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Sample records for actively toxic pfiesteria

  1. The standardized fish bioassay procedure for detecting and culturing actively toxic Pfiesteria, used by two reference laboratories for atlantic and gulf coast states.

    PubMed Central

    Burkholder, J M; Marshall, H G; Glasgow, H B; Seaborn, D W; Deamer-Melia, N J

    2001-01-01

    In the absence of purified standards of toxins from Pfiesteria species, appropriately conducted fish bioassays are the "gold standard" that must be used to detect toxic strains of Pfiesteria spp. from natural estuarine water or sediment samples and to culture actively toxic Pfiesteria. In this article, we describe the standardized steps of our fish bioassay as an abbreviated term for a procedure that includes two sets of trials with fish, following the Henle-Koch postulates modified for toxic rather than infectious agents. This procedure was developed in 1991, and has been refined over more than 12 years of experience in research with toxic Pfiesteria. The steps involve isolating toxic strains of Pfiesteria (or other potentially, as-yet-undetected, toxic Pfiesteria or Pfiesteria-like species) from fish-killing bioassays with natural samples; growing the clones with axenic algal prey; and retesting the isolates in a second set of fish bioassays. The specific environmental conditions used (e.g., temperature, salinity, light, other factors) must remain flexible, given the wide range of conditions from which natural estuarine samples are derived. We present a comparison of information provided for fish culture conditions, reported in international science journals in which such research is routinely published, and we provide information from more than 2,000 fish bioassays with toxic Pfiesteria, along with recommendations for suitable ranges and frequency of monitoring of environmental variables. We present data demonstrating that algal assays, unlike these standardized fish bioassays, should not be used to detect toxic strains of Pfiesteria spp. Finally, we recommend how quality control/assurance can be most rapidly advanced among laboratories engaged in studies that require research-quality isolates of toxic Pfiesteria spp. PMID:11677184

  2. Field ecology of toxic Pfiesteria complex species and a conservative analysis of their role in estuarine fish kills.

    PubMed Central

    Glasgow, H B; Burkholder, J M; Mallin, M A; Deamer-Melia, N J; Reed, R E

    2001-01-01

    Within the past decade, toxic Pfiesteria outbreaks have been documented in poorly flushed, eutrophic areas of the largest and second largest estuaries on the U.S. mainland. Here we summarize a decadal field effort in fish kill assessment, encompassing kills related to Pfiesteria (49 major kills in North Carolina estuaries since 1991 and 4 in Maryland estuaries in 1997) and to other factors such as low oxygen stress (79 major fish kills in North Carolina estuaries). The laboratory and field data considered in developing our protocols are described, including toxic Pfiesteria behavior, environmental conditions conducive to toxic Pfiesteria activity, and impacts of toxic clonal Pfiesteria on fish health. We outline the steps of the standardized fish bioassay procedure that has been used since 1991 to diagnose whether actively toxic Pfiesteria was present during estuarine fish kills. Detailed data are given for a 1998 toxic Pfiesteria outbreak in the Neuse Estuary in North Carolina to illustrate of the full suite of diagnostic steps completed. We demonstrate that our conservative approach in implicating toxic Pfiesteria involvement in fish kills has biased in favor of causes other than Pfiesteria. Data are summarized from experiments that have shown stimulation of toxic Pfiesteria strains by nutrient (N, P) enrichment, supporting field observations of highest abundance of toxic strains in eutrophic estuaries. On the basis of a decade of research on toxic Pfiesteria, we present a conceptual model of the seasonal dynamics of toxic strains as affected by changing food resources and weather patterns. We also recommend protocols and research approaches that will strengthen the science of fish kill assessment related to Pfiesteria and/or other causative factors. PMID:11677181

  3. State monitoring activities related to Pfiesteria-like organisms.

    PubMed Central

    Magnien, R E

    2001-01-01

    In response to potential threats to human health and fish populations, six states along the east coast of the United States initiated monitoring programs related to Pfiesteria-like organisms in 1998. These actions were taken in the wake of toxic outbreaks of Pfiesteria piscicida Steidinger & Burkholder in Maryland during 1997 and previous outbreaks in North Carolina. The monitoring programs have two major purposes. The first, rapid response, is to ensure public safety by responding immediately to conditions that may indicate the presence of Pfiesteria or related organisms in a toxic state. The second, comprehensive assessment, is to provide a more complete understanding of where Pfiesteria-like organisms may become a threat, to understand what factors may stimulate their growth and toxicity, and to evaluate the impacts of these organisms upon fish and other aquatic life. In states where human health studies are being conducted, the data from both types of monitoring are used to provide information on environmental exposure. The three elements included in each monitoring program are identification of Pfiesteria-like organisms, water quality measurements, and assessments of fish health. Identification of Pfiesteria-like organisms is a particularly difficult element of the monitoring programs, as these small species cannot be definitively identified using light microscopy; newly applied molecular techniques, however, are starting to provide alternatives to traditional methods. State monitoring programs also offer many opportunities for collaborations with research initiatives targeting both environmental and human health issues related to Pfiesteria-like organisms. PMID:11677180

  4. Responding to Pfiesteria piscicida (the fish killer): phantomatic ontologies, indeterminacy, and responsibility in toxic microbiology.

    PubMed

    Schrader, Astrid

    2010-04-01

    Based on an analysis of an ongoing scientific-political controversy over the toxicity of a fish-killing microorganism, this paper explores the relationship between responsibility and nonhuman contributions to agency in experimental practices. Research into the insidious effects of the dinoflagellates Pfiesteria piscicida (the fish killer) that thrive in waters over-enriched with nutrients, has received considerable attention by both the media and government agencies concerned with public and environmental health. After nearly two decades of research, the question of whether Pfiesteria can be regarded the 'causative agent' of massive fish kills in the estuaries of the US mid-Atlantic could not be scientifically settled. In contrast to policymakers, who attribute the absence of a scientific consensus to gaps in scientific knowledge and uncertainties regarding the identity and behavior of the potentially toxic dinoflagellates, I propose that an inseparable entanglement of Pfiesteria's identities and their toxic activities challenges conventional notions of causality that seek to establish a connection between independent events in linear time. Building on Karen Barad's framework of agential realism, I argue for a move from epistemological uncertainties to ontological indeterminacies that follow from Pfiesteria's contributions to agency, as the condition for responsible and objective science. In tracking discrepant experimental enactments of Pfiesteria that have been mobilized as evidence for and against their toxicity, I investigate how criteria for what counts as evidence get built into the experimental apparatuses and suggest that the joint possibilities of causality and responsibility vary with the temporalities of the objects enacted. This discussion seeks to highlight a thorough entanglement of epistemic/ontological concerns with the ecological/political relevance of particular experiments. Finally, I introduce a new kind of scientific object that--borrowing from

  5. Report from the NOAA workshops to standardize protocols for monitoring toxic Pfiesteria species and associated environmental conditions.

    PubMed

    Luttenberg, D; Turgeon, D; Higgins, J

    2001-10-01

    Long-term monitoring of water quality, fish health, and plankton communities in susceptible bodies of water is crucial to identify the environmental factors that contribute to outbreaks of toxic Pfiesteria complex (TPC) species. In the aftermath of the 1997 toxic Pfiesteria outbreaks in North Carolina and Maryland, federal and several state agencies agreed that there was a need to standardize monitoring protocols. The National Oceanic & Atmospheric Administration convened two workshops that brought together state, federal, and academic resource managers and scientific experts to a) seek consensus on responding to and monitoring potential toxic Pfiesteria outbreaks; b) recommend standard parameters and protocols to characterize water quality, fish health, and plankton at historical event sites and potentially susceptible sites; and c) discuss options for integrating monitoring data sets from different states into regional and national assessments. Workshop recommendations included the development of a three-tiered TPC monitoring strategy: Tier 1, rapid event response; Tier 2, comprehensive assessment; and Tier 3, routine monitoring. These tiers correspond to varying levels of water quality, fish health, and plankton monitoring frequency and intensity. Under the strategy, sites are prioritized, depending upon their history and susceptibility to TPC events, and assigned an appropriate level of monitoring activity. Participants also agreed upon a suite of water quality parameters that should be monitored. These recommendations provide guidance to state and federal agencies conducting rapid-response and assessment activities at sites of suspected toxic Pfiesteria outbreaks, as well as to states that are developing such monitoring programs for the first time.

  6. Characterization of ichthyocidal activity of Pfiesteria piscicida: dependence on the dinospore cell density.

    PubMed

    Drgon, Tomás; Saito, Keiko; Gillevet, Patrick M; Sikaroodi, Masoumeh; Whitaker, Brent; Krupatkina, Danara N; Argemi, Federico; Vasta, Gerardo R

    2005-01-01

    The ichthyocidal activity of Pfiesteria piscicida dinospores was examined in an aquarium bioassay format by exposing fish to either Pfiesteria-containing environmental sediments or clonal P. piscicida. The presence of Pfiesteria spp. and the complexity of the microbial assemblage in the bioassay were assessed by molecular approaches. Cell-free water from bioassays that yielded significant fish mortality failed to show ichthyocidal activity. Histopathological examination of moribund and dead fish failed to reveal the skin lesions reported elsewhere. Fish larvae within "cages" of variable mesh sizes were killed in those where the pore size exceeded that of Pfiesteria dinospores. In vitro exposure of fish larvae to clonal P. piscicida indicated that fish mortality was directly proportional to the dinospore cell density. Dinospores clustered around the mouth, eyes, and operculi, suggesting that fish health may be affected by their direct interaction with skin, gill epithelia, or mucous surfaces. Molecular fingerprinting revealed the presence of a very diverse microbial community of bacteria, protists, and fungi within bioassay aquaria containing environmental sediments. Some components of the microbial community were identified as potential fish pathogens, preventing the rigorous identification of Pfiesteria spp. as the only cause of fish death. In summary, our results strongly suggest (i) that this aquarium bioassay format, which has been extensively reported in the literature, is unsuitable to accurately assess the ichthyocidal activity of Pfiesteria spp. and (ii) that the ichthyocidal activity of Pfiesteria spp. is mostly due to direct interactions of the zoospores with fish skin and gill epithelia rather than to soluble factors.

  7. PFIESTERIA SHUMWAYAE KILLS FISH BY MICROPREDATION NOT ECOTOXIN SECRETION

    EPA Science Inventory

    Massive fish kills in mid-Atlantic USA estuaries involving several million Atlantic menhaden, Brevoortia tyrannus,have been attributed to dinoflagellates of the toxic Pfiesteria complex (TPC). Potent ichthyotoxins secreted during Pfiesteria blooms are thought to be responsible fo...

  8. Metal Complexes And Free Radical Toxins Produced By Pfiesteria Piscicida

    SciTech Connect

    Moeller, P.D.R.; Beauchesne, K.R.; Huncik, K.M.; Davis, W.C.; Christopher, S.J.; Riggs-Gelasco, P.; Gelasco, A.K.

    2009-06-03

    Metal-containing organic toxins produced by Pfiesteria piscicida were characterized, for the first time, by corroborating data obtained from five distinct instrumental methods: nuclear magnetic resonance spectroscopy (NMR), inductively coupled plasma mass spectrometry (ICPMS), liquid chromatography particle beam glow discharge mass spectrometry (LC/PB-GDMS), electron paramagnetic resonance spectroscopy (EPR), and X-ray absorption spectroscopy (XAS). The high toxicity of the metal-containing toxins is due to metal-mediated free radical production. This mode of activity explains the toxicity of Pfiesteria, as well as previously reported difficulty in observing the molecular target, due to the ephemeral nature of radical species. The toxins are highly labile in purified form, maintaining activity for only 2-5 days before all activity is lost. The multiple toxin congeners in active extracts are also susceptible to decomposition in the presence of white light, pH variations, and prolonged heat. These findings represent the first formal isolation and characterization of a radical forming toxic organic-ligated metal complex isolated from estuarine/marine dinoflagellates. These findings add to an increased understanding regarding the active role of metals interacting with biological systems in the estuarine environment, as well as their links and implications to human health.

  9. Metal Complexes and Free Radical Toxins Produced by Pfiesteria piscicida

    SciTech Connect

    Moeller,P.; Beauchesne, K.; Huncik, K.; Davis, W.; Christopher, S.; Riggs-Gelasco, P.; Gelasco, A.

    2007-01-01

    Metal-containing organic toxins produced by Pfiesteria piscicida were characterized, for the first time, by corroborating data obtained from five distinct instrumental methods: nuclear magnetic resonance spectroscopy (NMR), inductively coupled plasma mass spectrometry (ICP-MS), liquid chromatography particle beam glow discharge mass spectrometry (LC/PB-GDMS), electron paramagnetic resonance spectroscopy (EPR), and X-ray absorption spectroscopy (XAS). The high toxicity of the metal-containing toxins is due to metal-mediated free radical production. This mode of activity explains the toxicity of Pfiesteria, as well as previously reported difficulty in observing the molecular target, due to the ephemeral nature of radical species. The toxins are highly labile in purified form, maintaining activity for only 2-5 days before all activity is lost. The multiple toxin congeners in active extracts are also susceptible to decomposition in the presence of white light, pH variations, and prolonged heat. These findings represent the first formal isolation and characterization of a radical forming toxic organic-ligated metal complex isolated from estuarine/marine dinoflagellates. These findings add to an increased understanding regarding the active role of metals interacting with biological systems in the estuarine environment, as well as their links and implications to human health.

  10. Etiology and pathogenesis of skin ulcers in menhaden, Brevoortia tyrannis: does Pfiesteria piscicida play a role?

    USGS Publications Warehouse

    Blazer, V.; Vogelbein, W.K.; Densmore, C.; Kator, H.; Zwerner, D.; Lilley, J.

    2000-01-01

    The toxic dinoflagellate, Pfiesteria piscicida, is widely blamed for adverse human health effects, acute fish kills and skin lesion events in fishes, particularly menhaden, Brevoortia tyrannis, inhabiting coastal waters from Delaware to North Carolina, USA. In response, we initiated studies to clarify the etiology and pathogenesis of presumed 'Pfiesteria-specific' menhaden skin lesions. Histopathologically, all lesions (>150 fish examined) were associated with a highly invasive and pathogenic fungus eliciting severe tissue necrosis and intense granulomatous inflammation. Severity and extent of the host response indicates that ulcers were at least 1 week old or older. Maryland and Virginia currently use menhaden ulcers as one of several indicators of local Pfiesteria activity. However, their chronic nature, advanced age, and consistent fungal involvement suggest that their use for this purpose may not be valid. We recently isolated an Aphanomyces sp. from the menhaden lesions which by appearance in culture, temperature growth curves, pathogenicity studies in snakehead and positive immunohistochemical staining with polyclonal antibodies suggest the infectious agent is A. invadans (cause of epizootic ulcerative syndrome in Asia, Japan and Australia) or a very closely related species. Ongoing research will address pathogenicity of the fungus in menhaden, genetic comparisons of isolates, and the role of environmental stressors, including P. piscicida, in initiation of the infection. Copyright (C) 2000.

  11. Identification of amoebae implicated in the life cycle of Pfiesteria and Pfiesteria-like dinoflagellates

    USGS Publications Warehouse

    Peglar, M.T.; Nerad, T.A.; Anderson, O.R.; Gillevet, P.M.

    2004-01-01

    This study was undertaken to assess whether amoebae commonly found in mesohaline environments are in fact stages in the life cycles of Pfiesteria and Pfiesteria-like dinoflagellates. Primary isolations of amoebae and dinoflagellates were made from water and sediment samples from five tributaries of the Chesapeake Bay. Additional amoebae were also cloned from bioassay aquaria where fish mortality was attributed to Pfiesteria. Electron microscopy and small subunit (SSU) rRNA gene sequence analysis of these isolates clearly demonstrated that the commonly depicted amoeboid form of Pfiesteria is very likely a species of Korotnevella and is unrelated to Pfiesteria or Pfiesteria-like dinoflagellates. We have determined that the Pfiesteria and Pfiesteria-like dinoflagellates examined in this study undergo a typical homothallic life cycle without amoeboid stages. Furthermore, we have demonstrated that cloned amoebae sharing morphological characteristics described for stages in the life cycle of Pfiesteria do not transform into dinozoites. The strict clonal isolation and cultivation techniques used in this study substantially support the conclusion that the amoebae and some of the flagellates depicted in the life cycle of Pfiesteria are environmental contaminants of the Pfiesteria culture system and that the Ambush Predator Hypothesis needs to be rigorously reevaluated.

  12. CHEMOSENSORY ATTRACTION OF ZOOSPORES OF THE ESTUARINE DINOFLAGELLATES, PFIESTERIA PISCICIDA AND P. SHUMWAYAE, TO FINFISH MUCUS AND EXCRETA. (R825551)

    EPA Science Inventory

    Toxic strains of the estuarine dinoflagellates, Pfiesteria piscicida and P. shumwayae, can cause fish death and disease, whereas other estuarine `lookalike' species such as cryptoperidiniopsoids have not been ichthyotoxic under ecologically rel...

  13. Microfluorimetric analysis of a purinergic receptor (P2X7) in GH4C1 rat pituitary cells: effects of a bioactive substance produced by Pfiesteria piscicida.

    PubMed Central

    Melo, A C; Moeller, P D; Glasgow, H; Burkholder, J M; Ramsdell, J S

    2001-01-01

    Pfiesteria piscicida Steidinger & Burkholder is a toxic dinoflagellate that leads to fish and human toxicity. It produces a bioactive substance that leads to cytotoxicity of GH4C1 rat pituitary cells. Extracellular adenosine 5'-triphosphate (ATP) acting on P2X7 purinergic receptors induces the formation of a nonselective cation channel, causing elevation of the cytosolic free calcium followed by a characteristic permeabilization of the cell to progressively larger ions and subsequent cell lysis. We investigated whether GH4C1 rat pituitary cells express functional P2X7 receptors, and if so, are they activated by a bioactive substance isolated from toxic P. piscicida cultures. We tested the selective agonist 2'-3'-O-(benzoyl-4-benzoyl)-ATP (BzATP) and antagonists piridoxalphosphate-6-azophenyl-2'-4'-disulfonic acid (PPADS) and oxidized-ATP (oxATP) using elevated cytosolic free calcium in Fura-2 loaded cells, and induced permeability of these cells to the fluorescent dye YO-PRO-1 as end points. We demonstrated that in GH4C1 cells, BzATP induces both the elevation of cytosolic free calcium and the permeabilization of the cell membrane. ATP-induced membrane permeabilization was inhibited by PPADS reversibly and by oxATP irreversibly. The putative Pfiesteria toxin (pPfTx) also elevated cytosolic free calcium in Fura-2 in GH4C1 cells and increased the permeability to YO-PRO-1 in a manner inhibited fully by oxATP. This study indicates that GH4C1 cells express a purinoceptor with characteristics consistent with the P2X7 subtype, and that pPfTx mimics the kinetics of cell permeabilization by ATP. PMID:11677182

  14. Pfiesteria: review of the science and identification of research gaps. Report for the National Center for Environmental Health, Centers for Disease Control and Prevention.

    PubMed Central

    Samet, J; Bignami, G S; Feldman, R; Hawkins, W; Neff, J; Smayda, T

    2001-01-01

    In connection with the CDC National Conference on Pfiesteria, a multidisciplinary panel evaluated Pfiesteria-related research. The panel set out what was known and what was not known about adverse effects of the organism on estuarine ecology, fish, and human health; assessed the methods used in Pfiesteria research; and offered suggestions to address data gaps. The panel's expertise covered dinoflagellate ecology; fish pathology and toxicology; laboratory measurement of toxins, epidemiology, and neurology. The panel evaluated peer-reviewed and non-peer-reviewed literature available through June 2000 in a systematic conceptual framework that moved from the source of exposure, through exposure research and dose, to human health effects. Substantial uncertainties remain throughout the conceptual framework the panel used to guide its evaluation. Firm evidence demonstrates that Pfiesteria is toxic to fish, but the specific toxin has not been isolated or characterized. Laboratory and field evidence indicate that the organism has a complex life cycle. The consequences of human exposure to Pfiesteria toxin and the magnitude of the human health problem remain obscure. The patchwork of approaches used in clinical evaluation and surrogate measures of exposure to the toxin are major limitations of this work. To protect public health, the panel suggests that priority be given research that will provide better insight into the effects of Pfiesteria on human health. Key gaps include the identity and mechanism of action of the toxin(s), the incomplete description of effects of exposure in invertebrates, fish, and humans, and the nature and extent of exposures that place people at risk. PMID:11687383

  15. PFIESTERIA PISCICIDA-INDUCED COGNITIVE EFFECTS: VISUAL SIGNAL DETECTION PERFORMANCE AND REVERSAL.

    EPA Science Inventory

    Humans exposed to Pfiesteria piscicida report cognitive impairment. In a rat model, we showed that exposure to Pfiesteria impaired learning a new task, but not performance of previously-learned behavior. In this study, we characterized the behavioral effects of Pfiesteria in rats...

  16. Development of Real-Time PCR Assays for Rapid Detection of Pfiesteria piscicida and Related Dinoflagellates†

    PubMed Central

    Bowers, Holly A.; Tengs, Torstein; Glasgow, Howard B.; Burkholder, JoAnn M.; Rublee, Parke A.; Oldach, David W.

    2000-01-01

    Pfiesteria complex species are heterotrophic and mixotrophic dinoflagellates that have been recognized as harmful algal bloom species associated with adverse fish and human health effects along the East Coast of North America, particularly in its largest (Chesapeake Bay in Maryland) and second largest (Albermarle-Pamlico Sound in North Carolina) estuaries. In response to impacts on human health and the economy, monitoring programs to detect the organism have been implemented in affected areas. However, until recently, specific identification of the two toxic species known thus far, Pfiesteria piscicida and P. shumwayae (sp. nov.), required scanning electron microscopy (SEM). SEM is a labor-intensive process in which a small number of cells can be analyzed, posing limitations when the method is applied to environmental estuarine water samples. To overcome these problems, we developed a real-time PCR-based assay that permits rapid and specific identification of these organisms in culture and heterogeneous environmental water samples. Various factors likely to be encountered when assessing environmental samples were addressed, and assay specificity was validated through screening of a comprehensive panel of cultures, including the two recognized Pfiesteria species, morphologically similar species, and a wide range of other estuarine dinoflagellates. Assay sensitivity and sample stability were established for both unpreserved and fixative (acidic Lugol's solution)-preserved samples. The effects of background DNA on organism detection and enumeration were also explored, and based on these results, we conclude that the assay may be utilized to derive quantitative data. This real-time PCR-based method will be useful for many other applications, including adaptation for field-based technology. PMID:11055905

  17. Pfiesteria-related educational products and information resources available to the public, health officials, and researchers.

    PubMed

    Kleindinst, J L; Anderson, D M

    2001-10-01

    Public and political concerns about Pfiesteria from 1997 to the present vastly exceed the attention given to other harmful algal bloom (HAB) issues in the United States. To some extent, the intense focus on Pfiesteria has served to increase attention on HABs in general. Given the strong and continuing public, political, and research interests in Pfiesteria piscicida Steidinger & Burkholder and related organisms, there is a clear need for information and resources of many different types. This article provides information on Pfiesteria-related educational products and information resources available to the general public, health officials, and researchers. These resources are compiled into five categories: reports; website resources; state outreach and communication programs; fact sheets; and training manuals and documentaries. Over the last few years there has been rapid expansion in the amount of Pfiesteria-related information available, particularly on the Internet, and it is scattered among many different sources. PMID:11677177

  18. Effect of biotic and abiotic factors on in vitro proliferation, encystment, and excystment of Pfiesteria piscicida.

    PubMed

    Saito, Keiko; Drgon, Tomás; Krupatkina, Danara N; Drgonova, Jana; Terlizzi, Daniel E; Mercer, Natalia; Vasta, Gerardo R

    2007-10-01

    Pfiesteria spp. are mixotrophic armored dinoflagellates populating the Atlantic coastal waters of the United States. They have been a focus of intense research due to their reported association with several fish mortality events. We have now used a clonal culture of Pfiesteria piscicida and several new environmental isolates to describe growth characteristics, feeding, and factors contributing to the encystment and germination of the organism in both laboratory and environmental samples. We also discuss applied methods of detection of the different morphological forms of Pfiesteria in environmental samples. In summary, Pfiesteria, when grown with its algal prey, Rhodomonas sp., presents a typical growth curve with lag, exponential, and stationary phases, followed by encystment. The doubling time in exponential phase is about 12 h. The profiles of proliferation under a standard light cycle and in the dark were similar, although the peak cell densities were markedly lower when cells were grown in the dark. The addition of urea, chicken manure, and soil extracts did not enhance Pfiesteria proliferation, but crude unfiltered spent aquarium water did. Under conditions of food deprivation or cold (4 degrees C), Pfiesteria readily formed harvestable cysts that were further analyzed by PCR and scanning electron microscopy. The germination of Pfiesteria cysts in environmental sediment was enhanced by the presence of live fish: dinospores could be detected 13 to 15 days earlier and reached 5- to 10-times-higher peak cell densities with live fish than with artificial seawater or f/2 medium alone. The addition of ammonia, urea, nitrate, phosphate, or surprisingly, spent fish aquarium water had no effect. PMID:17704277

  19. STEROLS OF THE HETEROTROPHIC DINOFLAGELLATE, PFIESTERIA PISCICIDA (DINOPHYCEAE): IS THERE A LIPID BIOMARKER?

    EPA Science Inventory

    Within United States waters, blooms of the dinoflagellate, Pfiesteria piscicida, have been recorded on an almost regular basis in the Chesapeake Bay and surrounding mid-Atlantic regions for the last two decades. Despite the apparent significance of such blooms to the environment ...

