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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 361 records · Page 20
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Black carbon mixing state impacts on cloud microphysical properties: Effects of aerosol plume and environmental conditions

Black carbon (BC) is usually mixed with other aerosol species within individual aerosol particles. This mixture, along with the particles' size and morphology, determines the particles' optical and cloud condensation nuclei properties, and hence black carbon's climate impacts. In this study the particle-resolved aerosol model PartMC-MOSAIC was used to quantify the importance of black carbon mixing state for predicting cloud microphysical quantities. Based on a set of about 100 cloud parcel simulations a process level analysis framework was developed to attribute the response in cloud microphysical properties to changes in the underlying aerosol population ("plume effect") and the cloud parcel cooling rate ("parcel effect"). It shows that the response of cloud droplet number concentration to changes in BC emissions depends on the BC mixing state. When the aerosol population contains mainly aged BC particles an increase in BC emission results in increasing cloud droplet number concentrations ("additive effect"). In contrast, when the aerosol population contains mainly fresh BC particles they act as sinks for condensable gaseous species, resulting in a decrease in cloud droplet number concentration as BC emissions are increased ("competition effect"). Additionally, we quantified the error in cloud microphysical quantities when neglecting the information on BC mixing state, which is often done in aerosol models. Here, the errors ranged from -12% to +45% for the cloud droplet number fraction, from 0% to +1022% for the nucleation-scavenged black carbon (BC) mass fraction, from -12% to +4% for the effective radius, and from -30% to +60% for the relative dispersion.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Sanitary Waste Landfill Effects on an Invasive Wild Pig Population

Being opportunistic omnivores, wild pigs (Sus scrofa) readily feed on edible garbage. Given the presence of substantial volumes of edible food waste, large multi-county and regional municipal sanitary waste landfills constitute attractive forage resources for pigs, providing a year-round anthropogenic source of potentially high-quality forage. Our objective was to assess the effects that a large regional landfill has on the local pigs foraging in that facility's waste disposal cells. The landfill, located on the United States Department of Energy's Savannah River Site (SRS) in South Carolina, USA, became operational in 1998 and pigs began foraging there in 2001. By 2009 >100 pigs/night were observed foraging in the landfill, suggesting landfill establishment may have important consequences for population dynamics, public safety, and disease transmission. We evaluated changes in body mass, fetal litter size, numbers of pigs removed, and wild pig-vehicle collisions (WPVCs) before (1980–2000) and after (2001–2019) pigs began foraging in the landfill on SRS. Body mass during the after period increased to a greater extent for pigs in the vicinity of the landfill compared to pigs on the rest of SRS. Fetal litter size increased for pigs in the vicinity of the landfill, whereas it remained unchanged on the rest of SRS. Our density surrogate (number of pigs harvested) increased around the landfill during the after period by 2.9 times, whereas on the rest of the site it only increased by 53%. No WPVCs occurred adjacent to the landfill before 2001, but WPVCs increased along the 2 major roads bordering the landfill after 2001. Effects of sanitary waste landfills on wild pig populations scavenging there can present unique challenges to population management, control, public safety, and disease transmission. Potential approaches to address these challenges could be exclusion fencing to prevent access to the landfill's waste disposal cells or enhanced placement of waste cell covers to reduce access.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Brown tree snake ( Boiga irregularis ) population density and carcass locations following exposure to acetaminophen

Mass aerial delivery of dead mouse baits treated with acetaminophen has been evaluated as a means to reduce brown treesnake (Boiga irregularis) populations over large areas, increasing the likelihood of wide-scale eradication on Guam. Given the high density of snakes in some areas of their invasive range, eradication efforts could result in a resource pulse that may influence food web dynamics and the indirect transport of acetaminophen among trophic levels. In this study, we evaluated abundance, habitat type, and snake size (i.e., age) within two study sites on Guam, a secondary limestone forest (upland) and an abandoned coconut plantation (coastal), to determine how experimentally dosing snakes with acetaminophen is likely to influence carrion availability. We found snakes trapped in 3.24 ha plots occurred in greater abundance (population size = 72.5 snakes; SE = 8.8) and were significantly larger (978.6 mm, SE = 14.9) in the coastal than in the upland site (population size = 26.9, SE = 21.5; length = 903.0 mm, SE = 15.9). Despite these differences, carcasses of snakes that died after consuming acetaminophen-laced mice (80 mg) were recovered in consistent locations between sites, with 92% located on the ground, 4% in trees, and 4% found in rock cavities at both sites. Given that most snakes died on the ground rather than in the tree canopy, our results suggest that many poisoned snake carcasses will be accessible to a wide range of potential scavengers, possibly influencing food web dynamics and potentially contributing to indirect toxicant transfer within affected ecosystems.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Synthesis of Melanin Mediated Silver Nanoparticles from Aeromonas sp. SNS Using Response Surface Methodology: Characterization with the Biomedical Applications and Photocatalytic Degradation of Brilliant Green

