparticle induces cytotoxicity and mitochondrial dysfunction in RKO colon carcinoma cells. The occurrence of apoptosis, increased ROS level, reduced mitochondrial activity and formation of tubular intracellular structures are reported following exposure of ZnO nanoparticles in skin cells. Macrophages, monocytes, and dendritic cells are affected by ZnO nanoparticles. In addition, genotoxicity is also induced. The present review summarizes the literature on in vitro toxicity of ZnO nanoparticles (10–100 nm) on various cell lines

In vitro toxicity of zinc oxide nanoparticles: a review

Energy Technology Data Exchange (ETDEWEB)

Pandurangan, Muthuraman; Kim, Doo Hwan, E-mail: frenzram1980@gmail.com [Konkuk University, Department of Bioresources and Food Sciences (Korea, Republic of)

2015-03-15

The toxic effect of ZnO nanoparticles is due to their solubility. ZnO nanoparticles dissolve in the extracellular region, which in turn increases the intracellular [Zn{sup 2+}] level. The mechanism for increased intracellular [Zn{sup 2+}] level and ZnO nanoparticles dissolution in the medium is still unclear. Cytotoxicity, increased oxidative stress, increased intracellular [Ca{sup 2+}] level, decreased mitochondrial membrane potential, and interleukin-8 productions occur in the BEAS-2B bronchial epithelial cells and A549 alveolar adenocarcinoma cells following the exposure of ZnO nanoparticles. Confluent C2C12 cells are more resistant to ZnO nanoparticles compared to the sparse monolayer. Loss of 3T3-L1 cell viability, membrane leakage, and morphological changes occurs due to exposure of ZnO nanoparticles. ZnO nanoparticle induces cytotoxicity and mitochondrial dysfunction in RKO colon carcinoma cells. The occurrence of apoptosis, increased ROS level, reduced mitochondrial activity and formation of tubular intracellular structures are reported following exposure of ZnO nanoparticles in skin cells. Macrophages, monocytes, and dendritic cells are affected by ZnO nanoparticles. In addition, genotoxicity is also induced. The present review summarizes the literature on in vitro toxicity of ZnO nanoparticles (10–100 nm) on various cell lines.

Stathmin Mediates Hepatocyte Resistance to Death from Oxidative Stress by down Regulating JNK

Science.gov (United States)

Zhao, Enpeng; Amir, Muhammad; Lin, Yu; Czaja, Mark J.

2014-01-01

Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK). The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth. PMID:25285524

Stathmin mediates hepatocyte resistance to death from oxidative stress by down regulating JNK.

Directory of Open Access Journals (Sweden)

Enpeng Zhao

Full Text Available Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK. The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth.

Effect of Nano-Al2O3 on the Toxicity and Oxidative Stress of Copper towards Scenedesmus obliquus

Science.gov (United States)

Li, Xiaomin; Zhou, Suyang; Fan, Wenhong

2016-01-01

Nano-Al2O3 has been widely used in various industries; unfortunately, it can be released into the aquatic environment. Although nano-Al2O3 is believed to be of low toxicity, it can interact with other pollutants in water, such as heavy metals. However, the interactions between nano-Al2O3 and heavy metals as well as the effect of nano-Al2O3 on the toxicity of the metals have been rarely investigated. The current study investigated copper toxicity in the presence of nano-Al2O3 towards Scenedesmus obliquus. Superoxide dismutase activity and concentration of glutathione and malondialdehyde in cells were determined in order to quantify oxidative stress in this study. Results showed that the presence of nano-Al2O3 reduced the toxicity of Cu towards S. obliquus. The existence of nano-Al2O3 decreased the growth inhibition of S. obliquus. The accumulation of copper and the level of oxidative stress in algae were reduced in the presence of nano-Al2O3. Furthermore, lower copper accumulation was the main factor that mitigated copper toxicity with the addition of nano-Al2O3. The decreased copper uptake could be attributed to the adsorption of copper onto nanoparticles and the subsequent decrease of available copper in water. PMID:27294942

Vesicular (liposomal and nanoparticulated delivery of curcumin: a comparative study on carbon tetrachloride–mediated oxidative hepatocellular damage in rat model

Directory of Open Access Journals (Sweden)

Choudhury ST

2016-05-01

Full Text Available Somsubhra Thakur Choudhury,1 Nirmalendu Das,2 Swarupa Ghosh,2 Debasree Ghosh,2 Somsuta Chakraborty,2 Nahid Ali1 1Infectious Diseases and Immunology, 2Drug Development, Diagnostics and Biotechnology, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India Abstract: The liver plays a vital role in biotransforming and extricating xenobiotics and is thus prone to their toxicities. Short-term administration of carbon tetrachloride (CCl4 causes hepatic inflammation by enhancing cellular reactive oxygen species (ROS level, promoting mitochondrial dysfunction, and inducing cellular apoptosis. Curcumin is well accepted for its antioxidative and anti-inflammatory properties and can be considered as an effective therapeutic agent against hepatotoxicity. However, its therapeutic efficacy is compromised due to its insolubility in water. Vesicular delivery of curcumin can address this limitation and thereby enhance its effectiveness. In this study, it was observed that both liposomal and nanoparticulated formulations of curcumin could increase its efficacy significantly against hepatotoxicity by preventing cellular oxidative stress. However, the best protection could be obtained through the polymeric nanoparticle-mediated delivery of curcumin. Mitochondria have a pivotal role in ROS homeostasis and cell survivability. Along with the maintenance of cellular ROS levels, nanoparticulated curcumin also significantly (P<0.0001 increased cellular antioxidant enzymes, averted excessive mitochondrial destruction, and prevented total liver damage in CCl4-treated rats. The therapy not only prevented cells from oxidative damage but also arrested the intrinsic apoptotic pathway. In addition, it also decreased the fatty changes in hepatocytes, centrizonal necrosis, and portal inflammation evident from the histopathological analysis. To conclude, curcumin-loaded polymeric nanoparticles are more effective in comparison to liposomal curcumin in preventing CCl4

Aminopropyltriethoxysilane-mediated surface functionalization of hydroxyapatite nanoparticles: synthesis, characterization, and in vitro toxicity assay

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Wang S

2011-12-01

Full Text Available Shige Wang1, Shihui Wen2, Mingwu Shen2, Rui Guo2, Xueyan Cao2, Jianhua Wang3, Xiangyang Shi1,2,41State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 3Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 4Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, Funchal, PortugalBackground: We report on aminopropyltriethoxysilane (APTS-mediated surface modification of nanohydroxyapatite with different surface functional groups for potential biomedical applications. In this study, nanohydroxyapatite covalently linked with APTS (n-HA-APTS was reacted with acetic anhydride or succinic anhydride to produce neutralized (n-HA-APTS.Ac or negatively charged (n-HA-APTS.SAH nanohydroxyapatite, respectively. Nanohydroxyapatite formed with amine, acetyl, and carboxyl groups was extensively characterized using Fourier transform infrared spectroscopy, transmission electron microscopy, 1H nuclear magnetic resonance spectroscopy, X-ray diffraction, inductively coupled plasma-atomic emission spectroscopy, and zeta potential measurements.Results: In vitro 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide colorimetric assay revealed that the slight toxicity of the amine-functionalized n-HA-APTS could be eliminated by post-functionalization of APTS amines to form acetyl and carboxyl groups. Blood compatibility assessment demonstrated that the negligible hemolytic activity of the pristine nanohydroxyapatite particles did not appreciably change after APTS-mediated surface functionalization.Conclusion: APTS-mediated functionalization of nanohydroxyapatite with different surface groups may be useful for further functionalization of nanohydroxyapatite with biologically active materials, thereby providing possibilities for a broad range of

Mechanistic investigation of toxicity of chromium oxide nanoparticles in murine fibrosarcoma cells

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Alarifi S

2016-03-01

Full Text Available Saud Alarifi, Daoud Ali, Saad Alkahtani Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia Abstract: Chromium oxide nanoparticles (Cr2O3NPs are widely used in polymers and paints. In the present study, we aimed to determine the toxicity of Cr2O3NPs in murine fibrosarcoma (L929 cells. The cytotoxicity of Cr2O3NPs was measured by MTT and neutral red uptake assays; Cr2O3NPs had significant cytotoxic effects on L929 cells. Enhancement of intracellular reactive oxygen species was observed in L929 cells after exposure to Cr2O3NPs. Cr2O3NPs produced caspase-3, indicating that exposure to Cr2O3NPs induced apoptosis. After exposure to Cr2O3NPs, the cellular glutathione level decreased and lipid peroxidation, superoxide dismutase, and catalase increased in a dose- and time-dependent manner. By using single-cell gel tests, we also observed increased DNA damage in a Cr2O3NP exposure-duration- and dose-dependent fashion. Cell toxicity and DNA damage may be useful biomarkers for determining the safety of Cr2O3NPs in human and animal health. Keywords: Cr2O3NPs, L929 cells, MTT assay, oxidative stress 

O2-mediated oxidation of ferrous nitrosylated human serum heme-albumin is limited by nitrogen monoxide dissociation

International Nuclear Information System (INIS)

Ascenzi, Paolo; Gullotta, Francesca; Gioia, Magda; Coletta, Massimo; Fasano, Mauro

2011-01-01

Research highlights: → Human serum heme-albumin displays globin-like properties. → O 2 -mediated oxidation of ferrous nitrosylated human serum heme-albumin. → Allosteric modulation of human serum heme-albumin reactivity. → Rifampicin is an allosteric effector of human serum heme-albumin. → Human serum heme-albumin is a ROS and NOS scavenger. -- Abstract: Human serum heme-albumin (HSA-heme-Fe) displays globin-like properties. Here, kinetics of O 2 -mediated oxidation of ferrous nitrosylated HSA-heme-Fe (HSA-heme-Fe(II)-NO) is reported. Values of the first-order rate constants for O 2 -mediated oxidation of HSA-heme-Fe(II)-NO (i.e., for ferric HSA-heme-Fe formation) and for NO dissociation from HSA-heme-Fe(II)-NO (i.e., for NO replacement by CO) are k = 9.8 x 10 -5 and 8.3 x 10 -4 s -1 , and h = 1.3 x 10 -4 and 8.5 x 10 -4 s -1 , in the absence and presence of rifampicin, respectively, at pH = 7.0 and T = 20.0 o C. The coincidence of values of k and h indicates that NO dissociation represents the rate limiting step of O 2 -mediated oxidation of HSA-heme-Fe(II)-NO. Mixing HSA-heme-Fe(II)-NO with O 2 does not lead to the formation of the transient adduct(s), but leads to the final ferric HSA-heme-Fe derivative. These results reflect the fast O 2 -mediated oxidation of ferrous HSA-heme-Fe and highlight the role of drugs in modulating allosterically the heme-Fe-atom reactivity.

Diselenolane-mediated cellular uptake.

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Chuard, Nicolas; Poblador-Bahamonde, Amalia I; Zong, Lili; Bartolami, Eline; Hildebrandt, Jana; Weigand, Wolfgang; Sakai, Naomi; Matile, Stefan

2018-02-21

The emerging power of thiol-mediated uptake with strained disulfides called for a move from sulfur to selenium. We report that according to results with fluorescent model substrates, cellular uptake with 1,2-diselenolanes exceeds uptake with 1,2-dithiolanes and epidithiodiketopiperazines with regard to efficiency as well as intracellular localization. The diselenide analog of lipoic acid performs best. This 1,2-diselenolane delivers fluorophores efficiently to the cytosol of HeLa Kyoto cells, without detectable endosomal capture as with 1,2-dithiolanes or dominant escape into the nucleus as with epidithiodiketopiperazines. Diselenolane-mediated cytosolic delivery is non-toxic (MTT assay), sensitive to temperature but insensitive to inhibitors of endocytosis (chlorpromazine, methyl-β-cyclodextrin, wortmannin, cytochalasin B) and conventional thiol-mediated uptake (Ellman's reagent), and to serum. Selenophilicity, the extreme CSeSeC dihedral angle of 0° and the high but different acidity of primary and secondary selenols might all contribute to uptake. Thiol-exchange affinity chromatography is introduced as operational mimic of thiol-mediated uptake that provides, in combination with rate enhancement of DTT oxidation, direct experimental evidence for existence and nature of the involved selenosulfides.

Organic anion transporter (Slc22a) family members as mediators of toxicity

International Nuclear Information System (INIS)

Sweet, Douglas H.

2005-01-01

Exposure of the body to toxic organic anions is unavoidable and occurs from both intentional and unintentional sources. Many hormones, neurotransmitters, and waste products of cellular metabolism, or their metabolites, are organic anions. The same is true for a wide variety of medications, herbicides, pesticides, plant and animal toxins, and industrial chemicals and solvents. Rapid and efficient elimination of these substances is often the body's best defense for limiting both systemic exposure and the duration of their pharmacological or toxicological effects. For organic anions, active transepithelial transport across the renal proximal tubule followed by elimination via the urine is a major pathway in this detoxification process. Accordingly, a large number of organic anion transport proteins belonging to several different gene families have been identified and found to be expressed in the proximal nephron. The function of these transporters, in combination with the high volume of renal blood flow, predisposes the kidney to increased toxic susceptibility. Understanding how the kidney mediates the transport of organic anions is integral to achieving desired therapeutic outcomes in response to drug interactions and chemical exposures, to understanding the progression of some disease states, and to predicting the influence of genetic variation upon these processes. This review will focus on the organic anion transporter (OAT) family and discuss the known members, their mechanisms of action, subcellular localization, and current evidence implicating their function as a determinant of the toxicity of certain endogenous and xenobiotic agents

Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

International Nuclear Information System (INIS)

Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

2011-01-01

Highlights: → Toxicological implications associated with the use of NaNO 2 therapy to treat systemic cell-free Hb exposure are not well-defined. → Systemic Hb exposure followed by NaNO 2 infusion induces acute CNS toxicities in guinea pigs. → These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO 2 alone. → NaNO 2 -mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO 2 ) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO 2 with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO 2 on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO 2 , at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO 2 alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked by Glutamate Toxicity in Hippocampal Slices.

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Ludka, Fabiana K; Dal-Cim, Tharine; Binder, Luisa Bandeira; Constantino, Leandra Celso; Massari, Caio; Tasca, Carla I

2017-07-01

Atorvastatin has been shown to exert a neuroprotective action by counteracting glutamatergic toxicity. Recently, we have shown atorvastatin also exerts an antidepressant-like effect that depends on both glutamatergic and serotonergic systems modulation. Excitotoxicity is involved in several brain disorders including depression; thus, it is suggested that antidepressants may target glutamatergic system as a final common pathway. In this study, a comparison of the mechanisms involved in the putative neuroprotective effect of a repetitive atorvastatin or fluoxetine treatment against glutamate toxicity in hippocampal slices was performed. Adult Swiss mice were treated with atorvastatin (10 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.), once a day during seven consecutive days. On the eighth day, animals were killed and hippocampal slices were obtained and subjected to an in vitro protocol of glutamate toxicity. An acute treatment of atorvastatin or fluoxetine was not neuroprotective; however, the repeated atorvastatin or fluoxetine treatment prevented the decrease in cellular viability induced by glutamate in hippocampal slices. The loss of cellular viability induced by glutamate was accompanied by increased D-aspartate release, increased reactive oxygen species (ROS) and nitric oxide (NO) production, and impaired mitochondrial membrane potential. Atorvastatin or fluoxetine repeated treatment also presented an antidepressant-like effect in the tail suspension test. Atorvastatin or fluoxetine treatment was effective in protecting mice hippocampal slices from glutamate toxicity by preventing the oxidative stress and mitochondrial dysfunction.

Organophosphorus insecticides: Toxic effects and bioanalytical tests for evaluating toxicity during degradation processes

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Čolović Mirjana B.

2013-01-01

Full Text Available Organophosphorus insecticides have been the most applied group of insecticides for the last two decades. Their main toxic effects are related to irreversible inactivation of acetylcholinesterase (AChE. Actually, they covalently bind to serine OH group in the enzyme active site forming phosphorylated enzyme that cannot hydrolyze acetylcholine. Organophosphorus insecticides in the environment undergo the natural degradation pathway including mainly homogeneous and heterogeneous hydrolysis (especially at high pH generating non-inhibiting products. Additionally, thio organophosphates are easily oxidized by naturally present oxidants and UV light, forming more toxic and stable oxons. Thus, oxidative degradation procedures, generally referred as advanced oxidation processes (AOP, have been applied for their efficient removal from contaminated waters. The most applied bioassays to monitor the organophosphate toxicity i.e. the detoxification degree during AOP are Vibrio fischeri and AChE bioassays. Vibrio fischeri toxicity test exploits bioluminescence as the measure of luciferase activity of this marine bacterium, whereas AChE bioassay is based on AChE activity inhibition. Both bioanalytical techniques are rapid (several minutes, simple, sensitive and reproducible. Vibrio fischeri test seems to be a versatile indicator of toxic compounds generated in AOP for organophosphorus insecticides degradation. However, detection of neurotoxic AChE inhibitors, which can be formed in AOP of some organophosphates, requires AChE bioassays. Therefore, AChE toxicity test is more appropriate for monitoring the degradation processes of thio organophosphates, because more toxic oxo organophosphates might be formed and overlooked by Vibrio fischeri bioluminescence inhibition. In addition, during organophosphates removal by AOP, compounds with strong genotoxic potential may be formed, which cannot be detected by standard toxicity tests. For this reason, determination of

Oxidative stress in chemical toxicity

Energy Technology Data Exchange (ETDEWEB)

Kappus, H.

1986-05-01

The toxic effect of compounds which undergo redox cycling enzymatic one-electron reduction are reviewed. First of all, the enzymatic reduction of these compounds leads to reactive intermediates, mainly radicals which react with oxygen, whereby superoxide anion radicals are formed. Further oxygen metabolites are hydrogen peroxide, singlet oxygen and hydroxyl radicals. The role of these oxygen metabolites in toxicity is discussed. The occurrence of lipid peroxidation during redox cycling of quinonoide compounds, e.g., adriamycin, and the possible relationship to their toxicity is critically evaluated. It is shown that iron ions play a crucial role in lipid peroxidation induced by redox cycling compounds. DNA damage by metal chelates, e.g., bleomycin, is discussed on the basis of findings that enzymatic redox cycling of a bleomycin-iron complex has been observed. The involvement of hydroxyl radicals in bleomycin-induced DNA damage occurring during redox cycling in cell nuclei is claimed. Redox cycling of other substances, e.g., aromatic amines, is discussed in relation to carcinogenesis. Other chemical groups, e.g., nitroaromatic compounds, hydroxylamines and azo compounds are included. Other targets for oxygen radical attack, e.g., proteins, are also dealt with. It is concluded that oxygen radical formation by redox cycling may be a critical event in toxic effects of several compounds if the protective mechanisms of cells are overwhelmed.

Defect-mediated magnetism of transition metal doped zinc oxide thin films

Science.gov (United States)

Roberts, Bradley Kirk

Magnetism in transition metal doped wide band-gap materials is of interest to further the fundamental science of materials and future spintronics applications. Large inter-dopant separations require mediation of ferromagnetism by some method; carrier-mediated mechanisms are typically applicable to dilute magnetic semiconductors with low Curie temperatures. Dilute magnetic oxides, commonly with poor conductivity and TC above room temperature, cannot be described within this theory. Recent experiment and theory developments suggest that ferromagnetic exchange in these materials can be mediated by defects. This research includes experimental results justifying and developing this approach. Thin films of Cr doped ZnO (band gap ˜3.3 eV) were deposited with several processing variations to enhance the effects of either 0-dimensional (vacancy, hydrogen-related defect) or two-dimensional defects (surface/interface) and thereby affect magnetism and conductivity. We observe surface magnetism in dielectric thin films of oxygen-saturated ZnO:Cr with spontaneous magnetic moment and conductance dropping approximately exponentially with increasing thickness. Uniform defect concentrations would not result in such magnetic ordering behavior indicating that magnetism is mediated either by surface defects or differing concentrations of point defects near the surface. Polarized neutron reflectivity profiling confirms a magnetically active region of ˜8 nm at the film surface. Hydrogen is notoriously present as a defect and carrier dopant in ZnO, and artificial introduction of hydrogen in dielectric ZnO:Cr films results in varying electronic and magnetic behavior. Free carriers introduced with hydrogen doping are not spin-polarized requiring an alternative explanation for ferromagnetism. We find from positron annihilation spectroscopy measurements that hydrogen doping increases the concentration of an altered VZn-related defect (a preliminary interpretation) throughout the film, which

In vitro toxic effects of reduced graphene oxide nanosheets on lung cancer cells

Science.gov (United States)

Tabish, Tanveer A.; Pranjol, Md Zahidul I.; Hayat, Hasan; Rahat, Alma A. M.; Abdullah, Trefa M.; Whatmore, Jacqueline L.; Zhang, Shaowei

2017-12-01

The intriguing properties of reduced graphene oxide (rGO) have paved the way for a number of potential biomedical applications such as drug delivery, tissue engineering, gene delivery and bio-sensing. Over the last decade, there have been escalating concerns regarding the possible toxic effects, behaviour and fate of rGO in living systems and environments. This paper reports on integrative chemical-biological interactions of rGO with lung cancer cells, i.e. A549 and SKMES-1, to determine its potential toxicological impacts on them, as a function of its concentration. Cell viability, early and late apoptosis and necrosis were measured to determine oxidative stress potential, and induction of apoptosis for the first time by comparing two lung cancer cells. We also showed the general trend between cell death rates and concentrations for different cell types using a Gaussian process regression model. At low concentrations, rGO was shown to significantly produce late apoptosis and necrosis rather than early apoptotic events, suggesting that it was able to disintegrate the cellular membranes in a dose dependent manner. For the toxicity exposures undertaken, late apoptosis and necrosis occurred, which was most likely resultant from limited bioavailability of unmodified rGO in lung cancer cells.

Mediated electrochemical oxidation treatment for Rocky Flats combustible low-level mixed waste. Final report, FY 1993 and 1994

International Nuclear Information System (INIS)

Chiba, Z.; Lewis, P.R.; Murguia, L.C.

1994-09-01

Mediated Electrochemical Oxidation (MEO) is an aqueous process which destroys hazardous organics by oxidizing a mediator at the anode of an electrochemical cell; the mediator in turn oxidizes the organics within the bulk of the electrolyte. With this process organics can be nearly completely destroyed, that is, the carbon and hydrogen present in the hydrocarbon are almost entirely mineralized to carbon dioxide and water. The MEO process is also capable of dissolving radioactive materials, including difficult-to-dissolve compounds such as plutonium oxide. Hence, this process can treat mixed wastes, by destroying the hazardous organic components of the waste, and dissolving the radioactive components. The radioactive material can be recovered if desired, or disposed of as non-mixed radioactive waste. The process is inherently safe, since the hazardous and radioactive materials are completely contained in the aqueous phase, and the system operates at low temperatures (below 80 degree C) and at ambient pressures

Protection of HepG2 cells against acrolein toxicity by 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide via glutathione-mediated mechanism.

Science.gov (United States)

Shah, Halley; Speen, Adam M; Saunders, Christina; Brooke, Elizabeth A S; Nallasamy, Palanisamy; Zhu, Hong; Li, Y Robert; Jia, Zhenquan

2015-10-01

Acrolein is an environmental toxicant, mainly found in smoke released from incomplete combustion of organic matter. Several studies showed that exposure to acrolein can lead to liver damage. The mechanisms involved in acrolein-induced hepatocellular toxicity, however, are not completely understood. This study examined the cytotoxic mechanisms of acrolein on HepG2 cells. Acrolein at pathophysiological concentrations was shown to cause apoptotic cell death and an increase in levels of protein carbonyl and thiobarbituric acid reactive acid substances. Acrolein also rapidly depleted intracellular glutathione (GSH), GSH-linked glutathione-S-transferases, and aldose reductase, three critical cellular defenses that detoxify reactive aldehydes. Results further showed that depletion of cellular GSH by acrolein preceded the loss of cell viability. To further determine the role of cellular GSH in acrolein-mediated cytotoxicity, buthionine sulfoximine (BSO) was used to inhibit cellular GSH biosynthesis. It was observed that depletion of cellular GSH by BSO led to a marked potentiation of acrolein-mediated cytotoxicity in HepG2 cells. To further assess the contribution of these events to acrolein-induced cytotoxicity, triterpenoid compound 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) was used for induction of GSH. Induction of GSH by CDDO-Im afforded cytoprotection against acrolein toxicity in HepG2 cells. Furthermore, BSO significantly inhibited CDDO-Im-mediated induction in cellular GSH levels and also reversed cytoprotective effects of CDDO-Im in HepG2 cells. These results suggest that GSH is a predominant mechanism underlying acrolein-induced cytotoxicity as well as CDDO-Im-mediated cytoprotection. This study may provide understanding on the molecular action of acrolein which may be important to develop novel strategies for the prevention of acrolein-mediated toxicity. © 2014 by the Society for Experimental Biology and Medicine.

Suppression of Human T Cell Proliferation Mediated by the Cathepsin B Inhibitor, z-FA-FMK Is Due to Oxidative Stress.

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Tanuja Rajah

Full Text Available The cathepsin B inhibitor, benzyloxycarbonyl-phenylalanine-alanine-fluoromethyl ketone (z-FA-FMK readily inhibits anti-CD3-induced human T cell proliferation, whereas the analogue benzyloxycarbonyl-phenylalanine-alanine-diazomethyl ketone (z-FA-DMK had no effect. In contrast, benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK was toxic. The inhibition of T cell proliferation mediated by z-FA-FMK requires not only the FMK moiety, but also the benzyloxycarbonyl group at the N-terminal, suggesting some degree of specificity in z-FA-FMK-induced inhibition of primary T cell proliferation. We showed that z-FA-FMK treatment leads to a decrease in intracellular glutathione (GSH with a concomitant increase in reactive oxygen species (ROS levels in activated T cells. The inhibition of anti-CD3-induced T cell proliferation mediated by z-FA-FMK was abolished by the presence of low molecular weight thiols such as GSH, N-acetylcysteine (NAC and L-cysteine, whereas D-cysteine which cannot be metabolised to GSH has no effect. The inhibition of anti-CD3-induced up-regulation of CD25 and CD69 expression mediated by z-FA-FMK was also attenuated in the presence of exogenous GSH. Similar to cell proliferation, GSH, NAC and L-cysteine but not D-cysteine, completely restored the processing of caspase-8 and caspase-3 to their respective subunits in z-FA-FMK-treated activated T cells. Our collective results demonstrated that the inhibition of T cell activation and proliferation mediated by z-FA-FMK is due to oxidative stress via the depletion of GSH.

Toxic effects of ethylene oxide residues on bovine embryos in vitro.

Science.gov (United States)

Holyoak, G R; Wang, S; Liu, Y; Bunch, T D

1996-04-15

The potential of ethylene oxide (EtO) residues in exposed plastic tissue culture dishes to adversely affect bovine oocyte maturation, fertilization and subsequent embryonic development was monitored. In experiment 1, the effects of aeration time and aeration combined with washing of EtO-gassed culture dishes on the extent of residual toxicity were investigated. There was no cleavage in any treatment in which oocytes were matured and fertilized in dishes exposed to EtO. EtO residues caused functional degeneration of oocytes even when culture dishes were aerated for more than 12 days post EtO-exposure and repeatedly washed. In experiment 2, the residual toxicity of EtO gas on in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC) were evaluated. Cleavage rate significantly decreased and post-cleavage development was retarded in ova maintained in dishes treated with EtO either during IVM or IVF. EtO residues may be more detrimental to spermatozoa than to oocytes which may have been the primary cause of fertilization failure during IVF.

Cyanide-induced death of dopaminergic cells is mediated by uncoupling protein-2 up-regulation and reduced Bcl-2 expression

International Nuclear Information System (INIS)

Zhang, X.; Li, L.; Zhang, L.; Borowitz, J.L.; Isom, G.E.

2009-01-01

Cyanide is a potent inhibitor of mitochondrial oxidative metabolism and produces mitochondria-mediated death of dopaminergic neurons and sublethal intoxications that are associated with a Parkinson-like syndrome. Cyanide toxicity is enhanced when mitochondrial uncoupling is stimulated following up-regulation of uncoupling protein-2 (UCP-2). In this study, the role of a pro-survival protein, Bcl-2, in cyanide-mediated cell death was determined in a rat dopaminergic immortalized mesencephalic cell line (N27 cells). Following pharmacological up-regulation of UCP-2 by treatment with Wy14,643, cyanide reduced cellular Bcl-2 expression by increasing proteasomal degradation of the protein. The increased turnover of Bcl-2 was mediated by an increase of oxidative stress following UCP-2 up-regulation. The oxidative stress involved depletion of mitochondrial glutathione (mtGSH) and increased H 2 O 2 generation. Repletion of mtGSH by loading cells with glutathione ethyl ester reduced H 2 O 2 generation and in turn blocked the cyanide-induced decrease of Bcl-2. To determine if UCP-2 mediated the response, RNAi knock down was conducted. The RNAi decreased cyanide-induced depletion of mtGSH, reduced H 2 O 2 accumulation, and inhibited down-regulation of Bcl-2, thus blocking cell death. To confirm the role of Bcl-2 down-regulation in the cell death, it was shown that over-expression of Bcl-2 by cDNA transfection attenuated the enhancement of cyanide toxicity after UCP-2 up-regulation. It was concluded that UCP-2 up-regulation sensitizes cells to cyanide by increasing cellular oxidative stress, leading to an increase of Bcl-2 degradation. Then the reduced Bcl-2 levels sensitize the cells to cyanide-mediated cell death.

Silicon (Si) alleviates cotton (Gossypium hirsutum L.) from zinc (Zn) toxicity stress by limiting Zn uptake and oxidative damage.

Science.gov (United States)

Anwaar, Shad Ali; Ali, Shafaqat; Ali, Skhawat; Ishaque, Wajid; Farid, Mujahid; Farooq, Muhammad Ahsan; Najeeb, Ullah; Abbas, Farhat; Sharif, Muhammad

2015-03-01

Silicon (Si) is as an important fertilizer element, which has been found effective in enhancing plant tolerance to variety of biotic and a-biotic stresses. This study investigates the Si potential to alleviate zinc (Zn) toxicity stress in cotton (Gossypium hirsutum L.). Cotton plants were grown in hydroponics and exposed to different Zn concentration, 0, 25, and 50 μM, alone and/or in combination with 1 mM Si. Incremental Zn concentration in growth media instigated the cellular oxidative damage that was evident from elevated levels of hydrogen peroxide (H2O2), electrolyte leakage, and malondialdehyde (MDA) and consequently inhibited cotton growth, biomass, chlorophyll pigments, and photosynthetic process. Application of Si significantly suppressed Zn accumulation in various plant parts, i.e., roots, stems, and leaves and thus promoted biomass, photosynthetic, growth parameters, and antioxidant enzymes activity of Zn-stressed as well unstressed plants. In addition, Si reduced the MDA and H2O2 production and electrolyte leakage suggesting its role in protecting cotton plants from Zn toxicity-induced oxidative damage. Thus, the study indicated that exogenous Si application could improve growth and development of cotton crop experiencing Zn toxicity stress by limiting Zn bioavailability and oxidative damage.