  20. Screening wastewater for toxicity to activated sludge

    SciTech Connect

    Schneider, C.G.

    1987-01-01

    Several toxicity tests were compared to define their utility for prediction of toxicity to activated sludge. The tests included: (1) oxygen uptake rates in batch tests with activated sludge, (2) adenosine triphosphate (ATP) measurements in the same batch tests, (3) Warburg respirometer studies with activated sludge, and (4) a luminescent bacteria test (Microtox/sup TM/). An evaluation of the toxicity tests was made with several toxicants; nickel (II), mercury (II), 2,4-dichlorophenol (DCP) and 4,6-dinitro-o-cresol (DNOC). Because of differences in toxic mechanism, some of the toxicants produced greater toxic effects in some tests than in other tests. The ATP levels decreased significant when uncouplers of oxidative phosphorylation were studied (DCP and DNOC). Several procedures for measuring ATP were investigated and were found to be unsatisfactory when applied to activated sludge. A new method for extraction of ATP, which incorporated a sonic bath and trichloroacetic acid, was developed. The improved ATP method was used in the toxicity tests and for the additional studies. Current practice in environmental engineering relies on volatile suspended solids (VSS) as a measure of active biomass in activated sludge. After an improved ATP procedure was developed, ATP was investigated for estimation of active biomass. The fate of DCP in the toxicity tests was studied and an adsorptive mechanism was proposed that was based on membrane solubility. This mechanism explained the fate of DCP in the toxicity tests and is useful for understanding the fate of DCP in activated sludge.

  1. Effect of Biotic and Abiotic Factors on In Vitro Proliferation, Encystment, and Excystment of Pfiesteria piscicida▿ †

    PubMed Central

    Saito, Keiko; Drgon, Tomás; Krupatkina, Danara N.; Drgonova, Jana; Terlizzi, Daniel E.; Mercer, Natalia; Vasta, Gerardo R.

    2007-01-01

    Pfiesteria spp. are mixotrophic armored dinoflagellates populating the Atlantic coastal waters of the United States. They have been a focus of intense research due to their reported association with several fish mortality events. We have now used a clonal culture of Pfiesteria piscicida and several new environmental isolates to describe growth characteristics, feeding, and factors contributing to the encystment and germination of the organism in both laboratory and environmental samples. We also discuss applied methods of detection of the different morphological forms of Pfiesteria in environmental samples. In summary, Pfiesteria, when grown with its algal prey, Rhodomonas sp., presents a typical growth curve with lag, exponential, and stationary phases, followed by encystment. The doubling time in exponential phase is about 12 h. The profiles of proliferation under a standard light cycle and in the dark were similar, although the peak cell densities were markedly lower when cells were grown in the dark. The addition of urea, chicken manure, and soil extracts did not enhance Pfiesteria proliferation, but crude unfiltered spent aquarium water did. Under conditions of food deprivation or cold (4°C), Pfiesteria readily formed harvestable cysts that were further analyzed by PCR and scanning electron microscopy. The germination of Pfiesteria cysts in environmental sediment was enhanced by the presence of live fish: dinospores could be detected 13 to 15 days earlier and reached 5- to 10-times-higher peak cell densities with live fish than with artificial seawater or f/2 medium alone. The addition of ammonia, urea, nitrate, phosphate, or surprisingly, spent fish aquarium water had no effect. PMID:17704277

  2. Fish lesions in the Chesapeake Bay: Pfiesteria-like dinoflagellates and other etiologies.

    PubMed

    Kane, A S; Oldach, D; Reimschuessel, R

    1998-05-01

    Ulcerative lesions and mass mortalities of Atlantic estuarine fish, particularly menhaden (Brevoortia tyrannus), have been associated with exposure to Pfiesteria-like dinoflagellates and their toxins. We collected fish from the Chicamacomico River, Maryland, and observed solitary ulcerative lesions on the majority of menhaden sampled. One striped bass (Morone saxatilis) had an area of reddening around the base of the dorsal fin. Bluegill (Lepomis machrochirus), channel catfish (Ictalurus punctatus), yellow perch (Perca flavescens), and carp (Cyprinus carpio) were externally nonremarkable. Histologically ulcerative menhaden lesions demonstrated marked chronic inflammatory infiltrate in large areas of exposed necrotic muscle. The ulcers contained granulomata with fungal hyphae in the necrotic tissue. Gram negative rod-shaped bacteria were also observed in the lesions, a common finding in ulcers of aquatic organisms. Our data suggest that typical ulcerative lesions observed on fish from areas of Pfiesteria-like dinoflagellate blooms are reflective of dermatosis, which may be related to a variety of individual or combined environmental stressors. Exposure to dinoflagellate toxin)s) potentially represents one such stressor. The role of Pfiesteria-like dinoflagellate toxin in fish primary lesion development is currently under investigation. PMID:9601194

  3. Toxic industrial deposit remediation by ant activity

    NASA Astrophysics Data System (ADS)

    Jilkova, Veronika; Frouz, Jan

    2016-04-01

    Toxic industrial deposits are often contaminated by heavy metals and the substrates have low pH values. In such systems, soil development is thus slowed down by high toxicity and acidic conditions which are unfavourable to soil fauna. Ants (Hymenoptera, Formicidae) are considered tolerant to heavy metal pollution and are known to increase organic matter content and microbial activity in their nests. Here, we focused on soil remediation caused by three ant species (Formica sanguinea, Lasius niger, and Tetramorium sp.) in an ore-washery sedimentation basin near Chvaletice (Czech Republic). Soil samples were taken from the centre of ant nests and from the nest surroundings (>3 m from nests). Samples were then analyzed for microbial activity and biomass and contents of organic matter and nutrients. As a result, ant species that most influenced soil properties was F. sanguinea as there were higher microbial activity and total nitrogen and ammonia contents in ant nests than in the surrounding soil. We expected such a result because F. sanguinea builds conspicuous large nests and is a carnivorous species that brings substantial amounts of nitrogen in insect prey to their nests. Effects of the other two ant species might be lower because of smaller nests and different feeding habits as they rely mainly on honeydew from aphids or on plant seeds that do not contain much nutrients.

  4. AXENIC CULTIVATION OF THE HETEROTROPHIC DINOFLAGELLATE PFIESTERIA SHUMWAYAE AND OBSERVATIONS ON FEEDING BEHAVIOR(1).

    PubMed

    Skelton, Hayley M; Burkholder, JoAnn M; Parrow, Matthew W

    2008-12-01

    Pfiesteria shumwayae Glasgow et J. M. Burkh. [=Pseudopfiesteria shumwayae (Glasgow et J. M. Burkh.) Litaker, Steid., P. L. Mason, Shields et P. A. Tester] is a heterotrophic dinoflagellate commonly found in temperate, estuarine waters. P. shumwayae can feed on other protists, fish, and invertebrates, but research on the biochemical requirements of this species has been restricted by the lack of axenic cultures. An undefined, biphasic culture medium was formulated that supported the axenic growth of two of three strains of P. shumwayae. The medium contained chicken egg yolk as a major component. Successful growth depended on the method used to sterilize the medium, and maximum cell yields (10(4)  · mL(-1) ) were similar to those attained in previous research when P. shumwayae was cultured with living fish or microalgae. Additionally, P. shumwayae flagellate cells ingested particles present in the biphasic medium, allowing detailed observations of feeding behavior. This research is an initial step toward a chemically defined axenic culture medium and determination of P. shumwayae metabolic requirements.

  5. Propulsion Risk Reduction Activities for Non-Toxic Cryogenic Propulsion

    NASA Technical Reports Server (NTRS)

    Smith, Timothy D.; Klem, Mark D.; Fisher, Kenneth

    2010-01-01

    The Propulsion and Cryogenics Advanced Development (PCAD) Project s primary objective is to develop propulsion system technologies for non-toxic or "green" propellants. The PCAD project focuses on the development of non-toxic propulsion technologies needed to provide necessary data and relevant experience to support informed decisions on implementation of non-toxic propellants for space missions. Implementation of non-toxic propellants in high performance propulsion systems offers NASA an opportunity to consider other options than current hypergolic propellants. The PCAD Project is emphasizing technology efforts in reaction control system (RCS) thruster designs, ascent main engines (AME), and descent main engines (DME). PCAD has a series of tasks and contracts to conduct risk reduction and/or retirement activities to demonstrate that non-toxic cryogenic propellants can be a feasible option for space missions. Work has focused on 1) reducing the risk of liquid oxygen/liquid methane ignition, demonstrating the key enabling technologies, and validating performance levels for reaction control engines for use on descent and ascent stages; 2) demonstrating the key enabling technologies and validating performance levels for liquid oxygen/liquid methane ascent engines; and 3) demonstrating the key enabling technologies and validating performance levels for deep throttling liquid oxygen/liquid hydrogen descent engines. The progress of these risk reduction and/or retirement activities will be presented.

  6. Antioxidant, Antimicrobial Activity and Toxicity Test of Pilea microphylla

    PubMed Central

    Modarresi Chahardehi, Amir; Ibrahim, Darah; Fariza Sulaiman, Shaida

    2010-01-01

    A total of 9 plant extracts were tested, using two different kinds of extracting methods to evaluate the antioxidant and antimicrobial activities from Pilea microphylla (Urticaceae family) and including toxicity test. Antioxidant activity were tested by using DPPH free radical scavenging, also total phenolic contents and total flavonoid contents were determined. Toxicity assay carried out by using brine shrimps. Methanol extract of method I (ME I) showed the highest antioxidant activity at 69.51 ± 1.03. Chloroform extract of method I (CE I) showed the highest total phenolic contents at 72.10 ± 0.71 and chloroform extract of method II (CE II) showed the highest total flavonoid contents at 60.14 ± 0.33. The antimicrobial activity of Pilea microphylla extract was tested in vitro by using disc diffusion method and minimum inhibitory concentration (MIC). The Pilea microphylla extract showed antibacterial activity against some Gram negative and positive bacteria. The extracts did not exhibit antifungal and antiyeast activity. The hexane extract of method I (HE I) was not toxic against brine shrimp (LC50 value was 3880 μg/ml). Therefore, the extracts could be suitable as antimicrobial and antioxidative agents in food industry. PMID:20652052

  7. Toxicity and mutagenic activity of some selected Nigerian plants.

    PubMed

    Sowemimo, A A; Fakoya, F A; Awopetu, I; Omobuwajo, O R; Adesanya, S A

    2007-09-25

    The toxicity and mutagenic potential of most African plants implicated in the management of cancer have not been investigated. The ethanolic extracts of selected Nigerian plants were subsequently studied using the brine shrimp lethality tests, inhibition of telomerase activity and induction of chromosomal aberrations in vivo in rat lymphocytes. Morinda lucida root bark, Nymphaea lotus whole plant and Garcinia kola root were active in the three test systems. Bryophyllum calycinum whole plant, Annona senegalensis root, Hymenocardia acida stem bark, Erythrophleum suaveolens leaves and Spondiathus preussii stem bark were toxic to brine shrimps and caused chromosomal damage in rat lymphocytes. Ficus exasperata leaves, Chrysophyllum albidum root bark and Hibiscus sabdariffa leaves were non-toxic to all the three test systems. Chenopodium ambrosioides whole plant was non-toxic to brine shrimps and rat lymphocyte chromosomes but showed inhibition in the conventional telomerase assay indicating a possible selectivity for human chromosomes. The result justified the use of the first eight plants and Chenopodium ambrosioides in the management of cancer in south west Nigeria although they appear to be non-selective and their mode of action may be different from plant to plant. All these plants except Chenopodium ambrosioides are also mutagenic and cytotoxic.

  8. Adsorption effects of activated charcoal on metaldehyde toxicity in rats.

    PubMed

    Shintani, S; Goto, K; Endo, Y; Iwamoto, C; Ohata, K

    1999-02-01

    Metaldehyde has been widely used as a main ingredient of solid fuel for making fire and slug baits in Japan. It is also marketed as a color flame tablet for party goods (ENGELFIRE). Consequently, children have been poisoned by eating such tablets which they mistook for candy. As a result, poison information center calls are increasing. According to POISINDEX, the treatment for metaldehyde poisoning consists in prevention of adsorption by activated charcoal, seizure control and airway protection. However, the optimum dose of charcoal is not established. We studied the quantitative adsorption capacity of activated charcoal for acute oral toxicity of metaldehyde in rats. In vivo toxicity and absorption tests for metaldehyde in Wister rats were done. The detoxifying effect of activated charcoal on metaldehyde toxicity and inhibition of metaldehyde absorption were investigated. Ratios used of po activated charcoal given 30 min after dosing to 400 mg metaldehyde/kg po were 5:1, 2:1, 1:1, 0.5:1. Serum metaldehyde was determined by gas chromatography in the control group (no charcoal) and the various experimental groups. Metaldehyde mortality was completely prevented at the ratio of 5:1. Gastrointestinal absorption of metaldehyde was reduced significantly by 45.3% in comparison to the control rats. There was no acetaldehyde detected in the serum of the metaldehyde-dosed rats. Metaldehyde poisoning may be prevented by early po administration of activated charcoal in a ratio of > 5:1 compared to metaldehyde. The theory that acetaldehyde is the primary toxic agent in metaldehyde poisoning should be re-evaluated.

  9. Purification, toxicity, and antiendotoxin activity of polymyxin B nonapeptide.

    PubMed Central

    Danner, R L; Joiner, K A; Rubin, M; Patterson, W H; Johnson, N; Ayers, K M; Parrillo, J E

    1989-01-01

    Polymyxin B, a relatively toxic antibiotic, has potent endotoxin-neutralizing properties that may be beneficial as adjunctive therapy in gram-negative sepsis. Polymyxin B nonapeptide (deacylated polymyxin B) is devoid of antibiotic activity but retains the capacity to disorganize the outer membrane of gram-negative bacteria. To evaluate the potential therapeutic usefulness of this derivative, we produced purified polymyxin B nonapeptide, tested its in vivo toxicity in animals, and evaluated its in vitro antiendotoxin activity. Effectiveness as an antiendotoxin agent was assessed by examining the ability of polymyxin B nonapeptide to block the enhanced release of toxic oxygen radicals induced by lipopolysaccharide in human neutrophils (priming). In vivo, at doses of 1.5 and 3.0 mg/kg, polymyxin B nonapeptide did not exhibit the neuromuscular blocking, neurotoxic, or nephrotoxic effects that were observed with polymyxin B sulfate. Both polymyxin B and polymyxin B nonapeptide inhibited lipopolysaccharide-induced neutrophil priming in a concentration-dependent manner, but the parent compound, polymyxin B, was 63 times more effective on a weight basis. The inhibitory activity of both compounds, however, diminished rapidly when they were added after the start of the lipopolysaccharide-neutrophil incubation. We conclude that polymyxin B nonapeptide is less toxic than polymyxin B and, at the doses tested, lacks the neurotoxicity and nephrotoxicity of the parent compound. Polymyxin B nonapeptide retains the antiendotoxin activity of polymyxin B but is much less potent. The findings suggest that these compounds block an early step in the neutrophil priming process, possibly lipopolysaccharide attachment to or insertion into the neutrophil membrane. PMID:2554795

  10. Chronic Activation of FXR in Transgenic Mice Caused Perinatal Toxicity and Sensitized Mice to Cholesterol Toxicity

    PubMed Central

    Cheng, Qiuqiong; Inaba, Yuka; Lu, Peipei; Xu, Meishu; He, Jinhan; Zhao, Yueshui; Guo, Grace L.; Kuruba, Ramalinga; de la Vega, Rona; Evans, Rhobert W.; Li, Song

    2015-01-01

    The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage. PMID:25719402

  11. Antiulcerogenic Activity and Toxicity of Bauhinia holophylla Hydroalcoholic Extract

    PubMed Central

    Rozza, A. L.; Cesar, D. A. S.; Pieroni, L. G.; Saldanha, L. L.; Dokkedal, A. L.; De-Faria, F. M.; Souza-Brito, A. R. M.; Vilegas, W.; Takahira, R. K.; Pellizzon, C. H.

    2015-01-01

    Several species of Bauhinia are used in traditional medicine for the treatment of gastrointestinal diseases, diabetes, and inflammation, among other conditions. The aim of this study was to investigate the antiulcer effect of a hydroalcoholic extract from the leaves of B. holophylla. The chemical profile of the extract was determined by HPLC-PAD-ESI-IT-MS. A dose-effect relation was constructed using the ethanol-induced gastric ulcer model in male Wistar rats. Histological analyses and studies of antioxidant and anti-inflammatory activities were performed in stomach samples. The involvement of SH compounds, NO, K+ATP channels, and α2-adrenergic receptors in the gastroprotective effect was evaluated. A toxicity study was performed with a single oral dose of 5000 mg/kg. The extract was composed mainly of cyanoglucoside and flavonol-O-glycosides derivatives of quercetin and myricetin. SH compounds, NO release, K+ATP channel activation, and presynaptic α2-adrenergic receptor stimulation each proved to be involved in the antiulcer effect. The levels of GSH and activity of GR and GPx were increased, and the levels of TNF-α, IL-6 and IL-10 were modulated. There was an antidiarrheal effect and there were no signs of toxicity. B. holophylla presents antiulcer activity mainly by decreasing oxidative stress and attenuating the inflammatory response, without inducing side effects. PMID:25954316

  12. Using theoretical descriptors in structure activity relationships: Validating toxicity predictions

    SciTech Connect

    Famini, G.R.; Wilson, L.Y.; Chester, N.A.; Sterling, P.A.

    1995-12-01

    Quantitative Structure Activity Relationships (QSAR) and Linear Free Energy Relationships (LFER) are very useful for correlating toxicological data, and in characterizating trends in terms of structural and electronic effects. Several years ago, we developed a series of equations correlating a number of toxicity tests with theoretically determined descriptors. One of these tests was the Microtox test, using the degradation in light from Photobacteriurn phosphoreum. Recently, several new compounds have been tested in our laboratory using the Microtox test, and compared against the predicted values. The agreement between experimental and theoretical results will be discussed, as will reasons for {open_quotes}good{close_quotes} or {open_quotes}poor{close_quotes} predictions.

  13. 4-Alkynylphenylsilatranes: Insecticidal activity, mammalian toxicity, and mode of action

    SciTech Connect

    Horsham, M.A.; Palmer, C.J.; Cole, L.M.; Casida, J.E. )

    1990-08-01

    4-Ethynyl- and 4-(prop-1-ynyl)phenylsilatranes (N(CH{sub 2}CH{sub 2}O){sub 3}SiR, R = C{sub 6}H{sub 4}-4-C{triple bond}CH or C{sub 6}H{sub 4}-4-C{triple bond}CCH{sub 3}) are highly toxic to houseflies (pretreated with piperonyl butoxide) and milkweed bugs (topical LD{sub 50}s 3-14 {mu}g/g) and to mice (intraperitoneal LD{sub 50}s 0.4-0.9 mg/kg), and they are moderately potent inhibitors of the ({sup 35}S)-tert-butylbicyclophosphorothionate or TBPS binding site (GABA-gated chloride channel) of mouse brain membranes. Scatchard analysis indicates noncompetitive interaction of 4-ethynylphenylsilatrane with the TBPS binding site. Phenylsilatrane analogues with 4-substituents of H, CH{sub 3}, Cl, Br, and C{triple bond}CSi(CH{sub 3}){sub 3} are highly toxic to mice but have little or no activity in the insect and receptor assays. Radioligand binding studies with (4-{sup 3}H)phenylsilatrane failed to reveal a specific binding site in mouse brain. Silatranes with R = H, CH{sub 3}, CH{sub 2}Cl, CH{double bond}CH{sub 2}, OCH{sub 2}CH{sub 3}, and C{sub 6}H{sub 4}-4-CH{sub 2}CH{sub 3} are of little or no activity in the insect and mouse toxicity and TBPS binding site assays as are the trithia and monocyclic analogues of phenylsilatrane. 4-Alkynylphenylsilatranes are new probes to examine the GABA receptor-ionophore complex of insects and mammals.

  14. Antibacterial activity and toxicity of silver - nanosilver versus ionic silver

    NASA Astrophysics Data System (ADS)

    Kvitek, L.; Panacek, A.; Prucek, R.; Soukupova, J.; Vanickova, M.; Kolar, M.; Zboril, R.

    2011-07-01

    The in vitro study of antibacterial activity of silver nanoparticles (NPs), prepared via modified Tollens process, revealed high antibacterial activity even at very low concentrations around several units of mg/L. These concentrations are comparable with concentrations of ionic silver revealing same antibacterial effect. However, such low concentrations of silver NPs did not show acute cytotoxicity to mammalian cells - this occurs at concentrations higher than 60 mg/L of silver, while the cytotoxic level of ionic silver is much more lower (approx. 1 mg/L). Moreover, the silver NPs exhibit lower acute ecotoxicity against the eukaryotic organisms such as Paramecium caudatum, Monoraphidium sp. and D. melanogaster. The silver NPs are toxic to these organisms at the concentrations higher than 30 mg/L of silver. On contrary, ionic silver retains its cytoxicity and ecotoxicity even at the concentration equal to 1 mg/L. The performed experiments demonstrate significantly lower toxicity of silver NPs against the eukaryotic organisms than against the prokaryotic organisms.

  15. Pharmacokinetic and pharmacogenetic predictive markers of irinotecan activity and toxicity.

    PubMed

    Di Paolo, Antonello; Bocci, Guido; Polillo, Marialuisa; Del Re, Marzia; Di Desidero, Teresa; Lastella, Marianna; Danesi, Romano

    2011-12-01

    After the rapid development of new classes of antineoplastic drugs, research activities have focused their efforts to the identification of predictive markers of drug activity and tolerability. Irinotecan (CPT-11) may induce severe toxicities (diarrhea, neutropenia) that limit its clinical use, but the increasing knowledge of its pharmacokinetics offered a potential approach to treatment optimization. Pharmacokinetics, the first area of investigation, has identified markers such as biliary index, the relative extent of conversion and the glucuronidation ratio, which are capable to define the risk for severe adverse effects. Because of the existence of some issues concerning the adoption of pharmacokinetic strategies to optimize CPT-11 dose and schedule, analyses of genetic polymorphisms seemed to offer a more reliable and safer approach for the identification of patients at risk than pharmacokinetics. In this view, the uridine diphosphate glucuronosil transferase isoform 1A1 (UGT1A1) was associated with significant changes in disposition of CPT-11 and its metabolites, and consequently with treatment-induced toxicities. However, the complex pharmacokinetics of irinotecan and the involvement of several enzymes other than UGT (i.e., carboxyl estherases, CYP450 isoforms), and transmembrane transporters (ABCB1, ABCC1, ABCG2, SLCO1B1) make difficult the identification of patients with an optimal sensitivity and specificity, and a large part of variability among patients still remains unexplained. Furthermore, prospective clinical studies that should demonstrate the reliability of those pharmacokinetic and pharmacogenetic markers are still lacking. In the present review, pharmacokinetic and pharmacogenetic markers will be discussed. PMID:21787264

  16. Lectin coated MgO nanoparticle: its toxicity, antileishmanial activity, and macrophage activation.

    PubMed

    Jebali, Ali; Hekmatimoghaddam, Seyedhossein; Kazemi, Bahram; Allaveisie, Azra; Masoudi, Alireza; Daliri, Karim; Sedighi, Najme; Ranjbari, Javad

    2014-10-01

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

  17. Toxicity of 8-Hydroxyquinoline in Cryprinus carpio Using the Acute Toxicity Test, Hepatase Activity Analysis and the Comet Assay.

    PubMed

    Yan, Shuaiguo; Chen, Lili; Dou, Xiaofei; Qi, Meng; Du, Qiyan; He, Qiaoqiao; Nan, Mingge; Chang, Zhongjie; Nan, Ping

    2015-08-01

    To evaluate the environmental toxicity of 8-hydroxyquinoline (8-HOQ), an important industrial raw material found in China's major ornamental fish, Cryprinus carpio, using the acute toxicity test, hepatase activity analysis and the comet assay. The results indicated that 8-HOQ had significant acute toxicity in adult C. carpio with a 96 h-LC50 of 1.15 and 0.22 mg L(-1) hepatic quinoline residues as assessed by HPLC. 8-HOQ also induced genotoxicity in the form of strand breaks in the DNA of hepatic cells as shown by the comet assay. With regard to physiological toxicity, 8-HOQ induced a decrease in the activities of hepatic GOT and GPT with increased exposure concentration and time. These data suggest that 8-HOQ may be toxic to the health of aquatic organisms when accidentally released into aquatic ecosystems. The data also suggest that the comet assay may be used in biomonitoring to determine 8-HOQ genotoxicity and hepatic GPT and GOT activities may be potential biomarkers of physiological toxicity.