Melanin is ubiquitous in nature and has wide applications in cosmetics, agriculture, and medicine. The synthesized melanin from bacterium Aeromonas sp. SNS was further used as capping and reducing agents for synthesis of silver nanoparticles (AgNPs). The influence of the experimental parameters (AgNO{sub 3}, melanin concentrations, and temperature) and their interactions on the nanoparticle synthesis was optimized using response surface methodology (RSM). The Central Composite Design (CCD) with three independent variables was optimized for the effective synthesis of AgNPs. The optimized synthesis of AgNPs was achieved at the shortest time of 14.12 h in the presence of 2.62 mM AgNO{sub 3}, and 32.30 µg ml{sup −1} melanin concentration at 54.86 °C temperature. The synthesized AgNPs were characterized by means of UV–visible spectroscopy, FTIR, SEM, TEM, and PSD respectively. The AgNPs exhibited excellent antimicrobial activity against human and food-related pathogens. These AgNPs also have strong antioxidant potential which was estimated by DPPH, DMPD and FRAP radical scavenging assays. The 92.62% photocatalytic degradation of 250 PPM brilliant green was observed in 120 min. The present finding accelerates the melanin associated AgNPs could be used in the cosmetic and pharmaceutical industries as well as in textile industries as they have superior antimicrobial, antioxidant, and photocatalytic activity.

36 MATERIALS SCIENCE↗
DOE OSTI2017

Synthesis of new N-(pyridin-3-ylmethyl)-2-aminothiazoline derivatives possessing anticholinesterase and antiradical activity as potential multifunctional agents for the treatment of neurodegenerative diseases

New N-(pyridin-3-ylmethyl)-2-aminothiazolines containing various substituents at the 5 position of the thiazoline ring and the 4-tert-butylbenzyl, 4-isopropylbenzyl, or 4-fluorobenzyl moiety at the nitrogen atom of the amino group were synthesized. The inhibitory activity of the synthesized compounds against human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7), equine serum butyrylcholinesterase (BChE, EC 3.1.1.8), and porcine liver carboxylesterase (CaE, EC 3.1.1.1) was evaluated and their antioxidant properties were studied by ABTS assay. N-(Pyridin-3-ylmethyl)-2-aminothiazolines proveded to be very weak AChE inhibitors, while their inhibitory activity against BChE and CaE was structure-dependent. 2-Aminothiazolines containing the 4-tert-butylbenzyl moiety are more efficient BChE inhibitors compared to the derivatives containing the 4-isopropylbenzyl or 4-fluorobenzyl substituent. An analysis of the dependence of the esterase profile of N-(pyridin-3-ylmethyl)-2-aminothiazolines on the structure of the substituent at the 5 position of the thiazoline ring of these compounds demonstrated that the derivatives containing the iodomethyl substituent possess the highest anti-BChE activity, the compounds with R{sup 2} = H and R{sup 3} = CH{sub 2}I have the optimal esterase profile. Regardless of the structure of the substituents in the benzyl moiety, all N-(pyridin-3-ylmethyl)-2-aminothiazolines containing the iodomethyl substituent at the 5 position of the thiazoline ring exhibited high radical scavenging activity comparable with that of the standard antioxidant Trolox. N-(Pyridin-3-ylmethyl)-2-aminothiazolines were shown to be a new promising class of compounds for the design of multifunctional agents for the treatment of neurodegenerative diseases.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2012