Protective effects of exogenous β-hydroxybutyrate on paraquat toxicity in rat kidney

Energy Technology Data Exchange (ETDEWEB)

Wei, Teng; Tian, Wulin; Liu, Fangning; Xie, Guanghong, E-mail: xiegh@jlu.edu.cn

2014-05-16

Highlights: • β-Hydroxybutyrate inhibits paraquat-induced toxicity in rat kidney. • β-Hydroxybutyrate inhibits lipid peroxidation and caspase-mediated apoptosis. • β-Hydroxybutyrate increases the activities of SOD and CAT. • The study describes a novel finding for the renoprotective ability of β-hydroxybutyrate. - Abstract: In this study, we demonstrated the protective effects of β-hydroxybutyrate (β-HB) against paraquat (PQ)-induced kidney injury and elucidated the underlying molecular mechanisms. By histological examination and renal dysfunction specific markers (serum BUN and creatinine) assay, β-HB could protect the PQ-induced kidney injury in rat. PQ-induced kidney injury is associated with oxidative stress, which was measured by increased lipid peroxidation (MDA) and decreased intracellular anti-oxidative abilities (SOD, CAT and GSH). β-HB pretreatment significantly attenuated that. Caspase-mediated apoptosis pathway contributed importantly to PQ toxicity, as revealed by the activation of caspase-9/-3, cleavage of PARP, and regulation of Bcl-2 and Bax, which were also effectively blocked by β-HB. Moreover, treatment of PQ strongly decreased the nuclear Nrf2 levels. However, pre-treatment with β-HB effectively suppressed this action of PQ. This may imply the important role of β-HB on Nrf2 pathway. Taken together, this study provides a novel finding that β-HB has a renoprotective ability against paraquat-induced kidney injury.

Impact of alcohol on male reproductive hormones, oxidative stress and semen parameters in Sprague–Dawley rats

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A.A. Oremosu

2015-06-01

Conclusion: Acute and chronic administration of alcohol depletes testosterone levels, increases oxidative stress and decreases semen parameters. This impact of alcohol on testosterone levels is mediated by direct testicular toxicity and by altering the hormone feedback system in the pituitary gland and the hypothalamus.

The Voltage-dependent Anion Channel 1 Mediates Amyloid β Toxicity and Represents a Potential Target for Alzheimer Disease Therapy.

Science.gov (United States)

Smilansky, Angela; Dangoor, Liron; Nakdimon, Itay; Ben-Hail, Danya; Mizrachi, Dario; Shoshan-Barmatz, Varda

2015-12-25

The voltage-dependent anion channel 1 (VDAC1), found in the mitochondrial outer membrane, forms the main interface between mitochondrial and cellular metabolisms, mediates the passage of a variety of molecules across the mitochondrial outer membrane, and is central to mitochondria-mediated apoptosis. VDAC1 is overexpressed in post-mortem brains of Alzheimer disease (AD) patients. The development and progress of AD are associated with mitochondrial dysfunction resulting from the cytotoxic effects of accumulated amyloid β (Aβ). In this study we demonstrate the involvement of VDAC1 and a VDAC1 N-terminal peptide (VDAC1-N-Ter) in Aβ cell penetration and cell death induction. Aβ directly interacted with VDAC1 and VDAC1-N-Ter, as monitored by VDAC1 channel conductance, surface plasmon resonance, and microscale thermophoresis. Preincubated Aβ interacted with bilayer-reconstituted VDAC1 and increased its conductance ∼ 2-fold. Incubation of cells with Aβ resulted in mitochondria-mediated apoptotic cell death. However, the presence of non-cell-penetrating VDAC1-N-Ter peptide prevented Aβ cellular entry and Aβ-induced mitochondria-mediated apoptosis. Likewise, silencing VDAC1 expression by specific siRNA prevented Aβ entry into the cytosol as well as Aβ-induced toxicity. Finally, the mode of Aβ-mediated action involves detachment of mitochondria-bound hexokinase, induction of VDAC1 oligomerization, and cytochrome c release, a sequence of events leading to apoptosis. As such, we suggest that Aβ-mediated toxicity involves mitochondrial and plasma membrane VDAC1, leading to mitochondrial dysfunction and apoptosis induction. The VDAC1-N-Ter peptide targeting Aβ cytotoxicity is thus a potential new therapeutic strategy for AD treatment. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Arsenite Oxidation Potential of Native Microbial Communities from Arsenic-Rich Freshwaters.

Science.gov (United States)

Fazi, Stefano; Crognale, Simona; Casentini, Barbara; Amalfitano, Stefano; Lotti, Francesca; Rossetti, Simona

2016-07-01

Microorganisms play an important role in speciation and mobility of arsenic in the environment, by mediating redox transformations of both inorganic and organic species. Since arsenite [As(III)] is more toxic than arsenate [As(V)] to the biota, the microbial driven processes of As(V) reduction and As(III) oxidation may play a prominent role in mediating the environmental impact of arsenic contamination. However, little is known about the ecology and dynamics of As(III)-oxidizing populations within native microbial communities exposed to natural high levels of As. In this study, two techniques for single cell quantification (i.e., flow cytometry, CARD-FISH) were used to analyze the structure of aquatic microbial communities across a gradient of arsenic (As) contamination in different freshwater environments (i.e., groundwaters, surface and thermal waters). Moreover, we followed the structural evolution of these communities and their capacity to oxidize arsenite, when experimentally exposed to high As(III) concentrations in experimental microcosms. Betaproteobacteria and Deltaproteobacteria were the main groups retrieved in groundwaters and surface waters, while Beta and Gammaproteobacteria dominated the bacteria community in thermal waters. At the end of microcosm incubations, the communities were able to oxidize up to 95 % of arsenite, with an increase of Alphaproteobacteria in most of the experimental conditions. Finally, heterotrophic As(III)-oxidizing strains (one Alphaproteobacteria and two Gammaproteobacteria) were isolated from As rich waters. Our findings underlined that native microbial communities from different arsenic-contaminated freshwaters can efficiently perform arsenite oxidation, thus contributing to reduce the overall As toxicity to the aquatic biota.

Role of oxidative stress and DNA hydroxymethylation in the neurotoxicity of fine particulate matter

International Nuclear Information System (INIS)

Wei, Hongying; Feng, Yan; Liang, Fan; Cheng, Wei; Wu, Xiaomeng; Zhou, Ren; Wang, Yan

2017-01-01

Highlights: • Oxidative stress-mediated neurocytotoxicity and DNA hydroxymethylation abnormalities involved in neuronal pathology of PM 2.5 . • PM 2.5 particles and toxic compounds adsorbed on the particle caused different types of neurocytotoxicity. • DNA hydroxymethylation abnormalities participated in PM 2.5 -induced impairments in neurite outgrowth and synapse formation. - Abstract: Epidemiological studies have implicated fine particulate matter (PM 2.5 ) as a risk factor for neurodegenerative diseases and neurodevelopmental disorders. However, the underlying molecular mechanisms and the influences of different components remain largely elusive. Here, we extended our previous work to investigate the role of oxidative stress and DNA hydroxymethylation in neuronal pathology of PM 2.5 . We found PM 2.5 and its extracts (water-soluble extracts, organic extracts and carbon core component) differentially caused cell cycle arrest, cell apoptosis and the cell proliferation inhibition in neuronal cells. These effects were mechanistically related to each other and oxidative stress, suggesting PM 2.5 and toxic compounds adsorbed on the particles may cause different types of brain damages. In addition, PM 2.5 and its organic extracts increased global DNA hydroxymethylation and gene-specific DNA hydroxymethylation of neuronal genes, and subsequently interfered with their mRNA expression. The impairments in neuronal progression characterized with decreased length of neurite and reduced mRNA expression of neuronal markers and synaptic markers. The blocking effects of antioxidants demonstrated the involvement of oxidative stress-mediated hydroxymethylation abnormalities in PM 2.5 -induced defects in neurite outgrowth and synapse formation. Our results first revealed the role of oxidative stress-mediated abnormal DNA hydroxymethylation in neuronal impairments of PM 2.5 , and thoroughly evaluated the neurocytotoxicity of different components.

Activation of Nrf2-mediated oxidative stress response in macrophages by hypochlorous acid

International Nuclear Information System (INIS)

Pi Jingbo; Zhang Qiang; Woods, Courtney G.; Wong, Victoria; Collins, Sheila; Andersen, Melvin E.

2008-01-01

Hypochlorous acid (HOCl), a potent oxidant generated when chlorine gas reacts with water, is important in the pathogenesis of many disorders. Transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism that serves to maintain intracellular redox homeostasis and limit oxidative damage. In the present study, the effect of HOCl on Nrf2 activation was investigated in macrophages, one of the target cells of chlorine gas exposure. Exposure of RAW 264.7 macrophages to HOCl resulted in increased protein levels of Nrf2 in nuclear extractions, as well as a time- and dose-dependent increase in the expression of Nrf2 target genes, including heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 (NQO-1), glutamate cysteine ligase catalytic subunit (GCLC), and glutathione synthetase (GS). Additionally, intracellular glutathione (GSH), which is the prime scavenger for HOCl in cells, decreased within the first hour of HOCl exposure. The decline was followed by a GSH rebound that surpassed the initial basal levels by up to 4-fold. This reversal in GSH levels closely correlated with the gene expression profile of GCLC and GS. To study the mechanisms of Nrf2 activation in response to HOCl exposure, we examined the effects of several antioxidants on Nrf2-mediated response. Pretreatment with cell-permeable catalase, N-acetyl-L-cysteine or GSH-monoethyl ester markedly reduced expression of NQO-1 and GCLC under HOCl challenge conditions, suggesting intracellular ROS-scavenging capacity affects HOCl-induced Nrf2 activation. Importantly, pre-activation of Nrf2 with low concentrations of pro-oxidants protected the cells against HOCl-induced cell damage. Taken together, we provide direct evidence that HOCl activates Nrf2-mediated antioxidant response, which protects cells from oxidative damage

An assessment of the role of redox cycling in mediating the toxicity of paraquat and nitrofurantoin

Energy Technology Data Exchange (ETDEWEB)

Adam, A.; Cohen, G.M. (Univ. of London (England)); Smith, L.L. (Imperial Chemical Industries plc, Cheshire (England))

1990-04-01

The abilities of paraquat, diquat, and nitrofurantoin to undergo cyclic oxidation and reduction with rat microsomal systems have been assessed and compared to that of the potent redox cycler, menadione. Diquat and menadione were found to be potent redox cyclers with comparable abilities to elicit a nonstoichiometric increase in both the consumption of O{sub 2} and the oxidation of NADPH, compared to the amounts of substrate added. In contrast, paraquat and nitrofurantoin redox cycled poorly, being an order of magnitude less potent than either diquat or menadione. This was reflected in kinetic studies using lung and liver microsomes. In order to assess redox cycling of the substrates in an intact lung system, the O{sub 2} consumption of rat lung slices was measured in the presence of all four compounds. A small increase in lung slice O{sub 2} uptake was observed with paraquat in the first 2.5 hr of incubation, possibly because of redox cycling of a high intracellular concentration of paraquat resulting from active accumulation into target cells. This stimulation in O{sub 2} uptake was no longer observed when slices were incubated for a longer period or with higher paraquat concentrations (10{sup {minus}4}M), possibly because of toxic effects in target cells. These results together with the poor ability to redox cycle with microsomes and the absence of a specific uptake system highlight the problem of associating redox cycling and oxidative stress in the mechanism of nitrofurantoin toxicity.

A combined toxicity study of zinc oxide nanoparticles and vitamin C in food additives.

Science.gov (United States)

Wang, Yanli; Yuan, Lulu; Yao, Chenjie; Ding, Lin; Li, Chenchen; Fang, Jie; Sui, Keke; Liu, Yuanfang; Wu, Minghong

2014-12-21

At present, safety evaluation standards for nanofood additives are made based on the toxic effects of a single additive. Since the size, surface properties and chemical nature influence the toxicity of nanomaterials, the toxicity may have dramatically changed when nanomaterials are used as food additives in a complex system. Herein, we investigated the combined toxicity of zinc oxide nanoparticles (ZnO NPs) and vitamin C (Vc, ascorbic acid). The results showed that Vc increased the cytotoxicity significantly compared with that of the ZnO only NPs. When the cells were exposed to ZnO NPs at a concentration less than 15 mg L(-1), or to Vc at a concentration less than 300 mg L(-1), there was no significant cytotoxicity, both in the case of gastric epithelial cell line (GES-1) and neural stem cells (NSCs). However, when 15 mg L(-1) of ZnO NPs and 300 mg L(-1) of Vc were introduced to cells together, the cell viability decreased sharply indicating significant cytotoxicity. Moreover, the significant increase in toxicity was also shown in the in vivo experiments. The dose of the ZnO NPs and Vc used in the in vivo study was calculated according to the state of food and nutrition enhancer standard. After repeated oral exposure to ZnO NPs plus Vc, the injury of the liver and kidneys in mice has been indicated by the change of these indices. These findings demonstrate that the synergistic toxicity presented in a complex system is essential for the toxicological evaluation and safety assessment of nanofood.

Assessment of protective and anti-oxidant properties of Tribulus terrestris fruits against testicular toxicity in rats

Science.gov (United States)

Shalaby, Mostafa Abbas; Hammouda, Ashraf Abd El-Khalik

2014-01-01

Aims: This study was carried out to assess the protective and anti-oxidant activities of the methanolic extract of Tribulus terrestris fruits (METT) against sodium valproate (SVP)-induced testicular toxicity in rats. Materials and Methods: Fifty mature male rats were randomly divided into five equal groups (n = 10). Group 1 was used normal (negative) control, and the other four groups were intoxicated with SVP (500 mg/kg–1, orally) during the last week of the experiment. Group 2 was kept intoxicated (positive) control, and Groups 3, 4 and 5 were orally pre-treated with METT in daily doses 2.5, 5.0, and 10.0 mg/kg–1 for 60 days, respectively. Weights of sexual organs, serum testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, semen picture, testicular anti-oxidant capacity and histopathology of testes were the parameters used in this study. Results: Oral pre-treatment with METT significantly increased weights of testes and seminal vesicles; serum testosterone, FSH and LH levels and sperm motility, count and viability in SVP-intoxicated rats. METT enhanced the activity of testicular anti-oxidant enzymes and partially alleviated degenerative changes induced by SVP in testes. Conclusion: The pre-treatment with METT has protective and anti-oxidant effects in SVP-intoxicated rats. Mechanisms of this protective effect against testicular toxicity may be due to the increased release of testosterone, FSH and LH and the enhanced tissue anti-oxidant capacity. These results affirm the traditional use of T. terrestris fruits as an aphrodisiac for treating male sexual impotency and erectile dysfunction in patients. The study recommends that T. terrestris fruits may be beneficial for male patients suffering from infertility. PMID:26401358

Assessment of protective and anti-oxidant properties of Tribulus terrestris fruits against testicular toxicity in rats.

Science.gov (United States)

Shalaby, Mostafa Abbas; Hammouda, Ashraf Abd El-Khalik

2014-01-01

This study was carried out to assess the protective and anti-oxidant activities of the methanolic extract of Tribulus terrestris fruits (METT) against sodium valproate (SVP)-induced testicular toxicity in rats. Fifty mature male rats were randomly divided into five equal groups (n = 10). Group 1 was used normal (negative) control, and the other four groups were intoxicated with SVP (500 mg/kg(-1), orally) during the last week of the experiment. Group 2 was kept intoxicated (positive) control, and Groups 3, 4 and 5 were orally pre-treated with METT in daily doses 2.5, 5.0, and 10.0 mg/kg(-1) for 60 days, respectively. Weights of sexual organs, serum testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, semen picture, testicular anti-oxidant capacity and histopathology of testes were the parameters used in this study. Oral pre-treatment with METT significantly increased weights of testes and seminal vesicles; serum testosterone, FSH and LH levels and sperm motility, count and viability in SVP-intoxicated rats. METT enhanced the activity of testicular anti-oxidant enzymes and partially alleviated degenerative changes induced by SVP in testes. The pre-treatment with METT has protective and anti-oxidant effects in SVP-intoxicated rats. Mechanisms of this protective effect against testicular toxicity may be due to the increased release of testosterone, FSH and LH and the enhanced tissue anti-oxidant capacity. These results affirm the traditional use of T. terrestris fruits as an aphrodisiac for treating male sexual impotency and erectile dysfunction in patients. The study recommends that T. terrestris fruits may be beneficial for male patients suffering from infertility.

Oxidative Stress and Antioxidants in Tomato (Solanum lycopersicum) Plants Subjected to Boron Toxicity

Science.gov (United States)

Cervilla, Luis M.; Blasco, Begoña; Ríos, Juan J.; Romero, Luis; Ruiz, Juan M.

2007-01-01

Background and Aims Boron (B) toxicity triggers the formation of reactive oxygen species in plant tissues. However, there is still a lack of knowledge as to how B toxicity affects the plant antioxidant defence system. It has been suggested that ascorbate could be important against B stress, although existing information is limited in this respect. The objective of this study was to analyse how ascorbate and some other components of the antioxidant network respond to B toxicity. Methods Two tomato (Solanum lycopersicum) cultivars (‘Kosaco’ and ‘Josefina’) were subjected to 0·05 (control), 0·5 and 2 mm B. The following were studied in leaves: dry weight; relative leaf growth rate; total and free B; H2O2; malondialdehyde; ascorbate; glutathione; sugars; total non-enzymatic antioxidant activity, and the activity of superoxide dismutase, catalase, ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, glutathione reductase, ascorbate oxidase and l-galactose dehydrogenase. Key Results The B-toxicity treatments diminished growth and boosted the amount of B, malondialdehyde and H2O2 in the leaves of the two cultivars, these trends being more pronounced in ‘Josefina’ than in ‘Kosaco’. B toxicity increased ascorbate concentration in both cultivars and increased glutathione only in ‘Kosaco’. Activities of antioxidant- and ascorbate-metabolizing enzymes were also induced. Conclusions High B concentration in the culture medium provokes oxidative damage in tomato leaves and induces a general increase in antioxidant enzyme activity. In particular, B toxicity increased ascorbate pool size. It also increased the activity of l-galactose dehydrogenase, an enzyme involved in ascorbate biosynthesis, and the activity of enzymes of the Halliwell–Asada cycle. This work therefore provides a starting point towards a better understanding of the role of ascorbate in the plant response against B stress. PMID:17660516

Bilirubin and its oxidation products damage brain white matter

Science.gov (United States)

Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

2014-01-01

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

Nitrotyrosine formation in splenic toxicity of aniline

International Nuclear Information System (INIS)

Khan, M. Firoze; Wu Xiaohong; Kaphalia, Bhupendra S.; Boor, Paul J.; Ansari, G.A.S.

2003-01-01

Splenic toxicity of aniline is characterized by vascular congestion, hyperplasia, fibrosis and development of a variety of sarcomas in rats. However, the mechanisms of this selective splenic toxicity are not well understood. Previously we showed that aniline exposure causes oxidative damage to spleen. To further explore the oxidative mechanisms of aniline toxicity, we evaluated the contributions of nitric oxide. Nitric oxide reacts with superoxide anion to form peroxynitrite, a powerful oxidant that converts the tyrosine residues of proteins to nitrotyrosine (NT). Therefore, aim of this study was to establish the role of nitric oxide through the formation and localization of NT in the spleen of rats exposed to aniline. Male Sprague-Dawley (SD) rats were given 1 mmol/kg per day aniline hydrochloride in water by gavage for 7 days, while the controls received water only. Immunohistochemical analysis for NT showed an intense staining in the red pulp areas of spleen from aniline-treated rats, localized in macrophages and sinusoidal cells. Occasionally mild NT immunostaining was also evident in the white pulp. Western blot analyses of the post-nuclear fraction of the spleens showed major nitrated proteins with molecular weights of 49, 30 and 18 kDa. Immunohistochemical analysis of inducible nitric oxide synthase (iNOS) also showed increased expression in the red pulp of the spleens from aniline-treated rats; the cellular localization was similar to nitrated proteins. These studies suggest that oxidative stress in aniline toxicity also includes aberration in nitric oxide production leading to nitration of proteins. Functional consequences of such nitration will further elucidate the contribution of nitric oxide to the splenic toxicity of aniline

Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

Energy Technology Data Exchange (ETDEWEB)

Buehler, Paul W.; Butt, Omer I. [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); D' Agnillo, Felice, E-mail: felice.dagnillo@fda.hhs.gov [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

2011-06-10

Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

Role of Inflammation and Oxidative Stress Mediators in Gliomas

Directory of Open Access Journals (Sweden)

Alfredo Conti

2010-04-01

Full Text Available Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

Role of Inflammation and Oxidative Stress Mediators in Gliomas

Energy Technology Data Exchange (ETDEWEB)

Conti, Alfredo, E-mail: alfredo.conti@unime.it; Gulì, Carlo; La Torre, Domenico; Tomasello, Chiara; Angileri, Filippo F.; Aguennouz, M’Hammed [Department of Neuroscience and Department of Oncology, University of Messina, Policlinico Universitario, Via Consolare Valeria 1, 98125, Messina (Italy)

2010-04-26

Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

Role of Inflammation and Oxidative Stress Mediators in Gliomas

International Nuclear Information System (INIS)

Conti, Alfredo; Gulì, Carlo; La Torre, Domenico; Tomasello, Chiara; Angileri, Filippo F.; Aguennouz, M’Hammed

2010-01-01

Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment

Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

Directory of Open Access Journals (Sweden)

Radha Ananthakrishnan

2013-10-01

Full Text Available Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease.

Mediated electrochemical oxidation as an alternative to incineration for mixed wastes

International Nuclear Information System (INIS)

Chiba, Z.; Schumacher, B.; Lewis, P.; Murguia, L.

1995-02-01

Mediated Electrochemical Oxidation (MEO) is an aqueous process which oxidizes organics electrochemically at low temperatures and ambient pressures. The process can be used to treat mixed wastes containing hazardous organics by destroying the organic components of the wastes. The radioactive components of the wastes are dissolved in the electrolyte where they can be recovered if desired, or immobilized for disposal. The process of destroying organics is accomplished via a mediator, which is in the form of metallic ions in solution. At Lawrence Livermore National Laboratory (LLNL) we have worked with worked with several mediators, including silver, cobalt and cerium. We have tested mediators in nitric as well as sulfuric acids. We have recently completed extensive experimental studies on cobalt-sulfuric acid and silver-nitric acid systems for destroying the major organic components of Rocky Flats Plant combustible mixed wastes. Organics tested were: Trimsol (a cutting oil), cellulose (including paper and cloth), rubber (latex), plastics (Tyvek, polyethylene and polyvinyl chloride) and biomass (bacteria). The process was capable of destroying almost all of the organics tested, attaining high destruction efficiencies at reasonable coulombic efficiencies. The only exception was polyvinyl chloride, which was destroyed very slowly resulting in poor coulombic efficiencies. Besides the process development work mentioned above, we are working on the design of a pilot-plant scale integrated system to be installed in the Mixed Waste Management Facility (MWMF) at LLNL. The system will also be completely integrated with upstream and downstream processes (for example, feed preparation, off-gas and water treatment, and final forms encapsulation). The conceptual design for the NEO-MWMF system has been completed and preliminary design work has been initiated. Demonstration of the process with low-level mixed wastes is expected to commence in 1998

Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats

Directory of Open Access Journals (Sweden)

Nalabotu SK

2011-10-01

Full Text Available Siva K Nalabotu1,2, Madhukar B Kolli1,2, William E Triest3,4, Jane Y Ma5, Nandini DPK Manne2,6, Anjaiah Katta1,2, Hari S Addagarla2, Kevin M Rice2,6–8, Eric R Blough1,2,6,7,91Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C Edwards School of Medicine; 2Center for Diagnostic Nanosystems, Marshall University; 3Pathology and Laboratory Medicine Service, Veterans Affairs Medical Center; 4Section of Pathology, Department of Anatomy and Pathology, Joan C Edwards School of Medicine, Marshall University, Huntington; 5Health Effects Laboratory Division, NIOSH, Morgantown; 6Department of Biological Sciences; 7School of Kinesiology, College of Health Professions, Marshall University; 8Biotechnology Department, West Virginia State University; 9Department of Cardiology, Joan C Edwards School of Medicine, Marshall University Huntington, WV, USABackground: Cerium oxide (CeO2 nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats.Methods and results: Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05. Consistent with these data, rats exposed to CeO2 nanoparticles also exhibited reductions in liver weight (P < 0.05 and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO2 nanoparticles.Conclusion: Taken together, these data suggest that

Surface ligand dependent toxicity of zinc oxide nanoparticles in HepG2 cell model

International Nuclear Information System (INIS)

Bartczak, D; Baradez, M-O; Merson, S; Goenaga-Infante, H; Marshall, D

2013-01-01

Physicochemical properties of nanoparticles (NP) strongly affect their influence on cell behaviour, but can be significantly distorted by interactions with the proteins present in biological solutions. In this study we show how different surface functionalities of zinc oxide (ZnO) NP lead to changes in the size distribution and dissolution of the NP in serum containing cell culture media and how this impacts on NP toxicity. NPs capped with weakly bound large proteins undergo substantial transformations due to the exchange of the original surface ligands to the components of the cell culture media. Conversely, NP capped with a tight monolayer of small organic molecules or with covalently conjugated proteins show significantly higher stability. These differences in ligand exchange also affect the toxicity of the NP to the HepG2 liver cell model, with the NP capped with small organic molecules being more toxic than those capped with large proteins. This study highlights the importance of characterising NPs in biological media and the effect the media has during in-vitro analysis.

Electron Transfer Mediator Effects in Water Oxidation Catalysis by Solution and Surface-Bound Ruthenium Bpy-Dicarboxylate Complexes

Energy Technology Data Exchange (ETDEWEB)

Sheridan, Matthew V.; Sherman, Benjamin D.; Marquard, Seth L.; Fang, Zhen; Ashford, Dennis L.; Wee, Kyung-Ryang; Gold, Alexander S.; Alibabaei, Leila; Rudd, Jennifer A.; Coggins, Michael K.; Meyer, Thomas J.

2015-11-12

Electrocatalytic water oxidation by the catalyst, ruthenium 2,2'-bipyridine-6,6'-dicarboxylate (bda) bis-isoquinoline (isoq), [Ru(bda)(isoq)₂], 1, was investigated at metal oxide electrodes surface-derivatized with electron transfer (ET) mediators. At indium-doped tin oxide (ITO) in pH 7.2 in H₂PO₄–/HPO₄²– buffers in 0.5 M NaClO₄ with added acetonitrile (MeCN), the catalytic activity of 1 is enhanced by the surface-bound redox mediators [Ru (4,4'-PO₃H₂-bpy)(4,4'-R-bpy)₂]²⁺ (RuPbpyR₂²⁺, R = Br, H, Me, or OMe, bpy = 2,2'-bipyridine). Rate-limiting ET between the Ru³⁺ form of the mediator and the Ru^IV(O) form in the [Ru^V/IV(O)]^+/0 couple of 1 is observed at relatively high concentrations of HPO₄^2– buffer base under conditions where O···O bond formation is facilitated by atom-proton transfer (APT). For the solution [Ru(bpy)₃]^3+/2+ mediator couple and 1 as the catalyst, catalytic currents vary systematically with the concentration of mediator and the HPO₄^2– buffer base concentration. Electron transfer mediation of water oxidation catalysis was also investigated on nanoparticle TiO₂ electrodes co-loaded with catalyst [Ru(bda)(py-4-O(CH₂)₃-PO₃H₂)₂], 2, (py = pyridine) and RuPbpyR₂²⁺ (R = H, Me, or OMe) with an interplay between rate-limiting catalyst oxidation and rate-limiting O···O bond formation by APT. Lastly, the co-loaded assembly RuPbpyR₂²⁺ + 2 has been investigated in a dye-sensitized photoelectrosynthesis cell for water splitting.

Proteus mirabilis alleviates zinc toxicity by preventing oxidative stress in maize (Zea mays) plants.

Science.gov (United States)

Islam, Faisal; Yasmeen, Tahira; Riaz, Muhammad; Arif, Muhammad Saleem; Ali, Shafaqat; Raza, Syed Hammad

2014-12-01

Plant-associated bacteria can have beneficial effects on the growth and health of their host. However, the role of plant growth promoting bacteria (PGPR), under metal stress, has not been widely investigated. The present study investigated the possible mandatory role of plant growth promoting rhizobacteria in protecting plants from zinc (Zn) toxicity. The exposure of maize plants to 50µM zinc inhibited biomass production, decreased chlorophyll, total soluble protein and strongly increased accumulation of Zn in both root and shoot. Similarly, Zn enhanced hydrogen peroxide, electrolyte leakage and lipid peroxidation as indicated by malondaldehyde accumulation. Pre-soaking with novel Zn tolerant bacterial strain Proteus mirabilis (ZK1) isolated zinc (Zn) contaminated soil, alleviated the negative effect of Zn on growth and led to a decrease in oxidative injuries caused by Zn. Furthermore, strain ZK1 significantly enhanced the activities of catalase, guaiacol peroxidase, superoxide dismutase and ascorbic acid but lowered the Proline accumulation in Zn stressed plants. The results suggested that the inoculation of Zea mays plants with P. mirabilis during an earlier growth period could be related to its plant growth promoting activities and avoidance of cumulative damage upon exposure to Zn, thus reducing the negative consequences of oxidative stress caused by heavy metal toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Toxicity of thallium on isolated rat liver mitochondria: the role of oxidative stress and MPT pore opening.

Science.gov (United States)

Eskandari, M R; Mashayekhi, Vida; Aslani, Majid; Hosseini, Mir-Jamal

2015-02-01

Thallium(I) is a highly toxic heavy metal; however, up to now, its mechanisms are poorly understood. The authors' previous studies showed that this compound could induce reactive oxygen species (ROS) formation, reduced glutathione (GSH) oxidation, membrane lipid peroxidation, and mitochondrial membrane potential (MMP) collapse in isolated rat hepatocyte. Because the liver is the storage site of thallium, it seems that the liver mitochondria are one of the important targets for hepatotoxicity. In this investigation, the effects of thallium on mitochondria were studied to investigate its mechanisms of toxicity. Mitochondria were isolated from rat liver and incubated with different concentrations of thallium (25-200 µM). Thallium(I)-treated mitochondria showed a marked elevation in oxidative stress parameters accompanied by MMP collapse when compared with the control group. These results showed that different concentrations of thallium (25-200 µM) induced a significant (P thallium(I)-induced liver toxicity is a result of the disruptive effect of this metal on the mitochondrial respiratory complexes (I, II, and IV), which are the obvious causes of metal-induced ROS formation and ATP depletion. The latter two events, in turn, trigger cell death signaling via opening of mitochondrial permeability transition pore and cytochrome c expulsion. © 2013 Wiley Periodicals, Inc.

Degradation of lipid regulators by the UV/chlorine process: Radical mechanisms, chlorine oxide radical (ClO•)-mediated transformation pathways and toxicity changes.