  18. Toxicity of 8-Hydroxyquinoline in Cryprinus carpio Using the Acute Toxicity Test, Hepatase Activity Analysis and the Comet Assay.

    PubMed

    Yan, Shuaiguo; Chen, Lili; Dou, Xiaofei; Qi, Meng; Du, Qiyan; He, Qiaoqiao; Nan, Mingge; Chang, Zhongjie; Nan, Ping

    2015-08-01

    To evaluate the environmental toxicity of 8-hydroxyquinoline (8-HOQ), an important industrial raw material found in China's major ornamental fish, Cryprinus carpio, using the acute toxicity test, hepatase activity analysis and the comet assay. The results indicated that 8-HOQ had significant acute toxicity in adult C. carpio with a 96 h-LC50 of 1.15 and 0.22 mg L(-1) hepatic quinoline residues as assessed by HPLC. 8-HOQ also induced genotoxicity in the form of strand breaks in the DNA of hepatic cells as shown by the comet assay. With regard to physiological toxicity, 8-HOQ induced a decrease in the activities of hepatic GOT and GPT with increased exposure concentration and time. These data suggest that 8-HOQ may be toxic to the health of aquatic organisms when accidentally released into aquatic ecosystems. The data also suggest that the comet assay may be used in biomonitoring to determine 8-HOQ genotoxicity and hepatic GPT and GOT activities may be potential biomarkers of physiological toxicity. PMID:26067700

  19. Hormonal activity, cytotoxicity and developmental toxicity of UV filters.

    PubMed

    Balázs, Adrienn; Krifaton, Csilla; Orosz, Ivett; Szoboszlay, Sándor; Kovács, Róbert; Csenki, Zsolt; Urbányi, Béla; Kriszt, Balázs

    2016-09-01

    Ultraviolet (UV) filters are commonly used compounds in personal care products and polymer based materials, as they can absorb solar energy in the UVA and UVB spectrum. However, they are able to bind to hormone receptors and have several and different types of hormonal activities determined by in vitro assays. One of the aims of this work was to measure the hormonal and cytotoxic activities of four frequently used UV filters using bioluminescence based yeast test organisms. Using Saccharomyces cerevisiae BLYES and BLYAS strains allowed the rapid and reliable detection of agonist and antagonist hormonal activities, whereas BLYR strain served to measure cytotoxicity. Results confirmed that all tested UV filters show multiple hormonal activities. Cytotoxicity is detected only in the case of benzophenone-3. Research data on the toxic effects of benzophenone-3, especially on aquatic organisms are scarce, so further investigations were carried out regarding its cytotoxic and teratogenic effects on bacteria and zebrafish (Danio rerio) embryos, respectively. Results revealed the cytotoxicity of benzophenone-3 not only to yeasts but to bacteria, as well as its ability to influence zebrafish embryo hatching and development.

  20. Hormonal activity, cytotoxicity and developmental toxicity of UV filters.

    PubMed

    Balázs, Adrienn; Krifaton, Csilla; Orosz, Ivett; Szoboszlay, Sándor; Kovács, Róbert; Csenki, Zsolt; Urbányi, Béla; Kriszt, Balázs

    2016-09-01

    Ultraviolet (UV) filters are commonly used compounds in personal care products and polymer based materials, as they can absorb solar energy in the UVA and UVB spectrum. However, they are able to bind to hormone receptors and have several and different types of hormonal activities determined by in vitro assays. One of the aims of this work was to measure the hormonal and cytotoxic activities of four frequently used UV filters using bioluminescence based yeast test organisms. Using Saccharomyces cerevisiae BLYES and BLYAS strains allowed the rapid and reliable detection of agonist and antagonist hormonal activities, whereas BLYR strain served to measure cytotoxicity. Results confirmed that all tested UV filters show multiple hormonal activities. Cytotoxicity is detected only in the case of benzophenone-3. Research data on the toxic effects of benzophenone-3, especially on aquatic organisms are scarce, so further investigations were carried out regarding its cytotoxic and teratogenic effects on bacteria and zebrafish (Danio rerio) embryos, respectively. Results revealed the cytotoxicity of benzophenone-3 not only to yeasts but to bacteria, as well as its ability to influence zebrafish embryo hatching and development. PMID:27208882

  1. Isolation of the major component in white snakeroot that is toxic after microsomal activation: possible explanation of sporadic toxicity of white snakeroot plants and extracts.

    PubMed

    Beier, R C; Norman, J O; Reagor, J C; Rees, M S; Mundy, B P

    1993-01-01

    Tremetone, the major toxic component in white snakeroot (Eupatorium rugosum Houtt) extracts, was isolated following an in vitro bioactivity assay. Microsomal activation was required to produce a product toxic to murine melanoma (B16F1) cells as well as five other mammalian cell cultures. The metabolic activation product(s) of tremetone is suspected to be responsible for the toxic activity of the plant. Tremetone is also smoothly converted to dehydrotremetone in the plant and cell free homogenates, and readily decomposes to dehydrotremetone in extracts. Dehydrotremetone is not toxic even after microsomal activation. The efficient conversion of tremetone to dehydrotremetone may explain why white snakeroot plant material and extracts have varied activities, and why a previous claim that tremetone was responsible for the toxic activity of white snakeroot was withdrawn. Rayless goldenrod extracts show the same toxic activity as white snakeroot and the toxic activity of rayless goldenrod is most likely due to tremetone. PMID:8167948

  2. Rapid toxicity testing based on yeast respiratory activity

    SciTech Connect

    Haubenstricker, M.E. ); Meier, P.G.; Mancy, K.H. ); Brabec, M.J. )

    1990-05-01

    Rapid and economical techniques are needed to determine the effects of environmental contaminants. At present, the main methods to assess the impact of pollutants are based on chemical analysis of the samples. Invertebrate and vertebrate exposures have been used over the last two decades in assessing acute and chronic toxicities. However, these tests are labor intensive and require several days to complete. An alternative to whole organism exposure is to determine toxic effects in monocellular systems. Another approach for assessing toxicity is to monitor sensitive, nonspecific, subcellular target sites such as mitochondria. Changes in mitochondrial function which could indicate a toxic effect can be demonstrated readily after addition of a foreign substance. In initial assessments of various chemicals, rat liver mitochondria (RLM) were evaluated as a biological sensor of toxicity. False toxicity assessments will result if these ions are present even though they are generally considered nontoxic. Because of these disadvantages, an alternative mitochondrial system, such as found in bakers yeast, was evaluated.

  3. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

    PubMed

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R

    2014-07-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single

  4. Modulation of zinc toxicity by tissue plasminogen activator.

    PubMed

    Siddiq, Mustafa M; Tsirka, Stella E

    2004-01-01

    The tissue plasminogen activator (tPA)-plasmin proteolytic system mediates excitotoxin-induced neurodegeneration in vivo and in cell culture. tPA also confers neuroprotection from zinc toxicity in cell culture through a proteolysis-independent mechanism. This raises two questions: what is this non-enzymatic mechanism, and why tPA does not synergize with zinc to promote neuronal cell death? We show here that zinc binds to tPA and inhibits its activity in a dose-dependent fashion, thus terminating its protease-dependent neurotoxic capacity. We extend the previously reported culture findings to demonstrate that elevated zinc is neurotoxic in vivo, and even more so when tPA is absent. Thus, physiological levels of tPA confer protection from elevated free zinc. Mechanistically, tPA promotes movement of zinc into hippocampal neuron cells through voltage-sensitive Ca(2+) channels and Ca(2+)-permeable AMPA/KA channels. Therefore, zinc and tPA each appear to be able to limit the potential of the other to facilitate neurodegeneration, a reciprocal set of actions that may be critical in the hippocampus where tPA is secreted during the nonpathological conditions of learning and memory at sites known to be repositories of free and sequestered zinc.

  5. STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

    EPA Science Inventory

    Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

    Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

  6. Uptake and toxicity of polycyclic aromatic hydrocarbons in terrestrial springtails--studying bioconcentration kinetics and linking toxicity to chemical activity.

    PubMed

    Schmidt, Stine Nørgaard; Smith, Kilian Eric Christopher; Holmstrup, Martin; Mayer, Philipp

    2013-02-01

    Passive dosing applies a polymer loaded with test compound(s) to establish and maintain constant exposure in laboratory experiments. Passive dosing with the silicone poly(dimethylsiloxane) was used to control exposure of the terrestrial springtail Folsomia candida to six polycyclic aromatic hydrocarbons (PAHs) in bioconcentration and toxicity experiments. Folsomia candida could move freely on the PAH-loaded silicone, resulting in exposure via air and direct contact. The bioconcentration kinetics indicated efficient uptake of naphthalene, anthracene, and pyrene through air and (near) equilibrium partitioning of these PAHs to lipids and possibly the waxy layer of the springtail cuticle. Toxicities of naphthalene, phenanthrene, and pyrene were related to chemical activity, which quantifies the energetic level and drives spontaneous processes including diffusive biouptake. Chemical activity-response relationships yielded effective lethal chemical activities (La50s) well within the expected range for baseline toxicity (0.01-0.1). Effective lethal body burdens for naphthalene and pyrene exceeded the expected range of 2 to 8 mmol kg(-1) fresh weight, which again indicated the waxy layer to be a sorbing phase. Finally, chemical activities were converted into equilibrium partitioning concentrations in lipids yielding effective lethal concentrations for naphthalene and phenanthrene in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Passive dosing was a practical approach for tightly controlling PAH exposure, which in turn provided new experimental possibilities and findings. PMID:23147567

  7. Rapid toxicity testing based on mitochondrial respiratory activity

    SciTech Connect

    Haubenstricker, M.E. ); Holodnick, S.E.; Mancy, K.H. ); Brabec, M.J. )

    1990-05-01

    The need exists for rapid and inexpensive methods to determine the health effects of environmental contaminants on biological systems. One of the current research approaches for assessing cytotoxicity is to monitor the respiratory activity of the mitochondrion, a sensitive, nonspecific subcellular target site. Detected changes in mitochondrial function after the addition of a test chemical could be correlated to toxic effects. Mitochondrial respiration can be characterized by three indices: state 3 and state 4 respiratory rates, and the respiratory control ratio (RCR). State 4, the idle or resting state, results when coupled mitochondrial respire in a medium containing inorganic phosphate and a Kreb's cycle substrate in the absence of a phosphate acceptor such as adenosine diphosphate (ADP). In the presence of ADP the respiration rate increases to a maximum (state 3), accompanied by phosphorylation of ADP to adenosine triphosphate (ATP). The ratio of state 3 to state 4, or RCR, indicates how tightly the oxidative phosphorylation process is coupled. The synthesis of ATP by mitochondria is influenced by a number of compounds, most of which are either uncouplers or inhibitors.

  8. Hepatoprotective activity of Moringa oleifera against cadmium toxicity in rats

    PubMed Central

    Toppo, Reetu; Roy, Birendra Kumar; Gora, Ravuri Halley; Baxla, Sushma Lalita; Kumar, Prabhat

    2015-01-01

    Aim: The present investigation has been conducted to evaluate the hepatoprotective activity of Moringa oleifera against cadmium-induced toxicity in rats. Materials and Methods: For this study, 18 Wistar albino rats were taken. Control group, Group I rats were given cadmium chloride @ 200 ppm per kg and Group II rats were treated with M. oleifera extract @ 500 mg/kg along with cadmium chloride @ 200 ppm per kg (daily oral for 28 days). On 29th day, animals were slaughtered and various parameters were determined. Serum biomarkers, oxidative stress parameters, histomorphological examination were carried out with estimation of cadmium concentration in liver tissues. Results: Oral administration of cadmium chloride @ 200 ppm/kg for 28 days resulted in a significant increase in aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), significant (p≤0.01) increase of lipid peroxidation (LPO) and decrease in superoxide dismutase (SOD), and increase in cadmium accumulation in liver. Treatment with M. oleifera @ 500 mg/kg significantly (p<0.01) decreased the elevated ALP, AST, ALT, LPO levels and increase in SOD levels, and as compared to cadmium chloride treated group. However, there was no significant difference in cadmium concentration in liver when compared with cadmium chloride treated group. Conclusion: The study conclude that supplementation of M. oleifera (500 mg/kg), daily oral for 28 days has shown protection against cadmium-induced hepatotoxicity. PMID:27047130

  9. Microsomal activation of constituents of white snakeroot (Eupatorium rugosum Houtt) to form toxic products.

    PubMed

    Beier, R C; Norman, J O; Irvin, T R; Witzel, D A

    1987-04-01

    Components of white snakeroot, a plant toxic to livestock and human beings, were activated by Aroclor 1254-induced rat liver microsomes. The toxic products of microsomal activation were evaluated in murine melanoma (B16F1) cell cultures. Toxic products in white snakeroot were inactive in cell culture systems without microsomal activation. This activation system revealed that at least 2 fractions of white snakeroot were metabolically activated to cytotoxic agents. The autocatalytic inactivator of cytochrome P-450, 1-aminobenzotriazole, inhibited activation of white snakeroot constituents by rat liver microsomes. PMID:3592355

  10. Pharmacological activity and toxicity of some neurotropic agents under conditions of experimental hypodynamia

    NASA Technical Reports Server (NTRS)

    Kirichek, L. T.

    1980-01-01

    The indices of pharmacological range, risk coefficients, ED50, LD50, the size of the area of toxic activity, and maximal tolerated and absolute lethal doses were compared in hypodynamic mice. The pharmacological activity of the test neurotropic agents exhibiting a central action underwent change, but their toxicity remained unchanged.

  11. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

    PubMed Central

    2012-01-01

    Background Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. Methods/Design The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Results Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic

  12. Estimating Toxicity Pathway Activating Doses for High Throughput Chemical Risk Assessments

    EPA Science Inventory

    Estimating a Toxicity Pathway Activating Dose (TPAD) from in vitro assays as an analog to a reference dose (RfD) derived from in vivo toxicity tests would facilitate high throughput risk assessments of thousands of data-poor environmental chemicals. Estimating a TPAD requires def...

  13. Quantitative structure-activity relationships for toxicity of nonpolar narcotic chemicals to Pseudokirchneriella subcapitata.

    PubMed

    Hsieh, Shih-Hung; Hsu, Chih-Hsiung; Tsai, Din-Yu; Chen, Chung-Yuan

    2006-11-01

    This study presents data for 27 nonpolar narcotic compounds regarding toxicity to Pseudokirchneriella subcapitata as evaluated using a closed-system algal toxicity test with an exposure time of 48 h. Two test endpoints, dissolved oxygen production and algal growth rate, were used to assess the toxicity of nonpolar narcotic chemicals on algae. Hydrophobicity (1-octanol-water partition coefficient [K(OW)]) provided satisfactory descriptions for the toxicity of nonpolar narcotic compounds, and quantitative structure-activity relationships based on log K(OW) were established. The relative sensitivity of various aquatic organisms to nonpolar chemicals was as follows: P. subcapitata > Vibriofischeri > or = Nitrosomonas sp. > fathead minnow > Daphnia magna > polytox > activated sludge. In addition, linear relationships were found between the toxicity observed in P. subcapitata and other aquatic organisms, except in the case of Nitrosomonas sp. Therefore, for nonpolar toxicants, the closed-system technique applied in the present study can be an ideal surrogate for other tests, such as fathead minnow and D. magna, that are either time-consuming or labor-intensive. However, because the current toxicity database is based primarily on the conventional batch tests, it cannot provide adequate assessment regarding the effects of various organic toxicants. Therefore, more extensive research is needed to revise the database for the toxicity of organic compounds on phytoplankton using the closed-system technique.

  14. Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

  15. Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides

    EPA Science Inventory

    Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eight...

  16. Lead Toxicity to the Performance, Viability, And Community Composition of Activated Sludge Microorganisms

    SciTech Connect

    Yuan, L; Zhi, W; Liu, YS; Karyala, S; Vikesland, PJ; Chen, X; Zhang, HS

    2015-01-20

    Lead (Pb) is a prominent toxic metal in natural and engineered systems. Current knowledge on Pb toxicity to the activated sludge has been limited to short-term (<= 24 h) toxicity. The effect of extended Pb exposure on process performance, bacterial viability, and community compositions remains unknown. We quantified the 24-h and 7-day Pb toxicity to chemical oxygen demand (COD) and NH3-N removal, bacterial viability, and community compositions using lab-scale experiments. Our results showed that 7-day toxicity was significantly higher than the short-term 24-h toxicity. Ammonia-oxidizing bacteria were more susceptible than the heterotrophs to Pb toxicity. The specific oxygen uptake rate responded quickly to Pb addition and could serve as a rapid indicator for detecting Pb pollutions. Microbial viability decreased linearly with the amount of added Pb at extended exposure. The bacterial community diversity was markedly reduced with elevated Pb concentrations. Surface analysis suggested that the adsorbed form of Pb could have contributed to its toxicity along with the dissolved form. Our study provides for the first time a systematic investigation of the effect of extended exposure of Pb on the performance and microbiology of aerobic treatment processes, and it indicates that long-term Pb toxicity has been underappreciated by previous studies.

  17. Lead toxicity to the performance, viability, and community composition of activated sludge microorganisms.

    PubMed

    Yuan, Li; Zhi, Wei; Liu, Yangsheng; Karyala, Saikumar; Vikesland, Peter J; Chen, Xi; Zhang, Husen

    2015-01-20

    Lead (Pb) is a prominent toxic metal in natural and engineered systems. Current knowledge on Pb toxicity to the activated sludge has been limited to short-term (≤24 h) toxicity. The effect of extended Pb exposure on process performance, bacterial viability, and community compositions remains unknown. We quantified the 24-h and 7-day Pb toxicity to chemical oxygen demand (COD) and NH3–N removal, bacterial viability, and community compositions using lab-scale experiments. Our results showed that 7-day toxicity was significantly higher than the short-term 24-h toxicity. Ammonia-oxidizing bacteria were more susceptible than the heterotrophs to Pb toxicity. The specific oxygen uptake rate responded quickly to Pb addition and could serve as a rapid indicator for detecting Pb pollutions. Microbial viability decreased linearly with the amount of added Pb at extended exposure. The bacterial community diversity was markedly reduced with elevated Pb concentrations. Surface analysis suggested that the adsorbed form of Pb could have contributed to its toxicity along with the dissolved form. Our study provides for the first time a systematic investigation of the effect of extended exposure of Pb on the performance and microbiology of aerobic treatment processes, and it indicates that long-term Pb toxicity has been underappreciated by previous studies. PMID:25536278

  18. Toxicity of N-substituted aromatics to acetoclastic methanogenic activity in granular sludge.

    PubMed Central

    Donlon, B A; Razo-Flores, E; Field, J A; Lettinga, G

    1995-01-01

    N-substituted aromatics are important priority pollutants entering the environment primarily through anthropogenic activities associated with the industrial production of dyes, explosives, pesticides, and pharmaceuticals. Anaerobic treatment of wastewaters discharged by these industries could potentially be problematical as a result of the high toxicity of N-substituted aromatics. The objective of this study was to examine the structure-toxicity relationships of N-substituted aromatic compounds to acetoclastic methanogenic bacteria. The toxicity was assayed in serum flasks by measuring methane production in granular sludge. Unacclimated cultures were used to minimize the biotransformation of the toxic organic chemicals during the test. The nature and the degree of the aromatic substitution were observed to have a profound effect on the toxicity of the test compound. Nitroaromatic compounds were, on the average, over 500-fold more toxic than their corresponding aromatic amines. Considering the facile reduction of nitro groups by anaerobic microorganisms, a dramatic detoxification of nitroaromatics towards methanogens can be expected to occur during anaerobic wastewater treatment. While the toxicity exerted by the N-substituted aromatic compounds was closely correlated with compound apolarity (log P), it was observed that at any given log P, N-substituted phenols had a toxicity that was 2 orders of magnitude higher than that of chlorophenols and alkylphenols. This indicates that toxicity due to the chemical reactivity of nitroaromatics is much more important than partitioning effects in bacterial membranes. PMID:8526501

  19. Toxicity of organic chemicals and their mixtures to activated sludge microorganisms

    SciTech Connect

    Hall, E.; Sun, B.; Prakash, J.; Nirmalakhandan, N.

    1996-05-01

    Toxicity of eight- and 10-component mixtures of several organic chemicals to activated sludge (A/S) microorganisms was analyzed. The joint toxic effects of the tested chemicals were found to be simply additive. The quantitative structure-activity relationship (QSAR) technique using molecular connectivity indices was used to develop single variable models to fit single chemical toxicity data. A QSAR-based approach is proposed to predict the concentrations of components in equitoxic mixtures that would jointly cause 50% inhibition of the A/S microorganisms. The validity of this predictive approach was demonstrated by comparing the predicted concentrations against those found experimentally.

  20. Diversity of dominant bacterial taxa in activated sludge promotes functional resistance following toxic shock loading.

    PubMed

    Saikaly, Pascal E; Oerther, Daniel B

    2011-04-01

    Examining the relationship between biodiversity and functional stability (resistance and resilience) of activated sludge bacterial communities following disturbance is an important first step towards developing strategies for the design of robust biological wastewater treatment systems. This study investigates the relationship between functional resistance and biodiversity of dominant bacterial taxa by subjecting activated sludge samples, with different levels of biodiversity, to toxic shock loading with cupric sulfate (Cu[II]), 3,5-dichlorophenol (3,5-DCP), or 4-nitrophenol (4-NP). Respirometric batch experiments were performed to determine the functional resistance of activated sludge bacterial community to the three toxicants. Functional resistance was estimated as the 30 min IC(50) or the concentration of toxicant that results in a 50% reduction in oxygen utilization rate compared to a referential state represented by a control receiving no toxicant. Biodiversity of dominant bacterial taxa was assessed using polymerase chain reaction-terminal restriction fragment length polymorphism (PCR-T-RFLP) targeting the 16S ribosomal RNA (16S rRNA) gene. Statistical analysis of 30 min IC(50) values and PCR-T-RFLP data showed a significant positive correlation (P < 0.05) between functional resistance and microbial diversity for each of the three toxicants tested. To our knowledge, this is the first study showing a positive correlation between biodiversity of dominant bacterial taxa in activated sludge and functional resistance. In this system, activated sludge bacterial communities with higher biodiversity are functionally more resistant to disturbance caused by toxic shock loading.

  1. Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

    PubMed Central

    Spiroux de Vendômois, Joël; Séralini, Gilles-Eric

    2014-01-01

    Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone. PMID:24719846

  2. Effects of Environmental Toxicants on Metabolic Activity of Natural Microbial Communities

    PubMed Central

    Barnhart, Carole L. H.; Vestal, J. Robie

    1983-01-01

    Two methods of measuring microbial activity were used to study the effects of toxicants on natural microbial communities. The methods were compared for suitability for toxicity testing, sensitivity, and adaptability to field applications. This study included measurements of the incorporation of 14C-labeled acetate into microbial lipids and microbial glucosidase activity. Activities were measured per unit biomass, determined as lipid phosphate. The effects of various organic and inorganic toxicants on various natural microbial communities were studied. Both methods were useful in detecting toxicity, and their comparative sensitivities varied with the system studied. In one system, the methods showed approximately the same sensitivities in testing the effects of metals, but the acetate incorporation method was more sensitive in detecting the toxicity of organic compounds. The incorporation method was used to study the effects of a point source of pollution on the microbiota of a receiving stream. Toxic doses were found to be two orders of magnitude higher in sediments than in water taken from the same site, indicating chelation or adsorption of the toxicant by the sediment. The microbiota taken from below a point source outfall was 2 to 100 times more resistant to the toxicants tested than was that taken from above the outfall. Downstream filtrates in most cases had an inhibitory effect on the natural microbiota taken from above the pollution source. The microbial methods were compared with commonly used bioassay methods, using higher organisms, and were found to be similar in ability to detect comparative toxicities of compounds, but were less sensitive than methods which use standard media because of the influences of environmental factors. PMID:16346432

  3. The current status and future applicability of quantitative structure-activity relationships (QSARs) in predicting toxicity.

    PubMed

    Cronin, Mark T D

    2002-12-01

    The current status of quantitative structure-activity relationships (QSARs) in predicting toxicity is assessed. Widespread use of these methods to predict toxicity from chemical structure is possible, both by industry to develop new compounds, and also by regulatory agencies. The current use of QSARs is restricted by the lack of suitable toxicity data available for modelling, the suitability of simplistic modelling approaches for the prediction of certain endpoints, and the poor definition and utilisation of the applicability domain of models. Suggestions to resolve these issues are made.