Cyanide binding to human plasma heme-hemopexin: A comparative study

Highlights: Black-Right-Pointing-Pointer Cyanide binding to ferric HHPX-heme-Fe. Black-Right-Pointing-Pointer Cyanide binding to ferrous HHPX-heme-Fe. Black-Right-Pointing-Pointer Dithionite-mediated reduction of ferric HHPX-heme-Fe-cyanide. Black-Right-Pointing-Pointer Cyanide binding to HHPX-heme-Fe is limited by ligand deprotonation. Black-Right-Pointing-Pointer Cyanide dissociation from HHPX-heme-Fe-cyanide is limited by ligand protonation. -- Abstract: Hemopexin (HPX) displays a pivotal role in heme scavenging and delivery to the liver. In turn, heme-Fe-hemopexin (HPX-heme-Fe) displays heme-based spectroscopic and reactivity properties. Here, kinetics and thermodynamics of cyanide binding to ferric and ferrous hexa-coordinate human plasma HPX-heme-Fe (HHPX-heme-Fe(III) and HHPX-heme-Fe(II), respectively), and for the dithionite-mediated reduction of the HHPX-heme-Fe(III)-cyanide complex, at pH 7.4 and 20.0 Degree-Sign C, are reported. Values of thermodynamic and kinetic parameters for cyanide binding to HHPX-heme-Fe(III) and HHPX-heme-Fe(II) are K = (4.1 {+-} 0.4) Multiplication-Sign 10{sup -6} M, k{sub on} = (6.9 {+-} 0.5) Multiplication-Sign 10{sup 1} M{sup -1} s{sup -1}, and k{sub off} = 2.8 Multiplication-Sign 10{sup -4} s{sup -1}; and H = (6 {+-} 1) Multiplication-Sign 10{sup -1} M, h{sub on} = 1.2 Multiplication-Sign 10{sup -1} M{sup -1} s{sup -1}, and h{sub off} = (7.1 {+-} 0.8) Multiplication-Sign 10{sup -2} s{sup -1}, respectively. The value of the rate constant for the dithionite-mediated reduction of the HHPX-heme-Fe(III)-cyanide complex is l = 8.9 {+-} 0.8 M{sup -1/2} s{sup -1}. HHPX-heme-Fe reactivity is modulated by proton acceptor/donor amino acid residue(s) (e.g., His236) assisting the deprotonation and protonation of the incoming and outgoing ligand, respectively.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly

Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. - Highlights: • We examined H{sub 2}O{sub 2} and GSH modulate HBV capsid assembly. • H{sub 2}O{sub 2} facilitates HBV capsid assembly in the presence of Hsp90. • GSH inhibits function of Hsp90 in facilitating HBV capsid assembly. • H{sub 2}O{sub 2} and GSH induce conformation change of Hsp90.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Molecular modeling and simulation studies of recombinant laccase from Yersinia enterocolitica suggests significant role in the biotransformation of non-steroidal anti-inflammatory drugs

The YacK gene from Yersinia enterocolitica strain 7, cloned in pET28a vector and expressed in Escherichia coli BL21 (DE3), showed laccase activity when oxidized with 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and guaiacol. The recombinant laccase protein was purified and characterized biochemically with a molecular mass of ≈58 KDa on SDS-PAGE and showed positive zymogram with ABTS. The protein was highly robust with optimum pH 9.0 and stable at 70 °C upto 12 h with residual activity of 70%. Kinetic constants, K{sub m} values, for ABTS and guaiacol were 675 μM and 2070 μM, respectively, with corresponding Vmax values of 0.125 μmol/ml/min and 6500 μmol/ml/min. It also possess antioxidative property against BSA and Cu{sup 2+}/H{sub 2}O{sub 2} model system. Constant pH MD simulation studies at different protonation states of the system showed ABTS to be most stable at acidic pH, whereas, diclofenac at neutral pH. Interestingly, aspirin drifted out of the binding pocket at acidic and neutral pH, but showed stable binding at alkaline pH. The biotransformation of diclofenac and aspirin by laccase also corroborated the in silico results. This is the first report on biotransformation of non-steroidal anti-inflammatory drugs (NSAIDs) using recombinant laccase from gut bacteria, supported by in silico simulation studies. - Highlights: • Laccase from Yersinia enterocolitica strain 7 was expressed in Escherichia coli BL21 (DE3). • Recombinant laccase was found to be thermostable and alkali tolerant. • The in silico and experimental studied proves the biotransformation of NSAIDs. • Laccase binds to ligands differentially under different protonation state. • Laccase also possesses free radical scavenging property.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Quenching of reactive intermediates during mechanochemical depolymerization of lignin