Science.gov (United States)

Kong, Xiujuan; Wu, Zihao; Ren, Ziran; Guo, Kaiheng; Hou, Shaodong; Hua, Zhechao; Li, Xuchun; Fang, Jingyun

2018-06-15

Degradation of three lipid regulators, i.e., gemfibrozil, bezafibrate and clofibric acid, by a UV/chlorine treatment was systematically investigated. The chlorine oxide radical (ClO • ) played an important role in the degradation of gemfibrozil and bezafibrate with second-order rate constants of 4.2 (±0.3) × 10 8  M -1  s -1 and 3.6 (±0.1) × 10 7  M -1  s -1 , respectively, whereas UV photolysis and the hydroxyl radical (HO • ) mainly contributed to the degradation of clofibric acid. The first-order rate constants (k') for the degradation of gemfibrozil and bezafibrate increased linearly with increasing chlorine dosage, primarily due to the linear increase in the ClO • concentration. The k' values for gemfibrozil, bezafibrate, and clofibric acid degradation decreased with increasing pH from 5.0 to 8.4; however, the contribution of the reactive chlorine species (RCS) increased. Degradation of gemfibrozil and bezafibrate was enhanced in the presence of Br - , whereas it was inhibited in the presence of natural organic matter (NOM). The presence of ammonia at a chlorine: ammonia molar ratio of 1:1 resulted in decreases in the k' values for gemfibrozil and bezafibrate of 69.7% and 7%, respectively, but led to an increase in that for clofibric acid of 61.8%. Degradation of gemfibrozil by ClO • was initiated by hydroxylation and chlorine substitution on the benzene ring. Then, subsequent hydroxylation, bond cleavage and chlorination reactions led to the formation of more stable products. Three chlorinated intermediates were identified during ClO • oxidation process. Formation of the chlorinated disinfection by-products chloral hydrate and 1,1,1-trichloropropanone was enhanced relative to that of other by-products. The acute toxicity of gemfibrozil to Vibrio fischeri increased significantly when subjected to direct UV photolysis, whereas it decreased when oxidized by ClO • . This study is the first to report the transformation pathway of a

In Vitro Ion Chelating, Antioxidative Mechanism of Extracts from Fruits and Barks of Tetrapleura tetraptera and Their Protective Effects against Fenton Mediated Toxicity of Metal Ions on Liver Homogenates

Directory of Open Access Journals (Sweden)

Bruno Moukette Moukette

2015-01-01

Full Text Available The aim of the present study was to investigate the antioxidant activity and protective potential of T. tetraptera extracts against ion toxicity. The antioxidant activity of the extracts was investigated spectrophotometrically against several radicals (1,1-diphenyl-2-picrylhydrazyl (DPPH•, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS•, hydroxyl radical (HO•, and nitric oxide (NO•, followed by the ferric reducing power, total phenols, flavonoid, and flavonol contents. The effects of the extracts on catalase (CAT, superoxide dismutase (SOD, and peroxidase activities were also determined using the standard methods as well as the polyphenol profile using HPLC. The results showed that the hydroethanolic extract of T. tetraptera (CFH has the lowest IC50 value with the DPPH, ABTS, OH, and NO radicals. The same extract also exhibited the significantly higher level of total phenols (37.24 ± 2.00 CAE/g dried extract; flavonoids (11.36 ± 1.88 QE/g dried extract; and flavonols contents (3.95 ± 0.39 QE/g dried extract. The HPLC profile of T. tetraptera revealed that eugenol (958.81 ± 00 mg/g DW, quercetin (353.78 ± 00 mg/g DW, and rutin (210.54 ± 00 mg/g DW were higher in the fruit than the bark extracts. In conclusion, extracts from T. tetraptera may act as a protector against oxidative mediated ion toxicity.

Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

Energy Technology Data Exchange (ETDEWEB)

Sharma, Bhupesh, E-mail: drbhupeshresearch@gmail.com; Sharma, P.M.

2013-11-15

Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment of learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good potential

Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

International Nuclear Information System (INIS)

Sharma, Bhupesh; Sharma, P.M.

2013-01-01

Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment of learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good potential in

Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma

NARCIS (Netherlands)

Maarsingh, H; Leusink, J; Bos, I Sophie T; Zaagsma, J; Meurs, H

2006-01-01

Background: Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO) production - due to competition with neuronal

Monascin from Monascus-Fermented Products Reduces Oxidative Stress and Amyloid-β Toxicity via DAF-16/FOXO in Caenorhabditis elegans.

Science.gov (United States)

Shi, Yeu-Ching; Pan, Tzu-Ming; Liao, Vivian Hsiu-Chuan

2016-09-28

Amyloid-β (Aβ)-induced oxidative stress and toxicity are leading risk factors for Alzheimer's disease (AD). Monascin (MS) is a novel compound proposed for antioxidative stress applications and is derived from an edible fungus secondary metabolite. This study assessed the effects of MS on oxidative stress, paralysis, Aβ accumulation, and lifespan in the nematode Caenorhabditis elegans and investigated its underlying mechanisms of action. The results showed that MS increased the survival of C. elegans under juglone-induced oxidative stress and attenuated endogenous levels of reactive oxygen species. Furthermore, MS induced a decline in Aβ-induced paralysis phenotype and Aβ deposits in the transgenic strains CL4176 and CL2006 of C. elegans, which expresses human muscle-specific Aβ1-42 in the cytoplasm of body wall muscle cells. In addition, mRNA levels of strain CL4176 of several antioxidant genes (sod-1, sod-2, sod-3, hsp16.2) and daf-16 were up-regulated by MS treatment when compared to the nontreated controls. Further evidence showed that MS treatment in C. elegans strains lacking DAF-16/FOXO did not affect paralysis or lifespan phenotypes. The findings indicate that MS reduces oxidative stress and Aβ toxicity via DAF-16 in C. elegans, suggesting that MS can be used for the prevention of AD-associated oxidative stress complications.

Alleviation of nickel toxicity in finger millet (Eleusine coracana L. germinating seedlings by exogenous application of salicylic acid and nitric oxide

Directory of Open Access Journals (Sweden)

Kasi Viswanath Kotapati

2017-06-01

Full Text Available This study investigated the effect of salicylic acid (SA and sodium nitroprusside (SNP; NO donor on nickel (Ni toxicity in germinating finger millet seedlings. Fourteen-day-old finger millet plants were subjected to 0.5 mmol L−1 Ni overload and treated with 0.2 mmol L−1 salicylic acid and 0.2 mmol L−1 sodium nitroprusside to lessen the toxic effect of Ni. The Ni overload led to high accumulation in the roots of growing plants compared to shoots, causing oxidative stress. It further reduced root and shoot length, dry mass, total chlorophyll, and mineral content. Exogenous addition of either 0.2 mmol L−1 SA or 0.2 mmol L−1 SNP reduced the toxic effect of Ni, and supplementation with both SA and SNP significantly reduced the toxic effect of Ni and increased root and shoot length, chlorophyll content, dry mass, and mineral concentration in Ni-treated plants. The results show that oxidative stress can be triggered in finger millet plants by Ni stress by induction of lipoxygenase activity, increase in levels of proline, O2•− radical, MDA, and H2O2, and reduction in the activity of antioxidant enzymes such as CAT, SOD, and APX in shoots and roots. Exogenous application of SA or SNP, specifically the combination of SA + SNP, protects finger millet plants from oxidative stress observed under Ni treatment.

Synthesis of Monodispersed Tantalum(V) oxide Nanospheres by an Ethylene Glycol Mediated Route

Science.gov (United States)

Tantalum(V) oxide (Ta2O5) nanospheres have been synthesized by a very simple ethylene glycol mediated route. The two-step process involves the formation of glycolate nanoparticles and their subsequent hydrolysis and calcination to generate the final Ta2O5 nanospheres. The synthes...

Computational consideration on advanced oxidation degradation of phenolic preservative, methylparaben, in water: mechanisms, kinetics, and toxicity assessments

Energy Technology Data Exchange (ETDEWEB)

Gao, Yanpeng [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); An, Taicheng, E-mail: antc99@gig.ac.cn [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Fang, Hansun [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Ji, Yuemeng; Li, Guiying [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China)

2014-08-15

Graphical abstract: - Highlights: • Computational approach is effective to reveal the transformation mechanism of MPB. • MPB degradation was more dependent on the [{sup •} OH] than temperature during AOPs. • O{sub 2} could enhance MPB degradation, but more harmful products were formed. • The risks of MPB products in natural waters should be considered seriously. • The risks of MPB products can be overlooked in AOPs due to short half-time. - Abstract: Hydroxyl radicals ({sup •} OH) are strong oxidants that can degrade organic pollutants in advanced oxidation processes (AOPs). The mechanisms, kinetics, and toxicity assessment of the {sup •} OH-initiated oxidative degradation of the phenolic preservative, methylparaben (MPB), were systematically investigated using a computational approach, as the supplementary information for experimental data. Results showed that MPB can be initially attacked by {sup •} OH via OH-addition and H-abstraction routes. Among these routes, the {sup •} OH addition to the C atom at the ortho-position of phenolic hydroxyl group was the most significant route. However, the methyl-H-abstraction route also cannot be neglected. Further, the formed transient intermediates, OH-adduct ({sup •} MPB-OH{sub 1}) and dehydrogenated radical ({sup •} MPB(-H)α), could be easily transformed to several stable degradation products in the presence of O{sub 2} and {sup •} OH. To better understand the potential toxicity of MPB and its products to aquatic organisms, both acute and chronic toxicities were assessed computationally at three trophic levels. Both MPB and its products, particularly the OH-addition products, are harmful to aquatic organisms. Therefore, the application of AOPs to remove MPB should be carefully performed for safe water treatment.

Toxicity assessment and comparison between two types of iron oxide nanoparticles in Mytilus galloprovincialis

Energy Technology Data Exchange (ETDEWEB)

Taze, Chrysa; Panetas, Ioannis [Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Kalogiannis, Stavros [Alexander Technological Educational Institution of Thessaloniki, Department of Nutrition and Dietetics, Thessaloniki (Greece); Feidantsis, Konstantinos [Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Gallios, George P. [Laboratory of General & Inorganic Chemical Technology, School of Chemistry, Aristotle University, GR-54124 Thessaloniki (Greece); Kastrinaki, Georgia [Aerosol & Particle Technology Laboratory, CERTH/CPERI, P.O. Box 60361, 57001 Thessaloniki (Greece); Konstandopoulos, Athanasios G. [Aerosol & Particle Technology Laboratory, CERTH/CPERI, P.O. Box 60361, 57001 Thessaloniki (Greece); Department of Chemical Engineering, Aristotle University, PO. Box 1517, 54006 Thessaloniki (Greece); Václavíková, Miroslava; Ivanicova, Lucia [Institute of Geotechnics, Slovak Academy of Sciences, Watsonova 45, SK-04001 Kosice (Slovakia); Kaloyianni, Martha, E-mail: kaloyian@bio.auth.gr [Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)

2016-03-15

Highlights: • The impact of two types of iron oxide nanoparticles on the physiological status of mussels was studied. • Oxidative parameters significantly changed after 1, 3, 7 days of exposure. • The nanoparticles induced oxidative stress to the animals. • All the parameters measured could be applied in biomonitoring studies. - Abstract: Nanoparticles (NPs), due to their increased application and production, are being released into the environment with unpredictable impact on the physiology of marine organisms, as well as on entire ecosystems and upcoming effects on human health. The aim of the present study was to evaluate and compare the oxidative responses of the mussel Mytilus galloprovincialis after exposure to iron oxide NPs and to iron oxide NPs incorporated into zeolite for 1, 3 and 7 days. Our results showed that both effectors induced changes on animal physiology by causing oxidative stress in hemocytes of exposed mussels compared to control animals. This was shown by the significant increase in reactive oxygen species (ROS) production, protein carbonylation, lipid peroxidation, ubiquitin conjugates and DNA damage. In addition an increase in prooxidant levels as measured by the prooxidant-antioxidant balance (PAB) assay was observed in exposed mussels’ hemolymph. The results show that ROS, DNA damage, protein and lipid oxidation, ubiquitin conjugates and PAB could constitute, after further investigation, reliable biomarkers for the evaluation of pollution or other environmental stressors. In addition, more studies are needed in order to ensure the safety of these NPs on various biomedical applications, since it is critical to design NPs that they meet the demands of application without causing cellular toxicity.

Toxicity assessment and comparison between two types of iron oxide nanoparticles in Mytilus galloprovincialis

International Nuclear Information System (INIS)

Taze, Chrysa; Panetas, Ioannis; Kalogiannis, Stavros; Feidantsis, Konstantinos; Gallios, George P.; Kastrinaki, Georgia; Konstandopoulos, Athanasios G.; Václavíková, Miroslava; Ivanicova, Lucia; Kaloyianni, Martha

2016-01-01

Highlights: • The impact of two types of iron oxide nanoparticles on the physiological status of mussels was studied. • Oxidative parameters significantly changed after 1, 3, 7 days of exposure. • The nanoparticles induced oxidative stress to the animals. • All the parameters measured could be applied in biomonitoring studies. - Abstract: Nanoparticles (NPs), due to their increased application and production, are being released into the environment with unpredictable impact on the physiology of marine organisms, as well as on entire ecosystems and upcoming effects on human health. The aim of the present study was to evaluate and compare the oxidative responses of the mussel Mytilus galloprovincialis after exposure to iron oxide NPs and to iron oxide NPs incorporated into zeolite for 1, 3 and 7 days. Our results showed that both effectors induced changes on animal physiology by causing oxidative stress in hemocytes of exposed mussels compared to control animals. This was shown by the significant increase in reactive oxygen species (ROS) production, protein carbonylation, lipid peroxidation, ubiquitin conjugates and DNA damage. In addition an increase in prooxidant levels as measured by the prooxidant-antioxidant balance (PAB) assay was observed in exposed mussels’ hemolymph. The results show that ROS, DNA damage, protein and lipid oxidation, ubiquitin conjugates and PAB could constitute, after further investigation, reliable biomarkers for the evaluation of pollution or other environmental stressors. In addition, more studies are needed in order to ensure the safety of these NPs on various biomedical applications, since it is critical to design NPs that they meet the demands of application without causing cellular toxicity.

Toxicity of nano- and micro-sized silver particles in human hepatocyte cell line L02

International Nuclear Information System (INIS)

Liu Pengpeng; Guan Rongfa; Jiang Jiaxin; Liu Mingqi; Huang Guangrong; Chen Xiaoting; Ye Xingqian

2011-01-01

Silver nanoparticles (Ag NPs) previously classified as antimicrobial agents have been widely used in consumers and industrial products, especially food storage material. Ag NPs used as antimicrobial agents may be found in liver. Thus, examination of the ability of Ag NPs to penetrate the liver is warranted. The aim of the study was to determine the optimal viability assay for using with Ag NPs in order to assess their toxicity to liver cells. For toxicity evaluations, cellular morphology, mitochondrial function (3-(4, 5-dimethylazol-2-yl)-2, 5-diphenyl-tetrazolium bromide, MTT assay), membrane leakage of lactate dehydrogenase (lactate dehydrogenase, LDH release assay), Oxidative stress markers (malonaldehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)), DNA damage (single cell gel eletrophoresis, SCGE assay), and protein damage were assessed under control and exposed conditions (24 h of exposure). The results showed that mitochondrial function decreased significantly in cells exposed to Ag NPs at 25 μg·mL -1 . LDH leakage significantly increased in cells exposed to Ag NPs (≥ 25 μg mL -1 ) while micro-sized silver particles tested displayed LDH leakage only at higher doses (100 μg·mL -1 ). The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, increase in SOD levels and lead to lipid peroxidation, which suggested that cytotoxicity of Ag NPs in liver cells might be mediated through oxidative stress. The results demonstrates that Ag NPs lead to cellular morphological modifications, LDH leakage, mitochondrial dysfunction, and cause increased generation of ROS, depletion of GSH, lipid peroxidation, oxidative DNA damage and protein damage. Though the exact mechanism behind Ag NPs

Toxicity of nano- and micro-sized silver particles in human hepatocyte cell line L02

Science.gov (United States)

Liu, Pengpeng; Guan, Rongfa; Ye, Xingqian; Jiang, Jiaxin; Liu, Mingqi; Huang, Guangrong; Chen, Xiaoting

2011-07-01

Silver nanoparticles (Ag NPs) previously classified as antimicrobial agents have been widely used in consumers and industrial products, especially food storage material. Ag NPs used as antimicrobial agents may be found in liver. Thus, examination of the ability of Ag NPs to penetrate the liver is warranted. The aim of the study was to determine the optimal viability assay for using with Ag NPs in order to assess their toxicity to liver cells. For toxicity evaluations, cellular morphology, mitochondrial function (3-(4, 5-dimethylazol-2-yl)-2, 5-diphenyl-tetrazolium bromide, MTT assay), membrane leakage of lactate dehydrogenase (lactate dehydrogenase, LDH release assay), Oxidative stress markers (malonaldehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)), DNA damage (single cell gel eletrophoresis, SCGE assay), and protein damage were assessed under control and exposed conditions (24 h of exposure). The results showed that mitochondrial function decreased significantly in cells exposed to Ag NPs at 25 μg·mL-1. LDH leakage significantly increased in cells exposed to Ag NPs (>= 25 μg mL-1) while micro-sized silver particles tested displayed LDH leakage only at higher doses (100 μg·mL-1). The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, increase in SOD levels and lead to lipid peroxidation, which suggested that cytotoxicity of Ag NPs in liver cells might be mediated through oxidative stress. The results demonstrates that Ag NPs lead to cellular morphological modifications, LDH leakage, mitochondrial dysfunction, and cause increased generation of ROS, depletion of GSH, lipid peroxidation, oxidative DNA damage and protein damage. Though the exact mechanism behind Ag NPs

Toxicity of nano- and micro-sized silver particles in human hepatocyte cell line L02

Energy Technology Data Exchange (ETDEWEB)

Liu Pengpeng; Guan Rongfa; Jiang Jiaxin; Liu Mingqi; Huang Guangrong; Chen Xiaoting [Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, College of Life Sciences, China Jiliang University, Hangzhou 310018 (China); Ye Xingqian, E-mail: rfguan@163.com [Department of Food Science and Nutrition, School of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310029 (China)

2011-07-06

Silver nanoparticles (Ag NPs) previously classified as antimicrobial agents have been widely used in consumers and industrial products, especially food storage material. Ag NPs used as antimicrobial agents may be found in liver. Thus, examination of the ability of Ag NPs to penetrate the liver is warranted. The aim of the study was to determine the optimal viability assay for using with Ag NPs in order to assess their toxicity to liver cells. For toxicity evaluations, cellular morphology, mitochondrial function (3-(4, 5-dimethylazol-2-yl)-2, 5-diphenyl-tetrazolium bromide, MTT assay), membrane leakage of lactate dehydrogenase (lactate dehydrogenase, LDH release assay), Oxidative stress markers (malonaldehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)), DNA damage (single cell gel eletrophoresis, SCGE assay), and protein damage were assessed under control and exposed conditions (24 h of exposure). The results showed that mitochondrial function decreased significantly in cells exposed to Ag NPs at 25 {mu}g{center_dot}mL{sup -1}. LDH leakage significantly increased in cells exposed to Ag NPs ({>=} 25 {mu}g mL{sup -1}) while micro-sized silver particles tested displayed LDH leakage only at higher doses (100 {mu}g{center_dot}mL{sup -1}). The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, increase in SOD levels and lead to lipid peroxidation, which suggested that cytotoxicity of Ag NPs in liver cells might be mediated through oxidative stress. The results demonstrates that Ag NPs lead to cellular morphological modifications, LDH leakage, mitochondrial dysfunction, and cause increased generation of ROS, depletion of GSH, lipid peroxidation, oxidative DNA damage and protein damage

Molecular toxicity mechanism of nanosilver

Directory of Open Access Journals (Sweden)

Danielle McShan

2014-03-01

Full Text Available Silver is an ancient antibiotic that has found many new uses due to its unique properties on the nanoscale. Due to its presence in many consumer products, the toxicity of nanosilver has become a hot topic. This review summarizes recent advances, particularly the molecular mechanism of nanosilver toxicity. The surface of nanosilver can easily be oxidized by O2 and other molecules in the environmental and biological systems leading to the release of Ag+, a known toxic ion. Therefore, nanosilver toxicity is closely related to the release of Ag+. In fact, it is difficult to determine what portion of the toxicity is from the nano-form and what is from the ionic form. The surface oxidation rate is closely related to the nanosilver surface coating, coexisting molecules, especially thiol-containing compounds, lighting conditions, and the interaction of nanosilver with nucleic acids, lipid molecules, and proteins in a biological system. Nanosilver has been shown to penetrate the cell and become internalized. Thus, nanosilver often acts as a source of Ag+ inside the cell. One of the main mechanisms of toxicity is that it causes oxidative stress through the generation of reactive oxygen species and causes damage to cellular components including DNA damage, activation of antioxidant enzymes, depletion of antioxidant molecules (e.g., glutathione, binding and disabling of proteins, and damage to the cell membrane. Several major questions remain to be answered: (1 the toxic contribution from the ionic form versus the nano-form; (2 key enzymes and signaling pathways responsible for the toxicity; and (3 effect of coexisting molecules on the toxicity and its relationship to surface coating.

Prenatal development toxicity study of zinc oxide nanoparticles in rats

Directory of Open Access Journals (Sweden)

Hong JS

2014-12-01

Full Text Available Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+ NPs] zinc oxide nanoparticles, positively charged, 20 nm on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+ NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%; resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after

Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa.

Science.gov (United States)

Gurunathan, Sangiliyandi; Han, Jae Woong; Dayem, Ahmed Abdal; Eppakayala, Vasuki; Kim, Jin-Hoi

2012-01-01

Graphene holds great promise for potential use in next-generation electronic and photonic devices due to its unique high carrier mobility, good optical transparency, large surface area, and biocompatibility. The aim of this study was to investigate the antibacterial effects of graphene oxide (GO) and reduced graphene oxide (rGO) in Pseudomonas aeruginosa. In this work, we used a novel reducing agent, betamercaptoethanol (BME), for synthesis of graphene to avoid the use of toxic materials. To uncover the impacts of GO and rGO on human health, the antibacterial activity of two types of graphene-based material toward a bacterial model P. aeruginosa was studied and compared. The synthesized GO and rGO was characterized by ultraviolet-visible absorption spectroscopy, particle-size analyzer, X-ray diffraction, scanning electron microscopy and Raman spectroscopy. Further, to explain the antimicrobial activity of graphene oxide and reduced graphene oxide, we employed various assays, such as cell growth, cell viability, reactive oxygen species generation, and DNA fragmentation. Ultraviolet-visible spectra of the samples confirmed the transition of GO into graphene. Dynamic light-scattering analyses showed the average size among the two types of graphene materials. X-ray diffraction data validated the structure of graphene sheets, and high-resolution scanning electron microscopy was employed to investigate the morphologies of prepared graphene. Raman spectroscopy data indicated the removal of oxygen-containing functional groups from the surface of GO and the formation of graphene. The exposure of cells to GO and rGO induced the production of superoxide radical anion and loss of cell viability. Results suggest that the antibacterial activities are contributed to by loss of cell viability, induced oxidative stress, and DNA fragmentation. The antibacterial activities of GO and rGO against P. aeruginosa were compared. The loss of P. aeruginosa viability increased in a dose- and

Examining mechanism of toxicity of copper oxide nanoparticles to Saccharomyces cerevisiae and Caenorhabditis elegans

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Mashock, Michael J.

Copper oxide nanoparticles (CuO NPs) are an up and coming technology increasingly being used in industrial and consumer applications and thus may pose risk to humans and the environment. In the present study, the toxic effects of CuO NPs were studied with two model organisms Saccharomyces cerevisiae and Caenorhabditis elegans. The role of released Cu ions during dissolution of CuO NPs in growth media were studied with freshly suspended, aged NPs, and the released Cu 2+ fraction. Exposures to the different Cu treatments showed significant inhibition of S. cerevisiae cellular metabolic activity. Inhibition from the NPs was inversely proportional to size and was not fully explained by the released Cu ions. S. cerevisiae cultures grown under respiring conditions demonstrated greater metabolic sensitivity when exposed to CuO NPs compared to cultures undergoing fermentation. The cellular response to both CuO NPs and released Cu ions on gene expression was analyzed via microarray analysis after an acute exposure. It was observed that both copper exposures resulted in an increase in carbohydrate storage, a decrease in protein production, protein misfolding, increased membrane permeability, and cell cycle arrest. Cells exposed to NPs up-regulated genes related to oxidative phosphorylation but also may be inducing cell cycle arrest by a different mechanism than that observed with released Cu ions. The effect of CuO NPs on C. elegans was examined by using several toxicological endpoints. The CuO NPs displayed a more inhibitory effect, compared to copper sulfate, on nematode reproduction, feeding, and development. We investigated the effects of copper oxide nanoparticles and copper sulfate on neuronal health, a known tissue vulnerable to heavy metal toxicity. In transgenic C. eleganswith neurons expressing a green fluorescent protein reporter, neuronal degeneration was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, nematode

DISTINCT FUNCTIONS OF JNK AND C-JUN IN OXIDANT-INDUCED HEPATOCYTE DEATH

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Amir, Muhammad; Liu, Kun; Zhao, Enpeng; Czaja, Mark J.

2013-01-01

Overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling is a central mechanism of hepatocyte injury and death including that from oxidative stress. However, the functions of JNK and c-Jun are still unclear, and this pathway also inhibits hepatocyte death. Previous studies of menadione-induced oxidant stress demonstrated that toxicity resulted from sustained JNK/c-Jun activation as death was blocked by the c-Jun dominant negative TAM67. To further delineate the function of JNK/c-Jun signaling in hepatocyte injury from oxidant stress, the effects of direct JNK inhibition on menadione-induced death were examined. In contrast to the inhibitory effect of TAM67, pharmacological JNK inhibition by SP600125 sensitized the rat hepatocyte cell line RALA255-10G to death from menadione. SP600125 similarly sensitized mouse primary hepatocytes to menadione toxicity. Death from SP600125/menadione was c-Jun dependent as it was blocked by TAM67, but independent of c-Jun phosphorylation. Death occurred by apoptosis and necrosis and activation of the mitochondrial death pathway. Short hairpin RNA knockdowns of total JNK or JNK2 sensitized to death from menadione, whereas a jnk1 knockdown was protective. Jnk2 null mouse primary hepatocytes were also sensitized to menadione death. JNK inhibition magnified decreases in cellular ATP content and β-oxidation induced by menadione. This effect mediated cell death as chemical inhibition of β-oxidation also sensitized cells to death from menadione, and supplementation with the β-oxidation substrate oleate blocked death. Components of the JNK/c-Jun signaling pathway have opposing functions in hepatocyte oxidant stress with JNK2 mediating resistance to cell death and c-Jun promoting death. PMID:22644775

Hepatic toxicity of dronedarone in mice: Role of mitochondrial β-oxidation

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Felser, Andrea; Stoller, Andrea; Morand, Réjane; Schnell, Dominik; Donzelli, Massimiliano; Terracciano, Luigi; Bouitbir, Jamal; Krähenbühl, Stephan

2014-01-01

Highlights: • Dronedarone is not hepatotoxic to mice up to 200 mg/kg/day. • At 400 mg/kg/day dronedarone decreases food intake and inhibits hepatic fatty acid metabolism. • Impaired hepatic fatty acid metabolism is associated with increased hepatocyte apoptosis and serum transaminases. • Mice with subclinical impairment of β-oxidation are slightly more susceptible to dronaderone than wild type mice. - Abstract: Dronedarone is an amiodarone-like antiarrhythmic drug associated with severe liver injury. Since dronedarone inhibits mitochondrial respiration and β-oxidation in vitro, mitochondrial toxicity may also explain dronedarone-associated hepatotoxicity in vivo. We therefore studied hepatotoxicity of dronedarone (200 mg/kg/day for 2 weeks or 400 mg/kg/day for 1 week by intragastric gavage) in heterozygous juvenile visceral steatosis (jvs +/− ) and wild-type mice. Jvs +/− mice have reduced carnitine stores and are sensitive for mitochondrial β-oxidation inhibitors. Treatment with dronedarone 200 mg/kg/day had no effect on body weight, serum transaminases and bilirubin, and hepatic mitochondrial function in both wild-type and jvs +/− mice. In contrast, dronedarone 400 mg/kg/day was associated with a 10–15% drop in body weight, and a 3–5-fold increase in transaminases and bilirubin in wild-type mice and, more accentuated, in jvs +/− mice. In vivo metabolism of intraperitoneal 14 C-palmitate was impaired in wild-type, and, more accentuated, in jvs +/− mice treated with 400 mg/kg/day dronedarone compared to vehicle-treated mice. Impaired β-oxidation was also found in isolated mitochondria ex vivo. A likely explanation for these findings was a reduced activity of carnitine palmitoyltransferase 1a in liver mitochondria from dronedarone-treated mice. In contrast, dronedarone did not affect the activity of the respiratory chain ex vivo. We conclude that dronedarone inhibits mitochondrial β-oxidation in and ex vivo, but not the respiratory chain

Zinc oxide nanoparticles decrease the expression and activity of plasma membrane calcium ATPase, disrupt the intracellular calcium homeostasis in rat retinal ganglion cells.

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Guo, Dadong; Bi, Hongsheng; Wang, Daoguang; Wu, Qiuxin

2013-08-01

Zinc oxide nanoparticle is one of the most important materials with diverse applications. However, it has been reported that zinc oxide nanoparticles are toxic to organisms, and that oxidative stress is often hypothesized to be an important factor in cytotoxicity mediated by zinc oxide nanoparticles. Nevertheless, the mechanism of toxicity of zinc oxide nanoparticles has not been completely understood. In this study, we investigated the cytotoxic effect of zinc oxide nanoparticles and the possible molecular mechanism involved in calcium homeostasis mediated by plasma membrane calcium ATPase in rat retinal ganglion cells. Real-time cell electronic sensing assay showed that zinc oxide nanoparticles could exert cytotoxic effect on rat retinal ganglion cells in a concentration-dependent manner; flow cytometric analysis indicated that zinc oxide nanoparticles could lead to cell damage by inducing the overproduction of reactive oxygen species. Furthermore, zinc oxide nanoparticles could also apparently decrease the expression level and their activity of plasma membrane calcium ATPase, which finally disrupt the intracellular calcium homeostasis and result in cell death. Taken together, zinc oxide nanoparticles could apparently decrease the plasma membrane calcium ATPase expression, inhibit their activity, cause the elevated intracellular calcium ion level and disrupt the intracellular calcium homeostasis. Further, the disrupted calcium homeostasis will trigger mitochondrial dysfunction, generate excessive reactive oxygen species, and finally initiate cell death. Thus, the disrupted calcium homeostasis is involved in the zinc oxide nanoparticle-induced rat retinal ganglion cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.

Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

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Khan, Muhammad Sohail; Ali, Tahir; Kim, Min Woo; Jo, Myeung Hoon; Jo, Min Gi; Badshah, Haroon; Kim, Myeong Ok

2016-11-01

Several studies provide evidence that reactive oxygen species (ROS) are key mediators of various neurological disorders. Anthocyanins are polyphenolic compounds and are well known for their anti-oxidant and neuroprotective effects. In this study, we investigated the neuroprotective effects of anthocyanins (extracted from black soybean) against lipopolysaccharide (LPS)-induced ROS-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Intraperitoneal injection of LPS (250 μg/kg) for 7 days triggers elevated ROS and oxidative stress, which induces neuroinflammation and neurodegeneration in the adult mouse cortex. Treatment with 24 mg/kg/day of anthocyanins for 14 days in LPS-injected mice (7 days before and 7 days co-treated with LPS) attenuated elevated ROS and oxidative stress compared to mice that received LPS-injection alone. The immunoblotting results showed that anthocyanins reduced the level of the oxidative stress kinase phospho-c-Jun N-terminal Kinase 1 (p-JNK). The immunoblotting and morphological results showed that anthocyanins treatment significantly reduced LPS-induced-ROS-mediated neuroinflammation through inhibition of various inflammatory mediators, such as IL-1β, TNF-α and the transcription factor NF- k B. Anthocyanins treatment also reduced activated astrocytes and microglia in the cortex of LPS-injected mice, as indicated by reductions in GFAP and Iba-1, respectively. Anthocyanins also prevent overexpression of various apoptotic markers, i.e., Bax, cytosolic cytochrome C, cleaved caspase-3 and PARP-1. Immunohistochemical fluoro-jade B (FJB) and Nissl staining indicated that anthocyanins prevent LPS-induced neurodegeneration in the mouse cortex. Our results suggest that dietary flavonoids, such as anthocyanins, have antioxidant and neuroprotective activities that could be beneficial to various neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential risks from UV/H2O2 oxidation and UV photocatalysis: A review of toxic, assimilable, and sensory-unpleasant transformation products.