  4. Linking algal growth inhibition to chemical activity: baseline toxicity required 1% of saturation.

    PubMed

    Schmidt, Stine N; Mayer, Philipp

    2015-02-01

    Recently, high-quality data were published on the algal growth inhibition caused by 50 non-polar narcotic compounds, of which 39 were liquid compounds with defined water solubility. In the present study, the toxicity data for these liquids were applied to challenge the chemical activity range for baseline toxicity. First, the reported effective concentrations (EC50) were divided by the respective water solubilities (S water), since the obtained EC50/S water ratio essentially equals the effective chemical activity (Ea50). The majority of EC50/S water ratios were within the expected chemical activity range of 0.01-0.1 for baseline toxicity, and none of the ratios were significantly below 0.01. On a practical level, these findings suggest EC50 values for baseline toxicity to be at or above 1% of liquid solubility, which would have been accurate or conservative for all 39 liquids with defined water solubility in the applied dataset. On an environmental risk assessment level, predicted no-effect concentrations (PNECs) for baseline toxicity could even be set as a percentage of saturation, which can easily be extended to mixtures. However, EC50 values well below 1% of liquid saturation can still occur and would be a direct indication of excess toxicity.

  5. Automated swimming activity monitor for examining temporal patterns of toxicant effects on individual Daphnia magna.

    PubMed

    Bahrndorff, Simon; Michaelsen, Thomas Yssing; Jensen, Anne; Marcussen, Laurits Faarup; Nielsen, Majken Elley; Roslev, Peter

    2016-07-01

    Aquatic pollutants are often biologically active at low concentrations and impact on biota in combination with other abiotic stressors. Traditional toxicity tests may not detect these effects, and there is a need for sensitive high-throughput methods for detecting sublethal effects. We have evaluated an automated infra-red (IR) light-based monitor for recording the swimming activity of Daphnia magna to establish temporal patterns of toxicant effects on an individual level. Activity was recorded for 48 h and the sensitivity of the monitor was evaluated by exposing D. magna to the reference chemicals K2 Cr2 O7 at 15, 20 and 25 °C and 2,4-dichlorophenol at 20 °C. Significant effects (P < 0.001) of toxicant concentrations, exposure time and incubation temperatures were observed. At 15 °C, the swimming activity remained unchanged for 48 h at sublethal concentrations of K2 Cr2 O7 whereas activity at 20 and 25 °C was more biphasic with decreases in activity occurring after 12-18 h. A similar biphasic pattern was observed after 2,4-dichlorophenol exposure at 20 °C. EC50 values for 2,4-dichlorophenol and K2 Cr2 O7 determined from automated recording of swimming activity showed increasing toxicity with time corresponding to decreases in EC50 of 0.03-0.07 mg l(-1) h(-1) . EC50 values determined after 48 h were comparable or lower than EC50 values based on visual inspection according to ISO 6341. The results demonstrated that the swimming activity monitor is capable of detecting sublethal behavioural effects that are toxicant and temperature dependent. The method allows EC values to be established at different time points and can serve as a high-throughput screening tool in toxicity testing. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26198804

  6. Does the survivorship of activated resting stages in toxic environments provide cues for ballast water treatment?

    PubMed

    Alekseev, Victor; Makrushin, Andrey; Hwang, Jiang-Shiou

    2010-01-01

    The toxic effects of three inorganic metals (Cu, Cr, Hg), three organic (phenol, formalin, ammonium) chemicals, ozone-enriched water and peroxides (H2O2) on embryonic development were tested in 8 species from the Porifera, Bryozoa and Crustacea. Toxicants with lower molecular weight showed stronger negative impacts on post-diapause embryos than chemicals with higher molecular weight if related to the toxicity of the chemicals to active adult stages. Only few embryos of the cladoceran Moina macrocopa and none of the cladoceran Wlassicsia pannonica treated with peroxides at concentration 0.3% developed further. Ozone-enriched water had no significant effect on post-diapause embryonic development in cladocerans. Ammonium (the product of NH4OH dissociation) in concentration 100 mg/l and higher killed all embryos of M. macrocopa inside protective membranes. Peroxides and ammonium are suggested for the purification of ship ballast waters as effective, non-expensive and non-persistent toxic chemicals. Resting stages of invertebrates including at least Crustaceans, Porifera and Bryozoa seem to allow not only dispersal among toxic industrial environments such as ship ballast compartments, but may also endure serious pollution events common in seaports and estuaries. Artemia cysts due to their strong protection against different toxic substances are recommended as a model for studies of toxic effects in diapausing stages in polluted estuaries and marine environments. PMID:20356608

  7. Does the survivorship of activated resting stages in toxic environments provide cues for ballast water treatment?

    PubMed

    Alekseev, Victor; Makrushin, Andrey; Hwang, Jiang-Shiou

    2010-01-01

    The toxic effects of three inorganic metals (Cu, Cr, Hg), three organic (phenol, formalin, ammonium) chemicals, ozone-enriched water and peroxides (H2O2) on embryonic development were tested in 8 species from the Porifera, Bryozoa and Crustacea. Toxicants with lower molecular weight showed stronger negative impacts on post-diapause embryos than chemicals with higher molecular weight if related to the toxicity of the chemicals to active adult stages. Only few embryos of the cladoceran Moina macrocopa and none of the cladoceran Wlassicsia pannonica treated with peroxides at concentration 0.3% developed further. Ozone-enriched water had no significant effect on post-diapause embryonic development in cladocerans. Ammonium (the product of NH4OH dissociation) in concentration 100 mg/l and higher killed all embryos of M. macrocopa inside protective membranes. Peroxides and ammonium are suggested for the purification of ship ballast waters as effective, non-expensive and non-persistent toxic chemicals. Resting stages of invertebrates including at least Crustaceans, Porifera and Bryozoa seem to allow not only dispersal among toxic industrial environments such as ship ballast compartments, but may also endure serious pollution events common in seaports and estuaries. Artemia cysts due to their strong protection against different toxic substances are recommended as a model for studies of toxic effects in diapausing stages in polluted estuaries and marine environments.

  8. Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity.

    PubMed

    Mesnage, R; Bernay, B; Séralini, G-E

    2013-11-16

    Pesticides are always used in formulations as mixtures of an active principle with adjuvants. Glyphosate, the active ingredient of the major pesticide in the world, is an herbicide supposed to be specific on plant metabolism. Its adjuvants are generally considered as inert diluents. Since side effects for all these compounds have been claimed, we studied potential active principles for toxicity on human cells for 9 glyphosate-based formulations. For this we detailed their compositions and toxicities, and as controls we used a major adjuvant (the polyethoxylated tallowamine POE-15), glyphosate alone, and a total formulation without glyphosate. This was performed after 24h exposures on hepatic (HepG2), embryonic (HEK293) and placental (JEG3) cell lines. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. The compositions in adjuvants were analyzed by mass spectrometry. Here we demonstrate that all formulations are more toxic than glyphosate, and we separated experimentally three groups of formulations differentially toxic according to their concentrations in ethoxylated adjuvants. Among them, POE-15 clearly appears to be the most toxic principle against human cells, even if others are not excluded. It begins to be active with negative dose-dependent effects on cellular respiration and membrane integrity between 1 and 3ppm, at environmental/occupational doses. We demonstrate in addition that POE-15 induces necrosis when its first micellization process occurs, by contrast to glyphosate which is known to promote endocrine disrupting effects after entering cells. Altogether, these results challenge the establishment of guidance values such as the acceptable daily intake of glyphosate, when these are mostly based on a long term in vivo test of glyphosate alone. Since pesticides are always used with adjuvants that could change their toxicity, the necessity to assess their whole formulations as mixtures becomes obvious. This challenges

  9. Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity.

    PubMed

    Mesnage, R; Bernay, B; Séralini, G-E

    2013-11-16

    Pesticides are always used in formulations as mixtures of an active principle with adjuvants. Glyphosate, the active ingredient of the major pesticide in the world, is an herbicide supposed to be specific on plant metabolism. Its adjuvants are generally considered as inert diluents. Since side effects for all these compounds have been claimed, we studied potential active principles for toxicity on human cells for 9 glyphosate-based formulations. For this we detailed their compositions and toxicities, and as controls we used a major adjuvant (the polyethoxylated tallowamine POE-15), glyphosate alone, and a total formulation without glyphosate. This was performed after 24h exposures on hepatic (HepG2), embryonic (HEK293) and placental (JEG3) cell lines. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. The compositions in adjuvants were analyzed by mass spectrometry. Here we demonstrate that all formulations are more toxic than glyphosate, and we separated experimentally three groups of formulations differentially toxic according to their concentrations in ethoxylated adjuvants. Among them, POE-15 clearly appears to be the most toxic principle against human cells, even if others are not excluded. It begins to be active with negative dose-dependent effects on cellular respiration and membrane integrity between 1 and 3ppm, at environmental/occupational doses. We demonstrate in addition that POE-15 induces necrosis when its first micellization process occurs, by contrast to glyphosate which is known to promote endocrine disrupting effects after entering cells. Altogether, these results challenge the establishment of guidance values such as the acceptable daily intake of glyphosate, when these are mostly based on a long term in vivo test of glyphosate alone. Since pesticides are always used with adjuvants that could change their toxicity, the necessity to assess their whole formulations as mixtures becomes obvious. This challenges

  10. Toxicity of smoke to epiphytic ice nucleation-active bacteria.

    PubMed

    Zagory, D; Lindow, S E; Parmeter, J R

    1983-07-01

    Wheat straw smoke aerosols and liquid smoke condensates reduced significantly both the viability and the ice-nucleating activity of Pseudomonas syringae pv. syringae and Erwinia herbicola in vitro and on leaf surfaces in vivo. Highly significant reductions in numbers of bacterial ice nuclei on the surface of both corn and almond were observed after exposure to smoke aerosols. At -5 degrees C, frost injury to corn seedlings colonized by ice nucleation-active bacteria was reduced after exposure to smoke aerosols. Effects on -9 degrees C ice nuclei, although significant, were less than on ice nuclei active at -5 degrees C. These results suggest that smoke from wildfires or smudge pots may reduce plant frost susceptibility and sources of ice nuclei important in other natural processes under some conditions. PMID:16346333

  11. Simplifying complex QSAR's (quantitative structure-activity relationships) in toxicity studies with multivariate statistics

    SciTech Connect

    Niemi, G.J.; McKim, J.M.

    1988-07-01

    During the past several decades many quantitative structure-activity relationships (QSAR's) have been derived from relatively small data sets of chemicals in a homologous series and selected empirical observations. An alternative approach is to analyze large data sets consisting of heterogeneous groups of chemicals and to explore QSAR's among these chemicals for generalized patterns of chemical behavior. The use of exploratory multivariate statistical techniques for simplifying complex QSAR problems is demonstrated through the use of research data on biodegradation and mode of toxic action. In these examples, a large number of explanatory variables were examined to explore which variables might best explain whether a chemical biodegrades or whether a toxic response by an organism can be used to identify a mode of toxic action. In both cases, the procedures reduced the number of potential explanatory variables and generated hypotheses about biodegradation and mode of toxic action for future research without explicitly testing an existing hypothesis.

  12. A quantitative structure-activity relationship approach for assessing toxicity of mixture of organic compounds.

    PubMed

    Chang, C M; Ou, Y H; Liu, T-C; Lu, S-Y; Wang, M-K

    2016-06-01

    Four types of reactivity indices were employed to construct quantitative structure-activity relationships for the assessment of toxicity of organic chemical mixtures. Results of analysis indicated that the maximum positive charge of the hydrogen atom and the inverse of the apolar surface area are the most important descriptors for the toxicity of mixture of benzene and its derivatives to Vibrio fischeri. The toxicity of mixture of aromatic compounds to green alga Scenedesmus obliquus is mainly affected by the electron flow and electrostatic interactions. The electron-acceptance chemical potential and the maximum positive charge of the hydrogen atom are found to be the most important descriptors for the joint toxicity of aromatic compounds.

  13. Acute toxicity and anticonvulsant activity of liposomes containing nimodipine on pilocarpine-induced seizures in mice.

    PubMed

    Moreno, Lina Clara Gayoso e Almendra Ibiapina; Cavalcanti, Isabella Macário Ferro; Satyal, Prabodh; Santos-Magalhães, Nereide Stela; Rolim, Hercília Maria Lins; Freitas, Rivelilson Mendes

    2015-01-12

    Nimodipine has been shown to have an inhibitory action on seizures and brain damage in rodents. However, the pharmaceutical applicability of this drug is limited by its low solubility in gastrointestinal fluids and high first-pass effect in the liver, which leads to low bioavailability. These difficulties can be overcome through the use of liposomes. The aim of the present study is to evaluate the toxicity and anticonvulsant activity of liposomes containing nimodipine (NMD-Lipo) on pilocarpine-induced seizures. NMD-Lipo was prepared using the lipid-film hydration method. Central nervous system toxicity of NMD-Lipo was assessed by Hippocratic screening. Systemic toxicity was evaluated by analyses of biochemical and hematological parameters and by observing possible signs of toxicity. The possible anticonvulsant activity was tested by the pilocarpine model. The administration of the NMD-Lipo at doses of 0.1, 1, and 10 mg/kg caused no toxicity in animals. Furthermore, NMD-Lipo prevented the installation of 100% of the pilocarpine-induced seizures and prevented the death of 100% of the mice treated with pilocarpine. These data shown that NMD-Lipo has an anticonvulsant activity significantly superior to free NMD, suggesting that the liposomes promoted a drug controlled release by improving its bioavailability and consequently increasing its pharmacological activity.

  14. Analgesic activity, toxicity study and phytochemical screening of standardized Cinnomomum iners leaves methanolic extract

    PubMed Central

    Mustaffa, F.; Indurkar, J.; Ismail, S.; Mordi, M. N.; Ramanathan, S.; Mansor, S. M.

    2010-01-01

    Cinnomomum iners standardized leaves methanolic extract (CSLE) was subjected to analgesic, toxicity and phytochemical studies. The analgesic activity of CSLE was evaluated using formalin, hot plate and tail flick tests at doses of 100, 200 and 500 mg/kg. CSLE showed significant activity (P < 0.05) in the formalin model (late phase) on the rats at doses of 200 and 500 mg/kg. However, CSLE did not show activity in the hot plate and tail flick tests. The results obtained suggest that CSLE acts peripherally to relieve pain. For the toxicity study, CSLE was orally administered to the Swiss albino mice according to the Organization for Economic Co-Operation and Development (OECD) guideline 423. There was no lethality or toxic symptoms observed for all the tested doses throughout the 14-day period. Phytochemical screening of CSLE showed the presence of cardiac glycoside, flavonoid, polyphenol, saponin, sugar, tannin and terpenoid. PMID:21808545

  15. Toxicity and Estrogenic Endocrine Disrupting Activity of Phthalates and Their Mixtures

    PubMed Central

    Chen, Xueping; Xu, Shisan; Tan, Tianfeng; Lee, Sin Ting; Cheng, Shuk Han; Lee, Fred Wang Fat; Xu, Steven Jing Liang; Ho, Kin Chung

    2014-01-01

    Phthalates, widely used in flexible plastics and consumer products, have become ubiquitous contaminants worldwide. This study evaluated the acute toxicity and estrogenic endocrine disrupting activity of butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), di-n-octyl phthalate (DNOP) and their mixtures. Using a 72 h zebrafish embryo toxicity test, the LC50 values of BBP, DBP and a mixture of the six phthalates were found to be 0.72, 0.63 and 0.50 ppm, respectively. The other four phthalates did not cause more than 50% exposed embryo mortality even at their highest soluble concentrations. The typical toxicity symptoms caused by phthalates were death, tail curvature, necrosis, cardio edema and no touch response. Using an estrogen-responsive ChgH-EGFP transgenic medaka (Oryzias melastigma) eleutheroembryos based 24 h test, BBP demonstrated estrogenic activity, DBP, DEHP, DINP and the mixture of the six phthalates exhibited enhanced-estrogenic activity and DIDP and DNOP showed no enhanced- or anti-estrogenic activity. These findings highlighted the developmental toxicity of BBP and DBP, and the estrogenic endocrine disrupting activity of BBP, DBP, DEHP and DINP on intact organisms, indicating that the widespread use of these phthalates may cause potential health risks to human beings. PMID:24637910

  16. Toxicity and estrogenic endocrine disrupting activity of phthalates and their mixtures.

    PubMed

    Chen, Xueping; Xu, Shisan; Tan, Tianfeng; Lee, Sin Ting; Cheng, Shuk Han; Lee, Fred Wang Fat; Xu, Steven Jing Liang; Ho, Kin Chung

    2014-03-14

    Phthalates, widely used in flexible plastics and consumer products, have become ubiquitous contaminants worldwide. This study evaluated the acute toxicity and estrogenic endocrine disrupting activity of butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), di-n-octyl phthalate (DNOP) and their mixtures. Using a 72 h zebrafish embryo toxicity test, the LC50 values of BBP, DBP and a mixture of the six phthalates were found to be 0.72, 0.63 and 0.50 ppm, respectively. The other four phthalates did not cause more than 50% exposed embryo mortality even at their highest soluble concentrations. The typical toxicity symptoms caused by phthalates were death, tail curvature, necrosis, cardio edema and no touch response. Using an estrogen-responsive ChgH-EGFP transgenic medaka (Oryzias melastigma) eleutheroembryos based 24 h test, BBP demonstrated estrogenic activity, DBP, DEHP, DINP and the mixture of the six phthalates exhibited enhanced-estrogenic activity and DIDP and DNOP showed no enhanced- or anti-estrogenic activity. These findings highlighted the developmental toxicity of BBP and DBP, and the estrogenic endocrine disrupting activity of BBP, DBP, DEHP and DINP on intact organisms, indicating that the widespread use of these phthalates may cause potential health risks to human beings.

  17. Assessment of swimming activity as an indicator of sublethal toxicity to the fathead minnow

    SciTech Connect

    Hovland, D.N. Jr.

    1994-12-31

    A simple, sensitive acute-bioassay was developed that looks at spontaneous swimming activity as an indicator of sublethal effect due to toxic insult. Although a large amount of work has been done validating aquatic behavior testing, there are still no standardized testing procedures or protocols for their use in assessing environmental impact of pollutants. Attempts were made in this research to develop a behavioral test that was objective and provided a basis for standardization and use in effluent testing. Tests were performed using copper sulfate and zinc sulfate as reference toxicants. Testing procedures involved 24-hour exposures to a range of toxicant concentrations with 12 fathead minnows (Pimephales promelas) per concentration. Upon completion, during a 2-minute testing period in a cylindrical aquarium, individual fish were videotaped from above, then timed later to determine actual time in swimming motion, which was averaged for each concentration group. Results demonstrate the sensitivity of the test, as significant differences from controls in swimming activity were observed at concentrations of copper sulfate as low as 1.3 ppb and zinc sulfate as low as 3.5 ppb, both well below Federal criteria for water quality. It is hoped that further research will demonstrate the utility of sublethal, behavioral toxicity tests, and that these tests will be integrated into the battery of toxicity testing procedures currently used by regulatory agencies.

  18. pH-Dependent Metal Ion Toxicity Influences the Antibacterial Activity of Two Natural Mineral Mixtures

    PubMed Central

    Cunningham, Tanya M.; Koehl, Jennifer L.; Summers, Jack S.; Haydel, Shelley E.

    2010-01-01

    Background Recent studies have demonstrated that several mineral products sold for medicinal purposes demonstrate antimicrobial activity, but little is known about the physicochemical properties involved in antibacterial activity. Methodology/Principal Findings Using in vitro mineral suspension testing, we have identified two natural mineral mixtures, arbitrarily designated BY07 and CB07, with antibacterial activity against a broad-spectrum of bacterial pathogens. Mineral-derived aqueous leachates also exhibited antibacterial activity, revealing that chemical, not physical, mineral characteristics were responsible for the observed activity. The chemical properties essential for bactericidal activity against Escherichia coli were probed by testing antibacterial activity in the presence of metal chelators, the hydroxyl radical scavenger, thiourea, and varying pH levels. Chelation of the BY07 minerals with EDTA or desferrioxamine eliminated or reduced BY07 toxicity, respectively, suggesting a role of an acid-soluble metal species, particularly Fe3+ or other sequestered metal cations, in mineral toxicity. This conclusion was supported by NMR relaxation data, which indicated that BY07 and CB07 leachates contained higher concentrations of chemically accessible metal ions than leachates from non-bactericidal mineral samples. Conclusions/Significance We conclude that the acidic environment of the hydrated minerals significantly contributes to antibacterial activity by increasing the availability and toxicity of metal ions. These findings provide impetus for further investigation of the physiological effects of mineral products and their applications in complementary antibacterial therapies. PMID:20209160

  19. Developmental Exposure to a Dopaminergic Toxicant Produces Altered Locomotor Activity in Larval Zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after developmental exposure to various classes of prototypic drugs that act on the central nervous system. ...

  20. Transcytosis, Antitumor Activity and Toxicity of Staphylococcal Enterotoxin C2 as an Oral Administration Protein Drug

    PubMed Central

    Zhao, Wenbin; Li, Yangyang; Liu, Wenhui; Ding, Ding; Xu, Yingchun; Pan, Liqiang; Chen, Shuqing

    2016-01-01

    Staphylococcal enterotoxin C2 (SEC2) is a classical superantigen (SAg), which can tremendously activate T lymphocytes at very low dosage, thus exerting its powerful antitumor activity. As an intravenous protein drug and a bacterial toxin, SEC2 has some limitations including poor patient compliance and toxic side effects. In this research, we devoted our attention to studying the antitumor activity and toxicity of SEC2 as a potential oral administration protein drug. We proved that His-tagged SEC2 (SEC2-His) could undergo facilitated transcytosis on human colon adenocarcinoma (Caco-2) cells and SEC2-His was detected in the blood of rats after oral administration. Furthermore, oral SEC2-His caused massive cytokine release and immune cell enrichment around tumor tissue, leading to inhibition of tumor growth in vivo. Meanwhile, although SEC2-His was dosed up to 32 mg/kg in mice, no significant toxicity was observed. These data showed that SEC2 can cross the intestinal epithelium in an immunologically integral form, maintaining antitumor activity but with reduced systemic toxicity. Therefore, these results may have implications for developing SEC2 as an oral administration protein drug. PMID:27322320

  1. 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).

    PubMed

    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

  2. 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).

    PubMed

    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

  3. Short-term bioassays for microsome-activated toxicants using bovine submitochondrial particles (SMP)

    SciTech Connect

    Read, H.; Blondin, G.; Harkin, J.; Gustavson, K.; Vohmann, C.

    1994-12-31

    In vitro toxicity tests using SMP are good predictors of acute toxicity in standard fish and cell culture assays for a number of chemical classes. The tests are simple, fast (< 1 h), convenient and inexpensive. However, SMP assays are generally less sensitive to mutagenic chemicals activated after being metabolism by cytochrome P-450 enzymes. Protocols for assays incorporating rat liver microsomes have been devised, are under development and are being tested with a series of model compounds. Comparisons of procedures and of relative sensitivities with other in vitro and whole-organism bioassays will be presented.

  4. An integrated study of toxicant-induced inhibition of feeding and digestion activity in Daphnia magna

    SciTech Connect

    Coen, W.M. De; Janssen, C.R.; Persoone, G.

    1995-12-31

    Previous studies on D. magna exposed to xenobiotics have demonstrated that feeding inhibition can be used as a general indicator of toxic stress. In order to evaluate the consequences of the reduced food absorption on the energy balance of the organism, the effects of short-term exposure to sublethal toxicant concentrations of 8 chemicals on physiological (ingestion rate) and biochemical aspects (digestive enzyme activity) of the feeding process were investigated. The ingestion activity was assessed using a simple and sensitive method based on the use of fluorescent latex microbeads. The biochemical aspects of feeding were studied by analyzing the activity of 5 digestive enzymes, each responsible for the breakdown of one of the three major macromolecular constituents of the food (3 carbohydrases: amylase, cellulose and {beta}-galactosidase; trypsin and esterase). Using ingestion as an effect criterium, correlation analysis revealed a significant (p < 0.05) and positive (r{sup 2} = 0.89) correlation between the 1.5h EC50 value and the conventional acute toxicity endpoint (24hEC50). For 3 out of 5 enzymes studied a clear concentration-response relationship was observed. The 2h EC 10 value (inhibition) of {beta}-galactosidase activity and 2h EC5 value of trypsin and esterase activity showed a significant linear correlation (r{sup 2} respectively 0.98, 0.96 and 0.95) with the 24hEC50 value. The relationships between the physiological and biochemical effects will be discussed in the context of toxicant-induced homeostatic adjustments in the organism`s metabolism. Finally the potential use of both types of effect criteria as rapid screening tools in aquatic toxicity testing will be reviewed.

  5. [Copper and cadmium toxicities to activated sludge investigated with ToxTell biosensor].