Mechanochemical reactions are performed to depolymerize organosolv lignin with sodium hydroxide in a mixer ball mill. GPC analysis reveals that rapid depolymerization into small oligomers occurs within minutes of milling time, followed by a slower reduction in average relative molecular mass over the next 8 h of milling. Monomeric products are identified by GC–MS and quantified by GC-FID. The extent of depolymerization appears to be limited by repolymerization reactions that form bonds between products. Suppression of these repolymerization reactions can be achieved through the addition of methanol as a scavenger or adjustment of the moisture content of the feedstock. These modifications result in lower average relative molecular masses and higher yields of monomers. These results are an important step towards designing an efficient pathway for lignin valorization.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2012

Developing a robust geochemical and reactive transport model to evaluate possible sources of arsenic at the CO[subscript 2] sequestration natural analog site in Chimayo, New Mexico

Migration of carbon dioxide (CO{sub 2}) from deep storage formations into shallow drinking water aquifers is a possible system failure related to geologic CO{sub 2} sequestration. A CO{sub 2} leak may cause mineral precipitation/dissolution reactions, changes in aqueous speciation, and alteration of pH and redox conditions leading to potential increases of trace metal concentrations above EPA National Primary Drinking Water Standards. In this study, the Chimayo site (NM) was examined for site-specific impacts of shallow groundwater interacting with CO{sub 2} from deep storage formations. Major ion and trace element chemistry for the site have been previously studied. This work focuses on arsenic (As), which is regulated by the EPA under the Safe Drinking Water Act and for which some wells in the Chimayo area have concentrations higher than the maximum contaminant level (MCL). Statistical analysis of the existing Chimayo groundwater data indicates that As is strongly correlated with trace metals U and Pb indicating that their source may be from the same deep subsurface water. Batch experiments and materials characterization, such as: X-ray diffraction (XRD), scanning electron microscopy (SEM), and synchrotron micro X-ray fluorescence ({mu}-XRF), were used to identify As association with Fe-rich phases, such as clays or oxides, in the Chimayo sediments as the major factor controlling As fate in the subsurface. Batch laboratory experiments with Chimayo sediments and groundwater show that pH decreases as CO{sub 2} is introduced into the system and buffered by calcite. The introduction of CO{sub 2} causes an immediate increase in As solution concentration, which then decreases over time. A geochemical model was developed to simulate these batch experiments and successfully predicted the pH drop once CO{sub 2} was introduced into the experiment. In the model, sorption of As to illite, kaolinite and smectite through surface complexation proved to be the key reactions in simulating the drop in As concentration as a function of time in the batch experiments. Based on modeling, kaolinite precipitation is anticipated to occur during the experiment, which allows for additional sorption sites to form with time resulting in the slow decrease in As concentration. This mechanism can be viewed as trace metal 'scavenging' due to sorption caused secondary mineral precipitation. Since deep geologic transport of these trace metals to the shallow subsurface by brine or CO{sub 2} intrusion is critical to assessing environmental impacts, the effective retardation of trace metal transport is an important parameter to estimate and it is dependent on multiple coupled reactions. At the field scale, As mobility is retarded due to the influence of sorption reactions, which can affect environmental performance assessment studies of a sequestration site.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Structural analysis of carbohydrate binding by the macrophage mannose receptor CD206