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Wang, Wen-Long; Wu, Qian-Yuan; Huang, Nan; Xu, Zi-Bin; Lee, Min-Yong; Hu, Hong-Ying

2018-05-15

UV based advanced oxidation processes (UV-AOPs) that efficiently eliminate organic pollutants during water treatment have been the subject of numerous investigations. Most organic pollutants are not completely mineralized during UV-AOPs but are partially oxidized into transformation products (TPs), thereby adding complexity to the treated water and posing risks to humans, ecological systems, and the environment. While the degradation kinetics and mechanisms of pollutants have been widely documented, there is little information about the risks associated with TPs. In this review, we have collated recent knowledge about the harmful TPs that are generated in UV/H 2 O 2 and UV photocatalysis, two UV-AOPs that have been studied extensively. Toxic and assimilable TPs were ubiquitously observed in more than 80% of UV-AOPs of organic pollutants, of which the toxicity and assimilability levels changed with variations in the reaction conditions, such as the UV fluence and oxidant dosage. Previous studies and modeling assessments showed that toxic and assimilable TPs may be generated during hydroxylation, dealkylation, decarboxylation, and deamination. Among various reactions, TPs generated from dealkylation and decarboxylation were generally less and more toxic than the parent pollutants, respectively; TPs generated from decarboxylation and deamination were generally less and more assimilable than the parent pollutants, respectively. There is also potential concern about the sensory-unpleasant TPs generated by oxidations and subsequent metabolism of microorganisms. In this overview, we stress the need to include both the concentrations of organic pollutants and the evaluations of the risks from TPs for the quality assessments of the water treated by UV-AOPs. Copyright © 2018 Elsevier Ltd. All rights reserved.

The different behaviors of three oxidative mediators in probing the redox activities of the yeast Saccharomyces cerevisiae

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Zhao Jinsheng [Department of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059 (China); Wang Min [School of Medicine, Ehime University, Toon 791-0295 (Japan); Yang Zhenyu [Department of Chemistry, Nanchang University, Jiangxi 330047 (China); Wang Zhong [School of Medicine, Ehime University, Toon 791-0295 (Japan); Wang Huaisheng [Department of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059 (China); Yang Zhengyu [Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100101 (China)

2007-07-30

The different behaviors of three lipophilic mediators including 2-methyl-1,4-naphthalenedione(menadione), 2,6-dichlorophenolindophenol (DCPIP) and N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) in probing the redox activity of the yeast Saccharomyces cerevisiae were studied by several comparative factor-influencing experiments. Hydrophilic ferricyanide was employed as an extracellular electron acceptor, and constituted dual mediator system with each of three lipophilic mediators. Limiting-current microelectrode voltammetry was used to measure the quantity of ferrocyanide accumulations, giving a direct measure of the redox activity. It was found that under anaerobic condition, menadione interacts with anaerobic respiration pathway, whereas DCPIP and TMPD interact with fermentation pathway in the yeast. Based on the understanding of the interaction between the yeast and each of three mediators, three mediators were respectively employed in evaluating the toxicity of acetic acid on S. cerevisiae and, the results for the first showed that the mediators are complementary to each other when used as electron carriers in biotoxicity assay.

The different behaviors of three oxidative mediators in probing the redox activities of the yeast Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Zhao Jinsheng; Wang Min; Yang Zhenyu; Wang Zhong; Wang Huaisheng; Yang Zhengyu

2007-01-01

The different behaviors of three lipophilic mediators including 2-methyl-1,4-naphthalenedione(menadione), 2,6-dichlorophenolindophenol (DCPIP) and N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) in probing the redox activity of the yeast Saccharomyces cerevisiae were studied by several comparative factor-influencing experiments. Hydrophilic ferricyanide was employed as an extracellular electron acceptor, and constituted dual mediator system with each of three lipophilic mediators. Limiting-current microelectrode voltammetry was used to measure the quantity of ferrocyanide accumulations, giving a direct measure of the redox activity. It was found that under anaerobic condition, menadione interacts with anaerobic respiration pathway, whereas DCPIP and TMPD interact with fermentation pathway in the yeast. Based on the understanding of the interaction between the yeast and each of three mediators, three mediators were respectively employed in evaluating the toxicity of acetic acid on S. cerevisiae and, the results for the first showed that the mediators are complementary to each other when used as electron carriers in biotoxicity assay

Nitric oxide protects carbon assimilation process of watermelon from boron-induced oxidative injury.

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Farag, Mohamed; Najeeb, Ullah; Yang, Jinghua; Hu, Zhongyuan; Fang, Zhang Ming

2017-02-01

Nitric oxide (NO) mediates plant response to a variety of abiotic stresses; however, limited information is available on its effect on boron (B)-stressed watermelon plants. The present study investigates the mechanism through which NO protects watermelon seedlings from B deficiency and toxicity stresses. Five days old watermelon seedlings were exposed to B (0, 0.5 and 10 mg L -1 ) alone or with 75 μmole of NO donor sodium nitroprusside (SNP) for 30 days. Both low and high B concentrations in the media altered nutrient accumulation and impaired various physiological processes of watermelon seedlings, leading to a significant reduction in biomass production. The plants exposed to B deficient or toxic concentrations had 66 and 69% lower shoot dry weight, respectively compared with optimum B levels. B toxicity-induced growth inhibition of watermelon seedlings was associated with high B translocation to shoot tissues, which caused lipid membrane peroxidation (12% increase) and chlorophyll destruction (25% reduction). In contrast, B deficiency accelerated generation of reactive oxygen species (ROS), specifically OH -1 and induced cellular oxidative injury. Exogenously applied SNP promoted leaf chlorophyll, photosynthesis and consequently biomass production in B-stressed watermelon seedlings by reducing B accumulation, lipid membrane peroxidation and ROS generation. It also activated antioxidant enzymes such as SOD, POD and APX, and protected the seedlings from ROS-induced cellular burst. Copyright © 2016. Published by Elsevier Masson SAS.

Optical properties of cerium oxide (CeO2) nanoparticles synthesized by hydroxide mediated method

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Ali, Mawlood Maajal; Mahdi, Hadeel Salih; Parveen, Azra; Azam, Ameer

2018-05-01

The nanoparticles of cerium oxide have been successfully synthesized by hydroxide mediated method, using cerium nitrate and sodium hydroxide as precursors. The microstructural properties were analyzed by X-ray diffraction technique (XRD). The X-ray diffraction results show that the cerium oxide nanoparticles were in cubic structure. The optical absorption spectra of cerium oxide were recorded by UV-VIS spectrophotometer in the range of 320 to 600 nm and photoluminescence spectra in the range of 400-540 nm and have been presented. The energy band gap was determined by Tauc relationship. The crystallite size was determined from Debye-Scherer equation and came out to be 6.4 nm.

Study on the effect of reactive oxygen species-mediated oxidative stress on the activation of mitochondrial apoptosis and the tenderness of yak meat.

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Wang, Lin-Lin; Yu, Qun-Li; Han, Ling; Ma, Xiu-Li; Song, Ren-De; Zhao, Suo-Nan; Zhang, Wen-Hua

2018-04-01

This study investigated the effect of reactive oxygen species-mediated oxidative stress on activation of mitochondrial apoptosis and tenderness of yak meat during postmortem ageing. Oxidative stress degree, Ca 2+ levels, membrane permeability transition pore opening, mitochondrial membrane potential, apoptotic factors and the shear force were examined. Results showed that the ROS generated by H 2 O 2 significantly increased mitochondrial oxidative stress by decreasing the activities of superoxide dismutase, catalase and glutathione peroxidase, and increasing lipid peroxidation. Furthermore, oxidative stress enhanced Ca 2+ production and cytochrome c release, changed the levels of Bcl-2 family proteins and activated caspase-9 and -3 activities. Ultimately, oxidative stress increased the apoptosis rate and tenderness of yak meat. These observations confirmed that ROS-mediated oxidative stress participates in the activation of the apoptotic cascade reaction involving Ca 2+ and Bcl-2 family proteins. The results further suggested that ROS-mediated oxidative stress plays a significant role in meat tenderization through the mitochondrial apoptotic pathway. Copyright © 2017. Published by Elsevier Ltd.

Oxidation of diclofenac by aqueous chlorine dioxide: identification of major disinfection byproducts and toxicity evaluation.

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Wang, Yingling; Liu, Haijin; Liu, Guoguang; Xie, Youhai

2014-03-01

Diclofenac (DCF), a synthetic non-steroidal anti-inflammatory drug, is one of the most frequently detected pharmaceuticals in the aquatic environment. In this work, the mechanism and toxicity of DCF degradation by ClO2 under simulated water disinfection conditions were investigated. Experimental results indicate that rapid and significant oxidation of DCF occurred within the first few minutes; however, its mineralization process was longer than its degradation process. UPLC-MS and (1)H NMR spectroscopy were performed to identify major disinfection byproducts that were generated in three tentative degradation routes. The two main routes were based on initial decarboxylation of DCF on the aliphatic chain and hydroxylation of the phenylacetic acid moiety at the C-4 position. Subsequently, the formed aldehyde intermediates were the starting point for further multistep degradation involving decarboxylation, hydroxylation, and oxidation reactions of CN bond cleavage. The third route was based on transient preservation of chlorinated derivatives resulting from electrophilic attack by chlorine on the aromatic ring, which similarly underwent CN bond cleavage. Microtox bioassay was employed to evaluate the cytotoxicity of solutions treated by ClO2. The formation of more toxic mid-byproducts during the ClO2 disinfection process poses a potential risk to consumers. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of the role of oxidative stress, inflammation and apoptosis in the pulmonary and the hepatic toxicity induced by cerium oxide nanoparticles following intratracheal instillation in male Sprague-Dawley rats

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Nalabotu, Siva Krishna

The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data suggest that CeO2 nanoparticles may be toxic to lung cell lines in vitro and lung tissues in vivo. Other work has proposed that oxidative stress may play an important role in the toxicity; however, the exact mechanism of the toxicity, has to our knowledge, not been investigated. Similarly, it is not clear whether CeO2 nanoparticles exhibit systemic toxicity. Here, we investigate whether pulmonary exposure to CeO2 nanoparticles is associated with oxidative stress, inflammation and apoptosis in the lungs and liver of adult male Sprague-Dawley rats. Our data suggest that the intratracheal instillation of CeO2 nanoparticles can cause an increased lung weight to body weight ratio. Changes in lung weights were associated with the accumulation of cerium in the lungs, elevations in serum inflammatory markers, an increased Bax to Bcl-2 ratio, elevated caspase-3 protein levels, increased phosphorylation of p38-MAPK and diminished phosphorylation of ERK1/2-MAPK. Our findings from the study evaluating the possible translocation of CeO2 nanoparticles from the lungs to the liver suggest that CeO 2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase

Biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles in BALB/c mice

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Salimi M

2018-03-01

Full Text Available Marzieh Salimi,1,2 Saeed Sarkar,1,2 Samaneh Fathi,3 Ali Mohammad Alizadeh,4 Reza Saber,2,3 Fatemeh Moradi,5 Hamid Delavari6 1Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran; 2Research Center of Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Medical Nanotechnology, Tehran University of Medical Sciences, Tehran, Iran; 4Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Medical Physiology, Tehran University of Medical Sciences, Tehran, Iran; 6Department of Materials Science and Engineering, Tarbiat Modares University, Tehran, Iran Background: The possibility of using a specific nanoparticle in nanomedicine highly depends on its biodistribution profile and biocompatibility. Due to growing demand for iron oxide nanoparticles (IONPs and dendrimers in biomedical applications, this study was performed to assess the biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles (G4@IONPs. Materials and methods: IONPs were synthesized via co-precipitation and coated with the fourth generation (G4 of polyamidoamine (PAMAM dendrimer. To determine the biodistribution, 5 mg/mL G4@IONPs suspension was intraperitoneally injected into tumor-bearing BALB/c mice, and iron levels in blood and various organs, including the lung, liver, brain, heart, tumor, and kidney, were measured by inductively coupled plasma mass spectrometry (ICP-MS at 4, 8, 12, and 24 h after injection. Also, to investigate the toxicity of G4@IONPs, different concentrations of G4@IONPs were injected into BALB/c mice, and blood, renal, and hepatic factors were measured. Furthermore, histopathological staining was performed to investigate the effect of G4@IONPs on the liver and kidney tissues. Results: The results showed that the iron content was higher in the kidney, liver, and lung tissues 24 h after

LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism.

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Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Di Santo, Serena; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Del Ben, Maria; De Marco, Luigi; Pignatelli, Pasquale; Violi, Francesco

2014-11-01

Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Amyloid-linked cellular toxicity triggered by bacterial inclusion bodies

International Nuclear Information System (INIS)

Gonzalez-Montalban, Nuria; Villaverde, Antonio; Aris, Anna

2007-01-01

The aggregation of proteins in the form of amyloid fibrils and plaques is the characteristic feature of some pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. The mechanisms by which the aggregation processes result in cell damage are under intense investigation but recent data indicate that prefibrillar aggregates are the most proximate mediators of toxicity rather than mature fibrils. Since it has been shown that prefibrillar forms of the nondisease-related misfolded proteins are highly toxic to cultured mammalian cells we have studied the cytoxicity associated to bacterial inclusion bodies that have been recently described as protein deposits presenting amyloid-like structures. We have proved that bacterial inclusion bodies composed by a misfolding-prone β-galactosidase fusion protein are clearly toxic for mammalian cells but the β-galactosidase wild type enzyme forming more structured thermal aggregates does not impair cell viability, despite it also binds and enter into the cells. These results are in the line that the most cytotoxic aggregates are early prefibrilar assemblies but discard the hypothesis that the membrane destabilization is Key event to subsequent disruption of cellular processes, such as ion balance, oxidative state and the eventually cell death

Aryl hydrocarbon receptor 2 mediates the toxicity of Paclobutrazol on the digestive system of zebrafish embryos.

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Wang, Wen-Der; Chen, Guan-Ting; Hsu, Hwei-Jan; Wu, Chang-Yi

2015-02-01

Paclobutrazol (PBZ), a trazole-containing fungicide and plant growth retardant, has been widely used for over 30 years to regulate plant growth and promote early fruit setting. Long-term usage of PBZ in agriculture and natural environments has resulted in residual PBZ in the soil and water. Chronic exposure to waterborne PBZ can cause various physiological effects in fish, including hepatic steatosis, antioxidant activity, and disruption of spermatogenesis. We have previously shown that PBZ also affects the rates of zebrafish embryonic survival and hatching, and causes developmental failure of the head skeleton and eyes; here, we further show that PBZ has embryonic toxic effects on digestive organs of zebrafish, and describe the underlying mechanisms. PBZ treatment of embryos resulted in dose-dependent morphological and functional abnormalities of the digestive organs. Real-time RT-PCR and in situ hybridization were used to show that PBZ strongly induces cyp1a1 expression in the digestive system, and slightly induces ahr2 expression in zebrafish embryos. Knockdown of ahr2 with morpholino oligonucleotides prevents PBZ toxicity. Thus, the toxic effect of PBZ on digestive organs is mediated by AhR2, as was previously reported for retene and TCDD. These findings have implications for understanding the potential toxicity of PBZ during embryogenesis, and thus the potential impact of fungicides on public health and the environment. Copyright © 2014 Elsevier B.V. All rights reserved.

Oxidative stress augments toll-like receptor 8 mediated neutrophilic responses in healthy subjects

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Matsunaga Kazuto

2009-06-01

Full Text Available Abstract Background Excessive oxidative stress has been reported to be generated in inflamed tissues and contribute to the pathogenesis of inflammatory lung diseases, exacerbations of which induced by viral infections are associated with toll-like receptor (TLR activation. Among these receptors, TLR8 has been reported as a key receptor that recognizes single-strand RNA virus. However, it remains unknown whether TLR8 signaling is potentiated by oxidative stress. The aim of this study is to examine whether oxidative stress modulates TLR8 signaling in vitro. Methods Human peripheral blood neutrophils were obtained from healthy non-smokers and stimulated with TLR 7/8 agonist imidazoquinoline resiquimod (R848 in the presence or absence of hydrogen peroxide (H2O2. Neutrophilic responses including cytokine release, superoxide production and chemotaxis were examined, and the signal transduction was also analyzed. Results Activation of TLR8, but not TLR7, augmented IL-8 release. The R848-augmented IL-8 release was significantly potentiated by pretreatment with H2O2 (p L-cysteine reversed this potentiation. The combination of H2O2 and R848 significantly potentiated NF-kB phosphorylation and IkBα degradation. The H2O2-potentiated IL-8 release was suppressed by MG-132, a proteosome inhibitor, and by dexamethasone. The expressions of TLR8, myeloid differentiation primary response gene 88 (MyD88, and tumor necrosis factor receptor-associated factor 6 (TRAF6 were not affected by H2O2. Conclusion TLR8-mediated neutrophilic responses were markedly potentiated by oxidative stress, and the potentiation was mediated by enhanced NF-kB activation. These results suggest that oxidative stress might potentiate the neutrophilic inflammation during viral infection.

Nitric oxide as a mediator of gastrointestinal mucosal injury?—Say it ain't so

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Paul Kubes

1995-01-01

Full Text Available Nitric oxide has been suggested as a contributor to tissue injury in various experimental models of gastrointestinal inflammation. However, there is overwhelming evidence that nitric oxide is one of the most important mediators of mucosal defence, influencing such factors as mucus secretion, mucosal blood flow, ulcer repair and the activity of a variety of mucosal immunocytes. Nitric oxide has the capacity to down-regulate inflammatory responses in the gastrointestinal tract, to scavenge various free radical species and to protect the mucosa from injury induced by topical irritants. Moreover, questions can be raised regarding the evidence purported to support a role for nitric oxide in producing tissue injury. In this review, we provide an overview of the evidence supporting a role for nitric oxide in protecting the gastrointestinal tract from injury.

Investigation of toxic effects of imidazolium ionic liquids, [bmim][BF{sub 4}] and [omim][BF{sub 4}], on marine mussel Mytilus galloprovincialis with or without the presence of conventional solvents, such as acetone

Energy Technology Data Exchange (ETDEWEB)

Tsarpali, Vasiliki; Belavgeni, Alexia; Dailianis, Stefanos, E-mail: sdailianis@upatras.gr

2015-07-15

Highlights: • The toxic effects of [bmim][BF{sub 4}] and [omim][BF{sub 4}] on mussels were investigated. • Both ILs could induce lethal and nonlethal effects on Mytilus galloprovincialis. • Different extent of IL-mediated adverse effects was observed in mussel hemocytes. • The alkyl chain length and lipophilicity of ILs are crucial for their toxicity. • Acetone influences the oxidative and genotoxic effects of [omim][BF{sub 4}]. - Abstract: This study investigated the cytotoxic, oxidative and genotoxic effects of two commonly used imidazolium ionic liquids (ILs), [bmim][BF{sub 4}] (1-butyl-3-methylimidazolium) and [omim][BF{sub 4}] (1-methyl-3-octylimidazolium tetrafluoroborate), on the marine mussel Mytilus galloprovincialis, as well as whether acetone could mediate their toxic profile. In this context, mussels were firstly exposed to different concentrations of [bmim][BF{sub 4}] or [omim][BF{sub 4}], with or without the presence of acetone (at a final concentration of 0.06% v/v), for a period of 96 h, in order to determine the concentration that causes 50% mussel mortality (LC{sub 50} values) in each case. Thereafter, mussels were exposed to sub- and non-lethal concentrations of ILs for investigating their ability to cause lysosomal membrane impairment (with the use of neutral red retention assay/NRRT), superoxide anion and lipid peroxidation byproduct (malondialdehyde/MDA) formation, as well as DNA damage and formation of nuclear abnormalities in hemocytes. The results showed that [omim][BF{sub 4}] was more toxic than [bmim][BF{sub 4}] in all cases, while the presence of acetone resulted in a slight attenuation of its toxicity. The different toxic behavior of ILs was further revealed by the significantly lower levels of NRRT values observed in [omim][BF{sub 4}]-treated mussels, compared to those occurring in [bmim][BF{sub 4}] in all cases. Similarly, [bmim][BF{sub 4}]-mediated oxidative and genotoxic effects were observed only in the highest

Mitochondrial-Targeted Decyl-Triphenylphosphonium Enhances 2-Deoxy-D-Glucose Mediated Oxidative Stress and Clonogenic Killing of Multiple Myeloma Cells.

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Jeanine Schibler

Full Text Available Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266, using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog. In primary human MM samples, increased glycolytic gene expression correlated with poorer overall and event-free survival outcomes. Notably, stem-like cells showed increased mitochondrial mass, rhodamine 123 accumulation, and orthodox mitochondrial configuration while more condensed mitochondria were noted in the CD138high cells. Glycolytic inhibitor 2-deoxyglucose (2-DG induced ER stress as detected by qPCR (BiP, ATF4 and immunoblotting (BiP, CHOP and increased dihydroethidium probe oxidation both CD138low and CD138high cells. Treatment with a mitochondrial-targeting agent decyl-triphenylphosphonium (10-TPP increased intracellular steady-state pro-oxidant levels in stem-like and mature MM cells. Furthermore, 10-TPP mediated increases in mitochondrial oxidant production were suppressed by ectopic expression of manganese superoxide dismutase. Relative to 2-DG or 10-TPP alone, 2-DG plus 10-TPP combination showed increased caspase 3 activation in MM cells with minimal toxicity to the normal hematopoietic progenitor cells. Notably, treatment with polyethylene glycol conjugated catalase significantly reduced 2-DG and/or 10-TPP-induced apoptosis of MM cells. Also, the combination of 2-DG with 10-TPP decreased clonogenic survival of MM cells. Taken together, this study provides a novel strategy of metabolic oxidative stress-induced cytotoxicity of MM

Visible-Light-Driven Oxidation of Organic Substrates with Dioxygen Mediated by a [Ru(bpy)3 ](2+) /Laccase System.

Science.gov (United States)

Schneider, Ludovic; Mekmouche, Yasmina; Rousselot-Pailley, Pierre; Simaan, A Jalila; Robert, Viviane; Réglier, Marius; Aukauloo, Ally; Tron, Thierry

2015-09-21

Oxidation reactions are highly important chemical transformations that still require harsh reaction conditions and stoichiometric amounts of chemical oxidants that are often toxic. To circumvent these issues, olefins oxidation is achieved in mild conditions upon irradiation of an aqueous solution of the complex [Ru(bpy)3 ](2+) and the enzyme laccase. Epoxide formation is coupled to the light-driven reduction of O2 by [Ru(bpy)3 ](2+) /laccase system. The reactivity can be explained by dioxygen acting both as an oxidative agent and as renewable electron acceptor, avoiding the use of a sacrificial electron acceptor. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide

Science.gov (United States)

Wu, Qiuli; Zhao, Yunli; Fang, Jianpeng; Wang, Dayong

2014-05-01

Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals.Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO

Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf

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Subramanion L. Jothy

2013-01-01

Full Text Available Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of  ∙OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 μg/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats.

Nanotoxicology of Metal Oxide Nanoparticles

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Amedea B. Seabra

2015-06-01

Full Text Available This review discusses recent advances in the synthesis, characterization and toxicity of metal oxide nanoparticles obtained mainly through biogenic (green processes. The in vitro and in vivo toxicities of these oxides are discussed including a consideration of the factors important for safe use of these nanomaterials. The toxicities of different metal oxide nanoparticles are compared. The importance of biogenic synthesized metal oxide nanoparticles has been increasing in recent years; however, more studies aimed at better characterizing the potent toxicity of these nanoparticles are still necessary for nanosafely considerations and environmental perspectives. In this context, this review aims to inspire new research in the design of green approaches to obtain metal oxide nanoparticles for biomedical and technological applications and to highlight the critical need to fully investigate the nanotoxicity of these particles.

The development and evaluation of a continuous flow process for the lipase-mediated oxidation of alkenes

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Charlotte Wiles

2009-06-01

Full Text Available We report the use of an immobilised form of Candida antarctica lipase B, Novozym® 435, in a preliminary investigation into the development of a continuous flow reactor capable of performing the chemo-enzymatic oxidation of alkenes in high yield and purity, utilising the commercially available oxidant hydrogen peroxide (100 volumes. Initial investigations focussed on the lipase-mediated oxidation of 1-methylcyclohexene, with the optimised reaction conditions subsequently employed for the epoxidation of an array of aromatic and aliphatic alkenes in 97.6 to 99.5% yield and quantitative purity.

Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

Energy Technology Data Exchange (ETDEWEB)

Khan, Rehan; Khan, Abdul Quaiyoom; Qamar, Wajhul; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat, E-mail: sarwat786@rediffmail.com

2012-02-01

Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. Highlights: ► Cisplatin-induced colon toxicity is associated with oxidative stress and

Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

International Nuclear Information System (INIS)

Khan, Rehan; Khan, Abdul Quaiyoom; Qamar, Wajhul; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat

2012-01-01

Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. Highlights: ► Cisplatin-induced colon toxicity is associated with oxidative stress and

Temperature dependence of long-term cadmium toxicity in the zebrafish is not explained by liver oxidative stress: Evidence from transcript expression to physiology

International Nuclear Information System (INIS)

Vergauwen, Lucia; Hagenaars, An; Blust, Ronny; Knapen, Dries

2013-01-01

Standard ecotoxicity tests are performed at species’ specific standard temperatures, but temperature is known to affect chemical toxicity. A temperature increase has been shown to increase cadmium toxicity in several aquatic species but information in fish is scarce. Based on literature we hypothesize that with increasing temperature, cadmium accumulation and oxidative stress increase, resulting in increased toxicity. In this study zebrafish acclimated to 12, 18, 26 (standard temperature) or 34 °C for one month, were exposed to 5 μM cadmium for 4 or 28 days at the respective acclimation temperature. Cadmium toxicity (mortality) increased with increasing temperature. PCA showed that the high mortality at 34 °C was closely correlated to an increasing tissue cadmium accumulation with increasing temperature, but not to liver oxidative damage under the form of protein carbonyl content or lipid peroxidation (measured as malondialdehyde levels) or liver antioxidative potential. Instead, acclimation to 12 °C induced the highest oxidative damage to liver proteins and lipids, and transcript levels of glucose-6P-dehydrogenase, 6P-gluconate-dehydrogenase and glutathione peroxidase were particularly good markers of cold-induced oxidative stress. At this low temperature there was no interaction with cadmium exposure and there was no sign of cadmium sensitivity. Contrastingly, the combined effect of high temperature and cadmium exposure on mortality proved synergistic. Therefore we conclude that interactions between temperature and cadmium toxicity increased with increasing temperature and that this probably played part in increasing cadmium sensitivity. Increased cadmium compartmentalization and protein carbonyl content in liver of zebrafish acclimated to the standard temperature of 26 °C probably played part in increased sensitivity towards the same cadmium body burden compared to lower temperatures. On the one hand we recognize and this study even confirms the

trans-2-Tritylcyclohexanol as a chiral auxiliary in permanganate-mediated oxidative cyclization of 2-methylenehept-5-enoates: application to the synthesis of trans-(+)-linalool oxide.

Science.gov (United States)

Al Hazmi, Ali M; Sheikh, Nadeem S; Bataille, Carole J R; Al-Hadedi, Azzam A M; Watkin, Sam V; Luker, Tim J; Camp, Nicholas P; Brown, Richard C D

2014-10-03

The permanganate-mediated oxidative cyclization of a series of 2-methylenehept-5-eneoates bearing different chiral auxiliaries was investigated, leading to the discovery of trans-2-tritylcyclohexanol (TTC) as a highly effective chiral controller for the formation of the 2,5-substituted THF diol product with high diastereoselectivity (dr ∼97:3). Chiral resolution of (±)-TTC, prepared in one step from cyclohexene oxide, afforded (-)-(1S,2R)-TTC (er >99:1), which was applied to the synthesis of (+)-trans-(2S,5S)-linalool oxide.

Laccase/Mediator Systems

NARCIS (Netherlands)

Hilgers, Roelant; Vincken, Jean Paul; Gruppen, Harry; Kabel, Mirjam A.

2018-01-01

Laccase-mediator systems (LMS) have been widely studied for their capacity to oxidize the nonphenolic subunits of lignin (70-90% of the polymer). The phenolic subunits (10-30% of the polymer), which can also be oxidized without mediators, have received considerably less attention. Consequently, it

Toxicity Reduction of Reactive Red Dye-238 Using Advanced Oxidation Process by Solar Energy

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Riyad Al-Anbari

2017-09-01

Full Text Available Decolorization of red azo dye (Cibacron Red FN-R from synthetic wastewater has been investigated as a function of solar advanced oxidation process. The photocatalytic activity using ZnO as a photocatalysis has been estimated. Different parameters affected the removal efficiency, including pH of the solution, initial dye concentration and H2O2 concentration were evaluated to find out the optimum value of these parameters. The results proved that the optimal pH value was 8 and the most efficient H2O2 concentration was 100mg/L. Toxicity reduction percent for effluent solution was also monitored to assess the degradation process. This treatment method was able to strongly reduce the color and toxicity of reactive red dye-238 to about (99 and 80 % respectively. It can be concluded, from these experiments, that the using of ZnO as a photocatalysis was exhibited as economical and efficient treatment method to remove reactive red dye-238 from aqueous solution.

Omega-3 fatty acid oxidation products prevent vascular endothelial cell activation by coplanar polychlorinated biphenyls

International Nuclear Information System (INIS)

Majkova, Zuzana; Layne, Joseph; Sunkara, Manjula; Morris, Andrew J.; Toborek, Michal; Hennig, Bernhard

2011-01-01

Coplanar polychlorinated biphenyls (PCBs) may facilitate development of atherosclerosis by stimulating pro-inflammatory pathways in the vascular endothelium. Nutrition, including fish oil-derived long-chain omega-3 fatty acids, such as docosahexaenoic acid (DHA, 22:6ω-3), can reduce inflammation and thus the risk of atherosclerosis. We tested the hypothesis that cyclopentenone metabolites produced by oxidation of DHA can protect against PCB-induced endothelial cell dysfunction. Oxidized DHA (oxDHA) was prepared by incubation of the fatty acid with the free radical generator 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH). Cellular pretreatment with oxDHA prevented production of superoxide induced by PCB77, and subsequent activation of nuclear factor-κB (NF-κB). A 4 /J 4 -neuroprostanes (NPs) were identified and quantitated using HPLC ESI tandem mass spectrometry. Levels of these NPs were markedly increased after DHA oxidation with AAPH. The protective actions of oxDHA were reversed by treatment with sodium borohydride (NaBH 4 ), which concurrently abrogated A 4 /J 4 -NP formation. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) by PCB77 was markedly reduced by oxDHA, but not by un-oxidized DHA. These protective effects were proportional to the abundance of A 4 /J 4 NPs in the oxidized DHA sample. Treatment of cells with oxidized eicosapentaenoic acid (EPA, 20:5ω-3) also reduced MCP-1 expression, but less than oxDHA. Treatment with DHA-derived cyclopentenones also increased DNA binding of NF-E2-related factor-2 (Nrf2) and downstream expression of NAD(P)H:quinone oxidoreductase (NQO1), similarly to the Nrf-2 activator sulforaphane. Furthermore, sulforaphane prevented PCB77-induced MCP-1 expression, suggesting that activation of Nrf-2 mediates the observed protection against PCB77 toxicity. Our data implicate A 4 /J 4 -NPs as mediators of omega-3 fatty acid-mediated protection against the endothelial toxicity of coplanar PCBs.