    PubMed

    Wang, Xue-Jiang; Wang, Xin; Liu, Mian; Wu, Zhen; Yang, Lian-Zhen; Xia, Si-Qing

    2012-06-01

    Effects of different concentrations of Cu2+, Cu2+ and Cd2+ combined pollution on the removal performance of COD in activated sludge system were investigated, and the ToxTell biosensor with activated sludge was constructed to determine the toxicity of Cu2+, Cu2+ and Cd2+ combined pollution. The results showed that there was no significant impact on the activated sludge process when Cu2+ concentration was lower than 10 mg x L(-1), and the addition of Cd2+ enhanced the inhibition of COD removal, and the maximum inhibition efficiency of COD reached at about 1.5 h. With the increase of aeration time, the COD removal efficiency increased slowly again. The toxicity measurement with ToxTell biosensor was close to the biological effects (inhibition efficiencies of COD), which showed that the ToxTell biosensor could be used well in the early warming determination of Cu2+ and Cd2+ in the activated sludge process.

  6. Hepatoprotective activity of a new polyherbal formulation against paracetamol and D-galactosamine induced hepatic toxicity

    PubMed Central

    Khan, Mohammad Ahmed; Gupta, Arun; Kumar, Satyendra; Ahmad, Sayeed; Sastry, J. L. N.

    2015-01-01

    Objective: The present study was envisaged to evaluate the protective effect of polyherbal formulation, DRDC/AY/8060, developed by Dabur India Ltd., against paracetamol and D-galactosamine induced hepatic toxicities in Wistar rats. Materials and Methods: The study was carried out in two different experiments of 10 and 14 days against paracetamol and D-galactosamine, respectively. Animals were divided into different treatment groups (n = 6). The control group received normal saline, a toxicant group in two experiments received paracetamol 750 mg/kg p.o. every 72 h for 10 days and D-galactosamine 400 mg/kg i.p. single dose. The test formulation was used at the two dose levels of 120 and 240 mg/kg/day. Treatment groups treated with test formulations were also administered D-galactosamine as given in toxicant group. At the end of the dosing schedule, blood was withdrawn from the retrobulbar plexus of the animals for serum estimation of serum glutamate oxaloacetate transferase (SGOT), serum glutamate pyruvate trasnferase (SGPT), albumin, bilirubin, and alkaline phosphatase (ALP). Following the withdrawal of blood animals was sacrificed, and liver tissue was excised for estimation of thiobarbituric acid reactive substances (lipid peroxidation, malondialdehyde), tissue glutathione (GSH) and histopathological studies. Results: It was evident from the biochemical estimation that both paracetamol and galactosamine caused hepatotoxicity in the toxicant groups. However, treatment with DRDC/AY/8060 significantly (P < 0.001, vs. toxicant) reduced the levels of SGOT, SGPT, serum bilirubin, and ALP, as well as decreased lipid peroxidation. In addition, treatment with test formulation also significantly (P < 0.001, vs. toxicant) elevated serum albumin and GSH levels compared to toxicant groups. Conclusion: On the basis of these studies and comparative evaluation it can be concluded that the formulation DRDC/AY/8060 showed hepatoprotective activity against paracetamol and D

  7. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    SciTech Connect

    Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  8. The Association of Viral Activation with Penicillin Toxicity in Guinea Pigs and Hamsters 1

    PubMed Central

    Green, Robert H.

    1974-01-01

    Penicillin toxicity in the guinea pig may be manifested in several different ways, and it is proposed that these toxic effects be categorized into three syndromes: (1) toxic syndrome, characterized by acute fatal illness; (2) hemorrhagic syndrome, characterized by delayed illness with leukopenia and thrombocytopenia, and culminating in massive visceral hemorrhages; (3) chronic syndrome, characterized by retardation of growth and alopecia, a condition somewhat resembling “runt disease.” A virus having some of the properties of a parvovirus has been isolated repeatedly from animals ill or dying of penicillin-induced disease. This finding has been construed as being activation of a latent virus by this antibiotic, but the relationship, if any, of the phenomenon of viral activation to the syndromes produced by penicillin and its frequent lethal toxicity is unknown. That a strong association exists, however, has been established. Of some 60 guinea pigs which received injections of penicillin three developed tumors and four others were found to have gallstones. A virus similar or identical to the guinea pig virus also has been isolated from hamsters dying of penicillin-induced disease. It is hypothesized that the absorption of endotoxin, resulting from the well known change in intestinal flora caused by penicillin, produces a state of immunodeficiency which regularly gives rise to activation of a latent virus, and perhaps, rarely, to the development of malignant neoplasms. PMID:4446629

  9. Controlling a toxic shock of pentachlorophenol (PCP) to anaerobic digestion using activated carbon addition.

    PubMed

    Xiao, Yeyuan; De Araujo, Cecilia; Sze, Chun Chau; Stuckey, David C

    2015-04-01

    Several powdered and granular activated carbons (PACs and GACs) were tested for adsorption of pentachlorophenol (PCP) in bench-scale anaerobic digestion reactors to control the toxicity of PCP to acetoclastic methanogenesis. Results showed that the adsorption capacities of PAC were reduced by 21-54%, depending on the PAC addition time, in the presence of the methanogenic sludge compared to the controls without sludge. As a preventive measure, PAC at a low dose of 20% (mass ratio to the VSS) added 24 h prior to, or simultaneously with, the addition of PCP could completely eliminate the toxic effects of PCP. At the same dose, PAC also enabled methanogenesis to recover immediately after the sludge had been exposed to PCP for 24h. GAC was not effective in enabling the recovery of methanogenesis due to its slow adsorption kinetics; however, at a dose of 80% it could partially ameliorate the toxic shock of PCP. PMID:25665874

  10. Quantitative structure-activity relationship for toxicity of ionic liquids to Daphnia magna: aromaticity vs. lipophilicity.

    PubMed

    Roy, Kunal; Das, Rudra Narayan; Popelier, Paul L A

    2014-10-01

    Water solubility of ionic liquids (ILs) allows their dispersion into aquatic systems and raises concerns on their pollutant potential. Again, lipophilicity can contribute to the toxicity of ILs due to increased ability of the compounds to cross lipoidal bio-membranes. In the present work, we have performed statistical model development for toxicity of a set of ionic liquids to Daphnia magna, a widely accepted model organism for toxicity testing, using computed lipophilicity, atom-type fragment, quantum topological molecular similarity (QTMS) and extended topochemical atom (ETA) descriptors. The models have been developed and validated in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for quantitative structure-activity relationships (QSARs). The best partial least squares (PLS) model outperforms the previously reported multiple linear regression (MLR) model in statistical quality and predictive ability (R(2)=0.955, Q(2)=0.917, Rpred(2)=0.848). In this work, the ETA descriptors show importance of branching and aromaticity while the QTMS descriptor ellipticity efficiently shows which compounds are influential in the data set, with reference to the model. While obvious importance of lipophilicity is evident from the models, the best model clearly shows the importance of aromaticity suggesting that more lipophilic ILs with less toxicity may be designed by avoiding aromaticity, nitrogen atoms and increasing branching in the cationic structure. The developed quantitative models are in consonance with the recent hypothesis of importance of aromaticity for toxicity of ILs.

  11. Toxicity of ionic liquids: database and prediction via quantitative structure-activity relationship method.

    PubMed

    Zhao, Yongsheng; Zhao, Jihong; Huang, Ying; Zhou, Qing; Zhang, Xiangping; Zhang, Suojiang

    2014-08-15

    A comprehensive database on toxicity of ionic liquids (ILs) is established. The database includes over 4000 pieces of data. Based on the database, the relationship between IL's structure and its toxicity has been analyzed qualitatively. Furthermore, Quantitative Structure-Activity relationships (QSAR) model is conducted to predict the toxicities (EC50 values) of various ILs toward the Leukemia rat cell line IPC-81. Four parameters selected by the heuristic method (HM) are used to perform the studies of multiple linear regression (MLR) and support vector machine (SVM). The squared correlation coefficient (R(2)) and the root mean square error (RMSE) of training sets by two QSAR models are 0.918 and 0.959, 0.258 and 0.179, respectively. The prediction R(2) and RMSE of QSAR test sets by MLR model are 0.892 and 0.329, by SVM model are 0.958 and 0.234, respectively. The nonlinear model developed by SVM algorithm is much outperformed MLR, which indicates that SVM model is more reliable in the prediction of toxicity of ILs. This study shows that increasing the relative number of O atoms of molecules leads to decrease in the toxicity of ILs.

  12. Passive dosing of polycyclic aromatic hydrocarbon (PAH) mixtures to terrestrial springtails: linking mixture toxicity to chemical activities, equilibrium lipid concentrations, and toxic units.

    PubMed

    Schmidt, Stine N; Holmstrup, Martin; Smith, Kilian E C; Mayer, Philipp

    2013-07-01

    A 7-day mixture toxicity experiment with the terrestrial springtail Folsomia candida was conducted, and the effects were linked to three different mixture exposure parameters. Passive dosing from silicone was applied to tightly control exposure levels and compositions of 12 mixture treatments, containing the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene, and pyrene. Springtail lethality was then linked to sum chemical activities (∑a), sum equilibrium lipid concentrations (∑C(lipid eq.)), and sum toxic units (∑TU). In each case, the effects of all 12 mixture treatments could be fitted to one sigmoidal exposure-response relationship. The effective lethal chemical activity (La50) of 0.027 was well within the expected range for baseline toxicity of 0.01-0.1. Linking the effects to the lipid-based exposure parameter yielded an effective lethal concentration (LC(lipid eq 50)) of 133 mmol kg(-1) lipid in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Finally, the effective lethal toxic unit (LTU50) of 1.20 was rather close to the expected value of 1. Altogether, passive dosing provided tightly controlled mixture exposure in terms of both level and composition, while ∑a, ∑C(lipid eq.), and ∑TU allowed baseline toxicity to be linked to mixture exposure. PMID:23473585

  13. Passive dosing of polycyclic aromatic hydrocarbon (PAH) mixtures to terrestrial springtails: linking mixture toxicity to chemical activities, equilibrium lipid concentrations, and toxic units.

    PubMed

    Schmidt, Stine N; Holmstrup, Martin; Smith, Kilian E C; Mayer, Philipp

    2013-07-01

    A 7-day mixture toxicity experiment with the terrestrial springtail Folsomia candida was conducted, and the effects were linked to three different mixture exposure parameters. Passive dosing from silicone was applied to tightly control exposure levels and compositions of 12 mixture treatments, containing the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene, and pyrene. Springtail lethality was then linked to sum chemical activities (∑a), sum equilibrium lipid concentrations (∑C(lipid eq.)), and sum toxic units (∑TU). In each case, the effects of all 12 mixture treatments could be fitted to one sigmoidal exposure-response relationship. The effective lethal chemical activity (La50) of 0.027 was well within the expected range for baseline toxicity of 0.01-0.1. Linking the effects to the lipid-based exposure parameter yielded an effective lethal concentration (LC(lipid eq 50)) of 133 mmol kg(-1) lipid in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Finally, the effective lethal toxic unit (LTU50) of 1.20 was rather close to the expected value of 1. Altogether, passive dosing provided tightly controlled mixture exposure in terms of both level and composition, while ∑a, ∑C(lipid eq.), and ∑TU allowed baseline toxicity to be linked to mixture exposure.

  14. Carlina acaulis Exhibits Antioxidant Activity and Counteracts Aβ Toxicity in Caenorhabditis elegans.

    PubMed

    Link, Pille; Roth, Kevin; Sporer, Frank; Wink, Michael

    2016-01-01

    Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting Aβ toxicity were studied in the Caenorhabditis elegans model. A dichloromethane extract of the roots of C. acaulis was prepared and characterised via gas-liquid-chromatography/mass-spectrometry (GLC-MS). The in vitro antioxidant activity was confirmed via 2,2-diphenyl-1-picrylhydracyl assay. The extract was further separated by thin layer chromatography into two fractions, one of which was a fraction of the dichloromethane extract of C. acaulis containing mostly Carlina oxide (CarOx). Different strains of C. elegans were employed to study the expression of hsp-16.2p::GFP as a marker for oxidative stress, delocalisation of the transcription factor DAF-16 as a possible mechanism of antioxidant activity, the effect of the drug under lethal oxidative stress, and the effect against beta-amyloid (Aβ) toxicity in a paralysis assay. The C. acaulis extract and CarOx showed high antioxidant activity (stress reduction by 47% and 64%, respectively) in C. elegans and could activate the transcription factor DAF-16 which directs the expression of anti-stress genes. In paralysis assay, only the total extract was significantly active, delaying paralysis by 1.6 h. In conclusion, in vivo antioxidant activity was shown for C. acaulis for the first time in the C. elegans model. The active antioxidant compound is Carlina oxide. This activity, however, is not sufficient to counteract Aβ toxicity. Other mechanisms and possibly other active compounds are involved in this effect. PMID:27384550

  15. Cardiac Myocyte-Specific AHR Activation Phenocopies TCDD-Induced Toxicity in Zebrafish

    PubMed Central

    Lanham, Kevin A.; Plavicki, Jessica; Peterson, Richard E.; Heideman, Warren

    2014-01-01

    Exposure of zebrafish embryos to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activates the zebrafish aryl hydrocarbon receptor 2 (AHR) to produce developmental and cardiovascular toxicity. AHR is found in the heart; however, AHR activation by TCDD is not confined to the heart and occurs throughout the organism. In order to understand the cause of cardiotoxicity, we constructed a constitutively active AHR (caAHR) based on the zebrafish AHR2 and expressed it specifically in cardiomyocytes. We show that AHR activation within the cardiomyocytes can account for the heart failure induced by TCDD. Expression of the caAHR within the heart produced cardiac malformations, loss of circulation, and pericardial edema. The heart-specific activation of AHR reproduced several other well-characterized endpoints of TCDD toxicity outside of the cardiovascular system, including defects in swim bladder and craniofacial development. This work identifies a single cellular site of TCDD action, the myocardial cell, that can account for the severe cardiovascular collapse observed following early life stage exposure to TCDD, and contributes to other forms of toxicity. PMID:25037585

  16. Preparation, relative toxicity, chemotherapeutic activity, and pharmacokinetics of liposomal SJA-95: a new polyene macrolide antibiotic.

    PubMed

    Desai, Sandhya K; Naik, Suresh R

    2008-01-01

    The research work was designed to compare the relative toxicity, chemotherapeutic activity, and pharmacokinetic parameters of liposomal incorporated SJA-95 with that of free SJA-95, with an objective to reduce toxicity and improve therapeutic activity in vivo. Liposomal-incorporated SJA-95 (Lip SJA-95), prepared using the proliposome method, was found to exhibit a higher LD(50) value in mice, and the relative toxicity was about 2.5 times lower than that of the free drug. Lip SJA-95 treatment in experimental mice model of Candidiasis showed increased survival and reduced fungal loads in various organs. The pharmacokinetic profile of the free and liposomal drug was evaluated by administration of free and Lip SJA-95 intravenously to healthy albino rabbits in a crossover fashion. Lip SJA-95 showed an initial fall in plasma levels and longer half-life. The improved microbial clearance following treatment with Lip SJA-95 could be attributed partly to an increased tissue uptake, which was reflected in a marked increase in volume of distribution (V(d)) and longer half-life (T(1/2)). The present results clearly indicated that Lip SJA-95 treatment led to prolonged survival time, effective microbiological clearance, and reduced toxicity in the mice model of Candidiasis.

  17. Toxicity and mAChRs binding activity of Cassiopea xamachana venom from Puerto Rican coasts.

    PubMed

    Radwan, Faisal F Y; Román, Laura G; Baksi, Krishna; Burnett, Joseph W

    2005-01-01

    A separation of toxic components from the upside down jellyfish Cassiopea xamachana (Cx) was carried out to study their cytotoxic effects and examine whether these effects are combined with a binding activity to cell membrane receptors. Nematocysts containing toxins were isolated from the autolysed tentacles, ruptured by sonication, and the crude venom (CxTX) was separated from the pellets by ultracentrifugation. For identifying its bioactive components, CxTX was fractionated by gel filtration chromatography into six fractions (named fraction I-VI). The toxicity of CxTX and fractions was tested on mice; however, the hemolytic activity was tested on saline washed human erythrocytes. The LD50 of CxTX was 0.75 microg/g of mouse body and for fraction III, IV and VI were 0.28, 0.25 and 0.12 microg/g, respectively. Fractions I, II and V were not lethal at doses equivalent to LD50 1 microg/g. The hemolytic and phospholipase A2 (PLA2) activities of most fractions were well correlated with their mice toxicity. However, fraction VI, which contains the low molecular mass protein components (< or =10 kDa), has shown no PLA2 activity but highest toxicity to mice, highest hemolytic activity, and bound significantly to the acetylcholine muscarinic receptors (mAChRs) isolated from rat brain. The results suggested that fraction VI contains proteinaceous components contributing to most of cytolysis as well as membrane binding events. Meanwhile, fraction IV has shown high PLA2 that may contribute to the venom lethality and paralytic effects. PMID:15581689

  18. Contribution of reductase activity to quinone toxicity in three kinds of hepatic cells.

    PubMed

    Ishihara, Yasuhiro; Tsuji, Kaori; Ishii, Satomi; Kashiwagi, Kyoko; Shimamoto, Norio

    2012-01-01

    Two mechanisms have been proposed to explain quinone cytotoxicity: oxidative stress via the redox cycle, and the arylation of intracellular nucleophiles. The redox cycle is catalyzed by intracellular reductases, and therefore the toxicity of redox cycling quinone is considered to be closely associated with the reductase activity. This study examined the relationship between quinone toxicity and the intracellular reductase activity using 3 kinds of hepatic cells; rat primary hepatocytes, HepG2 and H4IIE. The intracellular reductase activity was; primary hepatocyte >HepG2>H4IIE. The three kinds of cells showed almost the same vulnerability to an arylating quinone, 1,4-naphthoquinone (NQ). However, the susceptibility to a redox cycling quinone, 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) was; primary hepatocyte>HepG2>H4IIE. In addition, the cytotoxicity elicited by DMNQ was significantly attenuated in HepG2 cells and almost completely suppressed in primary hepatocytes by diphenyleneiodonium chloride, a reductase inhibitor. These data suggest that cells with a high reductase activity are susceptible to redox cycling quinones. This study provides essential evidence to assess the toxicity of quinone-based drugs during their developmental processes.

  19. Non-toxic antifouling activity of polymeric 3-alkylpyridinium salts from the Mediterranean sponge Reniera sarai (Pulitzer-Finali).

    PubMed

    Faimali, Marco; Sepcić, Kristina; Turk, Tom; Geraci, Sebastiano

    2003-02-01

    The antifouling activity and toxicity of polymeric 3-alkylpyridinium salts (poly-APS) isolated from the Mediterranean sponge Reniera sarai were studied. The activity of these natural products was compared to that of zinc and copper complexes of pyrithione, two non-persistent booster biocides successfully used in current antifouling coatings. Larvae of Balanus amphitrite (cyprids and nauplii) were used to monitor settlement inhibition and the extent to which inhibition was due to toxicity. The microalga Tetraselmis suecica and larvae of the mussel Mytilus galloprovincialis were used in toxicity bioassays. Compared to the booster biocides, poly-APS were less effective at inhibiting cyprid settlement, but their effects were non toxic and reversible, with very low toxicity against the organisms used in the toxicity bioassays. Although encouraging, these results are not enough to warrant the use of poly-APS as a potential commercial antifoulant. They however justify possible future efforts to chemically synthesize poly-APS analogues for further tests. PMID:14618688

  20. Toxic effects of nanoparticles on bioluminescence activity, seed germination, and gene mutation.

    PubMed

    Ko, Kyung-Seok; Kong, In Chul

    2014-04-01

    The potential environmental toxicities of several metal oxide nanoparticles (NPs; CuO, TiO2, NiO, Fe2O3, ZnO, and Co3O4) were evaluated in the context of bioluminescence activity, seed germination, and bacterial gene mutation. The bioassays exhibited different sensitivities, i.e., each kind of NP exhibited a different level of toxicity in each of the bioassays. However, with a few exceptions, CuO and ZnO NPs had most toxic for germination of Lactuca seed (EC50 0.46 mg CuO/l) and bioluminescence (EC50 1.05 mg ZnO/l). Three NPs (Co3O4, TiO2, and Fe2O3) among all tested concentrations (max. 1,000 mg/l) showed no inhibitory effects on the tested organisms, except for Co3O4 NPs on bioluminescence activity (EC50 62.04 mg/l). The sensitivity of Lactuca seeds was greater than that of Raphanus seeds (EC50 0.46 mg CuO/l versus 26.84 mg CuO /l ). The ranking of metal toxicity levels on bioluminescence was in the order of ZnO > CuO > Co3O4 > NiO > Fe2O3, TiO2, while CuO > ZnO > NiO > Co3O4, Fe2O3, TiO2 on germination. No revertant mutagenic ratio (greater than 2.0) of Salmonella typhimurium TA 98 was observed under any tested condition. These findings demonstrate that several bioassays, as opposed to any single one, are needed for the accurate assessment of NP toxicity on ecosystems. PMID:24297479

  1. Acute toxicity of lead, chromium, and other heavy metals to ciliates from activated sludge plants

    SciTech Connect

    Madoni, P.; Gorbi, G. ); Davoli, D. )

    1994-09-01

    Numerous papers deal with the occurrence of heavy metals in the various components of freshwater ecosystems and sewage treatment systems. However, few papers refer to the presence and effect of heavy metals in populations of aquatic cilated protozoa. In particular, the lethal concentrations (LC50) of heavy metals in ciliate populations that colonize the activated sludge or the biofilm of waste treatment plants. Ciliated protozoa are very numerous in all types of aerobic biological-treatment systems. They play an important role in the purification process removing, through predation, the major part of dispersed bacteria that cause high turbidity in the final effluent. Changes in the community structure and types of ciliate species may affect the food web of these artifical ecosystems, and may also influence the biological performance of plants. Heavy metals can limit growth of protozoa in aquatic environments. The toxicity of heavy metals in biological treatment depends mainly upon two factors, namely, metal species and concentration. Although the resistance of biological systems to metal toxicity may be enhanced greatly by proper acclimatization, a too-high metal concentration may cause serious upsets in the system. It is important to determine the concentrations of heavy metals causing lethal effects on ciliates. Madoni recently studied the acute toxicity of cadmium, copper, mercury, and zinc on six species of ciliated protozoa from activated sludge plants. The present paper describes the toxic effects of lead and chromium (VI) on 6 cilate species. The acute toxicity of Cd, Cr, Cu, Hg, Pb, and Zn on two other ciliates (Drepanomonas revoluta and Spirostomum teres) is also reported. 18 refs., 4 tabs.

  2. "Inert" formulation ingredients with activity: toxicity of trisiloxane surfactant solutions to twospotted spider mites (Acari: Tetranychidae).

    PubMed

    Cowles, R S; Cowles, E A; McDermott, A M; Ramoutar, D

    2000-04-01

    Organosilicone molecules are important surfactant ingredients used in formulating pesticides. These methylated silicones are considered inert ingredients, but their superior surfactant properties allow them to wet, and either suffocate or disrupt important physiological processes in mites and insects. Aqueous solutions of the tri-siloxane surfactants Silwet L-77, Silwet 408, and Silwet 806 were bioassayed against adult female two-spotted spider mites, Tetranychus urticae Koch, with leaf dip methods to compare their toxicity with organosilicone molecules containing bulkier hydrophobic components. All three tri-siloxanes in aqueous solutions were equivalently toxic (LC50 = 5.5-8.9 ppm), whereas Silwet L-7607 solutions were less toxic (LC50 = 4,800 ppm) and Silwet L-7200 was nontoxic to mites. In another experiment, the toxicity of Silwet L-77 was affected by the wettability of leaf surfaces. The LC50 shifted from 22 to 84 ppm when mites were tested on bean and strawberry leaf disks, respectively. Droplet spreading on paraffin and surface tension were both related to the toxicity of surfactant solutions. Surface tensions of solutions below 23 mN/m caused > 90% mite mortality in leaf dip bioassays. A field test of Conserve SC and its formulation blank, with and without Dyne-Amic adjuvant (a vegetable oil-organosilicone surfactant mixture) revealed that Dyne-Amic had the greatest miticidal contribution, reducing mite populations by 70%, followed by formulation inactive ingredients. Spinosad, the listed active ingredient in Conserve, only contributed miticidal activity when synergized by Dyne-Amic. Researchers should include appropriate surfactant or formulation blank controls when testing insecticides or miticides, especially when using high spray volumes.

  3. Toxic effects of nanoparticles on bioluminescence activity, seed germination, and gene mutation.

    PubMed

    Ko, Kyung-Seok; Kong, In Chul

    2014-04-01

    The potential environmental toxicities of several metal oxide nanoparticles (NPs; CuO, TiO2, NiO, Fe2O3, ZnO, and Co3O4) were evaluated in the context of bioluminescence activity, seed germination, and bacterial gene mutation. The bioassays exhibited different sensitivities, i.e., each kind of NP exhibited a different level of toxicity in each of the bioassays. However, with a few exceptions, CuO and ZnO NPs had most toxic for germination of Lactuca seed (EC50 0.46 mg CuO/l) and bioluminescence (EC50 1.05 mg ZnO/l). Three NPs (Co3O4, TiO2, and Fe2O3) among all tested concentrations (max. 1,000 mg/l) showed no inhibitory effects on the tested organisms, except for Co3O4 NPs on bioluminescence activity (EC50 62.04 mg/l). The sensitivity of Lactuca seeds was greater than that of Raphanus seeds (EC50 0.46 mg CuO/l versus 26.84 mg CuO /l ). The ranking of metal toxicity levels on bioluminescence was in the order of ZnO > CuO > Co3O4 > NiO > Fe2O3, TiO2, while CuO > ZnO > NiO > Co3O4, Fe2O3, TiO2 on germination. No revertant mutagenic ratio (greater than 2.0) of Salmonella typhimurium TA 98 was observed under any tested condition. These findings demonstrate that several bioassays, as opposed to any single one, are needed for the accurate assessment of NP toxicity on ecosystems.