The human mannose receptor expressed on macrophages and hepatic endothelial cells scavenges released lysosomal enzymes, glycopeptide fragments of collagen, and pathogenic microorganisms and thus reduces damage following tissue injury. The receptor binds mannose, fucose, or N-acetylglucosamine (GlcNAc) residues on these targets. C-type carbohydrate recognition domain 4 (CRD4) of the receptor contains the site for Ca 2+ -dependent interaction with sugars. To investigate the details of CRD4 binding, glycan array screening was used to identify oligosaccharide ligands. The strongest signals were for glycans that contain either Manα1-2Man constituents or fucosein various linkages. The mechanisms of binding to monosaccharides and oligosaccharide substructures present in many of these ligands were examined in multiple crystal structures of CRD4. Binding of mannose residues to CRD4 results primarily from interaction of the equatorial 3- and 4-OH groups with a conserved principal Ca 2+ common to almost all sugar-binding C-type CRDs. In the Manα1-2Man complex, supplementary interactions with the reducing mannose residue explain the enhanced affinity for this disaccharide. Bound GlcNAc also interacts with the principal Ca 2+ through equatorial 3- and 4-OH groups, whereas fucose residues can bind in several orientations, through either the 2- and 3-OH groups or the 3- and 4-OH groups. Secondary contacts with additional sugars in fucose-containing oligosaccharides, such as the Lewis-a trisaccharide, provide enhanced affinity for these glycans. These results explain many of the biologically important interactions of the mannose receptor with both mammalian glycoproteins and microbes such as yeast and suggest additional classes of ligands that have not been previously identified

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

A non-aqueous sodium hexafluorophosphate-based electrolyte degradation study: Formation and mitigation of hydrofluoric acid

Fundamental characterization of battery electrolyte is crucial for rechargeable batteries. This work reports the chemical stability of sodium hexafluorophosphate (NaPF6)-based non-aqueous electrolytes containing different solvent mixtures (e.g., cyclic and acyclic carbonates) in the presence of water for Na-ion batteries. A degradation study is conducted using NaPF 6 -based electrolytes, highlighting the effect of two electrolyte additives, 2,2,2-trifluoroethoxy-2,2,2-ethoxy phosphazene (FM2) and fluoroethylene carbonate (FEC), on degradation and cell performance of full-cell Na-ion batteries. Hydrolysis of this salt in acidic condition is particularly prone to form hydrofluoric acid (HF), and can be observed in electrolytes made with battery grade carbonate solvents (<20 ppm of water). Here, degradation mechanisms of NaPF 6 -based electrolytes are studied using liquid nuclear magnetic resonance (NMR). Noticeable degradation takes place in high purity electrolytes with the presence of moisture to form HF and organophosphates in timeframes below the current shelf-life of the Na electrolytes. FEC is not efficient to protect the electrodes from being exposed to HF. On the other hand, FM2 is revealed as a “scavenger” of HF, which helps stabilize the shelf life of electrolytes that might contain or become exposed to water. Our study underscores the importance to understanding the degradation of electrolyte and improving stability toward better shelf life for sodium ion batteries.

25 ENERGY STORAGE↗
DOE OSTI2018

One-step reduction synthesis of Ag/Ag3PO4/AgBr sub-micron composites for enhanced visible photocatalytic degradation of methyl orange

Highlights: • Ag/Ag{sub 3}PO{sub 4}/AgBr photocatalysts were synthesized by a one-step reduction method. • The conditions affecting performances of the photocatalysts were optimized. • The main radicals responsible for degrading MO were investigated. • The Ag/Ag{sub 3}PO{sub 4}/AgBr photocatalyst presented excellent stability and recyclability. - Abstract: An efficient semiconductor composite, silver/silver orthophosphate/silver bromide, was successfully synthesized by a facile one-step reduction and ion exchange process. Its crystal structure, morphology, optical property, surface element composition were characterized by X-ray diffraction, scanning electron microscopy, ultraviolet-visible diffuse reflectance spectrometer and X-ray photoelectron spectrometer. The effects of composite proportion and synthesis duration on performances of as-prepared photocatalysts were investigated, and the results showed that Br/P molar ratio of 3 and the synthesis duration of 4 h were the optimum conditions. The radical scavenging experiments indicated that the hole and superoxide radical were the main active species in this reaction system. The Ag/Ag{sub 3}PO{sub 4}/AgBr-3 presented excellent stability and recyclability, maintaining 92% of degradation efficiency after 5 cycles. The good photocatalysis performance could be attributed to the formation of the heterojunction between Ag and Ag{sub 3}PO{sub 4}/AgBr.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2014

α-Dihydroxychalcone-glycoside (α-DHC) isolated from the heartwood of Pterocarpus marsupium inhibits LPS induced MAPK activation and up regulates HO-1 expression in murine RAW 264.7 macrophage