Oxidative stress mediated mitochondrial and vascular lesions as markers in the pathogenesis of Alzheimer disease.

Science.gov (United States)

Aliev, G; Priyadarshini, M; Reddy, V P; Grieg, N H; Kaminsky, Y; Cacabelos, R; Ashraf, G Md; Jabir, N R; Kamal, M A; Nikolenko, V N; Zamyatnin, A A; Benberin, V V; Bachurin, S O

2014-01-01

Mitochondrial dysfunction plausibly underlies the aging-associated brain degeneration. Mitochondria play a pivotal role in cellular bioenergetics and cell-survival. Oxidative stress consequent to chronic hypoperfusion induces mitochondrial damage, which is implicated as the primary cause of cerebrovascular accidents (CVA) mediated Alzheimer's disease (AD). The mitochondrial function deteriorates with aging, and the mitochondrial damage correlates with increased intracellular production of oxidants and pro-oxidants. The prolonged oxidative stress and the resultant hypoperfusion in the brain tissues stimulate the expression of nitric oxide synthase (NOS) enzymes, which further drives the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ROS and RNS collectively contributes to the dysfunction of the blood-brain barrier (BBB) and damage to the brain parenchymal cells. Delineating the molecular mechanisms of these processes may provide clues for the novel therapeutic targets for CVA and AD patients.

Assessment of D-methionine protecting cisplatin-induced otolith toxicity by vestibular-evoked myogenic potential tests, ATPase activities and oxidative state in guinea pigs.

Science.gov (United States)

Lo, Wu-Chia; Chang, Chih-Ming; Liao, Li-Jen; Wang, Chi-Te; Young, Yi-Ho; Chang, Yih-Leong; Cheng, Po-Wen

2015-01-01

To date, inadequate study has been devoted to the toxic vestibular effects caused by cisplatin. In addition, no electrophysiological examination has been conducted to assess cisplatin-induced otolith toxicity. The purposes of this study are thus two-fold: 1) to determine whether cervical vestibular-evoked myogenic potentials (VEMPs) and ocular VEMPs are practical electrophysiological methods of testing for cisplatin-induced otolith toxicity and 2) to examine if D-methionine (D-met) pre-injection would protect the otolith organs against cisplatin-induced changes in enzyme activities and/or oxidative status. Guinea pigs were intraperitoneally treated once daily with the following injections for seven consecutive days: sterile 0.9% saline control, cisplatin (5 mg/kg) only, D-met (300 mg/kg) only, or a combination of d-met (300 mg/kg) and cisplatin (5 mg/kg), respectively, with a 30 minute window in between. Each animal underwent the oVEMP and cVEMP tests before and after treatment. The changes in the biochemistry of the otolith organs, including membranous Na(+), K(+)-ATPase and Ca(2+)-ATPase, lipid peroxidation (LPO) levels and nitric oxide (NO) levels, were also evaluated. In the cisplatin-only treated guinea pigs, the mean amplitudes of the oVEMP tests were significantly (potolith dysfunction. D-Met attenuated the reduced ATPase activities and increased oxidative stress induced by cisplatin toxicity in the otolith organs. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of flexing and massage on in vivo human skin penetration and toxicity of zinc oxide nanoparticles.

Science.gov (United States)

Leite-Silva, Vânia R; Liu, David C; Sanchez, Washington Y; Studier, Hauke; Mohammed, Yousuf H; Holmes, Amy; Becker, Wolfgang; Grice, Jeffrey E; Benson, Heather Ae; Roberts, Michael S

2016-05-01

We assessed the effects of flexing and massage on human skin penetration and toxicity of topically applied coated and uncoated zinc oxide nanoparticles (˜75 nm) in vivo. Noninvasive multiphoton tomography with fluorescence lifetime imaging was used to evaluate the penetration of nanoparticles through the skin barrier and cellular apoptosis in the viable epidermis. All nanoparticles applied to skin with flexing and massage were retained in the stratum corneum or skin furrows. No significant penetration into the viable epidermis was seen and no cellular toxicity was detected. Exposure of normal in vivo human skin to these nanoparticles under common in-use conditions of flexing or massage is not associated with significant adverse events.

Astaxanthin from Haematococcus pluvialis Prevents Oxidative Stress on Human Endothelial Cells without Toxicity

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Philippe Régnier

2015-05-01

Full Text Available Astaxanthin, a powerful antioxidant, is a good candidate for the prevention of intracellular oxidative stress. The aim of the study was to compare the antioxidant activity of astaxanthin present in two natural extracts from Haematococcus pluvialis, a microalgae strain, with that of synthetic astaxanthin. Natural extracts were obtained either by solvent or supercritical extraction methods. UV, HPLC-DAD and (HPLC-(atmospheric pressure chemical ionization (APCI+/ion trap-MS characterizations of both natural extracts showed similar compositions of carotenoids, but different percentages in free astaxanthin and its ester derivatives. The Trolox equivalent antioxidant capacity (TEAC assay showed that natural extracts containing esters displayed stronger antioxidant activities than free astaxanthin. Their antioxidant capacities to inhibit intracellular oxidative stress were then evaluated on HUVEC cells. The intracellular antioxidant activity in natural extracts was approximately 90-times higher than synthetic astaxanthin (5 µM. No modification, neither in the morphology nor in the viability, of vascular human cells was observed by in vitro biocompatibility study up to 10 µM astaxanthin concentrations. Therefore, these results revealed the therapeutic potential of the natural extracts in vascular human cell protection against oxidative stress without toxicity, which could be exploited in prevention and/or treatment of cardiovascular diseases.

Toxicity of functional nano-micro zinc oxide tetrapods: impact of cell culture conditions, cellular age and material properties.

Science.gov (United States)

Papavlassopoulos, Heike; Mishra, Yogendra K; Kaps, Sören; Paulowicz, Ingo; Abdelaziz, Ramzy; Elbahri, Mady; Maser, Edmund; Adelung, Rainer; Röhl, Claudia

2014-01-01

With increasing production and applications of nanostructured zinc oxide, e.g., for biomedical and consumer products, the question of safety is getting more and more important. Different morphologies of zinc oxide structures have been synthesized and accordingly investigated. In this study, we have particularly focused on nano-micro ZnO tetrapods (ZnO-T), because their large scale fabrication has been made possible by a newly introduced flame transport synthesis approach which will probably lead to several new applications. Moreover, ZnO-T provide a completely different morphology then classical spherical ZnO nanoparticles. To get a better understanding of parameters that affect the interactions between ZnO-T and mammalian cells, and thus their biocompatibility, we have examined the impact of cell culture conditions as well as of material properties on cytotoxicity. Our results demonstrate that the cell density of fibroblasts in culture along with their age, i.e., the number of preceding cell divisions, strongly affect the cytotoxic potency of ZnO-T. Concerning the material properties, the toxic potency of ZnO-T is found to be significantly lower than that of spherical ZnO nanoparticles. Furthermore, the morphology of the ZnO-T influenced cellular toxicity in contrast to surface charges modified by UV illumination or O2 treatment and to the material age. Finally, we have observed that direct contact between tetrapods and cells increases their toxicity compared to transwell culture models which allow only an indirect effect via released zinc ions. The results reveal several parameters that can be of importance for the assessment of ZnO-T toxicity in cell cultures and for particle development.

Comparison of Oxidative Stresses Mediated by Different Crystalline Forms and Surface Modification of Titanium Dioxide Nanoparticles

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Karim Samy El-Said

2015-01-01

Full Text Available Titanium dioxide nanoparticles (TiO2 NPs are manufactured worldwide for use in a wide range of applications. There are two common crystalline forms of TiO2 anatase and rutile with different physical and chemical characteristics. We previously demonstrated that an increased DNA damage response is mediated by anatase crystalline form compared to rutile. In the present study, we conjugated TiO2 NPs with polyethylene glycol (PEG in order to reduce the genotoxicity and we evaluated some oxidative stress parameters to obtain information on the cellular mechanisms of DNA damage that operate in response to TiO2 NPs different crystalline forms exposure in hepatocarcinoma cell lines (HepG2. Our results indicated a significant increase in oxidative stress mediated by the anatase form of TiO2 NPs compared to rutile form. On the other hand, PEG modified TiO2 NPs showed a significant decrease in oxidative stress as compared to TiO2 NPs. These data suggested that the genotoxic potential of TiO2 NPs varies with crystalline form and surface modification.

Shape-dependent bactericidal activity of copper oxide nanoparticle mediated by DNA and membrane damage

International Nuclear Information System (INIS)

Laha, Dipranjan; Pramanik, Arindam; Laskar, Aparna; Jana, Madhurya; Pramanik, Panchanan; Karmakar, Parimal

2014-01-01

Highlights: • Spherical and sheet shaped copper oxide nanoparticles were synthesized. • Physical characterizations of these nanoparticles were done by TEM, DLS, XRD, FTIR. • They showed shape dependent antibacterial activity on different bacterial strain. • They induced both membrane damage and ROS mediated DNA damage in bacteria. - Abstract: In this work, we synthesized spherical and sheet shaped copper oxide nanoparticles and their physical characterizations were done by the X-ray diffraction, fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The antibacterial activity of these nanoparticles was determined on both gram positive and gram negative bacterial. Spherical shaped copper oxide nanoparticles showed more antibacterial property on gram positive bacteria where as sheet shaped copper oxide nanoparticles are more active on gram negative bacteria. We also demonstrated that copper oxide nanoparticles produced reactive oxygen species in both gram negative and gram positive bacteria. Furthermore, they induced membrane damage as determined by atomic force microscopy and scanning electron microscopy. Thus production of and membrane damage are major mechanisms of the bactericidal activity of these copper oxide nanoparticles. Finally it was concluded that antibacterial activity of nanoparticles depend on physicochemical properties of copper oxide nanoparticles and bacterial strain

Shape-dependent bactericidal activity of copper oxide nanoparticle mediated by DNA and membrane damage

Energy Technology Data Exchange (ETDEWEB)

Laha, Dipranjan; Pramanik, Arindam [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India); Laskar, Aparna [CSIR-Indian Institute of Chemical Biology, Kolkata 700032 (India); Jana, Madhurya [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India); Pramanik, Panchanan [Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India); Karmakar, Parimal, E-mail: pkarmakar_28@yahoo.co.in [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India)

2014-11-15

Highlights: • Spherical and sheet shaped copper oxide nanoparticles were synthesized. • Physical characterizations of these nanoparticles were done by TEM, DLS, XRD, FTIR. • They showed shape dependent antibacterial activity on different bacterial strain. • They induced both membrane damage and ROS mediated DNA damage in bacteria. - Abstract: In this work, we synthesized spherical and sheet shaped copper oxide nanoparticles and their physical characterizations were done by the X-ray diffraction, fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The antibacterial activity of these nanoparticles was determined on both gram positive and gram negative bacterial. Spherical shaped copper oxide nanoparticles showed more antibacterial property on gram positive bacteria where as sheet shaped copper oxide nanoparticles are more active on gram negative bacteria. We also demonstrated that copper oxide nanoparticles produced reactive oxygen species in both gram negative and gram positive bacteria. Furthermore, they induced membrane damage as determined by atomic force microscopy and scanning electron microscopy. Thus production of and membrane damage are major mechanisms of the bactericidal activity of these copper oxide nanoparticles. Finally it was concluded that antibacterial activity of nanoparticles depend on physicochemical properties of copper oxide nanoparticles and bacterial strain.

Surface characteristics, copper release, and toxicity of nano- and micrometer-sized copper and copper(II) oxide particles: a cross-disciplinary study.

OpenAIRE

Midander, Klara; Cronholm, Pontus; Karlsson, Hanna L.; Elihn, Karine; Moller, Lennart; Leygraf, Christofer; Wallinder, Inger Odnevall

2009-01-01

An interdisciplinary and multianalytical research effort is undertaken to assess the toxic aspects of thoroughly characterized nano- and micrometer-sized particles of oxidized metallic copper and copper(II) oxide in contact with cultivated lung cells, as well as copper release in relevant media. All particles, except micrometer-sized Cu, release more copper in serum-containing cell medium (supplemented Dulbecco's minimal essential medium) compared to identical exposures in phosphate-buffered ...

Induction of oxidative and nitrosative stresses in human retinal pigment epithelial cells by all-trans-retinal

Energy Technology Data Exchange (ETDEWEB)

Zhu, Xue [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China); Wang, Ke, E-mail: wangke@jsinm.org [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China); Zhang, Kai [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China); Zhou, Fanfan [Faculty of Pharmacy, University of Sydney, New South Wales 2006 (Australia); Zhu, Ling [Save Sight Institute, University of Sydney, New South Wales 2000 (Australia)

2016-10-15

Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up-regulation of reactive oxygen species (ROS) generation, activating mitochondrial-dependent and MAPKs signaling pathways, and finally resulting in apoptosis of ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS generation, indicating that NADPH oxidase activity was involved in atRAL-induced oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM-1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above effects could be dramatically blocked by using a nuclear factor kappa B (NF-κB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative stresses were mediated by NF-κB. The results provide better understanding of atRAL-induced toxicity in human RPE cells. - Highlights: • atRAL induces oxidative stress-mediated apoptosis in ARPE-19 cells. • atRAL induces oxidative stress-mediated inflammation in ARPE-19 cells. • NF-κB is involved in atRAL-induced oxidative and nitrosative stresses.

Induction of oxidative and nitrosative stresses in human retinal pigment epithelial cells by all-trans-retinal

International Nuclear Information System (INIS)

Zhu, Xue; Wang, Ke; Zhang, Kai; Zhou, Fanfan; Zhu, Ling

2016-01-01

Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up-regulation of reactive oxygen species (ROS) generation, activating mitochondrial-dependent and MAPKs signaling pathways, and finally resulting in apoptosis of ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS generation, indicating that NADPH oxidase activity was involved in atRAL-induced oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM-1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above effects could be dramatically blocked by using a nuclear factor kappa B (NF-κB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative stresses were mediated by NF-κB. The results provide better understanding of atRAL-induced toxicity in human RPE cells. - Highlights: • atRAL induces oxidative stress-mediated apoptosis in ARPE-19 cells. • atRAL induces oxidative stress-mediated inflammation in ARPE-19 cells. • NF-κB is involved in atRAL-induced oxidative and nitrosative stresses.

Toxicity and oxidative stress of different forms of organic selenium (Se) and dietary protein in mallard (Anas platyrhynchos) ducklings

Science.gov (United States)

Hoffman, D.; Heinz, G.; Eisemann, J.; Pendleton, G.

1994-01-01

High concentrations of Se have been found in aquatic food chains associated with irrigation drainwater and toxicity to fish and wildlife. Earlier studies have compared toxicities of Se as selenite and as seleno-DL-methionine (DL) in mallards. This study compares DL, seleno-L-methionine (L), selenized yeast (Y) and selenized wheat (W). Day-old mallard ducklings received an untreated diet (controls) containing 75% wheat (22% protein) or the same diet containing 15 or 30 ppm Se in the above forms. After 2 weeks blood and liver samples were collected for biochemical assays and Se analysis. All forms of selenium caused significant increases in plasma and hepatic glutathione peroxidase activities. Se as L was the most toxic, resulting in high mortality (64%) and impaired growth (>50%) and the greatest increase in ratio of oxidized to reduced glutathione with 30 ppm in the diet. Se as Y accumulated the least in liver. In a subsequent experiment with 30% dietary protein Se as L was less toxic.

Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

Energy Technology Data Exchange (ETDEWEB)

Wang, Lu; Gallagher, Evan P., E-mail: evang3@uw.edu

2013-01-15

Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidative stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function. -- Highlights: ► Oxidative stress is an important mechanism of Cd-mediated olfactory injury. ► Cd induces antioxidant gene expression in the zebrafish olfactory system. ► The

Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

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Klingelhoeffer Christoph

2012-05-01

Full Text Available Abstract Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L. The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods Effective concentration (EC50 values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 50 of 2.6–5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L, was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L. Conclusions Fifty-five percent of the human cancer cell lines tested were unable to protect themselves

Raphanus sativus extract protects against Zearalenone induced reproductive toxicity, oxidative stress and mutagenic alterations in male Balb/c mice.

Science.gov (United States)

Ben Salah-Abbès, Jalila; Abbès, Samir; Abdel-Wahhab, Mosaad A; Oueslati, Ridha

2009-04-01

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. There is unequivocal evidence of reproductive toxicity of ZEN in male mice although the mechanism of action is unknown. Several reports suggest that exposure to ZEN resulted in oxidative stress, genotoxicity and perturbation of reproductive parameters. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Raphanus sativus growing in Tunisia against ZEN-induced reproductive toxicity and oxidative stress. Fifty male Balb/c mice were divided into five groups and treated for 28 days as follows: the control group, olive oil-treated groups, another treated with ZEN (40 mg/kg b.w), the last one treated with R. sativus extract alone (15 mg/kg b.w) and the other with ZEN + R. sativus extract. Testis samples were collected for the epididymal sperm count, testosterone concentration, and MDA level, GPx, CAT and SOD activities. Blood samples were collected for different biochemical analyses. Also, RAPD-PCR method was performed to assess the antigenotoxic effect of the extract in germ cells. The results indicated that ZEN-induced toxicological effects in accordance to those reported in the literature: decreasing in the sperm number, testosterone level and antioxidant enzyme status. The RAPD-PCR analysis revealed an alteration in the DNA bands patterns between control and ZEN-treated mice. The extract alone, rich in many antioxidant compounds, was safe and succeeded in counteracting the oxidative stress and protect against the toxicity resulting from ZEN.

C-X-C Chemokine Receptor Type 4 Plays a Crucial Role in Mediating Oxidative Stress-Induced Podocyte Injury.

Science.gov (United States)

Mo, Hongyan; Wu, Qinyu; Miao, Jinhua; Luo, Congwei; Hong, Xue; Wang, Yongping; Tang, Lan; Hou, Fan Fan; Liu, Youhua; Zhou, Lili

2017-08-20

Oxidative stress plays a role in mediating podocyte injury and proteinuria. However, the underlying mechanism remains poorly understood. In this study, we investigated the potential role of C-X-C chemokine receptor type 4 (CXCR4), the receptor for stromal cell-derived factor 1α (SDF-1α), in mediating oxidative stress-induced podocyte injury. In mouse model of adriamycin nephropathy (ADR), CXCR4 expression was significantly induced in podocytes as early as 3 days. This was accompanied by an increased upregulation of oxidative stress in podocyte, as demonstrated by malondialdehyde assay, nitrotyrosine staining and secretion of 8-hydroxy-2'-deoxyguanosine in urine, and induction of NOX2 and NOX4, major subunits of NADPH oxidase. CXCR4 was also induced in human kidney biopsies with proteinuric kidney diseases and colocalized with advanced oxidation protein products (AOPPs), an established oxidative stress trigger. Using cultured podocytes and mouse model, we found that AOPPs induced significant loss of podocyte marker Wilms tumor 1 (WT1), nephrin, and podocalyxin, accompanied by upregulation of desmin both in vitro and in vivo. Furthermore, AOPPs worsened proteinuria and aggravated glomerulosclerosis in ADR. These effects were associated with marked activation of SDF-1α/CXCR4 axis in podocytes. Administration of AMD3100, a specific inhibitor of CXCR4, reduced proteinuria and ameliorated podocyte dysfunction and renal fibrosis triggered by AOPPs in mice. In glomerular miniorgan culture, AOPPs also induced CXCR4 expression and downregulated nephrin and WT1. Innovation and Conclusion: These results suggest that chemokine receptor CXCR4 plays a crucial role in mediating oxidative stress-induced podocyte injury, proteinuria, and renal fibrosis. CXCR4 could be a new target for mitigating podocyte injury, proteinuria, and glomerular sclerosis in proteinuric chronic kidney disease. Antioxid. Redox Signal. 27, 345-362.

Fingerprinting the reactive toxicity pathways of 50 drinking water disinfection by-products.

Science.gov (United States)

Stalter, Daniel; O'Malley, Elissa; von Gunten, Urs; Escher, Beate I

2016-03-15

A set of nine in vitro cellular bioassays indicative of different stages of the cellular toxicity pathway was applied to 50 disinfection by-products (DBPs) to obtain a better understanding of the commonalities and differences in the molecular mechanisms of reactive toxicity of DBPs. An Eschericia coli test battery revealed reactivity towards proteins/peptides for 64% of the compounds. 98% activated the NRf2-mediated oxidative stress response and 68% induced an adaptive stress response to genotoxic effects as indicated by the activation of the tumor suppressor protein p53. All DBPs reactive towards DNA in the E. coli assay and activating p53 also induced oxidative stress, confirming earlier studies that the latter could trigger DBP's carcinogenicity. The energy of the lowest unoccupied molecular orbital ELUMO as reactivity descriptor was linearly correlated with oxidative stress induction for trihalomethanes (r(2)=0.98) and haloacetamides (r(2)=0.58), indicating that potency of these DBPs is connected to electrophilicity. However, the descriptive power was poor for haloacetic acids (HAAs) and haloacetonitriles (r(2) (0.80, indicating that HAAs' potency is connected to both, electrophilicity and speciation. Based on the activation of oxidative stress response and the soft electrophilic character of most tested DBPs we hypothesize that indirect genotoxicity-e.g., through oxidative stress induction and/or enzyme inhibition-is more plausible than direct DNA damage for most investigated DBPs. The results provide not only a mechanistic understanding of the cellular effects of DBPs but the effect concentrations may also serve to evaluate mixture effects of DBPs in water samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced microbial decolorization of methyl red with oxidized carbon fiber as redox mediator

Energy Technology Data Exchange (ETDEWEB)

Emilia Rios-Del Toro, E. [División de Ciencias Ambientales, Instituto Potosino de Investigación Científica y Tecnológica (IPICyT), Camino a la Presa San José 2055, Col. Lomas 4a Sección, San Luis Potosí, SLP 78216 (Mexico); Celis, Lourdes B. [División de Geociencias Aplicadas, Instituto Potosino de Investigación Científica y Tecnológica (IPICyT), Camino a la Presa San José 2055, Col. Lomas 4a Sección, San Luis Potosí, SLP 78216 (Mexico); Cervantes, Francisco J. [División de Ciencias Ambientales, Instituto Potosino de Investigación Científica y Tecnológica (IPICyT), Camino a la Presa San José 2055, Col. Lomas 4a Sección, San Luis Potosí, SLP 78216 (Mexico); Rangel-Mendez, J. Rene, E-mail: rene@ipicyt.edu.mx [División de Ciencias Ambientales, Instituto Potosino de Investigación Científica y Tecnológica (IPICyT), Camino a la Presa San José 2055, Col. Lomas 4a Sección, San Luis Potosí, SLP 78216 (Mexico)

2013-09-15

Highlights: • Activated carbon fibers (ACFs) act as redox mediator. • Electron accepting capacity increased with oxidation time of ACF. •ACFs increased 8-fold the reduction of methyl red in biological assays. •Biofilm formed on the ACFs partly blocked their redox mediator capacity. -- Abstract: The anaerobic degradation of azo dyes under anaerobic conditions is possible but at a slow rate. Redox mediators (quinones, activated carbon) are used to improve the reduction rate. The aim of this work was to use activated carbon fiber (ACF) as a redox mediator for the anaerobic reduction of the azo dye methyl red. ACF was chemically modified with 8 M HNO{sub 3} to increase its redox-mediating capacity and used in chemical and anaerobic biological batch assays for the reduction of methyl red. ACF increased its redox-mediating capacity up to 3-fold in chemical assays; in biological assays ACF increased the reduction rate up to 8-fold compared to controls without ACF. However, since the ACF served as support for biomass, a biofilm formed on the fiber significantly reduced its redox-mediating capacity; substrate consumption suggested that the electron transport from ACF to methyl red was the rate-limiting step in the process. These results are the first evidence of the role of ACF as a redox mediator in the reductive decolorization of methyl red, in addition to the effect of biofilm attached to ACF on methyl red reduction. Due to the versatile characteristics of ACF and its redox-mediating capacity, carbon fibers could be used in biological wastewater treatment systems to accelerate the reductive transformation of pollutants commonly found in industrial effluents.

Enhanced microbial decolorization of methyl red with oxidized carbon fiber as redox mediator

International Nuclear Information System (INIS)

Emilia Rios-Del Toro, E.; Celis, Lourdes B.; Cervantes, Francisco J.; Rangel-Mendez, J. Rene

2013-01-01

Highlights: • Activated carbon fibers (ACFs) act as redox mediator. • Electron accepting capacity increased with oxidation time of ACF. •ACFs increased 8-fold the reduction of methyl red in biological assays. •Biofilm formed on the ACFs partly blocked their redox mediator capacity. -- Abstract: The anaerobic degradation of azo dyes under anaerobic conditions is possible but at a slow rate. Redox mediators (quinones, activated carbon) are used to improve the reduction rate. The aim of this work was to use activated carbon fiber (ACF) as a redox mediator for the anaerobic reduction of the azo dye methyl red. ACF was chemically modified with 8 M HNO 3 to increase its redox-mediating capacity and used in chemical and anaerobic biological batch assays for the reduction of methyl red. ACF increased its redox-mediating capacity up to 3-fold in chemical assays; in biological assays ACF increased the reduction rate up to 8-fold compared to controls without ACF. However, since the ACF served as support for biomass, a biofilm formed on the fiber significantly reduced its redox-mediating capacity; substrate consumption suggested that the electron transport from ACF to methyl red was the rate-limiting step in the process. These results are the first evidence of the role of ACF as a redox mediator in the reductive decolorization of methyl red, in addition to the effect of biofilm attached to ACF on methyl red reduction. Due to the versatile characteristics of ACF and its redox-mediating capacity, carbon fibers could be used in biological wastewater treatment systems to accelerate the reductive transformation of pollutants commonly found in industrial effluents

General aspects of metal toxicity.

Science.gov (United States)

Kozlowski, H; Kolkowska, P; Watly, J; Krzywoszynska, K; Potocki, S

2014-01-01

This review is focused on the general mechanisms of metal toxicity in humans. The possible and mainly confirmed mechanisms of their action are discussed. The metals are divided into four groups due to their toxic effects. First group comprises of metal ions acting as Fenton reaction catalyst mainly iron and copper. These types of metal ions participate in generation of the reactive oxygen species. Metals such as nickel, cadmium and chromium are considered as carcinogenic agents. Aluminum, lead and tin are involved in neurotoxicity. The representative of the last group is mercury, which may be considered as a generally toxic metal. Fenton reaction is a naturally occurring process producing most active oxygen species, hydroxyl radical: Fe(2+) + He2O2 ↔ Fe(3+) + OH(-) + OH(•) It is able to oxidize most of the biomolecules including DNA, proteins, lipids etc. The effect of toxicity depends on the damage of molecules i.e. production site of the hydroxyl radical. Chromium toxicity depends critically on its oxidation state. The most hazardous seems to be Cr(6+) (chromates) which are one of the strongest inorganic carcinogenic agents. Cr(6+) species act also as oxidative agents damaging among other nucleic acids. Redox inactive Al(3+), Cd(2+) or Hg(2+) may interfere with biology of other metal ions e.g. by occupying metal binding sites in biomolecules. All these aspects will be discussed in the review.

Water-mediated interactions between trimethylamine-N-oxide and urea.

Science.gov (United States)

Hunger, Johannes; Ottosson, Niklas; Mazur, Kamila; Bonn, Mischa; Bakker, Huib J

2015-01-07

The amphiphilic osmolyte trimethylamine-N-oxide (TMAO) is commonly found in natural organisms, where it counteracts biochemical stress associated with urea in aqueous environments. Despite the important role of TMAO as osmoprotectant, the mechanism behind TMAO's action has remained elusive. Here, we study the interaction between urea, TMAO, and water in solution using broadband (100 MHz-1.6 THz) dielectric spectroscopy. We find that the previously reported tight hydrogen bonds between 3 water molecules and the hydrophilic amine oxide group of TMAO, remain intact at all investigated concentrations of urea, showing that no significant hydrogen bonding occurs between the two co-solutes. Despite the absence of direct TMAO-urea interactions, the solute reorientation times of urea and TMAO show an anomalous nonlinear increase with concentration, for ternary mixtures containing equal amounts of TMAO and urea. The nonlinear increase of the reorientation correlates with changes in the viscosity, showing that the combination of TMAO and urea cooperatively enhances the hydrogen-bond structure of the ternary solutions. This nonlinear increase is indicative of water mediated interaction between the two solutes and is not observed if urea is combined with other amphiphilic solutes.

Mediated electrochemical oxidation of mixed wastes

International Nuclear Information System (INIS)

Chiba, Z.

1993-04-01

The Mediated Electrochemical Oxidation (MEO) process was studied for destroying low-level combustible mixed wastes at Rocky Flats Plant. Tests were performed with non-radioactive surrogate materials: Trimsol for contaminated cutting oils, and reagent-grade cellulose for contaminated cellulosic wastes. Extensive testing was carried out on Trimsol in both small laboratory-scale apparatus and on a large-scale system incorporating an industrial-size electrochemical cell. Preliminary tests were also carried out in the small-scale system with cellulose. Operating and system parameters that were studied were: use of a silver-nitric acid versus a cobalt-sulfuric acid system, effect of electrolyte temperature, effect of acid concentration, and effect of current density. Destruction and coulombic efficiencies were calculated using data obtained from continuous carbon dioxide monitors and total organic carbon (TOC) analysis of electrolyte samples. For Trimsol, the best performance was achieved with the silver-nitrate system at high acid concentrations, temperatures, and current densities. Destruction efficiencies of 99% or greater, and coulombic efficiencies up to 70% were obtained. For the cellulose, high destruction efficiencies and reasonable coulombic efficiencies were obtained for both silver-nitrate and cobalt-sulfate systems

Role of CYP2E1-mediated metabolism in the acute and vestibular toxicities of nineteen nitriles in the mouse.