  4. Hypoglycemic activity and acute oral toxicity of chromium methionine complexes in mice.

    PubMed

    Tang, Hai-yan; Xiao, Qing-gui; Xu, Hong-bin; Zhang, Yi

    2015-01-01

    The hypoglycemic activity of chromium methionine (CrMet) in alloxan-induced diabetic (AID) mice was investigated and compared with those of chromium trichloride hexahydrate (CrCl3·6H2O) and chromium nicotinate (CrNic) through a 15-day feeding experiment. The acute oral toxicity of CrMet was also investigated in ICR (Institute for Cancer Research) mice by a single oral gavage. The anti-diabetic activity of CrMet was explored in detail from the aspects of body weight (BW), blood glucose, triglyceride, total cholesterol, liver glycogen levels, aspartate transaminase (AST) and alanine transaminase (ALT) levels. The obtained results showed that CrMet had beneficial effects on glucose and lipid metabolism, and might possess hepatoprotective efficacy for diabetes. Daily treatment with 500 and 1000μg Cr/kg BW of CrMet in AID mice for 15 days indicated that this low-molecular-weight organic chromium complex had better bioavailability and more beneficial effects on diabetics than CrCl3·6H2O. CrMet also had advantage over CrNic in the control of AST and ALT activities. Acute toxicity studies revealed that CrMet had low toxicity potential and relatively high safety margins in mice with the LD50 value higher than 10.0g/kg BW. These findings suggest that CrMet might be of potential value in the therapy and protection of diabetes.

  5. The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin.

    PubMed

    Yasini, Seyed Ali; Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

    2015-11-01

    The first aim of this study was to synthesize nanocellulose conjugated with aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation. In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000 μg mL(-1), at various conditions. Then, the quantity of adsorption and release was separately measured. Furthermore, both toxicity and antibacterial activity of NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this study, MD simulation clearly showed the adsorption after 50 picoseconds. The adsorption tests revealed that the increase of incubation time and NCABP concentration, at range of 50-200 μg mL(-1), led to increase of adsorption. Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP could adsorb enrofloxacin, up to 1000 μg mL(-1), in different types of meat. Moreover, the increase of incubation time and temperature did not release enrofloxacin, but the increase of pH increased release. This study showed that both toxicity and antibacterial activity of enrofloxacin were decreased when exposed together with NCABP. PMID:26295691

  6. Toxicity of hemoglobin solutions: hemoglobin is a lipopolysaccharide (LPS) binding protein which enhances LPS biological activity.

    PubMed

    Roth, R I; Kaca, W

    1994-01-01

    Administration of alpha alpha-crosslinked stroma-free hemoglobin (SFH) as a cell-free resuscitation fluid is associated with multiple organ toxicities. Many of these toxicities are characteristic of the pathophysiological effects of bacterial endotoxins (lipopolysaccharide, LPS). To better understand the potential role of LPS in the observed in vivo toxicities of SFH, we examined mixtures of SFH and E. coli LPS for evidence of LPS-SFH complex formation. LPS-SFH complexes were demonstrated by three techniques: ultrafiltration through 300 kDa cut-off membranes, which distinguished LPS in complexes (87-89% < 300 kDa) from LPS alone (90% > 300 kDa); density centrifugation through 5% sucrose, which distinguished denser LPS alone from LPS-SFH complexes; and precipitation by 67% ethanol, which demonstrated 2-3 fold increased precipitability of complexes compared to SFH alone. Interaction of LPS with SFH was also associated with markedly increased biological activity of LPS, as manifested by enhancement of LPS activation of Limulus amebocyte lysate (LAL), increased release of human mononuclear cell tissue factor, and enhanced production of cultured human endothelial cell tissue factor. These results demonstrated that hemoglobin can serve as an endotoxin binding protein, and that this interaction results in the alteration of several LPS physical characteristics and enhancement of LPS biological activities.

  7. Toxic effects of Hoechst staining and UV irradiation on preimplantation development of parthenogenetically activated mouse oocytes.

    PubMed

    Versieren, Karen; Heindryckx, Björn; Qian, Chen; Gerris, Jan; De Sutter, Petra

    2014-02-01

    Parthenogenetic activation of oocytes is a helpful tool to obtain blastocysts, of which the inner cell mass may be used for derivation of embryonic stem cells. In order to improve activation and embryonic development after parthenogenesis, we tried to use sperm injection and subsequent removal of the sperm head to mimic the natural Ca2+ increases by release of the oocyte activating factor. Visualization of the sperm could be accomplished by Hoechst staining and ultraviolet (UV) light irradiation. To exclude negative effects of this treatment, we examined toxicity on activated mouse oocytes. After activation, oocytes were incubated in Hoechst 33342 or 33258 stain and exposed to UV irradiation. The effects on embryonic development were evaluated. Our results showed that both types of Hoechst combined with UV irradiation have toxic effects on parthenogenetically activated mouse oocytes. Although activation and cleavage rate were not affected, blastocyst formation was significantly reduced. Secondly, we used MitoTracker staining for removal of the sperm. Sperm heads were stained before injection and removed again after 1 h. However, staining was not visible anymore in all oocytes after intracytoplasmic sperm injection. In case the sperm could be removed, most oocytes died after 1 day. As MitoTracker was also not successful, alternative methods for sperm identification should be investigated.

  8. Interference sources in ATP bioluminescence assay of silica nanoparticle toxicity to activated sludge.

    PubMed

    Sibag, Mark; Kim, Seung Hwan; Kim, Choah; Kim, Hee Jun; Cho, Jinwoo

    2015-06-01

    ATP measurement provides an overview of the general state of microbial activity, and thus it has proven useful for the evaluation of nanoparticle toxicity in activated sludge. ATP bioluminescence assay, however, is susceptible to interference by the components of activated sludge other than biomass. This paper presents the interference identified specific to the use of this assay after activated sludge respiration inhibition test of silica nanoparticles (OECD 209). We observed a high degree of interference (90%) in the presence of 100 mg/L silica nanoparticles and a low level of ATP being measured (0.01 μM); and 30% interference by the synthetic medium regardless of silica nanoparticle concentration and ATP level in the samples. ATP measurement in activated sludge with different MLSS concentrations revealed interference of high biomass content. In conclusion, silica nanoparticles, synthetic medium and activated sludge samples themselves interfere with ATP bioluminescence; this will need to be considered in the evaluation of silica nanoparticle toxicity to activated sludge when this type of assay is used. PMID:25892589

  9. Interference sources in ATP bioluminescence assay of silica nanoparticle toxicity to activated sludge.

    PubMed

    Sibag, Mark; Kim, Seung Hwan; Kim, Choah; Kim, Hee Jun; Cho, Jinwoo

    2015-06-01

    ATP measurement provides an overview of the general state of microbial activity, and thus it has proven useful for the evaluation of nanoparticle toxicity in activated sludge. ATP bioluminescence assay, however, is susceptible to interference by the components of activated sludge other than biomass. This paper presents the interference identified specific to the use of this assay after activated sludge respiration inhibition test of silica nanoparticles (OECD 209). We observed a high degree of interference (90%) in the presence of 100 mg/L silica nanoparticles and a low level of ATP being measured (0.01 μM); and 30% interference by the synthetic medium regardless of silica nanoparticle concentration and ATP level in the samples. ATP measurement in activated sludge with different MLSS concentrations revealed interference of high biomass content. In conclusion, silica nanoparticles, synthetic medium and activated sludge samples themselves interfere with ATP bioluminescence; this will need to be considered in the evaluation of silica nanoparticle toxicity to activated sludge when this type of assay is used.

  10. Potential of activated carbon to decrease 2,4,6-trinitrotoluene toxicity and accelerate soil decontamination.

    PubMed

    Vasilyeva, G K; Kreslavski, V D; Oh, B T; Shea, P J

    2001-05-01

    Activated carbon can be used to decrease 2,4,6-trinitrotoluene (TNT) toxicity and promote bioremediation of highly contaminated soil. Adding activated carbon at 0.25, 0.75, and 1.0% (w/w) to Sharpsburg soil contaminated with 500, 1,000, and 2,000 mg TNT/kg decreased concentrations of TNT and its transformation products in soil solution to 5 mg/L or less, resulting in low toxicity to corn plants (Zea mays L.) and soil microorganisms. As much as 50% of the added TNT was rapidly bound to the soil-activated carbon matrix. Simultaneous accumulation of 2,4,6-trinitrobenzaldehyde (TNBAld) indicated that the activated carbon promoted oxidation of TNT. Some of the TNBAld was further oxidized to 1,3,5-trinitrobenzene, followed by reduction to 3,5-dinitroaniline. Reversibly bound TNT was gradually transformed to 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene, and both were bound to the soil-activated carbon matrix. The transformation and binding of TNT to soil were further promoted by incorporating shredded corn plants after growing for 52 d in the activated carbon-amended soil. After 120 d, these amendments reduced extractable TNT and transformation products by 91% in soil containing 2,000 mg TNT/kg, compared to 55% in unamended soil. These results demonstrate the potential use of activated carbon in combination with plants to promote in situ bioremediation of soils highly contaminated with explosives.

  11. Novel approaches to the use of cytochrome P450 activities in wildlife toxicity studies

    SciTech Connect

    VandenBerg, M.; Bosveld, A.T.C.

    1995-12-31

    Many wildlife toxicity studies, e.g. with avian species, use cytochrome P450 activities as markers for biological activities of environmental contaminants. It has been established that induction of CYP1A1 correlates with Ah-receptor mediated toxicity of dioxin-like compounds in many species. In addition, CYP1A1 plays a significant role in bioactivation of polycyclic aromatics. So far very few studies focused on the natural function of P450 isoenzymes in wildlife species. Besides classical hepatic CYP1A(1) associated activities, like EROD and AHH, several new techniques are available to study the activities of various CYP isoenzymes. Caffeine N-demethylation, testosterone and 17ss-estradiol hydroxylation patterns can provide new insights in the physiological function of P450 isoenzymes and the induction of the basal activities by chemicals. So far little interest was given to processes which occur after the DNA-receptor binding, e.g. changes in steroid hormone metabolism and pathways in environmental toxicology. This in spite of the fact that very subtle changes in steroid hormone levels may have significant physiological implications. This presentation will focus on some P450 activities, besides CYP1A(1), which might be important for development and reproduction. Some experimental approaches, limitations and techniques will be discussed which could lead to elucidation of the possible endocrine function of P450s.

  12. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    NASA Astrophysics Data System (ADS)

    Gou, MaLing; Shi, HuaShan; Guo, Gang; Men, Ke; Zhang, Juan; Zheng, Lan; Li, ZhiYong; Luo, Feng; Qian, ZhiYong; Zhao, Xia; Wei, YuQuan

    2011-03-01

    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ~ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  13. Mycorrhizal fungi modulate phytochemical production and antioxidant activity of Cichorium intybus L. (Asteraceae) under metal toxicity.

    PubMed

    Rozpądek, P; Wężowicz, K; Stojakowska, A; Malarz, J; Surówka, E; Sobczyk, Ł; Anielska, T; Ważny, R; Miszalski, Z; Turnau, K

    2014-10-01

    Cichorium intybus (common chicory), a perennial plant, common in anthropogenic sites, has been the object of a multitude of studies in recent years due to its high content of antioxidants utilized in pharmacy and food industry. Here, the role of arbuscular mycorrhizal fungi (AMF) in the biosynthesis of plant secondary metabolites and the activity of enzymatic antioxidants under toxic metal stress was studied. Plants inoculated with Rhizophagus irregularis and non-inoculated were grown on non-polluted and toxic metal enriched substrata. The results presented here indicate that AMF improves chicory fitness. Fresh and dry weight was found to be severely affected by the fungi and heavy metals. The concentration of hydroxycinnamates was increased in the shoots of mycorrhizal plants cultivated on non-polluted substrata, but no differences were found in plants cultivated on metal enriched substrata. The activity of SOD and H2O2 removing enzymes CAT and POX was elevated in the shoots of mycorrhizal plants regardless of the cultivation environment. Photochemical efficiency of inoculated chicory was significantly improved. Our results indicate that R. irregularis inoculation had a beneficial role in sustaining the plants ability to cope with the deleterious effects of metal toxicity.

  14. Relative toxicity and residual activity of insecticides used in blueberry pest management: mortality of natural enemies.

    PubMed

    Roubos, Craig R; Rodriguez-Saona, Cesar; Holdcraft, Robert; Mason, Keith S; Isaacs, Rufus

    2014-02-01

    A series of bioassays were conducted to determine the relative toxicities and residual activities of insecticides labeled for use in blueberry (Vaccinium corymbosum L.) on natural enemies, to identify products with low toxicity or short duration effects on biological control agents. In total, 14 insecticides were evaluated using treated petri dishes and four commercially available natural enemies (Aphidius colemani Viereck, Orius insidiosus [Say], Chrysoperla rufilabris [Burmeister], and Hippodamia convergens [Guérin-Menéville]). Dishes were aged under greenhouse conditions for 0, 3, 7, or 14 d before introducing insects to test residual activity. Acute effects (combined mortality and knockdown) varied by insecticide, residue age, and natural enemy species. Broad-spectrum insecticides caused high mortality to all biocontrol agents, whereas products approved for use in organic agriculture had little effect. The reduced-risk insecticide acetamiprid consistently caused significant acute effects, even after aging for 14 d. Methoxyfenozide, novaluron, and chlorantraniliprole, which also are classified as reduced-risk insecticides, had low toxicity, and along with the organic products could be compatible with biological control. This study provides information to guide blueberry growers in their selection of insecticides. Further research will be needed to determine whether adoption of a pest management program based on the use of more selective insecticides will result in higher levels of biological control in blueberry.

  15. An activated sludge-based biosensor for rapid IC50 estimation and on-line toxicity monitoring.

    PubMed

    Kong, Z; Vanrolleghem, P A; Verstraete, W

    1993-01-01

    The RODTOX (Rapid Oxygen Demand and TOXicity tester), an activated sludge-based respirographic biosensor, is a device for on-line monitoring of the short-term biochemical oxygen demand (stBOD) and potential toxicity of incoming wastewater on the basis of on-line interpretation of respirograms resulting from pulse additions of either calibration substrate or sample. The principle of toxicity detection is based on the comparison of calibration respirograms before and after receiving a potential toxicant. In this paper, the results of the RODTOX as an on-line toxicity monitor are presented. In addition, a simple and fast procedure to estimate the IC50 of a toxicant has been developed, and its validity and good repeatability demonstrated. The performance of this procedure is compared with that of the Microtox test.

  16. Comparative toxicity and structure-activity in Chlorella and Tetrahymena: Monosubstituted phenols

    SciTech Connect

    Jaworska, J.S.; Schultz, T.W. )

    1991-07-01

    The relative toxicity of selected monosubstituted phenols has been assessed by Kramer and Truemper in the Chlorella vulgaris assay. The authors examined population growth inhibition of this simple green algae under short-term static conditions for 33 derivatives. However, efforts to develop a strong predictive quantitative structure-activity relationship (QSAR) met with limited success because they modeled across modes of toxic action or segregated derivatives such as positional isomers (i.e., ortho-, meta-, para-). In an effort to further their understanding of the relationships of ecotoxic effects of phenols, the authors have evaluated the same derivatives reported by Kramer and Truemper in the Tetrahymena pyriformis population growth assay, compared the responses in both systems and developed QSARs for the Chlorella vulgaris data based on mechanisms of action.

  17. Redox-Active Selenium Compounds—From Toxicity and Cell Death to Cancer Treatment

    PubMed Central

    Misra, Sougat; Boylan, Mallory; Selvam, Arun; Spallholz, Julian E.; Björnstedt, Mikael

    2015-01-01

    Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed. PMID:25984742

  18. The chaperone activity and toxicity of ambroxol on Gaucher cells and normal mice.

    PubMed

    Luan, Zhuo; Li, Linjing; Higaki, Katsumi; Nanba, Eiji; Suzuki, Yoshiyuki; Ohno, Kousaku

    2013-04-01

    Gaucher disease (GD), caused by a defect of acid β-glucosidase (β-Glu), is one of the most common sphingolipidoses. Recently, ambroxol, an FDA-approved drug used to treat airway mucus hypersecretion and hyaline membrane disease in newborns, was identified as a chemical chaperone for GD. In the present study, we investigated the chaperone activity and toxicity of ambroxol on both cultured GD patient cells and normal mice. We found that ambroxol treatment significantly increased N370S, F213I, N188S/G193W and R120W mutant β-Glu activities in GD fibroblasts with low cytotoxicity. Additionally, we measured the β-Glu activity in the tissues of normal mice which received water containing increasing concentrations of ambroxol ad libitum for one week. No serious adverse effect was observed during this experiment. Ambroxol significantly increased the β-Glu activity in the spleen, heart and cerebellum of the mice. This result showed its oral availability and wide distribution and chaperone activity in the tissues, including the brain, and its lack of acute toxicity. These characteristics of ambroxol would make it a potential therapeutic chaperone in the treatment of GD with neurological manifestations.

  19. The chaperone activity and toxicity of ambroxol on Gaucher cells and normal mice.

    PubMed

    Luan, Zhuo; Li, Linjing; Higaki, Katsumi; Nanba, Eiji; Suzuki, Yoshiyuki; Ohno, Kousaku

    2013-04-01

    Gaucher disease (GD), caused by a defect of acid β-glucosidase (β-Glu), is one of the most common sphingolipidoses. Recently, ambroxol, an FDA-approved drug used to treat airway mucus hypersecretion and hyaline membrane disease in newborns, was identified as a chemical chaperone for GD. In the present study, we investigated the chaperone activity and toxicity of ambroxol on both cultured GD patient cells and normal mice. We found that ambroxol treatment significantly increased N370S, F213I, N188S/G193W and R120W mutant β-Glu activities in GD fibroblasts with low cytotoxicity. Additionally, we measured the β-Glu activity in the tissues of normal mice which received water containing increasing concentrations of ambroxol ad libitum for one week. No serious adverse effect was observed during this experiment. Ambroxol significantly increased the β-Glu activity in the spleen, heart and cerebellum of the mice. This result showed its oral availability and wide distribution and chaperone activity in the tissues, including the brain, and its lack of acute toxicity. These characteristics of ambroxol would make it a potential therapeutic chaperone in the treatment of GD with neurological manifestations. PMID:22682976

  20. Cytotoxicity, toxicity, and anticancer activity of Zingiber officinale Roscoe against cholangiocarcinoma.

    PubMed

    Plengsuriyakarn, Tullayakorn; Viyanant, Vithoon; Eursitthichai, Veerachai; Tesana, Smarn; Chaijaroenkul, Wanna; Itharat, Arunporn; Na-Bangchang, Kesara

    2012-01-01

    Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/ DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median IC50 (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and 27.86 μg/ml, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to

  1. Electrochemical oxidation of fluoroquinolone antibiotics: Mechanism, residual antibacterial activity and toxicity change.

    PubMed

    Zhu, Linyan; Santiago-Schübel, Beatrix; Xiao, Hongxia; Hollert, Henner; Kueppers, Stephan

    2016-10-01

    In this paper, we studied the electrochemical oxidation mechanisms of three typical fluoroquinolone antibiotics (FQs), and investigated residual antibacterial activity and toxicity changes after oxidation processes. Electrochemistry coupled to mass spectrometry (EC-MS) was used to study the oxidation processes of ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL). Eight oxidation products for each parent compound were identified and their chemical structures were elucidated. The transformation trend of each product, with the continuous increase of voltage from 0 to 3000 mV, was recorded by online EC-MS. The oxidation pathways were proposed based on the structural information and transformation trends of oxidation products. We found the oxidation mechanisms of FQs consisted of the hydroxylation and cleavage of piperazinyl ring via reactions with hydroxyl radicals, while the fluoroquinolone core remained intact. The antibacterial activity of the parent compounds and their oxidation mixtures was estimated using zone inhibition tests for gram-negative bacteria Salmonella typhimurium. It was found that the oxidation mixtures of CIP and NOR retained the antibacterial properties with lower activity compared to their parent compounds, while the antibacterial activity of OFL was almost eliminated after oxidation. Furthermore, the toxicity of the three FQs and their oxidation mixtures were evaluated using algal growth inhibition test (Desmodesmus subspicatus). The median effective concentration (EC50) values for the algal inhibition tests were calculated for the end point of growth rate. The toxicity of CIP and NOR to green algae after electrochemical oxidation, remained unchanged, while that of OFL significantly increased. The results presented in this paper contribute to an understanding of the electrochemical oxidation mechanisms of FQs, and highlight the potential environmental risks of FQs after electrochemical oxidation processes.

  2. Electrochemical oxidation of fluoroquinolone antibiotics: Mechanism, residual antibacterial activity and toxicity change.

    PubMed

    Zhu, Linyan; Santiago-Schübel, Beatrix; Xiao, Hongxia; Hollert, Henner; Kueppers, Stephan

    2016-10-01

    In this paper, we studied the electrochemical oxidation mechanisms of three typical fluoroquinolone antibiotics (FQs), and investigated residual antibacterial activity and toxicity changes after oxidation processes. Electrochemistry coupled to mass spectrometry (EC-MS) was used to study the oxidation processes of ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL). Eight oxidation products for each parent compound were identified and their chemical structures were elucidated. The transformation trend of each product, with the continuous increase of voltage from 0 to 3000 mV, was recorded by online EC-MS. The oxidation pathways were proposed based on the structural information and transformation trends of oxidation products. We found the oxidation mechanisms of FQs consisted of the hydroxylation and cleavage of piperazinyl ring via reactions with hydroxyl radicals, while the fluoroquinolone core remained intact. The antibacterial activity of the parent compounds and their oxidation mixtures was estimated using zone inhibition tests for gram-negative bacteria Salmonella typhimurium. It was found that the oxidation mixtures of CIP and NOR retained the antibacterial properties with lower activity compared to their parent compounds, while the antibacterial activity of OFL was almost eliminated after oxidation. Furthermore, the toxicity of the three FQs and their oxidation mixtures were evaluated using algal growth inhibition test (Desmodesmus subspicatus). The median effective concentration (EC50) values for the algal inhibition tests were calculated for the end point of growth rate. The toxicity of CIP and NOR to green algae after electrochemical oxidation, remained unchanged, while that of OFL significantly increased. The results presented in this paper contribute to an understanding of the electrochemical oxidation mechanisms of FQs, and highlight the potential environmental risks of FQs after electrochemical oxidation processes. PMID:27318447

  3. Repellent, antifeedant, and toxic activities of Lantana camara leaf extract against Reticulitermes flavipes (Isoptera: Rhinotermitidae).

    PubMed

    Yuan, Zhonglin; Hu, Xing Ping

    2012-12-01

    This study investigated biological activity of chloroform extract of dry Lantana camara 'Mozelle' leaves against the eastern subterranean termite, Reticulitermes flavipes (Kollar), an important structural pest. Repellent activity was assessed using a paper-disc choice test and a sand arena choice test. Antifeedant and toxic properties were assessed using a no-choice paper test and a topical application method. In the choice tests, significantly fewer termites made contact with treated paper-discs at test concentrations > or = 0.016 mg/cm2 (equivalent to 0.0023 wt:wt) or tunneled into treated sand at test concentrations > or = 0.125 mg/g, compared with control. In the no-choice tests, termite feeding activity was significantly reduced and termite mortality was greatly increased in treatments than control. Exposure to filter paper treated at 0.212 and 0.106 mg/cm2 (equivalent to 0.03 and 0.015 wt:wt) resulted in > 90% mortality and 78% reduction in feeding, and approximately 52% mortality and 40% reduction in feeding, respectively. Top-dorsal application led to > 60% mortality at 4 microg/termite. This study showed that the chloroform leaf extract of L. camara had excellent repellent and moderate toxic and antifeedant activities. PMID:23356077

  4. Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic

    PubMed Central

    2014-01-01

    Background The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. Methods The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of these extracts in vivo, female Swiss mice were treated with the extracts at doses of 500, 1000 and 2000 mg · kg-1 of body weight. The extracts were characterized by LC-MS, and the constituents were isolated and identified by chromatographic analysis of spectroscopic data. Results Of the 28 extracts, the methanol extract obtained from the leaves of Annona sylvatica showed anti-mycobacterial activity with an minimal inhibitory concentration (MIC) of 184.33 μg/mL, and the ethyl acetate fraction (EAF) resulting from liquid-liquid partitioning of the A. sylvatica extract showed an MIC of 115.2 μg/mL. The characterization of this extract by LC-MS identified flavonoids and acetogenins as its main constituents. The phytochemical study of the A. sylvatica EAF resulted in the isolation of quercetin, luteolin, and almunequin. Conclusions Among the compounds isolated from the EAF, luteolin and almunequin were the most promising, with MICs of 236.8

  5. Approaches to the Development of Human Health Toxicity Values for Active Pharmaceutical Ingredients in the Environment.