Three phenolic glycosides isolated from the heartwood of Pterocarpus marsupium showed significant free radical and superoxide ion scavenging activity and antioxidant potential that were comparable to, or several folds higher than those of standard antioxidants, trolox and ascorbic acid. The effective concentrations of these compounds were far below their cytotoxic levels. Compound 3, which was characterized to be α-dihydroxychalcone-glycoside (α-DHC), was the most potent one. Subsequent studies demonstrated that α-DHC effectively reduced nitric oxide and cytokine production by the LPS stimulated RAW 264.7 mouse macrophage cell line. The compound effectively attenuated the expression of inflammation-mediating enzymes COX-2 and iNOS at the mRNA as well as protein levels in a concentration dependent manner. It prevented phosphorylation of all the three MAPKs (JNK, ERK, p38) and eventually blocked the activation of downstream elements contributing to inflammation. Phosphorylation of IκB-α and subsequent translocation of NF-κB into the nucleus were restricted, while the expression of stress responsive gene HO-1 was up-regulated. α-DHC targeted Keap-1 by modifying its cysteine thiols, dissociating it from Nrf-2 and facilitating nuclear entry of the latter; and this in turn induced HO-1 expression. Thus α-DHC exerts its anti-inflammatory activity in a dual manner: by down regulating MAPKs and restricting nuclear stabilization of NF-κB at one end, and by disrupting Nrf-2–Keap-1 complex on the other. In conclusion, the anti-inflammatory potential together with its high therapeutic index envisages α-DHC as a prospective candidate molecule for the development of therapeutic strategy against inflammatory disorders. - Highlights: • α-DHC isolated from Pterocarpus marsupium has significant antioxidant potential. • α-DHC inhibits NO, IL-6, IL-1β, TNF-α production in LPS-stimulated RAW 264.7 cells. • α-DHC down-regulates of COX-2, iNOS expression in LPS-stimulated RAW 264.7 cells. • α-DHC down-regulates MAPK phosphorylation and nuclear translocation of NF-κB. • α-DHC induces ARE-regulated gene expression via Keap-1 modification.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

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

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.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Aldosterone induces fibrosis, oxidative stress and DNA damage in livers of male rats independent of blood pressure changes

Mineralocorticoid receptor blockers show antifibrotic potential in hepatic fibrosis. The mechanism of this protective effect is not known yet, although reactive oxygen species seem to play an important role. Here, we investigated the effects of elevated levels of aldosterone (Ald), the primary ligand of the mineralocorticoid receptor, on livers of rats in a hyperaldosteronism model: aldosterone-induced hypertension. Male Sprague–Dawley rats were treated for 4 weeks with aldosterone. To distinguish if damage caused in the liver depended on increased blood pressure or on increased Ald levels, the mineralocorticoid receptor antagonist spironolactone was given in a subtherapeutic dose, not normalizing blood pressure. To investigate the impact of oxidative stress, the antioxidant tempol was administered. Aldosterone induced fibrosis, detected histopathologically, and by expression analysis of the fibrosis marker, α-smooth muscle actin. Further, the mRNA amount of the profibrotic cytokine TGF-β was increased significantly. Fibrosis could be reduced by scavenging reactive oxygen species, and also by blocking the mineralocorticoid receptor. Furthermore, aldosterone treatment caused oxidative stress and DNA double strand breaks in livers, as well as the elevation of DNA repair activity. An increase of the transcription factor Nrf2, the main regulator of the antioxidative response could be observed, and of its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. All these effects of aldosterone were prevented by spironolactone and tempol. Already after 4 weeks of treatment, aldosteroneinfusion induced fibrosis in the liver. This effect was independent of elevated blood pressure. DNA damage caused by aldosterone might contribute to fibrosis progression when aldosterone is chronically increased. - Highlights: • Aldosterone has direct profibrotic effects on the liver independent of blood pressure. • Fibrosis is mediated by the mineralocorticoid receptor and oxidative stress. • Aldosterone induces transcription factor Nrf2 and Nrf2-regulated genes in the liver. • DNA damage caused by aldosterone might contribute to fibrosis progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

60 APPLIED LIFE SCIENCES↗