Science.gov (United States)

Saldaña-Ruíz, Sandra; Soler-Martín, Carla; Llorens, Jordi

2012-01-25

Allylnitrile, cis-crotononitrile, and 3,3'-iminodipropionitrile are known to cause vestibular toxicity in rodents, and evidence is available indicating that cis-2-pentenenitrile shares this effect. We evaluated nineteen nitriles for vestibular toxicity in wild type (129S1) and CYP2E1-null mice, including all the above, several neurotoxic nitriles, and structurally similar nitriles. A new acute toxicity test protocol was developed to facilitate evaluation of the vestibular toxicity by a specific behavioral test battery at doses up to sub-lethal levels while using a limited number of animals. A mean number of 8.5±0.3 animals per nitrile, strain and sex was necessary to obtain evidence of vestibular toxicity and optionally an estimation of the lethal dose. For several but not all nitriles, lethal doses significantly increased in CYP2E1-null mice. The protocol revealed the vestibular toxicity of five nitriles, including previously identified ototoxic compounds and one nitrile (trans-crotononitrile) known to have a different profile of neurotoxic effects in the rat. In all five cases, both sexes were affected and no decrease in susceptibility was apparent in CYP2E1-null mice respect to 129S1 mice. Fourteen nitriles caused no vestibular toxicity, including six nitriles tested in CYP2E1-null mice at doses significantly larger than the maximal doses that can be tested in wild type animals. We conclude that only a subset of low molecular weight nitriles is toxic to the vestibular system, that species-dependent differences exist in this vestibular toxicity, and that CYP2E1-mediated metabolism is not involved in this effect of nitriles although it has a role in the acute lethality of some of these compounds. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Preparation of Zeolite/Zinc Oxide Nanocomposites for toxic metals removal from water

Directory of Open Access Journals (Sweden)

Abdullah A. Alswata

Full Text Available This research work has proposed preparation of Zeolite/Zinc Oxide Nanocomposite (Zeolite/ZnO NCs by using a co-precipitation method. Then, the prepared Nanocomposite has been tested for adsorption of Lead Pb (II and Arsenic As (V from aqueous solution under the room pressure and temperature. After that, the prepared adsorbent has been studied by several techniques. For adsorption process; the effect of the adsorbent masses, contact time, PH and initial metals concentration as well as, the kinetics and isotherm for adsorption process have been investigated. The results revealed that; ZnO nanoparticles (NPs with average diameter 4.5 nm have successfully been loaded into Zeolite. The optimum parameters for the removal of the toxic metals 93% and 89% of Pb (II and As (V, respectively, in 100 mg/L aqua solutions were pH4, 0.15 g and 30 min. According to the obtained results; pseudo second-order kinetic and Langmuir isotherm model have higher correlation coefficients and provided a better agreement with the experimental data. The prepared sorbent showed an economical and effective way to remove the heavy toxic metals due to its ambient operation conditions, low- consumption energy and facile regeneration method. Keywords: Zeolite, ZnO, Nanocomposites, Adsorbent, Kinetic, Isotherm

Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity.

Science.gov (United States)

De, Soumita; Sen, Tuhinadri; Chatterjee, Mitali

2015-11-01

Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg(-1) b.w., p.o.) were administered with a single dose of MTX (20 mg kg(-1), b.w., i.p.) and its hepatoprotective efficacy was compared with folic acid (1 mg kg(-1) b.w., i.p.), conventionally used to minimize MTX-induced toxicity. MTX-induced hepatotoxicity was confirmed by increased activities of marker enzymes, alanine transaminase, aspartate transaminase, and alkaline phosphatase which were remitted by pre-treatment with PB and corroborated with histopathology. Additionally, MTX-induced hepatic oxidative stress which included increased generation of reactive oxygen species, enhanced lipid peroxidation, depleted levels of glutathione and decreased activities of antioxidant enzymes was effectively mitigated by PB, indicative that its promising antioxidant-mediated hepatoprotective activity was worthy of future pharmacological consideration.

Polydopamine-mediated surface-functionalization of graphene oxide for heavy metal ions removal

International Nuclear Information System (INIS)

Dong, Zhihui; Zhang, Feng; Wang, Dong; Liu, Xia; Jin, Jian

2015-01-01

By utilizing polydopamine (PD) nano-thick interlayer as mediator, polyethylenimine (PEI) brushes with abundant amine groups were grafted onto the surface of PD coated graphene oxide (GO) uniformly via a Michael-Addition reaction and produced a PEI–PD/GO composite nanosheets. The PEI–PD/GO composite exhibited an improved performance for adsorption of heavy metal ions as compared to PEI-coated GO and pure GO. The adsorption capacities for Cu 2+ , Cd 2+ , Pb 2+ , Hg 2+ are up to 87, 106, 197, and 110 mg/g, respectively. To further make the GO based composite operable, PEI–PD/RGO aerogel was prepared through hydrothermal and achieved a high surface area up to 373 m 2 /g. Although the adsorption capacity of PEI–PD/RGO aerogel for heavy metal ions decreases a little as compared to PEI–PD/GO composite dispersion (38, 32, 95, 113 mg/g corresponding to Cu 2+ , Cd 2+ , Pb 2+ , and Hg 2+ , respectively), it could be recycled several times in a simple way by releasing adsorbed metal ions, indicating its potential application for cleaning wastewater. - Graphical abstract: Polyethylenimine (PEI) brushes were grafted onto the surface of graphene oxide (GO) uniformly via a Michael-Addition reaction between the PEI and polydopamine interlayer coated on GO surface. The PEI–PD/GO composite exhibited an improved performance for adsorption of heavy metal ions compared to PEI-coated GO and pure GO. - Highlights: • We prepared polyethylenimine grafted polydopamine-mediated graphene oxide composites. • Introduction of PD layer increases metal ions adsorption capacity. • PEI–PD/RGO aerogel exhibited a superior adsorption performance. • PEI–PD/RGO aerogel can be recycled several times in a simple way

ROS dependent copper toxicity in Hydra-biochemical and molecular study.

Science.gov (United States)

Zeeshan, Mohammed; Murugadas, Anbazhagan; Ghaskadbi, Surendra; Rajendran, Ramasamy Babu; Akbarsha, Mohammad Abdulkader

2016-01-01

Copper, an essential microelement, is known to be toxic to aquatic life at concentrations higher than that could be tolerated. Copper-induced oxidative stress has been documented in vitro, yet the in vivo effects of metal-induced oxidative stress have not been extensively studied in the lower invertebrates. The objective of the present study has been to find the effect of ROS-mediated toxicity of environmentally relevant concentrations of copper at organismal and cellular levels in Hydra magnipapillata. Exposure to copper at sublethal concentrations (0.06 and 0.1mg/L) for 24 or 48h resulted in generation of significant levels of intracellular reactive oxygen species (ROS). We infer that the free radicals here originate predominantly at the lysosomes but partly at the mitochondria also as visualized by H2-DHCFDA staining. Quantitative real-time PCR of RNA extracted from copper-exposed polyps revealed dose-dependent up-regulation of all antioxidant response genes (CAT, SOD, GPx, GST, GR, G6PD). Concurrent increase of Hsp70 and FoxO genes suggests the ability of polyps to respond to stress, which at 48h was not the same as at 24h. Interestingly, the transcript levels of all genes were down-regulated at 48h as compared to 24h incubation period. Comet assay indicated copper as a powerful genotoxicant, and the DNA damage was dose- as well as duration-dependent. Western blotting of proteins (Bax, Bcl-2 and caspase-3) confirmed ROS-mediated mitochondrial cell death in copper-exposed animals. These changes correlated well with changes in morphology, regeneration and aspects of reproduction. Taken together, the results indicate increased production of intracellular ROS in Hydra on copper exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Celiac Disease, Inflammation and Oxidative Damage: A Nutrigenetic Approach

Directory of Open Access Journals (Sweden)

Letizia Saturni

2012-03-01

Full Text Available Celiac disease (CD, a common heritable chronic inflammatory condition of the small intestine caused by permanent intolerance to gluten/gliadin (prolamin, is characterized by a complex interplay between genetic and environmental factors. Developments in proteomics have provided an important contribution to the understanding of the biochemical and immunological aspects of the disease and the mechanisms involved in toxicity of prolamins. It has been demonstrated that some gliadin peptides resistant to complete proteolytic digestion may directly affect intestinal cell structure and functions by modulating gene expression and oxidative stress. In recent years, the creation of the two research fields Nutrigenomics and Nutrigenetics, has enabled the elucidation of some interactions between diet, nutrients and genes. Various dietary components including long chain ω-3 fatty acids, plant flavonoids, and carotenoids have been demonstrated to modulate oxidative stress, gene expression and production of inflammatory mediators. Therefore their adoption could preserve intestinal barrier integrity, play a protective role against toxicity of gliadin peptides and have a role in nutritional therapy of celiac disease.

Toxic response of nickel nanoparticles in human lung epithelial A549 cells.

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Ahamed, Maqusood

2011-06-01

Nickel nanoparticle (Ni NP) is increasingly used in modern industries such as catalysts, sensors and electronic applications. Due to wide-spread industrial applications the inhalation is the primary source of exposure to Ni NPs. However, data demonstrating the effect of Ni NPs on the pulmonary system remain scarce. The present study was designed to examine the toxic effect of human lung epithelial A549 cells treated with well characterized Ni NPs at the concentrations of 0, 1, 2, 5, 10 and 25 μg/ml for 24 and 48 h. Mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH), reactive oxygen species (ROS), membrane lipid peroxidation (LPO) and caspase-3 activity were assessed as toxicity end points. Results showed that Ni NPs reduced mitochondrial function and induced the leakage of LDH in dose and time-dependent manner. Ni NPs were also found to induce oxidative stress in dose and time-dependent manner indicated by depletion of GSH and induction of ROS and LPO. Further, activity of caspase-3 enzyme, marker of apoptosis was significantly higher in treated cells with time and Ni NPs dosage. The results exhibited significant toxicity of Ni NPs in human lung epithelial A549 cells which is likely to be mediated through oxidative stress. This study warrants more careful assessment of Ni NPs before their industrial applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Recombinant heat shock protein 27 (HSP27/HSPB1) protects against cadmium-induced oxidative stress and toxicity in human cervical cancer cells.

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Alvarez-Olmedo, Daiana G; Biaggio, Veronica S; Koumbadinga, Geremy A; Gómez, Nidia N; Shi, Chunhua; Ciocca, Daniel R; Batulan, Zarah; Fanelli, Mariel A; O'Brien, Edward R

2017-05-01

Cadmium (Cd) is a carcinogen with several well-described toxicological effects in humans, but its molecular mechanisms are still not fully understood. Overexpression of heat shock protein 27 (HSP27/HSPB1)-a multifunctional protein chaperone-has been shown to protect cells from oxidative damage and apoptosis triggered by Cd exposure. The aims of this work were to investigate the potential use of extracellular recombinant HSP27 to prevent/counteract Cd-induced cellular toxicity and to evaluate if peroxynitrite was involved in the development of Cd-induced toxicity. Here, we report that the harmful effects of Cd correlated with changes in oxidative stress markers: upregulation of reactive oxygen species, reduction in nitric oxide (NO) bioavailability, increment in lipid peroxidation, peroxynitrite (PN), and protein nitration; intracellular HSP27 was reduced. Treatments with Cd (100 μM) for 24 h or with the peroxynitrite donor, SIN-1, decreased HSP27 levels (~50%), suggesting that PN formation is responsible for the reduction of HSP27. Pre-treatments of the cells either with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) (a pharmacological inhibitor of NO synthase) or with recombinant HSP27 (rHSP27) attenuated the disruption of the cellular metabolism induced by Cd, increasing in a 55 and 52%, respectively, the cell viability measured by CCK-8. Cd induced necrotic cell death pathways, although apoptosis was also activated; pre-treatment with L-NAME or rHSP27 mitigated cell death. Our findings show for the first time a direct relationship between Cd-induced toxicity and PN production and a role for rHSP27 as a potential therapeutic agent that may counteract Cd toxicity.

Organ-Protective Effects of Red Wine Extract, Resveratrol, in Oxidative Stress-Mediated Reperfusion Injury

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Fu-Chao Liu

2015-01-01

Full Text Available Resveratrol, a polyphenol extracted from red wine, possesses potential antioxidative and anti-inflammatory effects, including the reduction of free radicals and proinflammatory mediators overproduction, the alteration of the expression of adhesion molecules, and the inhibition of neutrophil function. A growing body of evidence indicates that resveratrol plays an important role in reducing organ damage following ischemia- and hemorrhage-induced reperfusion injury. Such protective phenomenon is reported to be implicated in decreasing the formation and reaction of reactive oxygen species and pro-nflammatory cytokines, as well as the mediation of a variety of intracellular signaling pathways, including the nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, deacetylase sirtuin 1, mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, hemeoxygenase-1, and estrogen receptor-related pathways. Reperfusion injury is a complex pathophysiological process that involves multiple factors and pathways. The resveratrol is an effective reactive oxygen species scavenger that exhibits an antioxidative property. In this review, the organ-protective effects of resveratrol in oxidative stress-related reperfusion injury will be discussed.

Evaluation of zinc oxide nanoparticles toxicity on marine algae chlorella vulgaris through flow cytometric, cytotoxicity and oxidative stress analysis.

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Suman, T Y; Radhika Rajasree, S R; Kirubagaran, R

2015-03-01

The increasing industrial use of nanomaterials during the last decades poses a potential threat to the environment and in particular to organisms living in the aquatic environment. In the present study, the toxicity of zinc oxide nanoparticles (ZnO NPs) was investigated in Marine algae Chlorella vulgaris (C. vulgaris). High zinc dissociation from ZnONPs, releasing ionic zinc in seawater, is a potential route for zinc assimilation and ZnONPs toxicity. To examine the mechanism of toxicity, C. vulgaris were treated with 50mg/L, 100mg/L, 200mg/L and 300 mg/L ZnO NPs for 24h and 72h. The detailed cytotoxicity assay showed a substantial reduction in the viability dependent on dose and exposure. Further, flow cytometry revealed the significant reduction in C. vulgaris viable cells to higher ZnO NPs. Significant reductions in LDH level were noted for ZnO NPs at 300 mg/L concentration. The activity of antioxidant enzyme superoxide dismutase (SOD) significantly increased in the C. vulgaris exposed to 200mg/L and 300 mg/L ZnO NPs. The content of non-enzymatic antioxidant glutathione (GSH) significantly decreased in the groups with a ZnO NPs concentration of higher than 100mg/L. The level of lipid peroxidation (LPO) was found to increase as the ZnO NPs dose increased. The FT-IR analyses suggested surface chemical interaction between nanoparticles and algal cells. The substantial morphological changes and cell wall damage were confirmed through microscopic analyses (FESEM and CM). Copyright © 2014 Elsevier Inc. All rights reserved.

Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury

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Hernandez-Montes, Eva; Pollard, Susan E.; Vauzour, David; Jofre-Montseny, Laia; Rota, Cristina; Rimbach, Gerald; Weinberg, Peter D.; Spencer, Jeremy P.E.

2006-01-01

Cellular actions of isoflavones may mediate the beneficial health effects associated with high soy consumption. We have investigated protection by genistein and daidzein against oxidative stress-induced endothelial injury. Genistein but not daidzein protected endothelial cells from damage induced by oxidative stress. This protection was accompanied by decreases in intracellular glutathione levels that could be explained by the generation of glutathionyl conjugates of the oxidised genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone. Both isoflavones evoked increased protein expression of γ-glutamylcysteine synthetase-heavy subunit (γ-GCS-HS) and increased cytosolic accumulation and nuclear translocation of Nrf2. However, only genistein led to increases in the cytosolic accumulation and nuclear translocation of Nrf1 and the increased expression of and activity of glutathione peroxidase. These results suggest that genistein-induced protective effects depend primarily on the activation of glutathione peroxidase mediated by Nrf1 activation, and not on Nrf2 activation or increases in glutathione synthesis

Photoenhanced Toxicity of Petroleum to Aquatic Invertebrates and Fish

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Photoenhanced toxicity is a distinct mechanism of petroleum toxicity that is mediated by the interaction of solar radiation with specific polycyclic aromatic compounds in oil. Phototoxicity is observed as a twofold to greater than 1000-fold increase in chemical toxicity to aquati...

Comparative Toxicity of Nanoparticulate CuO and ZnO to Soil Bacterial Communities

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Rousk, Johannes; Ackermann, Kathrin; Curling, Simon F.; Jones, Davey L.

2012-01-01

The increasing industrial application of metal oxide Engineered Nano-Particles (ENPs) is likely to increase their environmental release to soils. While the potential of metal oxide ENPs as environmental toxicants has been shown, lack of suitable control treatments have compromised the power of many previous assessments. We evaluated the ecotoxicity of ENP (nano) forms of Zn and Cu oxides in two different soils by measuring their ability to inhibit bacterial growth. We could show a direct acute toxicity of nano-CuO acting on soil bacteria while the macroparticulate (bulk) form of CuO was not toxic. In comparison, CuSO4 was more toxic than either oxide form. Unlike Cu, all forms of Zn were toxic to soil bacteria, and the bulk-ZnO was more toxic than the nano-ZnO. The ZnSO4 addition was not consistently more toxic than the oxide forms. Consistently, we found a tight link between the dissolved concentration of metal in solution and the inhibition of bacterial growth. The inconsistent toxicological response between soils could be explained by different resulting concentrations of metals in soil solution. Our findings suggested that the principal mechanism of toxicity was dissolution of metal oxides and sulphates into a metal ion form known to be highly toxic to bacteria, and not a direct effect of nano-sized particles acting on bacteria. We propose that integrated efforts toward directly assessing bioavailable metal concentrations are more valuable than spending resources to reassess ecotoxicology of ENPs separately from general metal toxicity. PMID:22479561

The allosteric behavior of Fur mediates oxidative stress signal transduction in Helicobacter pylori

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Simone ePelliciari

2015-08-01

Full Text Available The microaerophilic gastric pathogen Helicobacter pylori is exposed to oxidative stress originating from the aerobic environment, the oxidative burst of phagocytes and the formation of reactive oxygen species, catalyzed by iron excess. Accordingly, the expression of genes involved in oxidative stress defense have been repeatedly linked to the ferric uptake regulator Fur. Moreover, mutations in the Fur protein affect the resistance to metronidazole, likely due to loss-of-function in the regulation of genes involved in redox control. Although many advances in the molecular understanding of HpFur function were made, little is known about the mechanisms that enable Fur to mediate the responses to oxidative stress.Here we show that iron-inducible, apo-Fur repressed genes, such as pfr and hydA, are induced shortly after oxidative stress, while their oxidative induction is lost in a fur knockout strain. On the contrary, holo-Fur repressed genes, such as frpB1 and fecA1, vary modestly in response to oxidative stress. This indicates that the oxidative stress signal specifically targets apo-Fur repressed genes, rather than impairing indiscriminately the regulatory function of Fur. Footprinting analyses showed that the oxidative signal strongly impairs the binding affinity of Fur towards apo-operators, while the binding towards holo-operators is less affected. Further evidence is presented that a reduced state of Fur is needed to maintain apo-repression, while oxidative conditions shift the preferred binding architecture of Fur towards the holo-operator binding conformation, even in the absence of iron. Together the results demonstrate that the allosteric regulation of Fur enables transduction of oxidative stress signals in H. pylori, supporting the concept that apo-Fur repressed genes can be considered oxidation inducible Fur regulatory targets. These findings may have important implications in the study of H. pylori treatment and resistance to

Proinflammatory effects and oxidative stress within human bronchial epithelial cells exposed to atmospheric particulate matter (PM2.5 and PM>2.5) collected from Cotonou, Benin

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Cachon, Boris Fresnel; Firmin, Stéphane; Verdin, Anthony; Ayi-Fanou, Lucie

2014-01-01

After particulate matter (PM) collection in Cotonou (Benin), a complete physicochemical characterization of PM 2.5 and PM >2.5 was led. Then, their adverse health effects were evaluated by using in vitro culture of human lung cells. BEAS-2B (bronchial epithelial cells) were intoxicated during short-term exposure at increasing PM concentrations (1.5–96 μg/cm 2 ) to determine global cytotoxicity. Hence, cells were exposed to 3 and 12 μg/cm 2 to investigate the potential biological imbalance generated by PM toxicity. Our findings showed the ability of both PM to induce oxidative stress and to cause inflammatory cytokines/chemokines gene expression and secretion. Furthermore, PM were able to induce gene expression of enzymes involved in the xenobiotic metabolism pathway. Strong correlations between gene expression of metabolizing enzymes, proinflammatory responses and cell cycle alteration were found, as well as between proinflammatory responses and cell viability. Stress oxidant parameters were highly correlated with expression and protein secretion of inflammatory mediators. Highlights: • The aim of this study was to investigate the toxic potential of collected particles. • Toxicological effects were determined by using human bronchial epithelial cells. • Both particles induced oxidative stress, proinflammatory response and cell alterations. • Metabolizing enzymes were linked to proinflammatory responses and cell alterations. • Oxidative stress was highly correlated to the proinflammatory mediators. -- This study evidences the toxic potential of African fine and coarse particulate matters on respiratory epithelial cells

Toxic effects of maternal zearalenone exposure on intestinal oxidative stress, barrier function, immunological and morphological changes in rats.

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Min Liu

Full Text Available The present study was conducted to investigate the effects of maternal zearalenone (ZEN exposure on the intestine of pregnant Sprague-Dawley (SD rats and its offspring. Ninety-six pregnant SD rats were randomly divided into four groups and were fed with diets containing ZEN at concentrations of 0.3 mg/kg, 48.5 mg/kg, 97.6 mg/kg or 146.0 mg/kg from gestation days (GD 1 to 7. All rats were fed with mycotoxin-free diet until their offspring were weaned at three weeks of age. The small intestinal fragments from pregnant rats at GD8, weaned dams and pups were collected and studied for toxic effects of ZEN on antioxidant status, immune response, expression of junction proteins, and morphology. The results showed that ZEN induced oxidative stress, affected the villous structure and reduced the expression of junction proteins claudin-4, occludin and connexin43 (Cx43 in a dose-dependent manner in pregnant rats. Different effects on the expression of cytokines were also observed both in mRNA and protein levels in these pregnant groups. Ingestion of high levels of ZEN caused irreversible damage in weaned dams, such as oxidative stress, decreased villi hight and low expression of junction proteins and cytokines. Decreased expression of jejunal interleukin-8 (IL-8 and increased expression of gastrointestinal glutathione peroxidase (GPx2 mRNA were detected in weaned offspring, indicating long-term damage caused by maternal ZEN. We also found that the Nrf2 expression both in mRNA and protein levels were up-regulated in the ZEN-treated groups of pregnant dams and the high-dose of ZEN group of weaned dams. The data indicate that modulation of Nrf2-mediated pathway is one of mechanism via which ZEN affects gut wall antioxidant and inflammatory responses.

Sustained antimicrobial activity and reduced toxicity of oxidative biocides through biodegradable microparticles.

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Sofokleous, Panagiotis; Ali, Shanom; Wilson, Peter; Buanz, Asma; Gaisford, Simon; Mistry, Dharmit; Fellows, Adrian; Day, Richard M

2017-12-01

The spread of antibiotic-resistant pathogens requires new treatments. Small molecule precursor compounds that produce oxidative biocides with well-established antimicrobial properties could provide a range of new therapeutic products to combat resistant infections. The aim of this study was to investigate a novel biomaterials-based approach for the manufacture, targeted delivery and controlled release of a peroxygen donor (sodium percarbonate) combined with an acetyl donor (tetraacetylethylenediamine) to deliver local antimicrobial activity via a dynamic equilibrium mixture of hydrogen peroxide and peracetic acid. Entrapment of the pre-cursor compounds into hierarchically structured degradable microparticles was achieved using an innovative dry manufacturing process involving thermally induced phase separation (TIPS) that circumvented compound decomposition associated with conventional microparticle manufacture. The microparticles provided controlled release of hydrogen peroxide and peracetic acid that led to rapid and sustained killing of multiple drug-resistant organisms (methicillin-resistant Staphylococcus aureus and carbapenem-resistant Escherichia coli) without associated cytotoxicity in vitro nor intracutaneous reactivity in vivo. The results from this study demonstrate for the first time that microparticles loaded with acetyl and peroxygen donors retain their antimicrobial activity whilst eliciting no host toxicity. In doing so, it overcomes the detrimental effects that have prevented oxidative biocides from being used as alternatives to conventional antibiotics. The manuscript explores a novel approach to utilize the antimicrobial activity of oxidative species for sustained killing of multiple drug-resistant organisms without causing collateral tissue damage. The results demonstrate, for the first time, the ability to load pre-cursor compounds into porous polymeric structures that results in their release and conversion into oxidative species in a

Thermal oxidation for air toxics control

International Nuclear Information System (INIS)

Pennington, R.L.

1991-01-01

The Administration projects annual expenditures of $1.1 billion by 1995, increasing to $6.7 billion by 2005, in order to comply with the new Clean Air Act Title III hazardous air pollutant requirements. The Title III requirements include 189 hazardous air pollutants which must be reduced or eliminated by 2003. Twenty of the 189 listed pollutants account for approximately 75 percent of all hazardous air pollutant emissions. Ninety percent of these 20 pollutants can be effectively controlled through one or mote of the thermal oxidation technologies. This paper reports that the advantages and disadvantages of each thermal oxidation technology vary substantially and must be reviewed for each application in order to establish the most effective thermal oxidation solution. Effective thermal oxidation will meet MACT (maximum achievable control technology) emission standards

Toxicity and Immunogenicity in Murine Melanoma following Exposure to Physical Plasma-Derived Oxidants

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Sander Bekeschus

2017-01-01

Full Text Available Metastatic melanoma is an aggressive and deadly disease. Therapeutic advance has been achieved by antitumor chemo- and radiotherapy. These modalities involve the generation of reactive oxygen and nitrogen species, affecting cellular viability, migration, and immunogenicity. Such species are also created by cold physical plasma, an ionized gas capable of redox modulating cells and tissues without thermal damage. Cold plasma has been suggested for anticancer therapy. Here, melanoma cell toxicity, motility, and immunogenicity of murine metastatic melanoma cells were investigated following plasma exposure in vitro. Cells were oxidized by plasma, leading to decreased metabolic activity and cell death. Moreover, plasma decelerated melanoma cell growth, viability, and cell cycling. This was accompanied by increased cellular stiffness and upregulation of zonula occludens 1 protein in the cell membrane. Importantly, expression levels of immunogenic cell surface molecules such as major histocompatibility complex I, calreticulin, and melanocortin receptor 1 were significantly increased in response to plasma. Finally, plasma treatment significantly decreased the release of vascular endothelial growth factor, a molecule with importance in angiogenesis. Altogether, these results suggest beneficial toxicity of cold plasma in murine melanomas with a concomitant immunogenicity of potential interest in oncology.

Oxidative degradation of triclosan by potassium permanganate: Kinetics, degradation products, reaction mechanism, and toxicity evaluation.

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Chen, Jing; Qu, Ruijuan; Pan, Xiaoxue; Wang, Zunyao

2016-10-15

In this study, we systematically investigated the potential applicability of potassium permanganate for removal of triclosan (TCS) in water treatment. A series of kinetic experiments were carried out to study the influence of various factors, including the pH, oxidant doses, temperature, and presence of typical anions (Cl(-), SO4(2-), NO3(-)), humic acid (HA), and fulvic acid (FA) on triclosan removal. The optimal reaction conditions were: pH = 8.0, [TCS]0:[KMnO4]0 = 1:2.5, and T = 25 °C, where 20 mg/L of TCS could be completely degraded in 120 s. However, the rate of TCS (20 μg/L) oxidation by KMnO4 ([TCS]0:[KMnO4]0 = 1:2.5) was 1.64 × 10(-3) mg L(-1)·h(-1), lower than that at an initial concentration of 20 mg/L (2.24 × 10(3) mg L(-1)·h(-1)). A total of eleven products were detected by liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-Q-TOF-MS) analysis, including phenol and its derivatives, benzoquinone, an organic acid, and aldehyde. Two main reaction pathways involving CO bond cleavage (-C(8)O(7)-) and benzene ring opening (in the less chlorinated benzene ring) were proposed, and were further confirmed based on frontier electron density calculations and point charges. Furthermore, the changes in the toxicity of the reaction solution during TCS oxidation by KMnO4 were evaluated by using both the luminescent bacteria Photobacterium phosphoreum and the water flea Daphnia magna. The toxicity of 20 mg/L triclosan to D. magna and P. phosphoreum after 60 min was reduced by 95.2% and 43.0%, respectively. Phenol and 1,4-benzoquinone, the two representative degradation products formed during permanganate oxidation, would yield low concentrations of DBPs (STHMFP, 20.99-278.97 μg/mg; SHAAFP, 7.86 × 10(-4)-45.77 μg/mg) after chlorination and chloramination. Overall, KMnO4 can be used as an effective oxidizing agent for TCS removal in water and wastewater treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibition of the mitochondrial enzyme ABAD restores the amyloid-β-mediated deregulation of estradiol.

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Yun-An Lim

Full Text Available Alzheimer's disease (AD is a conformational disease that is characterized by amyloid-β (Aβ deposition in the brain. Aβ exerts its toxicity in part by receptor-mediated interactions that cause down-stream protein misfolding and aggregation, as well as mitochondrial dysfunction. Recent reports indicate that Aβ may also interact directly with intracellular proteins such as the mitochondrial enzyme ABAD (Aβ binding alcohol dehydrogenase in executing its toxic effects. Mitochondrial dysfunction occurs early in AD, and Aβ's toxicity is in part mediated by inhibition of ABAD as shown previously with an ABAD decoy peptide. Here, we employed AG18051, a novel small ABAD-specific compound inhibitor, to investigate the role of ABAD in Aβ toxicity. Using SH-SY5Y neuroblastoma cells, we found that AG18051 partially blocked the Aβ-ABAD interaction in a pull-down assay while it also prevented the Aβ42-induced down-regulation of ABAD activity, as measured by levels of estradiol, a known hormone and product of ABAD activity. Furthermore, AG18051 is protective against Aβ42 toxicity, as measured by LDH release and MTT absorbance. Specifically, AG18051 reduced Aβ42-induced impairment of mitochondrial respiration and oxidative stress as shown by reduced ROS (reactive oxygen species levels. Guided by our previous finding of shared aspects of the toxicity of Aβ and human amylin (HA, with the latter forming aggregates in Type 2 diabetes mellitus (T2DM pancreas, we determined whether AG18051 would also confer protection from HA toxicity. We found that the inhibitor conferred only partial protection from HA toxicity indicating distinct pathomechanisms of the two amyloidogenic agents. Taken together, our results present the inhibition of ABAD by compounds such as AG18051 as a promising therapeutic strategy for the prevention and treatment of AD, and suggest levels of estradiol as a suitable read-out.

Effect of trifluoperazine on toxicity, HIF-1α induction and hepatocyte regeneration in acetaminophen toxicity in mice

Energy Technology Data Exchange (ETDEWEB)

Chaudhuri, Shubhra, E-mail: SCHAUDHURI@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); McCullough, Sandra S., E-mail: mcculloughsandras@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Hennings, Leah, E-mail: lhennings@uams.edu [Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Brown, Aliza T., E-mail: brownalizat@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Li, Shun-Hwa [Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI (United States); Simpson, Pippa M., E-mail: psimpson@mcw.edu [Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI (United States); Hinson, Jack A., E-mail: hinsonjacka@uams.edu [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); James, Laura P., E-mail: jameslaurap@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States)

2012-10-15

Oxidative stress and mitochondrial permeability transition (MPT) are important mechanisms in acetaminophen (APAP) toxicity. The MPT inhibitor trifluoperazine (TFP) reduced MPT, oxidative stress, and toxicity in freshly isolated hepatocytes treated with APAP. Since hypoxia inducible factor-one alpha (HIF-1α) is induced very early in APAP toxicity, a role for oxidative stress in the induction has been postulated. In the present study, the effect of TFP on toxicity and HIF-1α induction in B6C3F1 male mice treated with APAP was examined. Mice received TFP (10 mg/kg, oral gavage) prior to APAP (200 mg/kg IP) and at 7 and 36 h after APAP. Measures of metabolism (hepatic glutathione and APAP protein adducts) were comparable in the two groups of mice. Toxicity was decreased in the APAP/TFP mice at 2, 4, and 8 h, compared to the APAP mice. At 24 and 48 h, there were no significant differences in toxicity between the two groups. TFP lowered HIF-1α induction but also reduced the expression of proliferating cell nuclear antigen, a marker of hepatocyte regeneration. TFP can also inhibit phospholipase A{sub 2}, and cytosolic and secretory PLA{sub 2} activity levels were reduced in the APAP/TFP mice compared to the APAP mice. TFP also lowered prostaglandin E{sub 2} expression, a known mechanism of cytoprotection. In summary, the MPT inhibitor TFP delayed the onset of toxicity and lowered HIF-1α induction in APAP treated mice. TFP also reduced PGE{sub 2} expression and hepatocyte regeneration, likely through a mechanism involving PLA{sub 2}. -- Highlights: ► Trifluoperazine reduced acetaminophen toxicity and lowered HIF-1α induction. ► Trifluoperazine had no effect on the metabolism of acetaminophen. ► Trifluoperazine reduced hepatocyte regeneration. ► Trifluoperazine reduced phospholipase A{sub 2} activity and prostaglandin E{sub 2} levels.