    PubMed

    Sorell, Tamara L

    2016-01-01

    Management of active pharmaceutical ingredients (API) in the environment is challenging because these substances represent a large and diverse group of compounds. Advanced wastewater treatment technologies that can remove API tend to be costly. Because of the potential resources required to address API in the environment, there is a need to establish environmental benchmarks that can serve as targets for treatment and release. To date, there are several different approaches that have been taken to derive human health toxicity values for API. These methods include traditional risk assessment approaches that calculate "safe" doses using experimental data and uncertainty (safety) factors; point of departure (POD), which starts from a therapeutic human dose and applies uncertainty factors; and threshold of toxicological concern (TTC), a generic approach that establishes threshold values across broad classes of chemicals based on chemical structure. To evaluate the use of these approaches, each of these methods was applied to three API commonly encountered in the environment: acetaminophen, caffeine, and chlorpromazine. The results indicate that the various methods of estimating toxicity values produce highly varying doses. Associated doses are well below typical intakes, or toxicity thresholds cannot be derived due to a lack of information. No uniform approach can be applied to establishing thresholds for multiple substances. Rather, an individualized approach will need to be applied to each target API. PMID:26338232

  6. Induction of siderophore activity in Anabaena spp. and its moderation of copper toxicity

    SciTech Connect

    Clarke, S.E.; Stuart, J.; Sanders-Loehr, J.

    1987-05-01

    Growth of Anabaena sp. strain 7120 (in the absence of chelators or added iron) was inhibited by the addition of 2.1 to 6.5 ..mu..M copper and was abolished by copper concentrations of 10 /sup +/M or higher. When the copper was chelated to schizokinen, the toxic effects were eliminated. Analysis of culture filtrates showed that the cupric schizokinen remains in the medium, thereby lowering the amount of copper taken up by the cells. Although this organism actively transports ferric schizokinen, it apparently does not recognize the cupric complex. Thus, Anabaena sp. is protected from copper toxicity under conditions in which siderophore is being produced. For cells grown in low iron, the accumulation of extracellular schizokinen was observed to parallel cell growth and continue well into stationary phase. The actual iron status of the organism was monitored by using iron uptake velocity as an assay. Cultures grown on 0.1 ..mu..M added iron were found to be severely iron limited upon reaching stationary phase, thus explaining the continued production of schizokinen. These data show that the siderophore system in Anabaena spp. has developed primarily as a response to iron starvation and that additional functions such as alleviation of copper toxicity or allelopathic inhibition of other algal species are merely secondary benefits.

  7. Quantitative structure-activity relationships for chemical toxicity to environmental bacteria

    SciTech Connect

    Blum, D.J.; Speece, R.E. )

    1991-10-01

    Quantitative structure-activity relationships (QSARs) were developed for nonreactive chemical toxicity to each of four groups of bacteria of importance in environmental engineering: aerobic heterotrophs, methanogens, Nitrosomonas, and Microtox. The QSARs were based on chemicals covering a range of structures and including important environmental pollutants (i.e., chlorinated and other substituted benzenes, phenols, and aliphatic hydrocarbons). QSARs were developed for each chemical class and for combinations of chemical classes. Three QSAR methods (groups of chemical describing parameters) were evaluated for their accuracy and ease of use: log P, linear solvation energy relationships (LSER), and molecular connectivity. Successful QSARs were found for each group of bacteria and by each method, with correlation coefficients (adjusted r2) between 0.79 and 0.95. LSER QSARs incorporated the widest range of chemicals with the greatest accuracy. Log P and molecular connectivity QSARs are easier to use because their parameters are readily available. Outliers from the QSARs likely due to reactive toxicity included acryls, low pKa compounds, and aldehydes. Nitro compounds and chlorinated aliphatic hydrocarbons and alcohols showed enhanced toxicity to the methanogens only. Chemicals with low IC50 concentrations (log IC50 mumol/liter less than 1.5) were often outliers for Nitrosomonas. QSARs were validated statistically and with literature data. A suggested method is provided for use of the QSARs.

  8. Approaches to the Development of Human Health Toxicity Values for Active Pharmaceutical Ingredients in the Environment.

    PubMed

    Sorell, Tamara L

    2016-01-01

    Management of active pharmaceutical ingredients (API) in the environment is challenging because these substances represent a large and diverse group of compounds. Advanced wastewater treatment technologies that can remove API tend to be costly. Because of the potential resources required to address API in the environment, there is a need to establish environmental benchmarks that can serve as targets for treatment and release. To date, there are several different approaches that have been taken to derive human health toxicity values for API. These methods include traditional risk assessment approaches that calculate "safe" doses using experimental data and uncertainty (safety) factors; point of departure (POD), which starts from a therapeutic human dose and applies uncertainty factors; and threshold of toxicological concern (TTC), a generic approach that establishes threshold values across broad classes of chemicals based on chemical structure. To evaluate the use of these approaches, each of these methods was applied to three API commonly encountered in the environment: acetaminophen, caffeine, and chlorpromazine. The results indicate that the various methods of estimating toxicity values produce highly varying doses. Associated doses are well below typical intakes, or toxicity thresholds cannot be derived due to a lack of information. No uniform approach can be applied to establishing thresholds for multiple substances. Rather, an individualized approach will need to be applied to each target API.

  9. Identification of alpha-beta unsaturated aldehydes as sources of toxicity to activated sludge biomass in polyester manufacturing wastewater.

    PubMed

    Caffaro-Filho, R A; Wagner, R; Umbuzeiro, G A; Grossman, M J; Durrant, L R

    2010-01-01

    Wastewater generated in industrial production processes are often contaminated by hazardous chemicals. Characterization by means of toxicity-directed analysis is useful for identifying which fractions of a waste stream possess the most toxicity. We applied this approach to evaluate toxic components of a polyester manufacturing wastewater. Using the reduction in oxygen uptake rate of activated sludge as an indicator of toxicity, it was determined that increasing the pH from 3 to 11 followed by air stripping significantly reduced the toxicity of the wastewater. Comparative headspace GC/MS analysis of wastewater at different pHs selected a group of Volatile Organic Compounds (VOCs) associated with the observed effect of air stripping at pH 11. Ten of these compounds were identified as alpha,beta unsaturated aldehydes (acrolein (2-propenal) congeners); these compounds are known to be toxic as well as mutagenic. Confirmation that these compounds were a cause of toxicity was achieved by demonstrating that removal of these compounds by air stripping significantly reduced the wastewater mutagenic potency in a Salmonella mutagenicity assay. Formation of these volatile compounds by base catalyzed aldol condensation at pH 11 may account for the effectiveness of air stripping in reducing toxicity. To date there is no record in the literature about the toxicity and presence of acrolein congeners in polyester manufacturing wastewater.

  10. New Non-Toxic Semi-Synthetic Derivatives from Natural Diterpenes Displaying Anti-Tuberculosis Activity.

    PubMed

    Matos, Priscilla M; Mahoney, Brian; Chan, Yohan; Day, David P; Cabral, Mirela M W; Martins, Carlos H G; Santos, Raquel A; Bastos, Jairo K; Page, Philip C Bulman; Heleno, Vladimir C G

    2015-10-07

    We report herein the synthesis of six diterpene derivatives, three of which are new, generated through known organic chemistry reactions that allowed structural modification of the existing natural products kaurenoic acid (1) and copalic acid (2). The new compounds were fully characterized using high resolution mass spectrometry, infrared spectroscopy, ¹H- and (13)C-NMR experiments. We also report the evaluation of the anti-tuberculosis potential for all compounds, which showed some promising results for Micobacterium tuberculosis inhibition. Moreover, the toxicity for each of the most active compounds was also assessed.

  11. Acute toxicity, antiedematogenic activity, and chemical constituents of Palicourea rigida Kunth.

    PubMed

    Alves, Vanessa G; da Rosa, Elisa A; de Arruda, Laura L M; Rocha, Bruno A; Bersani Amado, Ciomar A; Santin, Silvana M O; Pomini, Armando M; da Silva, Cleuza C

    2016-03-01

    The phytochemical study of the leaves, roots, and flowers of Palicourea rigida led to the isolation of the triterpenes betulinic acid (1) and lupeol (2), the diterpene phytol (3), and the iridoid glycosides sweroside (4) and secoxyloganin (5). These compounds were identified using NMR 1H and 13C and comparing the spectra with published data. We studied the antiedematogenic activity of crude extracts from the organs, and of different fractions, in mice and found that the n-hexane fraction of the leaf extract significantly inhibited the ear edema resulting from croton oil administration. The crude extract from leaves was not acutely toxic to the mice. PMID:26927220

  12. Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidants activity in vitro.

    PubMed

    Mattei, R; Dias, R F; Espínola, E B; Carlini, E A; Barros, S B

    1998-03-01

    The effects on toxic and behavioral levels of guarana (Paullinia cupana) were assessed in rats and mice subsequent to acute and chronic administrations and were compared to those produced by Ginseng (Panax ginseng). Experimental parameters included tests for antioxidant capacity in vitro and measured in vivo, toxicological screening, progress in weight, motor activity, death rate, and histopathological examination of the viscera. Guarana showed an antioxidant effect because, even at low concentrations (1.2 microg/ml), it inhibited the process of lipid peroxidation. In high doses of 1000-2000 mg/kg (i.p. and p.o.) it did not induce significant alterations in parameters for toxicological screening. No effects on motor activity were observed, neither did guarana alter the hypnotic effect of pentobarbital. Ginseng (250-1000 mg/kg i.p.), however, elicited reductions in motor activity, eyelid ptosis and bristling fur. Consumption of liquids containing guarana or ginseng and progress in weight of the animals remained at levels similar to the controls, even after prolonged administration. The percentage mortality was equivalent in control and in treated groups. The absence of toxicity of guarana was also demonstrated by histopathological examination, with no alteration being detected in heart, lungs, stomach, small and large intestine, liver, pancreas, kidneys, bladder and spleen. PMID:9582000

  13. Hepatoprotective activity of white horehound (Marrubium vulgare) extract against cyclophosphamide toxicity in male rats.

    PubMed

    Ettaya, Amani; Dhibi, Sabah; Samout, Noura; Elfeki, Abdelfettah; Hfaiedh, Najla

    2016-04-01

    The hepatoprotective activity of Marrubium vulgare against cyclophosphamide toxicity in Wistar rats was evaluated. Adult male rats were divided into 4 groups of 6 each: a control group, a group injected with cyclophosphamide (150 mg·kg(-1)) for 3 days, a group orally given a M. vulgare aqueous extract ((500 mg of dry leaves)·kg(-1)·day(-1)) for 30 days then treated with cyclophosphamide, and a group receiving only M. vulgare for 30 days. After 33 days of treatment, activities of alanine amino transferase (ALAT), aspartate amino transferase (ASAT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were determined in serum. Moreover, lipid peroxidation level and superoxide dismutase (SOD) activities, catalase (CAT) and glutathione peroxidase (GPx) were measured in liver. Alterations of these hepatic biomarkers and increased lipid peroxidation confirmed cyclophosphamide-induced liver toxicity. Cyclophosphamide also decreased the enzymatic defense system against oxidative stress. However, when this drug was administered in rats given M. vulgare extract, all the biological parameters underwent much less alteration. Administration of M. vulgare extract was found to be beneficial by attenuating cyclophosphamide-induced liver damage. The protective effect of the plant is mainly attributed to its antioxidant properties and the existence of phenolic acids and flavonoids, as highlighted by HPLC-based analysis.

  14. Food Preference and Foraging Activity of Ants: Recommendations for Field Applications of Low-Toxicity Baits

    PubMed Central

    Nyamukondiwa, Casper; Addison, Pia

    2014-01-01

    Control of ants using baits of low toxicity cannot be effective without knowledge of bait distribution patterns and bait station densities, which are determined by ants' foraging activities. Furthermore, the success of toxic baits also depends upon attractiveness of bait carriers. Here, we assessed ground and vine foraging activity and food preferences for the three ant species (Linepithema humile (Mayr) (Hymenoptera: Formicidae), Anoplolepis custodiens (F. Smith) and Crematogaster peringueyi Emery) under field conditions. We found that L. humile's vineyard foraging activity was high and that movement of ant bait by C. peringueyi and A. custodiens in the vineyard was relatively low. Consequently, more bait stations need to be dispensed for more effective control of C. peringueyi and A. custodiens than for L. humile. Different bait densities are discussed for the various ant species. Food preference trials indicated that vineyard foraging ants preferred wet bait attractants over dry ones, making liquids the most ideal carriers for baiting these ants. Linepithema humile was attracted to 25% sugar water, while C. peringueyi was attracted to both 25% sugar water and honey. Anoplolepis custodiens was attracted to tuna but was also attracted to 25% sugar water. Thus, future bait formulations should be tailor made to suit these specific food requirements if baits are to be successful in ant pest management. PMID:25373195

  15. Antibiofilm Activity, Compound Characterization, and Acute Toxicity of Extract from a Novel Bacterial Species of Paenibacillus

    PubMed Central

    Alasil, Saad Musbah; Omar, Rahmat; Yusof, Mohd Yasim

    2014-01-01

    The effectiveness of many antimicrobial agents is currently decreasing; therefore, it is important to search for alternative therapeutics. Our study was carried out to assess the in vitro antibiofilm activity using microtiter plate assay, to characterize the bioactive compounds using Ultra Performance Liquid Chromatography-Diode Array Detection and Liquid Chromatography-Mass Spectrometry and to test the oral acute toxicity on Sprague Dawley rats of extract derived from a novel bacterial species of Paenibacillus strain 139SI. Our results indicate that the crude extract and its three identified compounds exhibit strong antibiofilm activity against a broad range of clinically important pathogens. Three potential compounds were identified including an amino acid antibiotic C8H20N3O4P (MW 253.237), phospholipase A2 inhibitor C21H36O5 (MW 368.512), and an antibacterial agent C14H11N3O2 (MW 253.260). The acute toxicity test indicates that the mortality rate among all rats was low and that the biochemical parameters, hematological profile, and histopathology examination of liver and kidneys showed no significant differences between experimental groups (P > 0.05). Overall, our findings suggest that the extract and its purified compounds derived from novel Paenibacillus sp. are nontoxic exhibiting strong antibiofilm activity against Gram-positive and Gram-negative pathogens that can be useful towards new therapeutic management of biofilm-associated infections. PMID:24790603

  16. Hepatoprotective activity of white horehound (Marrubium vulgare) extract against cyclophosphamide toxicity in male rats.

    PubMed

    Ettaya, Amani; Dhibi, Sabah; Samout, Noura; Elfeki, Abdelfettah; Hfaiedh, Najla

    2016-04-01

    The hepatoprotective activity of Marrubium vulgare against cyclophosphamide toxicity in Wistar rats was evaluated. Adult male rats were divided into 4 groups of 6 each: a control group, a group injected with cyclophosphamide (150 mg·kg(-1)) for 3 days, a group orally given a M. vulgare aqueous extract ((500 mg of dry leaves)·kg(-1)·day(-1)) for 30 days then treated with cyclophosphamide, and a group receiving only M. vulgare for 30 days. After 33 days of treatment, activities of alanine amino transferase (ALAT), aspartate amino transferase (ASAT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were determined in serum. Moreover, lipid peroxidation level and superoxide dismutase (SOD) activities, catalase (CAT) and glutathione peroxidase (GPx) were measured in liver. Alterations of these hepatic biomarkers and increased lipid peroxidation confirmed cyclophosphamide-induced liver toxicity. Cyclophosphamide also decreased the enzymatic defense system against oxidative stress. However, when this drug was administered in rats given M. vulgare extract, all the biological parameters underwent much less alteration. Administration of M. vulgare extract was found to be beneficial by attenuating cyclophosphamide-induced liver damage. The protective effect of the plant is mainly attributed to its antioxidant properties and the existence of phenolic acids and flavonoids, as highlighted by HPLC-based analysis. PMID:26886858

  17. Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidants activity in vitro.

    PubMed

    Mattei, R; Dias, R F; Espínola, E B; Carlini, E A; Barros, S B

    1998-03-01

    The effects on toxic and behavioral levels of guarana (Paullinia cupana) were assessed in rats and mice subsequent to acute and chronic administrations and were compared to those produced by Ginseng (Panax ginseng). Experimental parameters included tests for antioxidant capacity in vitro and measured in vivo, toxicological screening, progress in weight, motor activity, death rate, and histopathological examination of the viscera. Guarana showed an antioxidant effect because, even at low concentrations (1.2 microg/ml), it inhibited the process of lipid peroxidation. In high doses of 1000-2000 mg/kg (i.p. and p.o.) it did not induce significant alterations in parameters for toxicological screening. No effects on motor activity were observed, neither did guarana alter the hypnotic effect of pentobarbital. Ginseng (250-1000 mg/kg i.p.), however, elicited reductions in motor activity, eyelid ptosis and bristling fur. Consumption of liquids containing guarana or ginseng and progress in weight of the animals remained at levels similar to the controls, even after prolonged administration. The percentage mortality was equivalent in control and in treated groups. The absence of toxicity of guarana was also demonstrated by histopathological examination, with no alteration being detected in heart, lungs, stomach, small and large intestine, liver, pancreas, kidneys, bladder and spleen.

  18. Food preference and foraging activity of ants: recommendations for field applications of low-toxicity baits.

    PubMed

    Nyamukondiwa, Casper; Addison, Pia

    2014-04-10

    Control of ants using baits of low toxicity cannot be effective without knowledge of bait distribution patterns and bait station densities, which are determined by ants' foraging activities. Furthermore, the success of toxic baits also depends upon attractiveness of bait carriers. Here, we assessed ground and vine foraging activity and food preferences for the three ant species ( Linepithema humile (Mayr) (Hymenoptera: Formicidae), Anoplolepis custodiens (F. Smith) and Crematogaster peringueyi Emery) under field conditions. We found that L. humile's vineyard foraging activity was high and that movement of ant bait by C. peringueyi and A. custodiens in the vineyard was relatively low. Consequently, more bait stations need to be dispensed for more effective control of C. peringueyi and A. custodiens than for L. humile. Different bait densities are discussed for the various ant species. Food preference trials indicated that vineyard foraging ants preferred wet bait attractants over dry ones, making liquids the most ideal carriers for baiting these ants. Linepithema humile was attracted to 25% sugar water, while C. peringueyi was attracted to both 25% sugar water and honey. Anoplolepis custodiens was attracted to tuna but was also attracted to 25% sugar water. Thus, future bait formulations should be tailor made to suit these specific food requirements if baits are to be successful in ant pest management.

  19. The Toxic Effect of Manganese on the Acetylcholinesterase Activity in Rat Brains

    PubMed Central

    Yousefi Babadi, Vahid; Sadeghi, Leila; Shirani, Kobra; Malekirad, Ali Akbar; Rezaei, Mohammad

    2014-01-01

    Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. Accumulation of manganese damages central nervous system and causes Parkinson's disease-like syndrome called manganism. Mn neurotoxicity has been suggested to involve an imbalance between the DAergic and cholinergic systems. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated by changing of AChE activity that resulted in oxidative stress. Therefore we focused the effect of Mn in AChE activity in the rat's brain by MnCl2 injection intraperitoneally and analyzed their brains after time intervals. This study used different acute doses in short time course and different chronic doses at different exposing time to investigate which of them (exposing dose or time) is more important in Mn toxic effect. Results showed toxic effect of Mn is highly dose dependent and AChE activity in presence of chronic dose in 8 weeks reaches acute dose in only 2 days. PMID:25246936

  20. Cellular Interaction and Toxicity Depends on Physiochemical Properties and Surface Modification of Redox Active Nanomaterials

    PubMed Central

    Dowding, Janet M.; Das, Soumen; Kumar, Amit; Dosani, Talib; McCormack, Rameech; Gupta, Ankur; Sayle, Thi X. T.; Sayle, Dean C.; von Kalm, Laurence; Seal, Sudipta; Self, William T.

    2013-01-01

    The study of the chemical and biological properties of CeO2 NPs (CNPs) has expanded recently due to its therapeutic potential, and the methods used to synthesize these materials are diverse. Moreover, conflicting reports exists regarding the toxicity of CNP. To help resolve these discrepancies, we must first determine whether CeO2 NPs made by different methods are similar or different in their physiochemical and catalytic properties. In this paper, we have synthesized several forms of CNPs using identical precursors through a wet chemical process but using different oxidizer/reducer H2O2 (CNP1), NH4OH (CNP2) or hexamethylenetetramine (HMT-CNP1). Physiochemical properties of these CeO2 NPs were extensively studied and found to be different depending on the preparation methods. Unlike CNP1 and CNP2, HMT-CNP1 were readily taken into endothelial cells and their aggregation can be visualized using light microscopy. Exposure to HMT-CNP1 also reduced cell viability (MTT) at a 10-fold lower concentration than CNP1 or CNP2. Surprisingly, exposure to HMT-CNP1 led to substantial decreases in the ATP levels. Mechanistic studies revealed that HMT-CNP1 exhibited substantial ATPase (phosphatase) activity. Though CNP2 also exhibits ATPase activity, CNP1 lacked ATPase activity. The difference in catalytic (ATPase) activity of different CeO2 NPs preparation may be due to differences in their morphology and oxygen extraction energy. These results suggest the combination of increased uptake and ATPase activity of HMT-CNP1 may underlie the biomechanism of the toxicity of this preparation of CNPs, and may suggest ATPase activity should be considered when synthesizing CNPs for use in biomedical applications. PMID:23668322

  1. Electrophoretic and densitometric analysis of esterase activity as an indicator of mercury toxicity

    SciTech Connect

    Benton, M.J.; Guttman, S.I.

    1995-12-31

    In an earlier experiment, esterase activity as determined by starch gel electrophoresis was absent in larval caddisflies (Nectopsyche albida) that succumbed to mercury exposure, but was present in control larvae. To test the effects of mercury exposure duration on esterase activity, additional larval N. albida were exposed under conditions identical to those in the earlier experiment, and esterase activity was determined by electrophoresis of several live individuals every 12 hours. To test the effects of mercury concentration on esterase activity, homogenates of unexposed N. albida were electrophoresed, and esterase activity was determined using esterase-specific stains spiked with various concentrations of mercury. Following both experiments, esterase activity was quantified by laser densitometry of stained electrophoresis gels, Results indicate that: (1) inorganic mercury inhibited esterase activity, (2) inhibition increased with exposure time, and (3) inhibition increased with mercury concentration. Esterase inhibition may be a causal factor in mortality related to mercury exposure. Quantification of esterase activity by densitometry of electrophoretic gels may be an alternative method of rapid toxicity assessment.

  2. Bioactivation of the Nasal Toxicant 2,6-Dichlorobenzonitrile: An Assessment of Metabolic Activity in Human Nasal Mucosa and Identification of Indicators of Exposure and Potential Toxicity

    PubMed Central

    Xie, Fang; D’Agostino, Jaime; Zhou, Xin; Ding, Xinxin

    2013-01-01

    The herbicide 2,6-dichlorobenzonitrile (DCBN) is a potent nasal toxicant in rodents; however it is not known whether DCBN causes similar nasal toxicity in humans. The tissue-selective toxicity of DCBN in mouse nasal mucosa is largely dependent on target tissue bioactivation by CYP2A5. The human orthologs of CYP2A5, CYP2A6 and CYP2A13, are both expressed in nasal mucosa, and are capable of activating DCBN. In this study, we directly determined the ability of human nasal mucosa to bioactivate DCBN. We also tested the suitability of a glutathione conjugate of DCBN (GS-DCBN) or its derivatives as biomarkers of DCBN exposure and nasal toxicity in mouse models. We found that human fetal nasal-mucosa microsomes catalyze the formation of GS-DCBN, with a Km value comparable to that of adult mouse nasal-mucosa microsomes. The activity of the human nasal-mucosa microsomes was inhibited by 8-methoxypsoralen, a known CYP2A inhibitor. GS-DCBN and its metabolites were detected in the nasal mucosa and nasal-wash fluid obtained from DCBN-treated mice, in amounts that increased with escalations in DCBN dose, and they were all still detectable at 24 h after a DCBN treatment (at 10 mg/kg). Further studies in Cyp2a5-null mice indicated that GS-DCBN and its metabolites in nasal-wash fluid were generated in the nasal mucosa, rather than in other organs. Thus, our data indicate for the first time that the human nasal mucosa is capable of bioactivating DCBN, and that GS-DCBN and its metabolites in nasal-wash fluid may collectively serve as indicators of DCBN exposure and potential nasal toxicity in humans. PMID:23360412

  3. Use of quantitative shape-activity relationships to model the photoinduced toxicity of polycyclic aromatic hydrocarbons: Electron density shape features accurately predict toxicity

    SciTech Connect

    Mezey, P.G.; Zimpel, Z.; Warburton, P.; Walker, P.D.; Irvine, D.G.; Huang, X.D.; Dixon, D.G.; Greenberg, B.M.