Investigation of toxic effects of imidazolium ionic liquids, [bmim][BF4] and [omim][BF4], on marine mussel Mytilus galloprovincialis with or without the presence of conventional solvents, such as acetone.

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Tsarpali, Vasiliki; Belavgeni, Alexia; Dailianis, Stefanos

2015-07-01

This study investigated the cytotoxic, oxidative and genotoxic effects of two commonly used imidazolium ionic liquids (ILs), [bmim][BF4] (1-butyl-3-methylimidazolium) and [omim][BF4] (1-methyl-3-octylimidazolium tetrafluoroborate), on the marine mussel Mytilus galloprovincialis, as well as whether acetone could mediate their toxic profile. In this context, mussels were firstly exposed to different concentrations of [bmim][BF4] or [omim][BF4], with or without the presence of acetone (at a final concentration of 0.06% v/v), for a period of 96h, in order to determine the concentration that causes 50% mussel mortality (LC50 values) in each case. Thereafter, mussels were exposed to sub- and non-lethal concentrations of ILs for investigating their ability to cause lysosomal membrane impairment (with the use of neutral red retention assay/NRRT), superoxide anion and lipid peroxidation byproduct (malondialdehyde/MDA) formation, as well as DNA damage and formation of nuclear abnormalities in hemocytes. The results showed that [omim][BF4] was more toxic than [bmim][BF4] in all cases, while the presence of acetone resulted in a slight attenuation of its toxicity. The different toxic behavior of ILs was further revealed by the significantly lower levels of NRRT values observed in [omim][BF4]-treated mussels, compared to those occurring in [bmim][BF4] in all cases. Similarly, [bmim][BF4]-mediated oxidative and genotoxic effects were observed only in the highest concentration tested (10mgL(-1)), while [omim][BF4]-mediated effects were enhanced at lower concentrations (0.01-0.05mgL(-1)). Overall, the present study showed that [bmim][BF4] and [omim][BF4] could induce not only lethal but also nonlethal effects on mussel M. galloprovincialis. The extent of [bmim][BF4] and/or [omim][BF4]-mediated effects could be ascribed to the length of each IL alkyl chain, as well as to their lipophilicity. Moreover, the role of acetone on the obtained toxic effects of the specific ILs was

A miniaturized electrochemical toxicity biosensor based on graphene oxide quantum dots/carboxylated carbon nanotubes for assessment of priority pollutants

Energy Technology Data Exchange (ETDEWEB)

Zhu, Xiaolin; Wu, Guanlan; Lu, Nan [School of Environment, Northeast Normal University, Changchun 130117 (China); Yuan, Xing, E-mail: yuanx@nenu.edu.cn [School of Environment, Northeast Normal University, Changchun 130117 (China); Li, Baikun, E-mail: baikun@engr.uconn.edu [Department of Civil and Environmental Engineering, University of Connecticut, Storrs, CT 06269 (United States)

2017-02-15

Highlights: • Graphene oxide quantum dots/carboxylated carbon nanotubes hybrid was developed. • The cytotoxicity detection vessel was miniaturized to the 96-well plate. • The electrochemical behavior of HepG2 cell was investigated for the first time. • The mixture signal of adenine and hypoxanthine was separated successfully. • The biosensor was used to assess the toxicity of heavy metals and phenols. - Abstract: The study presented a sensitive and miniaturized cell-based electrochemical biosensor to assess the toxicity of priority pollutants in the aquatic environment. Human hepatoma (HepG2) cells were used as the biological recognition agent to measure the changes of electrochemical signals and reflect the cell viability. The graphene oxide quantum dots/carboxylated carbon nanotubes hybrid was developed in a facile and green way. Based on the hybrid composite modified pencil graphite electrode, the cell culture and detection vessel was miniaturized to a 96-well plate instead of the traditional culture dish. In addition, three sensitive electrochemical signals attributed to guanine/xanthine, adenine, and hypoxanthine were detected simultaneously. The biosensor was used to evaluate the toxicity of six priority pollutants, including Cd, Hg, Pb, 2,4-dinitrophenol, 2,4,6-trichlorophenol, and pentachlorophenol. The 24 h IC{sub 50} values obtained by the electrochemical biosensor were lower than those of conventional MTT assay, suggesting the enhanced sensitivity of the electrochemical assay towards heavy metals and phenols. This platform enables the label-free and sensitive detection of cell physiological status with multi-parameters and constitutes a promising approach for toxicity detection of pollutants. It makes possible for automatical and high-throughput analysis on nucleotide catabolism, which may be critical for life science and toxicology.

Promotion of Water-mediated Carbon Removal by Nanostructured Barium Oxide/nickel Interfaces

Energy Technology Data Exchange (ETDEWEB)

L Yang; Y Choi; W Qin; H Chen; K Blinn; M Liu; P Liu; J Bai; T Tyson; M Liu

2011-12-31

The existing Ni-yttria-stabilized zirconia anodes in solid oxide fuel cells (SOFCs) perform poorly in carbon-containing fuels because of coking and deactivation at desired operating temperatures. Here we report a new anode with nanostructured barium oxide/nickel (BaO/Ni) interfaces for low-cost SOFCs, demonstrating high power density and stability in C{sub 3}H{sub 8}, CO and gasified carbon fuels at 750 C. Synchrotron-based X-ray analyses and microscopy reveal that nanosized BaO islands grow on the Ni surface, creating numerous nanostructured BaO/Ni interfaces that readily adsorb water and facilitate water-mediated carbon removal reactions. Density functional theory calculations predict that the dissociated OH from H2O on BaO reacts with C on Ni near the BaO/Ni interface to produce CO and H species, which are then electrochemically oxidized at the triple-phase boundaries of the anode. This anode offers potential for ushering in a new generation of SOFCs for efficient, low-emission conversion of readily available fuels to electricity.

A novel approach reveals that zinc oxide nanoparticles are bioavailable and toxic after dietary exposures

Science.gov (United States)

Croteau, M.-N.; Dybowska, A.D.; Luoma, S.N.; Valsami-Jones, E.

2011-01-01

If engineered nanomaterials are released into the environment, some are likely to end up associated with the food of animals due to aggregation and sorption processes. However, few studies have considered dietary exposure of nanomaterials. Here we show that zinc (Zn) from isotopically modified 67ZnO particles is efficiently assimilated by freshwater snails when ingested with food. The 67Zn from nano-sized 67ZnO appears as bioavailable as 67Zn internalized by diatoms. Apparent agglomeration of the zinc oxide (ZnO) particles did not reduce bioavailability, nor preclude toxicity. In the diet, ZnO nanoparticles damage digestion: snails ate less, defecated less and inefficiently processed the ingested food when exposed to high concentrations of ZnO. It was not clear whether the toxicity was due to the high Zn dose achieved with nanoparticles or to the ZnO nanoparticles themselves. Further study of exposure from nanoparticles in food would greatly benefit assessment of ecological and human health risks. ?? 2011 Informa UK, Ltd.

Cellular toxicity following application of adeno-associated viral vector-mediated RNA interference in the nervous system

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Verhaagen Joost

2010-02-01

Full Text Available Abstract Background After a spinal cord lesion, axon regeneration is inhibited by the presence of a diversity of inhibitory molecules in the lesion environment. At and around the lesion site myelin-associated inhibitors, chondroitin sulfate proteoglycans (CSPGs and several axon guidance molecules, including all members of the secreted (class 3 Semaphorins, are expressed. Interfering with multiple inhibitory signals could potentially enhance the previously reported beneficial effects of blocking single molecules. RNA interference (RNAi is a tool that can be used to simultaneously silence expression of multiple genes. In this study we aimed to employ adeno-associated virus (AAV mediated expression of short hairpin RNAs (shRNAs to target all Semaphorin class 3 signaling by knocking down its receptors, Neuropilin 1 (Npn-1 and Neuropilin 2 (Npn-2. Results We have successfully generated shRNAs that knock down Npn-1 and Npn-2 in a neuronal cell line. We detected substantial knockdown of Npn-2 mRNA when AAV5 viral vector particles expressing Npn-2 specific shRNAs were injected in dorsal root ganglia (DRG of the rat. Unexpectedly however, AAV1-mediated expression of Npn-2 shRNAs and a control shRNA in the red nucleus resulted in an adverse tissue response and neuronal degeneration. The observed toxicity was dose dependent and was not seen with control GFP expressing AAV vectors, implicating the shRNAs as the causative toxic agents. Conclusions RNAi is a powerful tool to knock down Semaphorin receptor expression in neuronal cells in vitro and in vivo. However, when shRNAs are expressed at high levels in CNS neurons, they trigger an adverse tissue response leading to neuronal degradation.

Iron oxide-mediated semiconductor photocatalysis vs. heterogeneous photo-Fenton treatment of viruses in wastewater. Impact of the oxide particle size.

Science.gov (United States)

Giannakis, Stefanos; Liu, Siting; Carratalà, Anna; Rtimi, Sami; Talebi Amiri, Masoud; Bensimon, Michaël; Pulgarin, César

2017-10-05

The photo-Fenton process is recognized as a promising technique towards microorganism disinfection in wastewater, but its efficiency is hampered at near-neutral pH operating values. In this work, we overcome these obstacles by using the heterogeneous photo-Fenton process as the default disinfecting technique, targeting MS2 coliphage in wastewater. The use of low concentrations of iron oxides in wastewater without H 2 O 2 (wüstite, maghemite, magnetite) has demonstrated limited semiconductor-mediated MS2 inactivation. Changing the operational pH and the size of the oxide particles indicated that the isoelectric point of the iron oxides and the active surface area are crucial in the success of the process, and the possible underlying mechanisms are investigated. Furthermore, the addition of low amounts of Fe-oxides (1mgL -1 ) and H 2 O 2 in the system (1, 5 and 10mgL -1 ) greatly enhanced the inactivation process, leading to heterogeneous photo-Fenton processes on the surface of the magnetically separable oxides used. Additionally, photo-dissolution of iron in the bulk, lead to homogeneous photo-Fenton, further aided by the complexation by the dissolved organic matter in the solution. Finally, we assess the impact of the presence of the bacterial host and the difference caused by the different iron sources (salts, oxides) and the Fe-oxide size (normal, nano-sized). Copyright © 2017 Elsevier B.V. All rights reserved.

Myotoxic reactions to lipid-lowering therapy are associated with altered oxidation of fatty acids.

Science.gov (United States)

Phillips, Paul S; Ciaraldi, Theodore P; Kim, Dong-Lim; Verity, M Anthony; Wolfson, Tanya; Henry, Robert R

2009-02-01

Despite exceptional efficacy and safety, fear of muscle toxicity remains a major reason statins are underutilized. Evidence suggests that statin muscle toxicity may be mediated by abnormalities in lipid metabolism. To test the hypothesis that myotubes from patients intolerant of lipid-lowering therapies have abnormal fatty acid oxidation (FAO) responses we compared muscle from 11 subjects with statin intolerance (Intolerant) with muscle from seven statin-naive volunteers undergoing knee arthroplasty (Comparator). Gross muscle pathology was graded and skeletal muscle cell cultures were produced from each subject. FAO was assessed following treatment with increasing statin concentrations. There was no difference in muscle biopsy myopathy scores between the groups. Basal octanoate oxidation was greater in Intolerant than in Comparator subjects (P = 0.03). Lovastatin-stimulated palmitate oxidation tended to be greater for Intolerant compared to Control subjects' myotubes (P = 0.07 for 5 microM and P = 0.06 for 20 microM lovastatin). In conclusion abnormalities in FAO of Intolerant subjects appear to be an intrinsic characteristic of these subjects that can be measured in their cultured myotubes.

Role of oxidative stress in liver and kidney in uranium toxicity after chronic exposure

International Nuclear Information System (INIS)

Poisson - Moreau-De-Lizoreux, C.

2013-01-01

Uranium is a radioactive heavy metal found in the environment. Due to its natural presence and to civil and militaries activities, general population can be exposed to U throughout drinking water or contaminated food. The pro/anti-oxidative system is a defense system which is often implicated in case of acute exposure to U. The aim of this thesis is to study the role of the pro/anti-oxidative system after chronic exposure to U in the liver and the kidney. After chronic exposure of rats to different U concentrations, this radionuclide accumulated in the organs in proportion to U intake; until 6 μg.g -1 of kidney tissues. U is localized in nucleus of the proximal tubular cells of the kidney. No nephrotoxicity was described even for the higher U level in drinking water and a reinforcement of the pro/anti-oxidative system with an increase in glutathione is observed. The study of U internal contamination in Nrf2 deficient mice, a cytoprotective transcription factor involved in the anti-oxidative defense has been realized. U accumulate more in Nrf2 mice than in WT mice but the biologic effects of U on the pro/anti-oxidative system did not seem to implicate Nrf2. At the cell level, a correlation between U distribution in HepG2 cells and the biological effects on this system is observed after U exposure at low concentrations. Soluble distribution of U is observed in cell nucleus. The apparition of U precipitates is correlated to the establishment of the adaptive mechanisms overtime which are overwhelmed and lead to a cellular toxicity at higher U level. In conclusion, these results suggest that the reinforcement of pro/anti-oxidative system could be an adaptive mechanism after chronic exposure at low U concentration. (author) [fr

UV/H2O2 advanced oxidation for abatement of organophosphorous pesticides and the effects on various toxicity screening assays.

Science.gov (United States)

Parker, Austa M; Lester, Yaal; Spangler, Emily K; von Gunten, Urs; Linden, Karl G

2017-09-01

Advanced oxidation processes (AOPs) are utilized due to their ability to treat emerging contaminants with the fast reacting and non-selective hydroxyl radical (OH). Organophosphorous insecticides are common drinking water contaminants, with 12 different compounds of this class being found on the US EPA's most recent Candidate Contaminant List (CCL4). The use of the AOP UV/H 2 O 2 for the treatment of organophosphorous insecticides was explored in this study, by coupling biological and analytical tools to follow the abatement of the target compounds. Four insecticides were explored for advanced oxidation treatment: acephate, dicrotophos, fenamiphos, and methamidophos. All four compounds were fast reacting with OH, all reacting with second order rate constants ≥5.5 × 10 9  M -1 s -1 . Three major endpoints of toxicity were studied: estrogenicity, genotoxicity (mutagenicity) and neurotoxicity. None of the target compounds showed any estrogenic activity, while all compounds showed an active genotoxic (mutagenic) response (AMES II assay) and most compounds had some level of neurotoxic activity. AOP treatment did not induce any estrogenic activity, and reduced the compounds' neurotoxicity and genotoxicity in all but one case. Methamidophos degradation by UV/H 2 O 2 resulted in an increase in genotoxicity, likely due to the formation of toxic transformation products. The increase in toxicity gradually decreased with time, possibly due to hydrolysis of the transformation products formed. This study provides insights into parent compound abatement and the changes in toxicity due to transformation products. Copyright © 2017 Elsevier Ltd. All rights reserved.

The study of the mechanism of arsenite toxicity in respiration-deficient cells reveals that NADPH oxidase-derived superoxide promotes the same downstream events mediated by mitochondrial superoxide in respiration-proficient cells

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Guidarelli, Andrea; Fiorani, Mara; Carloni, Silvia; Cerioni, Liana; Balduini, Walter; Cantoni, Orazio, E-mail: orazio.cantoni@uniurb.it

2016-09-15

We herein report the results from a comparative study of arsenite toxicity in respiration-proficient (RP) and -deficient (RD) U937 cells. An initial characterization of these cells led to the demonstration that the respiration-deficient phenotype is not associated with apparent changes in mitochondrial mass and membrane potential. In addition, similar levels of superoxide (O{sub 2}{sup .-}) were generated by RP and RD cells in response to stimuli specifically triggering respiratory chain-independent mitochondrial mechanisms or extramitochondrial, NADPH-oxidase dependent, mechanisms. At the concentration of 2.5 μM, arsenite elicited selective formation of O{sub 2}{sup .-} in the respiratory chain of RP cells, with hardly any contribution of the above mechanisms. Under these conditions, O{sub 2}{sup .-} triggered downstream events leading to endoplasmic reticulum (ER) stress, autophagy and apoptosis. RD cells challenged with similar levels of arsenite failed to generate O{sub 2}{sup .-} because of the lack of a functional respiratory chain and were therefore resistant to the toxic effects mediated by the metalloid. Their resistance, however, was lost after exposure to four fold greater concentrations of arsenite, coincidentally with the release of O{sub 2}{sup .-} mediated by NADPH oxidase. Interestingly, extramitochondrial O{sub 2}{sup .-} triggered the same downstream events and an identical mode of death previously observed in RP cells. Taken together, the results obtained in this study indicate that arsenite toxicity is strictly dependent on O{sub 2}{sup .-} availability that, regardless of whether generated in the mitochondrial or extramitochondrial compartments, triggers similar downstream events leading to ER stress, autophagy and apoptosis. - Highlights: • Mitochondrial superoxide mediates arsenite toxicity in respiration-proficient cells. • NADPH-derived superoxide mediates arsenite toxicity in respiration-deficient cells. • Arsenite causes apoptosis

Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress.

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Merve Baysal

Full Text Available Levetiracetam (LEV is an antiepileptic drug commonly used in the treatment of epilepsy because of its excellent safety profile in all age groups. It is remarkable that there are no studies evaluating the toxic effects of this drug on the male reproductive system, as it is commonly used in male patients of reproductive age. From this point of view, our aim was to evaluate the possible toxic effects of LEV on the male reproductive system. Therefore, LEV was administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive days. At the end of this period, alterations to body and organ weights were calculated, and sperm concentration, motility, and morphology were investigated by a computer-assisted sperm analysis system. Sperm DNA damage was determined by comet assay and histopathological examination of the testes was carried out. Serum testosterone, follicle-stimulating hormone (FSH, and luteinizing hormone (LH levels were measured by ELISAs to determine the effects of hormonal status, while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in the testes were measured by colorimetric assay kits to determine the role of oxidative status in potential toxicity. According to the results, sperm quality was decreased by LEV treatment in a dose-dependent manner. LEV induced significant DNA damage in the 150 and 300 mg/kg LEV-administered groups. Histopathology of the testes showed that LEV resulted in testicular injury in the 300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were significantly decreased in the 300 mg/kg LEV-administered group. Glutathione, superoxide dismutase, and catalase levels were significantly decreased in all experimental groups while malondialdehyde levels were significantly increased in 150 and 300 mg/kg LEV-administered groups. According to these results, it was determined that LEV administration decreased sperm quality and it was alleged that hormonal alteration and

Huperzine A Alleviates Oxidative Glutamate Toxicity in Hippocampal HT22 Cells via Activating BDNF/TrkB-Dependent PI3K/Akt/mTOR Signaling Pathway.

Science.gov (United States)

Mao, Xiao-Yuan; Zhou, Hong-Hao; Li, Xi; Liu, Zhao-Qian

2016-08-01

Oxidative glutamate toxicity is involved in diverse neurological disorders including epilepsy and ischemic stroke. Our present work aimed to assess protective effects of huperzine A (HupA) against oxidative glutamate toxicity in a mouse-derived hippocampal HT22 cells and explore its potential mechanisms. Cell survival and cell injury were analyzed by MTT method and LDH release assay, respectively. The production of ROS was measured by detection kits. Protein expressions of BDNF, phosphor-TrkB (p-TrkB), TrkB, phosphor-Akt (p-Akt), Akt, phosphor-mTOR (p-mTOR), mTOR, phosphor-p70s6 (p-p70s6) kinase, p70s6 kinase, Bcl-2, Bax, and β-actin were assayed via Western blot analysis. Enzyme-linked immunosorbent assay was employed to measure the contents of nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Our findings illustrated 10 μM HupA for 24 h significantly protected HT22 from cellular damage and suppressed the generation of ROS. Additionally, after treating with LY294002 or wortmannin [the selective inhibitors of phosphatidylinositol 3 kinase (PI3K)], HupA dramatically prevented the down-regulations of p-Akt, p-mTOR, and p-p70s6 kinase in HT22 cells under oxidative toxicity. Furthermore, it was observed that the protein levels of BDNF and p-TrkB were evidently enhanced after co-treatment with HupA and glutamate in HT22 cells. The elevations of p-Akt and p-mTOR were abrogated under toxic conditions after blockade of TrkB by TrkB IgG. Cellular apoptosis was significantly suppressed (decreased caspase-3 activity and enhanced Bcl-2 protein level) after HupA treatment. It was concluded that HupA attenuated oxidative glutamate toxicity in murine hippocampal HT22 cells via activating BDNF/TrkB-dependent PI3K/Akt/mTOR signaling pathway.

The toxicity of chlorpyrifos on the early life stage of zebrafish: a survey on the endpoints at development, locomotor behavior, oxidative stress and immunotoxicity.

Science.gov (United States)

Jin, Yuanxiang; Liu, Zhenzhen; Peng, Tao; Fu, Zhengwei

2015-04-01

Chlorpyrifos (CPF) is one of the most toxic pesticides in aquatic ecosystem, but its toxicity mechanisms to fish are still not fully understood. This study examined the toxicity targets of CPF in early life stage of zebrafish on the endpoints at developmental toxicity, neurotoxicity, oxidative stress and immunotoxicity. Firstly, CPF exposure decreased the body length, inhibited the hatchability and heart rate, and resulted in a number of morphological abnormalities, primarily spinal deformities (SD) and pericardial edema (PE), in larval zebrafish. Secondly, the free swimming activities and the swimming behaviors of the larvae in response to the stimulation of light-to-dark photoperiod transition were significantly influenced by the exposure to 100 and 300 μg/L CPF. In addition, the activity of acetylcholinesterase (AChE) and the transcription of some genes related to neurotoxicity were also influenced by CPF exposure. Thirdly, CPF exposure induced oxidative stress in the larval zebrafish. The malondialdehyde (MDA) levels increased and the glutathione (GSH) contents decreased significantly in a concentration-dependent manner after the exposure to CPF for 96 hours post fertilization (hpf). CPF affected not only the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S-transferase (GST), but also the transcriptional levels of their respective genes. Finally, the mRNA levels of the main cytokines including tumor necrosis factor α (Tnfα), interferon (Ifn), interleukin-1 beta (Il-1β), interleukin 6 (Il6), complement factor 4 (C4) in the larvae increased significantly after the exposure to 100 or 300 μg/L CPF for 96 hpf, suggesting that the innate immune system disturbed by CPF in larvae. Taken together, our results suggested that CPF had the potential to cause developmental toxicity, behavior alterations, oxidative stress and immunotoxicity in the larval zebrafish. Copyright © 2015 Elsevier Ltd. All rights

Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Del Regno, Marisanta; Adesso, Simona; Popolo, Ada [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy); Quaroni, Andrea [Department of Biomedical Sciences, Cornell University, Veterinary Research Tower, Cornell University, Ithaca, NY 14853–6401 (United States); Autore, Giuseppina [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy); Severino, Lorella [Department of Pathology and Animal Health, Division of Toxicology, School of Veterinary Medicine, University of Naples “Federico II”, Via Delpino 1, 80137 Naples (Italy); Marzocco, Stefania, E-mail: smarzocco@unisa.it [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy)

2015-06-01

Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern. - Highlights: • Nivalenol induces oxidative stress in intestinal epithelial cells (IECs). • Nivalenol increases deoxynivalenol pro-oxidant effects in IECs. • Nivalenol and deoxynivalenol trigger antioxidant response IECs. • These results indicate the importance of mycotoxins co-contamination.

Characterization of the Adaptive Response to Trichloroethylene-Mediated Stresses in Ralstonia pickettii PKO1

OpenAIRE

Park, Joonhong; Kukor, Jerome J.; Abriola, Linda M.

2002-01-01

In Ralstonia pickettii PKO1, a denitrifying toluene oxidizer that carries a toluene-3-monooxygenase (T3MO) pathway, the biodegradation of toluene and trichloroethylene (TCE) by the organism is induced by TCE at high concentrations. In this study, the effect of TCE preexposure was studied in the context of bacterial protective response to TCE-mediated toxicity in this organism. The results of TCE degradation experiments showed that cells induced by TCE at 110 mg/liter were more tolerant to TCE...

Kinetics and thermodynamics of oxidation mediated reaction in L-cysteine and its methyl and ethyl esters in dimethyl sulfoxide-d6 by NMR spectroscopy

Science.gov (United States)

Dougherty, Ryan J.; Singh, Jaideep; Krishnan, V. V.

2017-03-01

L-Cysteine (L-Cys), L-Cysteine methyl ester (L-CysME) or L-Cysteine ethyl ester (L-CysEE), when dissolved in dimethyl sulfoxide, undergoes an oxidation process. This process is slow enough and leads to nuclear magnetic resonance (NMR) spectral changes that could be monitored in real time. The oxidation mediated transition is modeled as a pseudo-first order kinetics and the thermodynamic parameters are estimated using the Eyring's formulation. L-Cysteine and their esters are often used as biological models due to the remarkable thiol group that can be found in different oxidation states. This oxidation mediated transition is due to the combination of thiol oxidation to a disulfide followed by solvent-induced effects may be relevant in designing cysteine-based molecular models.

Involvement of the nitric oxide in melatonin-mediated protection against injury.

Science.gov (United States)

Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

2018-05-01

Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Dityrosine, 3,4-Dihydroxyphenylalanine (DOPA), and radical formation from tyrosine residues on milk proteins with globular and flexible structures as a result of riboflavin-mediated photo-oxidation

DEFF Research Database (Denmark)

Dalsgaard, Trine Kastrup; Nielsen, Jacob Holm; Brown, Bronwyn

2011-01-01

Riboflavin-mediated photo-oxidative damage to protein Tyr residues has been examined to determine whether protein structure influences competing protein oxidation pathways in single proteins and protein mixtures. EPR studies resulted in the detection of Tyr-derived o-semiquione radicals, with thi......Riboflavin-mediated photo-oxidative damage to protein Tyr residues has been examined to determine whether protein structure influences competing protein oxidation pathways in single proteins and protein mixtures. EPR studies resulted in the detection of Tyr-derived o-semiquione radicals...

Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

Directory of Open Access Journals (Sweden)

T.I. Omotayo

2015-04-01

Full Text Available The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.

Nanotoxicity of pure silica mediated through oxidant generation rather than glutathione depletion in human lung epithelial cells.

Science.gov (United States)

Akhtar, Mohd Javed; Ahamed, Maqusood; Kumar, Sudhir; Siddiqui, Huma; Patil, Govil; Ashquin, Mohd; Ahmad, Iqbal

2010-10-09

Though, oxidative stress has been implicated in silica nanoparticles induced toxicity both in vitro and in vivo, but no similarities exist regarding dose-response relationship. This discrepancy may, partly, be due to associated impurities of trace metals that may present in varying amounts. Here, cytotoxicity and oxidative stress parameters of two sizes (10 nm and 80 nm) of pure silica nanoparticles was determined in human lung epithelial cells (A549 cells). Both sizes of silica nanoparticles induced dose-dependent cytotoxicity as measured by MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and lactate dehydrogenase (LDH) assays. Silica nanoparticles were also found to induce oxidative stress in dose-dependent manner indicated by induction of reactive oxygen species (ROS) generation, and membrane lipid peroxidation (LPO). However, both sizes of silica nanoparticles had little effect on intracellular glutathione (GSH) level and the activities of glutathione metabolizing enzymes; glutathione reductase (GR) and glutathione peroxidase (GPx). Buthionine-[S,R]-sulfoximine (BSO) plus silica nanoparticles did not result in significant GSH depletion than that caused by BSO alone nor N-acetyl cysteine (NAC) afforded significant protection from ROS and LPO induced by silica nanoparticles. The rather unaltered level of GSH is also supported by finding no appreciable alteration in the level of GR and GPx. Our data suggest that the silica nanoparticles exert toxicity in A549 cells through the oxidant generation (ROS and LPO) rather than the depletion of GSH. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A natural pharma standard supplement formulation to control treatment-related toxicity and oxidative stress in genitourinary cancer: a preliminary study.

Science.gov (United States)

Ledda, A; Belcaro, G; Dugall, M; Luzzi, R; Hosoi, M; Feragalli, B; Cotellese, R; Cosentino, V; Cosentino, M; Eggenhoffner, R; Pellizzato, M; Fratter, A; Giacomelli, L

2017-09-01

Oncological treatments are associated with toxicities that may decrease compliance to treatment in most genitourinary cancer patients. Supplementation with pharmaceutical-standardized supplement may be a supplementary method to control the side effects after chemo- and radiotherapy and the increased oxidative stress associated to treatments. This registry study evaluated a natural combination of supplements containing curcumin, cordyceps, and astaxanthin (Oncotris™) used as supplementary management in genitourinary cancer patients who had undergone oncological therapy. Patients with genitourinary cancers (prostate or bladder malignancies) who had undergone and completed cancer treatments (radiotherapy, chemotherapy or intravesical immunotherapy with increased oxidative stress and residual symptoms) were recruited in this registry, supplement study. Registry subjects (n = 61) freely decided to follow either a standard management (SM) (control group = 35) or SM plus oral daily supplementation (supplement group = 26). Evaluation of severity of treatment-related residual side effects, blood count test, prostate-specific antigen (PSA) test and plasma free radicals (oxidative stress) were performed at inclusion and at the end of the observational period (6 weeks). Two patients dropped out during the registry. Therefore, the analysis included 59 participants: 26 individuals in the supplementation group and 33 in the control group. In the supplement group, the intensity of signs and symptoms (treatment-related) and residual side effects significantly decreased at 6 weeks: minimal changes were observed in controls. Supplementation with Oncotris™ was associated with a significant improvement in blood cell count and with a decreased level of plasmatic PSA and oxidative stress. Naturally-derived supplements, specifically Oncotris™ (patent pending), could support the body to overcome the treatment-related toxicities - and the relative oxidative stress in cancer patients.

Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

Science.gov (United States)

Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

2015-11-01

Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

An epigenetic signal encoded protection mechanism is activated by graphene oxide to inhibit its induced reproductive toxicity in Caenorhabditis elegans.

Science.gov (United States)

Zhao, Yunli; Wu, Qiuli; Wang, Dayong

2016-02-01

Although many studies have suggested the adverse effects of engineered nanomaterials (ENMs), the self-protection mechanisms for organisms against ENMs toxicity are still largely unclear. Using Caenorhabditis elegans as an in vivo assay system, our results suggest the toxicity of graphene oxide in reducing reproductive capacity by inducing damage on gonad development. The observed reproductive toxicity of GO on gonad development was due to the combinational effect of germline apoptosis and cell cycle arrest, and DNA damage activation might act as an inducer for this combinational effect. For the underlying molecular mechanism of reproductive toxicity of GO, we raised a signaling cascade of HUS-1/CLK-2-CEP-1-EGL-1-CED-4-CED-3 to explain the roles of core apoptosis signaling pathway and DNA damage checkpoints. Moreover, we identified a miRNA regulation mechanism activated by GO to suppress its induced reproductive toxicity. A mir-360 regulation mechanism was activated by GO to suppress its induced DNA damage-apoptosis signaling cascade through affecting component of CEP-1. Our identified epigenetic signal encoded protection mechanism activated by GO suggests a novel self-protection mechanism for organisms against the ENMs toxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

MUTYH mediates the toxicity of combined DNA 6-thioguanine and UVA radiation

Science.gov (United States)

De Luca, Gabriele; Leopardi, Paola; Mancuso, Maria Teresa; Casorelli, Ida; Pichierri, Pietro; Karran, Peter; Bignami, Margherita

2015-01-01

The therapeutic thiopurines, including the immunosuppressant azathioprine (Aza) cause the accumulation of the UVA photosensitizer 6-thioguanine (6-TG) in the DNA of the patients' cells. DNA 6-TG and UVA are synergistically cytotoxic and their interaction causes oxidative damage. The MUTYH DNA glycosylase participates in the base excision repair of oxidized DNA bases. Using Mutyh-nullmouse fibroblasts (MEFs) we examined whether MUTYH provides protection against the lethal effects of combined DNA 6-TG/UVA. Surprisingly, Mutyh-null MEFs were more resistant than wild-type MEFs, despite accumulating higher levels of DNA 8-oxo-7,8-dihydroguanine (8-oxoG). Their enhanced 6-TG/UVA resistance reflected the absence of the MUTYH protein and MEFs expressing enzymatically-dead human variants were as sensitive as wild-type cells. Consistent with their enhanced resistance, Mutyh-null cells sustained fewer DNA strand breaks and lower levels of chromosomal damage after 6-TG/UVA. Although 6-TG/UVA treatment caused early checkpoint activation irrespective of the MUTYH status, Mutyh-null cells failed to arrest in S-phase at late time points. MUTYH-dependent toxicity was also apparent in vivo. Mutyh−/−mice survived better than wild-type during a 12-month chronicexposure to Aza/UVA treatments that significantly increased levels of skin DNA 8-oxoG. Two squamous cell skin carcinomas arose in Aza/UVA treated Mutyh−/− mice whereas similarly treated wild-type animals remained tumor-free. PMID:25638157

Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms

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Johan Øvrevik

2015-07-01

Full Text Available Inflammation is considered to play a central role in a diverse range of disease outcomes associated with exposure to various types of inhalable particulates. The initial mechanisms through which particles trigger cellular responses leading to activation of inflammatory responses are crucial to clarify in order to understand what physico-chemical characteristics govern the inflammogenic activity of particulate matter and why some particles are more harmful than others. Recent research suggests that molecular triggering mechanisms involved in activation of proinflammatory genes and onset of inflammatory reactions by particles or soluble particle components can be categorized into direct formation of reactive oxygen species (ROS with subsequent oxidative stress, interaction with the lipid layer of cellular membranes, activation of cell surface receptors, and direct interactions with intracellular molecular targets. The present review focuses on the immediate effects and responses in cells exposed to particles and central down-stream signaling mechanisms involved in regulation of proinflammatory genes, with special emphasis on the role of oxidant and non-oxidant triggering mechanisms. Importantly, ROS act as a central second-messenger in a variety of signaling pathways. Even non-oxidant mediated triggering mechanisms are therefore also likely to activate downstream redox-regulated events.

A review of acrylamide toxicity and its mechanism

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Ehsan Zamani

2017-05-01

Full Text Available Acrylamide (AA is an important industrial chemical agent that is mainly used in the production of polymers and copolymers. Recently it has been attention because of its production in the diet at high-temperature (>120 ºC processes such as cooking, frying, toasting, roasting or baking of high carbohydrate foods. According to high exposure to acrylamide, recognition of its toxic effect is necessary. Neurotoxicity, reproductive toxicity and immunotoxicity of AA were observed in several studies. There isn’t a clear mechanism that justifies this toxicity. In this study we reviewed the mechanisms of AA toxicity especially oxidative stress and apoptosis. AA can cause neurotoxicity, reproductive toxicity and genotoxicity on animal models. It showed neurotoxicity in human. We suggested the oxidative stress is the main factor for inducing of acrylamide toxicities. We advised that modifying of food processing methods can be as a good way for decreasing of AA production in foods.

Linking hydrogen-mediated boron toxicity tolerance with improvement of root elongation, water status and reactive oxygen species balance: a case study for rice.

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Wang, Yu; Duan, Xingliang; Xu, Sheng; Wang, Ren; Ouyang, Zhaozeng; Shen, Wenbiao

2016-12-01

Boron is essential for plant growth but hazardous when present in excess. As the antioxidant properties of hydrogen gas (H 2 ) were recently described in plants, oxidative stress induced by excess boron was investigated along with other biological responses during rice (Oryza sativa) seed germination to study the beneficial role of H 2 METHODS: Rice seeds were pretreated with exogenous H 2 Using physiological, pharmacological and molecular approaches, the production of endogenous H 2 , growth status, reactive oxygen species (ROS) balance and relative gene expression in rice were measured under boron stress to investigate mechanisms of H 2 -mediated boron toxicity tolerance. In our test, boron-inhibited seed germination and seedling growth, and endogenous H 2 production, were obviously blocked by exogenously applying H 2 The re-establishment of ROS balance was confirmed by reduced lipid peroxidation and ROS accumulation. Meanwhile, activities of catalase (CAT) and peroxidase (POX) were increased. Suppression of pectin methylesterase (PME) activity and downregulation of PME transcripts by H 2 were consistent with the alleviation of root growth inhibition caused by boron. Water status was improved as well. This result was confirmed by the upregulation of genes encoding specific aquaporins (AQPs), the maintenance of low osmotic potential and high content of soluble sugar. Increased transcription of representative AQP genes (PIP2;7 in particular) and BOR2 along with decreased BOR1 mRNA may contribute to lowering boron accumulation. Hydrogen provides boron toxicity tolerance mainly by improving root elongation, water status and ROS balance. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Nanotoxicity: An Interplay of Oxidative Stress, Inflammation and Cell Death

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Puja Khanna

2015-06-01

Full Text Available Nanoparticles are emerging as a useful tool for a wide variety of biomedical, consumer and instrumental applications that include drug delivery systems, biosensors and environmental sensors. In particular, nanoparticles have been shown to offer greater specificity with enhanced bioavailability and less detrimental side effects as compared to the existing conventional therapies in nanomedicine. Hence, bionanotechnology has been receiving immense attention in recent years. However, despite the extensive use of nanoparticles today, there is still a limited understanding of nanoparticle-mediated toxicity. Both in vivo and in vitro studies have shown that nanoparticles are closely associated with toxicity by increasing intracellular reactive oxygen species (ROS levels and/or the levels of pro-inflammatory mediators. The homeostatic redox state of the host becomes disrupted upon ROS induction by nanoparticles. Nanoparticles are also known to up-regulate the transcription of various pro-inflammatory genes, including tumor necrosis factor-α and IL (interleukins-1, IL-6 and IL-8, by activating nuclear factor-kappa B (NF-κB signaling. These sequential molecular and cellular events are known to cause oxidative stress, followed by severe cellular genotoxicity and then programmed cell death. However, the exact molecular mechanisms underlying nanotoxicity are not fully understood. This lack of knowledge is a significant impediment in the use of nanoparticles in vivo. In this review, we will provide an assessment of signaling pathways that are involved in the nanoparticle- induced oxidative stress and propose possible strategies to circumvent nanotoxicity.

Nanotoxicity: An Interplay of Oxidative Stress, Inflammation and Cell Death.

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Khanna, Puja; Ong, Cynthia; Bay, Boon Huat; Baeg, Gyeong Hun

2015-06-30

Nanoparticles are emerging as a useful tool for a wide variety of biomedical, consumer and instrumental applications that include drug delivery systems, biosensors and environmental sensors. In particular, nanoparticles have been shown to offer greater specificity with enhanced bioavailability and less detrimental side effects as compared to the existing conventional therapies in nanomedicine. Hence, bionanotechnology has been receiving immense attention in recent years. However, despite the extensive use of nanoparticles today, there is still a limited understanding of nanoparticle-mediated toxicity. Both in vivo and in vitro studies have shown that nanoparticles are closely associated with toxicity by increasing intracellular reactive oxygen species (ROS) levels and/or the levels of pro-inflammatory mediators. The homeostatic redox state of the host becomes disrupted upon ROS induction by nanoparticles. Nanoparticles are also known to up-regulate the transcription of various pro-inflammatory genes, including tumor necrosis factor-α and IL (interleukins)-1, IL-6 and IL-8, by activating nuclear factor-kappa B (NF-κB) signaling. These sequential molecular and cellular events are known to cause oxidative stress, followed by severe cellular genotoxicity and then programmed cell death. However, the exact molecular mechanisms underlying nanotoxicity are not fully understood. This lack of knowledge is a significant impediment in the use of nanoparticles in vivo . In this review, we will provide an assessment of signaling pathways that are involved in the nanoparticle- induced oxidative stress and propose possible strategies to circumvent nanotoxicity.

Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in Streptozotocin-Induced Diabetic Rats

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Mohammad Reza Hajizadeh

2014-03-01

Full Text Available Background: It has been proposed that oxidative stress may contribute to the development of testicular abnormalities in diabetes. Morus alba leaf extract (MAE has hypoglycemic and antioxidant properties. We, therefore, explored the impact of the administration of MAE on steroidogenesis in diabetic rats. Methods: To address this hypothesis, we measured the serum level of glucose, insulin, and free testosterone (Ts as well as oxidative stress parameters (including glutathione peroxidase, glutathione reductase, total antioxidant capacity, and malondialdehyde in the testis of control, untreated and MAE-treated (1 g/day/kg diabetic rats. In order to determine the likely mechanism of MAE action on Ts levels, we analyzed the quantitative mRNA expression level of the two key steroidogenic proteins, namely steroid acute regulatory protein (StAR and P450 cholesterol side-chain cleavage enzyme (P450scc, by real-time PCR. Results: The MAE-treated diabetic rats had significantly decreased glucose levels and on the other hand increased insulin and free Ts levels than the untreated diabetic rats. In addition, the administration of MAE to the diabetic rats restored the oxidative stress parameters toward control. Induction of diabetes decreased testicular StAR mRNA expression by 66% and MAE treatment enhanced mRNA expression to the same level of the control group. However, the expression of P540scc was not significantly decreased in the diabetic group as compared to the control group. Conclusion: Our findings indicated that MAE significantly increased Ts production in the diabetic rats, probably through the induction of StAR mRNA expression levels. Administration of MAE to experimental models of diabetes can effectively attenuate oxidative stress-mediated testosterone depletion. Please cite this article as: Hajizadeh MR, Eftekhar E, Zal F, Jaffarian A, Mostafavi-Pour Z. Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women.

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Diamanti-Kandarakis, Evanthia; Papalou, Olga; Kandaraki, Eleni A; Kassi, Georgia

2017-02-01

Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. © 2017 European Society of Endocrinology.

The nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo-inducing phenol monobenzone.

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Arowojolu, Omotayo A; Orlow, Seth J; Elbuluk, Nada; Manga, Prashiela

2017-07-01

Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

β-Amyloid promotes accumulation of lipid peroxides by inhibiting CD36-mediated clearance of oxidized lipoproteins

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Khan Tayeba

2004-11-01

Full Text Available Abstract Background Recent studies suggest that hypercholesterolemia, an established risk factor for atherosclerosis, is also a risk factor for Alzheimer's disease. The myeloid scavenger receptor CD36 binds oxidized lipoproteins that accumulate with hypercholesterolemia and mediates their clearance from the circulation and peripheral tissues. Recently, we demonstrated that CD36 also binds fibrillar β-amyloid and initiates a signaling cascade that regulates microglial recruitment and activation. As increased lipoprotein oxidation and accumulation of lipid peroxidation products have been reported in Alzheimer's disease, we investigated whether β-amyloid altered oxidized lipoprotein clearance via CD36. Methods The availability of mice genetically deficient in class A (SRAI & II and class B (CD36 scavenger receptors has facilitated studies to discriminate their individual actions. Using primary microglia and macrophages, we assessed the impact of Aβ on: (a cholesterol ester accumulation by GC-MS and neutral lipid staining, (b binding, uptake and degradation of 125I-labeled oxidized lipoproteins via CD36, SR-A and CD36/SR-A-independent pathways, (c expression of SR-A and CD36. In addition, using mice with targeted deletions in essential kinases in the CD36-signaling cascade, we investigated whether Aβ-CD36 signaling altered metabolism of oxidized lipoproteins. Results In primary microglia and macrophages, Aβ inhibited binding, uptake and degradation of oxidized low density lipoprotein (oxLDL in a dose-dependent manner. While untreated cells accumulated abundant cholesterol ester in the presence of oxLDL, cells treated with Aβ were devoid of cholesterol ester. Pretreatment of cells with Aβ did not affect subsequent degradation of oxidized lipoproteins, indicating that lysosomal accumulation of Aβ did not disrupt this degradation pathway. Using mice with targeted deletions of the scavenger receptors, we demonstrated that Aβ inhibited oxidized

Morus alba leaf extract mediates neuroprotection against glyphosate-induced toxicity and biochemical alterations in the brain.

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Rebai, Olfa; Belkhir, Manel; Boujelben, Adnen; Fattouch, Sami; Amri, Mohamed

2017-04-01

Recent studies demonstrate that glyphosate exposure is associated with oxidative stress and some neurological disorders such as Parkinson's pathology. Therefore, phytochemicals, in particular phenolic compounds, have attracted increasing attention as potential agents for neuroprotection. In the present study, we investigate the impact of glyphosate on the rat brain following i.p. injection and the possible molecular target of neuroprotective activity of the phenolic fraction from Morus alba leaf extract (MALE) and its ability to reduce oxidative damage in the brain. Wistar rats from 180 to 240 g were i.p. treated with a single dose of glyphosate (100 mg kg -1 b.w.) or MALE (100 μg mL -1  kg -1 b.w.) for 2 weeks. Brain homogenates were used to evaluate neurotoxicity induced by the pesticide. For this, biochemical parameters were measured. Data shows that MALE regulated oxidative stress and counteracted glyphosate-induced deleterious effects and oxidative damage in the brain, as it abrogated LDH, protein carbonyls, and malonyldialdehyde. MALE also appears to be able to scavenge H 2 O 2 levels, maintain iron and Ca 2+ homeostasis, and increase SOD activity. Thus, in vivo results showed that mulberry leaf extract is a potent protector against glyphosate-induced toxicity, and its protective effect could result from synergism or antagonism between the various bioactive phenolic compounds in the acetonic fraction from M. alba leaf extract.

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

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Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze, E-mail: mfkhan@utmb.edu

2013-11-15

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure resulted in

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

International Nuclear Information System (INIS)

Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze

2013-01-01

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure resulted in

Exercise promotes collateral artery growth mediated by monocytic nitric oxide.

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Schirmer, Stephan H; Millenaar, Dominic N; Werner, Christian; Schuh, Lisa; Degen, Achim; Bettink, Stephanie I; Lipp, Peter; van Rooijen, Nico; Meyer, Tim; Böhm, Michael; Laufs, Ulrich

2015-08-01

Collateral artery growth (arteriogenesis) is an important adaptive response to hampered arterial perfusion. It is unknown whether preventive physical exercise before limb ischemia can improve arteriogenesis and modulate mononuclear cell function. This study aimed at investigating the effects of endurance exercise before arterial occlusion on MNC function and collateral artery growth. After 3 weeks of voluntary treadmill exercise, ligation of the right femoral artery was performed in mice. Hindlimb perfusion immediately after surgery did not differ from sedentary mice. However, previous exercise improved perfusion restoration ≤7 days after femoral artery ligation, also when exercise was stopped at ligation. This was accompanied by an accumulation of peri-collateral macrophages and increased expression of endothelial nitric oxide synthase and inducible nitric oxide synthase (iNOS) in hindlimb collateral and in MNC of blood and spleen. Systemic monocyte and macrophage depletion by liposomal clodronate but not splenectomy attenuated exercise-induced perfusion restoration, collateral artery growth, peri-collateral macrophage accumulation, and upregulation of iNOS. iNOS-deficient mice did not show exercise-induced perfusion restoration. Transplantation of bone marrow-derived MNC from iNOS-deficient mice into wild-type animals inhibited exercise-induced collateral artery growth. In contrast to sedentary controls, thrice weekly aerobic exercise training for 6 months in humans increased peripheral blood MNC iNOS expression. Circulating mononuclear cell-derived inducible nitric oxide is an important mediator of exercise-induced collateral artery growth. © 2015 American Heart Association, Inc.

Intracellular conversion of environmental nitrate and nitrite to nitric oxide with resulting developmental toxicity to the crustacean Daphnia magna.

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Bethany R Hannas

2010-08-01

Full Text Available Nitrate and nitrite (jointly referred to herein as NO(x are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NO(x undergo intracellular conversion to the potent signaling molecule nitric oxide resulting in the disruption of endocrine-regulated processes.These experiments were performed with insect cells (Drosophila S2 and whole organisms Daphnia magna. We first evaluated the ability of cells to convert nitrate (NO(3(- and nitrite (NO(2(- to nitric oxide using amperometric real-time nitric oxide detection. Both NO(3(- and NO(2(- were converted to nitric oxide in a substrate concentration-dependent manner. Further, nitric oxide trapping and fluorescent visualization studies revealed that perinatal daphnids readily convert NO(2(- to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control and to concentrations of NO(3(- and NO(2(-. All three compounds interfered with normal embryo development and reduced daphnid fecundity. Developmental abnormalities were characteristic of those elicited by compounds that interfere with ecdysteroid signaling. However, no compelling evidence was generated to indicate that nitric oxide reduced ecdysteroid titers.Results demonstrate that nitrite elicits developmental and reproductive toxicity at environmentally relevant concentrations due likely to its intracellular conversion to nitric oxide.

Bromide-free TEMPO-mediated oxidation of primary alcohol groups in starch and methyl alpha-D-glucopyranoside.

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Bragd, P L; Besemer, A C; van Bekkum, H

2000-09-22

TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl)-mediated oxidation of potato starch and methyl alpha-D-glucopyranoside (MGP) was performed in the absence of sodium bromide (NaBr) as co-catalyst, solely using sodium hypochlorite (NaOCl) as the primary oxidant. The low reaction rate associated with a bromide-free process was increased by performing the oxidation at increased temperatures. The reaction proceeded stoichiometrically and with high selectivity and with only minor depolymerisation, provided that temperature and pH were kept or = 25 degrees C) and under more alkaline conditions (pH > or = 9.0) degradation of the starch skeleton occurred. Simultaneously, side-reactions of the nitrosonium ion lowered the yield of the oxidation. Despite the absence of the NaBr catalyst, the reaction rate-controlling step was found to be the oxidation of the primary hydroxyl groups with the nitrosonium ion. The reaction was first-order in MGP and in TEMPO.

Mediated effect of ultrasound treated Diclofenac on mussel hemocytes: First evidence for the involvement of respiratory burst enzymes in the induction of DCF-mediated unspecific mode of action.

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Toufexi, Eirini; Dailianis, Stefanos; Vlastos, Dimitris; Manariotis, Ioannis D

2016-06-01

The present study investigates the toxic behavior of diclofenac (DCF) before and after its ultrasound (US) treatment, as well as the involvement of intracellular target molecules, such as NADPH oxidase and NO synthase, in the DCF-induced adverse effects on hemocytes of mussel Mytilus galloprovincialis. In this context, appropriate volumes (350 and 500mL) of DCF solutions (at concentrations of 2, 2.5, 5 and 10mgL(-1)) were treated under different ultrasound operating conditions (frequency at 582 and 862kHz, electric power density at 133 and 167W) for assessing US method efficiency. In parallel, DCF and US DCF-mediated cytotoxic (in terms of cell viability measured with the use of neutral red uptake/NRU method), oxidative (in terms of superoxide anions/(.)O2(-), nitric oxides such as NO2(-) and lipid peroxidation products, such as malondialdehyde/MDA content) and genotoxic (DNA damage measured by the use of Comet assay method) effects were investigated in hemocytes exposed for 1h to 5, 10 and 100ngL(-1) and 1, 10 and 20μgL(-1) of DCF. The involvement of NADPH oxidase and NO synthase to the DCF-induced toxicity was further investigated by the use of 10μΜ L-NAME, a NO synthase inhibitor and 10μΜ DPI, a NADPH oxidase inhibitor. According to the results, 350mL of 2mgL(-1) DCF showed higher degradation (>50%) under 167W electric power density and frequency at 862kHz for 120min, compared to degradation in all other cases, followed by a significant elimination of its toxicity. Specifically, US DCF-treated hemocytes showed a significant attenuation of DCF-mediated cytotoxic, oxidative and genotoxic effects, which appeared to be caused by NADPH oxidase and NO synthase activation, since their inhibition was followed by a significant elimination of (.)O2(-) and NO2(-) generation and the concomitant oxidative damage within cells. The results of the present study showed for the first time that unspecific mode of action of DCF, associated with the induction of NADPH oxidase

Acylcarnitine Profiles in Acetaminophen Toxicity in the Mouse: Comparison to Toxicity, Metabolism and Hepatocyte Regeneration

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Jack Hinson

2013-08-01

Full Text Available High doses of acetaminophen (APAP result in hepatotoxicity that involves metabolic activation of the parent compound, covalent binding of the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI to liver proteins, and depletion of hepatic glutathione. Impaired fatty acid β-oxidation has been implicated in previous studies of APAP-induced hepatotoxicity. To better understand relationships between toxicity and fatty acid β-oxidation in the liver in APAP toxicity, metabolomic assays for long chain acylcarnitines were examined in relationship to established markers of liver toxicity, oxidative metabolism, and liver regeneration in a time course study in mice. Male B6C3F1 mice were treated with APAP (200 mg/kg IP or saline and sacrificed at 1, 2, 4, 8, 24 or 48 h after APAP. At 1 h, hepatic glutathione was depleted and APAP protein adducts were markedly increased. Alanine aminotransferase (ALT levels were elevated at 4 and 8 h, while proliferating cell nuclear antigen (PCNA expression, indicative of hepatocyte regeneration, was apparent at 24 h and 48 h. Elevations of palmitoyl, oleoyl and myristoyl carnitine were apparent by 2–4 h, concurrent with the onset of Oil Red O staining in liver sections. By 8 h, acylcarnitine levels were below baseline levels and remained low at 24 and 48 h. A partial least squares (PLS model suggested a direct association of acylcarnitine accumulation in serum to APAP protein adduct and hepatic glutathione levels in mice. Overall, the kinetics of serum acylcarnitines in APAP toxicity in mice followed a biphasic pattern involving early elevation after the metabolism phases of toxicity and later depletion of acylcarnitines.

Synergistic Effects of Zinc Oxide Nanoparticles and Fatty Acids on Toxicity to Caco-2 Cells

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Cao, Yi; Roursgaard, Martin; Kermanizadeh, Ali

2015-01-01

epithelial (Caco-2) cells. The ZnO NPs exposure concentration dependently induced cytotoxicity to Caco-2 cells showing as reduced proliferation and activity measured by 3 different assays. PA exposure induced cytotoxicity, and coexposure to ZnO NPs and PA showed the largest cytotoxic effects. The presence......Fatty acids exposure may increase sensitivity of intestinal epithelial cells to cytotoxic effects of zinc oxide (ZnO) nanoparticles (NPs). This study evaluated the synergistic effects of ZnO NPs and palmitic acid (PA) or free fatty acids (FFAs) mixture (oleic/PA 2:1) on toxicity to human colon...

Non-specific phospholipase C4 mediates response to aluminum toxicity in Arabidopsis thaliana

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Přemysl ePejchar

2015-02-01

Full Text Available Aluminum ions (Al have been recognized as a major toxic factor for crop production in acidic soils. The first indication of the Al toxicity in plants is the cessation of root growth, but the mechanism of root growth inhibition is largely unknown. Here we examined the impact of Al on the expression, activity and function of the non-specific phospholipase C4 (NPC4, a plasma membrane-bound isoform of NPC, a member of the plant phospholipase family, in Arabidopsis thaliana.We observed a lower expression of NPC4 using GUS assay and a decreased formation of labeled diacylglycerol, product of NPC activity, using fluorescently labeled phosphatidylcholine as a phospholipase substrate in Arabidopsis WT seedlings treated with AlCl3 for 2 h. The effect on in situ NPC activity persisted for longer Al treatment periods (8, 14 h. Interestingly, in seedlings overexpressing NPC4, the Al-mediated NPC-inhibiting effect was alleviated at 14 h. However, in vitro activity and localization of NPC4 were not affected by Al, thus excluding direct inhibition by Al ions or possible translocation of NPC4 as the mechanisms involved in NPC-inhibiting effect. Furthermore, the growth of tobacco pollen tubes rapidly arrested by Al was partially rescued by the overexpression of AtNPC4 while Arabidopsis npc4 knockout lines were found to be more sensitive to Al stress during long-term exposure of Al at low phosphate conditions.Our observations suggest that NPC4 plays a role in both early and long-term responses to Al stress.

Dopamine-mediated oxidation of methionine 127 in α-synuclein causes cytotoxicity and oligomerization of α-synuclein.

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Kazuhiro Nakaso

Full Text Available Parkinson's disease (PD is a neurodegenerative disorder characterized by the selective loss of dopaminergic neurons and the presence of Lewy bodies. Many recent studies focused on the interaction between α-synuclein (α-syn and dopamine in the pathogenesis of PD, and fluorescent anisotropy suggested that the C-terminal region of α-syn may be a target for modification by dopamine. However, it is not well understood why PD-related pathogenesis occurs selectively in dopaminergic neurons. We investigated the interaction between dopamine and α-syn with regard to cytotoxicity. A soluble oligomer was formed by co-incubating α-syn and dopamine in vitro. To clarify the effect of dopamine on α-syn in cells, we generated PC12 cells expressing human α-syn, as well as the α-syn mutants, M116A, Y125D, M127A, S129A, and M116A/M127A, in a tetracycline-inducible manner (PC12-TetOFF-α-syn. Overexpression of wildtype α-syn in catecholaminergic PC12 cells decreased cell viability in long-term cultures, while a competitive inhibitor of tyrosine hydroxylase blocked this vulnerability, suggesting that α-syn-related cytotoxicity is associated with dopamine metabolism. The vulnerabilities of all mutant cell lines were lower than that of wildtype α-syn-expressing cells. Moreover, α-syn containing dopamine-mediated oxidized methionine (Met(O was detected in PC12-TetOFF-α-syn. Met(O was lower in methionine mutant cells, especially in the M127A or M116A/M127A mutants, but also in the Y125D and S129A mutants. Co-incubation of dopamine and the 125YEMPS129 peptide enhanced the production of H2O2, which may oxidize methionine residues and convert them to Met(O. Y125- or S129-lacking peptides did not enhance the dopamine-related production of H2O2. Our results suggest that M127 is the major target for oxidative modification by dopamine, and that Y125 and S129 may act as enhancers of this modification. These results may describe a mechanism of dopaminergic neuron

The effect of laurel leaf extract against toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in cultured rat hepatocytes.

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Turkez, Hasan; Geyikoglu, Fatime

2011-12-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a very toxic environmental pollutant that raises great public concern about its impact on human health. Recent studies indicate that laurel leaf extract exhibits antioxidant properties that can counter the toxic effects of certain compounds in the liver. The aim of this study was to assess how effective LE is against the toxicity of TCDD in a primary culture of rat hepatocytes. The extract (50 mg L(-1), 100 mg L(-1), and 200 mg L(-1)) was added to cultures alone or with TCDD (1.61 mg L(-1) and 3.22 mg L(-1)) for 48 hours. Cell viability was measured using the [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and the lactate dehydrogenase (LDH) cytotoxicity assay, while oxidative damage was assessed by measuring total antioxidant capacity (TAC) and total oxidative stress (TOS). DNA damage was also analysed using the micronucleus (MN) assay of the cultured hepatocytes. TCDD alone lowered, and laurel extract had no effect on cell viability. TCDD also increased TOS and significantly decreased TAC. It significantly increased the frequency of micronucleated hepatocytes in a dose-dependent manner. In cultures exposed to LE alone, TOS did not change and TAC significantly increased in a dose-dependent manner. Added to TCDD, laurel countered its toxic effects and showed protective effects against TCDD-mediated DNA damage. This points to the therapeutic potential of laurel against TCDD toxicity in the liver.

A broad spectrum catalytic system for removal of toxic organics from water by deep oxidation. 1998 annual progress report

International Nuclear Information System (INIS)

Sen, A.

1998-01-01

'Toxic organics and polymers pose a serious threat to the environment, especially when they are present in aquatic systems. The objective of the research is the design of practical procedures for the removal and/or recycling of such pollutants by oxidation. This report summarizes the work performed in the first one and half years of a three year project. The authors had earlier described a catalytic system for the deep oxidation of toxic organics, such as benzene, phenol and substituted phenols, aliphatic and aromatic halogenated compounds, organophosphorus, and organosulfur compounds [1]. In this system, metallic palladium was found to catalyze the oxidation of the substrate by dioxygen in aqueous medium at 80--100 C in the presence of carbon monoxide. For all the substrates examined, deep oxidation to carbon monoxide, carbon dioxide, and water occurred in high yields, resulting in up to several hundred turnovers over a 24 h period. Because of a pressing need for new procedures for the destruction of chemical warfare agents, the authors have examined in detail the deep oxidation of appropriate model compounds containing phosphorus-carbon and sulfur-carbon bonds using the same catalytic system. The result is the first observation of the efficient catalytic oxidative cleavage of phosphorus-carbon and sulfur-carbon bonds under mild conditions, using dioxygen as the oxidant [2]. In addition to the achievements described above, they have unpublished results in several other areas. For example, they have investigated the possibility of using dihydrogen rather than carbon monoxide as a coreductant in the catalytic deep oxidation of substrates. Even more attractive from a practical standpoint is the possibility of using a mixture of carbon monoxide and dihydrogen (synthesis gas). Indeed, experiments indicated that it is possible to substitute carbon monoxide by dihydrogen or synthesis gas. Significantly, in the case of nitro compounds, the deep oxidation in fact proceeded

A novel theory: biological processes mostly involve two types of mediators, namely general and specific mediators Endogenous small radicals such as superoxide and nitric oxide may play a role of general mediator in biological processes.

Science.gov (United States)

Mo, Jian

2005-01-01

A great number of papers have shown that free radicals as well as bioactive molecules can play a role of mediator in a wide spectrum of biological processes, but the biological actions and chemical reactivity of the free radicals are quite different from that of the bioactive molecules, and that a wide variety of bioactive molecules can be easily modified by free radicals due to having functional groups sensitive to redox, and the significance of the interaction between the free radicals and the bioactive molecules in biological processes has been confirmed by the results of some in vitro and in vivo studies. Based on these evidence, this article presented a novel theory about the mediators of biological processes. The essentials of the theory are: (a) mediators of biological processes can be classified into general and specific mediators; the general mediators include two types of free radicals, namely superoxide and nitric oxide; the specific mediators include a wide variety of bioactive molecules, such as specific enzymes, transcription factors, cytokines and eicosanoids; (b) a general mediator can modify almost any class of the biomolecules, and thus play a role of mediator in nearly every biological process via diverse mechanisms; a specific mediator always acts selectively on certain classes of the biomolecules, and may play a role of mediator in different biological processes via a same mechanism; (c) biological processes are mostly controlled by networks of their mediators, so the free radicals can regulate the last consequence of a biological process by modifying some types of the bioactive molecules, or in cooperation with these bioactive molecules; the biological actions of superoxide and nitric oxide may be synergistic or antagonistic. According to this theory, keeping the integrity of these networks and the balance between the free radicals and the bioactive molecules as well as the balance between the free radicals and the free radical scavengers