    1998-07-01

    The quantitative shape-activity relationship (QShAR) methodology, based on accurate three-dimensional electron densities and detailed shape analysis methods, has been applied to a Lemna gibba photoinduced toxicity data set of 16 polycyclic aromatic hydrocarbon (PAH) molecules. In the first phase of the studies, a shape fragment QShAR database of PAHs was developed. The results provide a very good match to toxicity based on a combination of the local shape features of single rings in comparison to the central ring of anthracene and a more global shape feature involving larger molecular fragments. The local shape feature appears as a descriptor of the susceptibility of PAHs to photomodification and the global shape feature is probably related to photosensitization activity.

  4. Chitosan-isoniazid conjugates: Synthesis, evaluation of tuberculostatic activity, biodegradability and toxicity.

    PubMed

    Berezin, Alexander S; Skorik, Yury A

    2015-08-20

    Novel water-soluble chitosan-isoniazid conjugates were synthesized by two methods: (1) the carbodiimide method using isoniazid (INH) and N-(2-carboxyethyl)chitosan (CEC), and (2) the reaction between INH and N-(3-chloro-2-hydroxypropyl)chitosan (CHPC). The solubility of the conjugates under physiological conditions was enhanced by phosphorylation. Method (1) is preferable in terms of obtaining conjugates with a high content of active substance; depending on reaction conditions, the degree of substitution in the INH-CEC conjugates varies from 0.08 to 0.39. Ultrasound treatment increased the reaction rate by a factor of 1.3-1.5, but caused partial degradation of the polymer. Consecutive modification led to a considerable decrease in polymer biodegradability in the following order: chitosan>CEC or CHPC>conjugate. In vitro screening of the antimicrobial activity against Mycobacterium tuberculosis H37Rv demonstrated a comparable or slightly higher minimum inhibitory concentration for conjugates than for INH itself (0.20, 0.25, and 1.05 μg INH/mL for INH, CEC-INH, and CHPC-INH, respectively). A slug mucosal irritation test employing Limax flavus revealed a lower toxicity for the conjugates than for INH by a factor of 3-4; the most noticeable toxicity decrease was observed for the conjugates obtained by method (1). Studies of acute toxicity in mice revealed a 3-4-fold increase in median lethal dose for the conjugates compared with INH (LD50 210, 850, and 650 mg INH/kg for INH, CEC-INH, and CHPC-INH, respectively).

  5. Daphnia and fish toxicity of (benzo)triazoles: validated QSAR models, and interspecies quantitative activity-activity modelling.

    PubMed

    Cassani, Stefano; Kovarich, Simona; Papa, Ester; Roy, Partha Pratim; van der Wal, Leon; Gramatica, Paola

    2013-08-15

    Due to their chemical properties synthetic triazoles and benzo-triazoles ((B)TAZs) are mainly distributed to the water compartments in the environment, and because of their wide use the potential effects on aquatic organisms are cause of concern. Non testing approaches like those based on quantitative structure-activity relationships (QSARs) are valuable tools to maximize the information contained in existing experimental data and predict missing information while minimizing animal testing. In the present study, externally validated QSAR models for the prediction of acute (B)TAZs toxicity in Daphnia magna and Oncorhynchus mykiss have been developed according to the principles for the validation of QSARs and their acceptability for regulatory purposes, proposed by the Organization for Economic Co-operation and Development (OECD). These models are based on theoretical molecular descriptors, and are statistically robust, externally predictive and characterized by a verifiable structural applicability domain. They have been applied to predict acute toxicity for over 300 (B)TAZs without experimental data, many of which are in the pre-registration list of the REACH regulation. Additionally, a model based on quantitative activity-activity relationships (QAAR) has been developed, which allows for interspecies extrapolation from daphnids to fish. The importance of QSAR/QAAR, especially when dealing with specific chemical classes like (B)TAZs, for screening and prioritization of pollutants under REACH, has been highlighted.

  6. Overoxidation of chloroplast 2-Cys peroxiredoxins: balancing toxic and signaling activities of hydrogen peroxide

    PubMed Central

    Puerto-Galán, Leonor; Pérez-Ruiz, Juan M.; Ferrández, Julia; Cano, Beatriz; Naranjo, Belén; Nájera, Victoria A.; González, Maricruz; Lindahl, Anna M.; Cejudo, Francisco J.

    2013-01-01

    Photosynthesis, the primary source of biomass and oxygen into the biosphere, involves the transport of electrons in the presence of oxygen and, therefore, chloroplasts constitute an important source of reactive oxygen species, including hydrogen peroxide. If accumulated at high level, hydrogen peroxide may exert a toxic effect; however, it is as well an important second messenger. In order to balance the toxic and signaling activities of hydrogen peroxide its level has to be tightly controlled. To this end, chloroplasts are equipped with different antioxidant systems such as 2-Cys peroxiredoxins (2-Cys Prxs), thiol-based peroxidases able to reduce hydrogen and organic peroxides. At high peroxide concentrations the peroxidase function of 2-Cys Prxs may become inactivated through a process of overoxidation. This inactivation has been proposed to explain the signaling function of hydrogen peroxide in eukaryotes, whereas in prokaryotes, the 2-Cys Prxs of which were considered to be insensitive to overoxidation, the signaling activity of hydrogen peroxide is less relevant. Here we discuss the current knowledge about the mechanisms controlling 2-Cys Prx overoxidation in chloroplasts, organelles with an important signaling function in plants. Given the prokaryotic origin of chloroplasts, we discuss the occurrence of 2-Cys Prx overoxidation in cyanobacteria with the aim of identifying similarities between chloroplasts and their ancestors regarding their response to hydrogen peroxide. PMID:23967002

  7. Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodin.

    PubMed

    Brkanac, Sandra Radić; Gerić, Marko; Gajski, Goran; Vujčić, Valerija; Garaj-Vrhovac, Vera; Kremer, Dario; Domijan, Ana-Marija

    2015-12-01

    In the present study toxicity of Frangula alnus Mill. bark, widely used as laxative, was investigated. Human peripheral blood lymphocytes (HPBLs) were treated with F. alnus bark extract or emodin (emodin is bark component with laxative property), and cytotoxicity, genotoxicity and parameters of oxidative stress were assessed. Also, polyphenol content of bark extract and antioxidant activity of the extract and emodin measured by DPPH, ABTS and FRAP methods were examined. The bark extract (500 μg/ml) produced cell death and DNA damage, while level of ROS changed at 250 μg/ml. Emodin induced cell death and DNA damage at 150 μg/ml and 200 μg/ml, respectively, and the increase of ROS was observed at 25 μg/ml. These results suggest that both, bark extract and emodin, are cyto/genotoxic to HPBLs and that oxidative stress is involved in the mechanism of their toxicity. The results on antioxidant activity showed that, unlike emodin, bark extract possess moderate antioxidant capacity (44.6%, 46.8% and 2.25 mmol Fe(2+)/g measured by DPPH, ABTS and FRAP assay, respectively) that can be related to relatively high phenolic content (116.07 mg/g). However, due to toxicological properties use of F. alnus bark as well as emodin-containing preparations should be taken with caution. PMID:26399165

  8. Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodin.

    PubMed

    Brkanac, Sandra Radić; Gerić, Marko; Gajski, Goran; Vujčić, Valerija; Garaj-Vrhovac, Vera; Kremer, Dario; Domijan, Ana-Marija

    2015-12-01

    In the present study toxicity of Frangula alnus Mill. bark, widely used as laxative, was investigated. Human peripheral blood lymphocytes (HPBLs) were treated with F. alnus bark extract or emodin (emodin is bark component with laxative property), and cytotoxicity, genotoxicity and parameters of oxidative stress were assessed. Also, polyphenol content of bark extract and antioxidant activity of the extract and emodin measured by DPPH, ABTS and FRAP methods were examined. The bark extract (500 μg/ml) produced cell death and DNA damage, while level of ROS changed at 250 μg/ml. Emodin induced cell death and DNA damage at 150 μg/ml and 200 μg/ml, respectively, and the increase of ROS was observed at 25 μg/ml. These results suggest that both, bark extract and emodin, are cyto/genotoxic to HPBLs and that oxidative stress is involved in the mechanism of their toxicity. The results on antioxidant activity showed that, unlike emodin, bark extract possess moderate antioxidant capacity (44.6%, 46.8% and 2.25 mmol Fe(2+)/g measured by DPPH, ABTS and FRAP assay, respectively) that can be related to relatively high phenolic content (116.07 mg/g). However, due to toxicological properties use of F. alnus bark as well as emodin-containing preparations should be taken with caution.

  9. Toxicity of magnetic chitosan micro and nanoparticles as carriers for biologically active substances.

    PubMed

    Leitgeb, Maja; Heržič, Katja; Podrepšek, Gordana Hojnik; Hojski, Aljaž; Crnjac, Anton; Knez, Zeljko

    2014-01-01

    Nanoparticles of inorganic magnetic core surrounded by layers of functional coatings are potential representatives of nanostructures for immobilization of bio-substances. Magnetic nanoparticles (MNPs) are often bound in aggregates due to a strong magnetic dipole, which has a lot of advantages, such as large surface area for binding biologically active substances. Chitosan is a polysaccharide polymer that is non-toxic, hydrophilic, biocompatible and has hydroxy and amino groups in its structure. Because of these chemical and biological properties it is a desirable bio-product for immobilization of enzymes and for binding of other biologically active substances. Magnetic micro and nanoparticles were synthesized with chitosan by three different methods; microemulsion process, suspension cross-linking technique and covalent binding of chitosan. Toxic effect of the prepared magnetic particles was determined as well and was examined on five different bacterial cultures; Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis and Klebsiella pneumoniae. At concentrations of 10-30 mg of magnetic particles per 0.5 McFarland Standard solution of E. coli and per 400 CFU of S. aureus, P. aeruginosa, E. faecalis in K. pneumonia, no inhibition on the chosen bacterial cultures was detected. PMID:24664338

  10. Overoxidation of chloroplast 2-Cys peroxiredoxins: balancing toxic and signaling activities of hydrogen peroxide.

    PubMed

    Puerto-Galán, Leonor; Pérez-Ruiz, Juan M; Ferrández, Julia; Cano, Beatriz; Naranjo, Belén; Nájera, Victoria A; González, Maricruz; Lindahl, Anna M; Cejudo, Francisco J

    2013-01-01

    Photosynthesis, the primary source of biomass and oxygen into the biosphere, involves the transport of electrons in the presence of oxygen and, therefore, chloroplasts constitute an important source of reactive oxygen species, including hydrogen peroxide. If accumulated at high level, hydrogen peroxide may exert a toxic effect; however, it is as well an important second messenger. In order to balance the toxic and signaling activities of hydrogen peroxide its level has to be tightly controlled. To this end, chloroplasts are equipped with different antioxidant systems such as 2-Cys peroxiredoxins (2-Cys Prxs), thiol-based peroxidases able to reduce hydrogen and organic peroxides. At high peroxide concentrations the peroxidase function of 2-Cys Prxs may become inactivated through a process of overoxidation. This inactivation has been proposed to explain the signaling function of hydrogen peroxide in eukaryotes, whereas in prokaryotes, the 2-Cys Prxs of which were considered to be insensitive to overoxidation, the signaling activity of hydrogen peroxide is less relevant. Here we discuss the current knowledge about the mechanisms controlling 2-Cys Prx overoxidation in chloroplasts, organelles with an important signaling function in plants. Given the prokaryotic origin of chloroplasts, we discuss the occurrence of 2-Cys Prx overoxidation in cyanobacteria with the aim of identifying similarities between chloroplasts and their ancestors regarding their response to hydrogen peroxide.

  11. The assessment of inflammatory activity and toxicity of treated sewage using RAW264.7 cells

    PubMed Central

    Makene, Vedastus W.

    2015-01-01

    Abstract Toxicity and inflammatory activity of wastewater samples were evaluated using RAW264.7 cells as a bioassay model. The RAW264.7 cell cultures were exposed to sterile filtered wastewater samples collected from a sewage treatment plant. Cell viability was evaluated using WST‐1 and XTT assays. Inflammatory effects of samples were assessed by determination of nitric oxide (NO) and interleukin 6 (IL‐6). The NO was estimated using the Griess reaction and IL‐6 was measured by enzyme‐linked immunoassay. All samples had no toxicity effects to RAW264.7 cells, however they significantly (P < 0.001) induced NO and IL‐6 production. The highest NO (12.5 ± 0.38 μM) and IL‐6 (25383.84 ± 2327 pg/mL) production was induced by postbiofiltration sample. Final effluent induced the lowest inflammatory response, which indicates effective sewage treatment. In conclusion, wastewater samples can induce inflammatory activities in RAW264.7 cells. The RAW264.7 cells, therefore, can be used as a model for monitoring the quality of treated sewage. PMID:26900395

  12. A cationic tetrapyrrole inhibits toxic activities of the cellular prion protein

    PubMed Central

    Massignan, Tania; Cimini, Sara; Stincardini, Claudia; Cerovic, Milica; Vanni, Ilaria; Elezgarai, Saioa R.; Moreno, Jorge; Stravalaci, Matteo; Negro, Alessandro; Sangiovanni, Valeria; Restelli, Elena; Riccardi, Geraldina; Gobbi, Marco; Castilla, Joaquín; Borsello, Tiziana; Nonno, Romolo; Biasini, Emiliano

    2016-01-01

    Prion diseases are rare neurodegenerative conditions associated with the conformational conversion of the cellular prion protein (PrPC) into PrPSc, a self-replicating isoform (prion) that accumulates in the central nervous system of affected individuals. The structure of PrPSc is poorly defined, and likely to be heterogeneous, as suggested by the existence of different prion strains. The latter represents a relevant problem for therapy in prion diseases, as some potent anti-prion compounds have shown strain-specificity. Designing therapeutics that target PrPC may provide an opportunity to overcome these problems. PrPC ligands may theoretically inhibit the replication of multiple prion strains, by acting on the common substrate of any prion replication reaction. Here, we characterized the properties of a cationic tetrapyrrole [Fe(III)-TMPyP], which was previously shown to bind PrPC, and inhibit the replication of a mouse prion strain. We report that the compound is active against multiple prion strains in vitro and in cells. Interestingly, we also find that Fe(III)-TMPyP inhibits several PrPC-related toxic activities, including the channel-forming ability of a PrP mutant, and the PrPC-dependent synaptotoxicity of amyloid-β (Aβ) oligomers, which are associated with Alzheimer’s Disease. These results demonstrate that molecules binding to PrPC may produce a dual effect of blocking prion replication and inhibiting PrPC-mediated toxicity. PMID:26976106

  13. Antidiarrheal activity and acute oral toxicity of Mentha longifolia L. essential oil

    PubMed Central

    Jalilzadeh-Amin, Ghader; Maham, Massoud

    2015-01-01

    Objectives: Mentha longifolia L. (Lamiaceae) is an annual herb that is used in the Iranian traditional medicine for treating stomach and intestinal disorders. The purpose of this study was to determine the protective effect of M. longifolia on experimental diarrhea in a rat model. Materials and Methods: The antidiarrheal activity of essential oil of M. longifolia (20-80 mg/kg) was investigated against castor oil-induced diarrhea in rats using loperamide as the standard reference drug. In acute toxicity evaluation, rats were orally administrated with single dose of EOML at doses ranging from 10 to 1000 mg/kg. Results: EOML caused a significant (p<0.05) and dose-dependent decrease of gastrointestinal transit, nevertheless, it could not block the inhibitory effect of atropine (0.1 mg/kg). EOML at oral doses of 20 and 80 mg/kg protected the animals against castor oil-induced diarrhea significantly (p<0.05). EOML decreased the intestinal fluid accumulation as indicated by the significantly (p<0.05 to p<0.001) decrease compared to control. The oral LD50 of EOML was found to be 470 mg/kg in rat. Conclusion: Since the inhibition of intestinal hyperactivity and hypersecretory are the bases of the treatment of diarrhea, results obtained in the present study suggest that EOML is endowed with antidiarrheal activity. EOML is moderately toxic for oral medication. PMID:25949954

  14. Subchronic Toxicity Study in Rats of Two New Ethyl-Carbamates with Ixodicidal Activity

    PubMed Central

    Prado-Ochoa, María Guadalupe; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    Female and male Wistar rats were used to determine the subchronic oral toxicities of two new ethyl-carbamates with ixodicidal activities (ethyl-4-bromphenyl-carbamate and ethyl-4-chlorphenyl-carbamate). The evaluated carbamates were administered in the drinking water (12.5, 25 and 50 mg/kg/day) for 90 days. Exposure to the evaluated carbamates did not cause mortality or clinical signs and did not affect food consumption or weight gain. However, exposure to these carbamates produced alterations in water consumption, hematocrit, percentages of reticulocytes, plasma proteins, some biochemical parameters (aspartate aminotransferase, gamma-glutamyl transpeptidase, cholinesterase, and creatinine activities), thiobarbituric acid reactive substances, and the relative weight of the spleen. Histologically, slight pathological alterations were found in the liver that were consistent with the observed biochemical alterations. The nonobserved adverse effect levels (NOAELs) of the evaluated carbamates were 12.5 mg/kg/day for both the female and male rats. The low severity and reversibility of the majority of the observed alterations suggest that the evaluated carbamates have low subchronic toxicity. PMID:24818142

  15. An epigenetic signal encoded protection mechanism is activated by graphene oxide to inhibit its induced reproductive toxicity in Caenorhabditis elegans.

    PubMed

    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.

  16. Metabolic Activation of Rhein: Insights into the Potential Toxicity Induced by Rhein-Containing Herbs.

    PubMed

    Yuan, Yuan; Zheng, Jiyue; Wang, Meiyu; Li, Yuan; Ruan, Jianqing; Zhang, Hongjian

    2016-07-20

    Rhein is a major component of the many medicinal herbs such as rhubarb. Despite wide use, intoxication cases associated with rhein-containing herbs are often reported. The present work aimed to investigate if rhein was subject to metabolic activation leading to toxicity. Upon incubations with different species of liver microsomes, three monoglucuronides were identified, corresponding to two hydroxyl glucuronides and one acyl glucuronide via the carboxyl group, respectively. Further study revealed that rhein acyl glucuronide was chemically reactive, and showed cytotoxicity toward hepatocarcinoma cells. In addition, significant species differences in glucuronidation of rhein were observed between laboratory animals and humans. Reaction phenotyping experiments demonstrated that rhein acyl glucuronide was catalyzed predominantly by uridine 5'-diphospho-glucuronosyltransferase 1A1, 1A9, and 2B7. Taken together, the present study confirmed that rhein could be metabolically activated via the formation of acyl glucuronide, especially in human. PMID:27362917

  17. Toxicity of biorational insecticides: activity against the green peach aphid, Myzus persicae (Sulzer).

    PubMed

    Edelson, Jonathan V; Duthie, J; Roberts, W

    2002-03-01

    The relationship between dose for each of four biorational insecticides (pyrethrins, neem extract, capsiacin extract, insecticidal soap) and mortality of the green peach aphid (Myzus persicae) was determined using a laboratory bioassay. These insecticides were toxic to aphids and paired mixtures of the insecticides provided synergistic activity as measured by aphid mortality under the laboratory bioassay conditions. Capsiacin extracts were found to provide low levels of mortality alone but acted synergistically in mixtures with the other insecticides and provided higher than expected levels of mortality. Activity as determined in the laboratory for each insecticide was not evident under field-use conditions in five separate experiments. Under field conditions and using common application methods, these insecticides did not provide significant levels of control of aphids.

  18. Partial in vitro analysis of toxic and antigenic activities of eleven Peruvian pitviper snake venoms.

    PubMed

    Guerra-Duarte, C; Lopes-Peixoto, J; Fonseca-de-Souza, B R; Stransky, S; Oliveira, D; Schneider, F S; Lopes-de-Souza, L; Bonilla, C; Silva, W; Tintaya, B; Yarleque, A; Chávez-Olórtegui, C

    2015-12-15

    This work used eleven Peruvian snake venoms (Bothrops andianus, Bothrops atrox, Bothrops barnetti, Bothrops castelnaudi, Bothriopsis chloromelas, Bothrocophias microphthalmus, Bothrops neuwiedi, Bothriopsis oligolepis, Bothriopsis peruviana, Bothrops pictus and Bothriopsis taeniata) to perform in vitro experimentation and determine its main characteristics. Hyaluronidase (HYAL), phospholipase A2 (PLA2), snake venom metalloproteinase (SVMP), snake venom serine protease (SVSP) and L-amino acid oxidase (LAAO) activities; toxicity by cell viability assays using MGSO3, VERO and HeLa cell lineages; and crossed immunoreactivity with Peruvian (PAV) and Brazilian (BAV) antibothropic polyvalent antivenoms, through ELISA and Western Blotting assays, were determined. Results show that the activities tested in this study were not similar amongst the venoms and each species present their own peculiarities, highlighting the diversity within Bothrops complex. All venoms were capable of reducing cell viability of all tested lineages. It was also demonstrated the crossed recognition of all tested venoms by both antivenoms. PMID:26365916

  19. In vitro studies of acute toxicity mechanisms and structure-activity relationships of nonionic surfactants in fish

    SciTech Connect

    Bodishbauah, D.F.

    1994-12-31

    In fish, gills are believed to be a primary target for a number of toxicants. Gills perform the essential systemic functions of gas exchange, waste elimination, and ion/pH balance, and are exposed to ambient environmental toxicant levels. Qualitative gill morphology changes are easily observed, but quantitative measures of impaired function are difficult. This in vitro technique utilizes the opercular epithelium of the mummichog, Fundulus heteroclitus, as a surrogate for gill epithelium in mechanistic toxicity and structure-activity studies. This model has long been used by electrophysiologists studying osmoregulation in marine fish. Effects on trans-epithelial potential (TEP) and/or short-circuit current (I{sub sc}) across the opercular epithelium can be made for any pollutant of interest, using an epithelial voltage clamp and Ussing chamber. The nonionic synthetic surfactant class, alkylphenol ethoxylates, were chosen as a model toxicant class to test this experimental model. Synthetic surfactants are ubiquitous waterborne pollutants, with annual North American usage approaching eight billion pounds. Surfactants are recognized as potent, acute gill toxicants in fish. The exact mechanism of toxicity has yet to be elucidated. These compounds proved to be potent inhibitors of both TEP and I{sub sc} in vitro, at dose levels comparable to those causing lethality, suggesting that impaired osmoregulation plays a role in their acute toxicity. Similar structure-activity relationships were found for the endpoints of acute lethality to F. heteroclitus and impaired in vitro epithelial transport.

  20. Aryl hydrocarbon receptor activation and developmental toxicity in zebrafish in response to soil extracts containing unsubstituted and oxygenated PAHs.

    PubMed

    Wincent, Emma; Jönsson, Maria E; Bottai, Matteo; Lundstedt, Staffan; Dreij, Kristian

    2015-03-17

    Many industrial sites are polluted by complex mixtures of polycyclic aromatic compounds (PACs). Besides polycyclic aromatic hydrocarbons (PAHs), these mixtures often contain significant amounts of more polar PACs including oxygenated PAHs (oxy-PAHs). The effects of oxy-PAHs are, however, poorly known. Here we used zebrafish embryos to examine toxicities and transcriptional changes induced by PAC containing soil extracts from three different industrial sites: a gasworks (GAS), a former wood preservation site (WOOD), and a coke oven (COKE), and to PAH and oxy-PAH containing fractions of these. All extracts induced aryl hydrocarbon receptor (Ahr)-regulated mRNAs, malformations, and mortality. The WOOD extract was most toxic and the GAS extract least toxic. The extracts induced glutathione transferases and heat shock protein 70, suggesting that the toxicity also involved oxidative stress. With all extracts, Ahr2-knock-down reduced the toxicity, indicating a significant Ahr2-dependence on the effects. Ahr2-knock-down was most effective with the PAH fraction of the WOOD extract and with the oxy-PAH fraction of the COKE extract. Our results indicate that oxy-PAH containing mixtures can be as potent Ahr activators and developmental toxicants as PAHs. In addition to Ahr activating potency, the profile of cytochrome P4501 inhibitors may also determine the toxic potency of the extracts. PMID:25715055

  1. [Detection of fungal metabolites showing toxic activity through Artemia salina bioassay].

    PubMed

    González, Ana María; Presa, Maximiliano; Latorre, María Gabriela; Lurá, María Cristina

    2007-03-01

    The aim of this study was to detect toxic metabolites from fungi contaminating food and medicinal herbs by applying the toxicity assay to Artemia salina. According to toxicity percentages, the extracts were classified as nontoxic (NT), slightly toxic (ST), toxic (T) and highly toxic (HT). Those classified as T and HT were assayed for mycotoxins. Only 6 out of 71 strains were found to be T (8.5%) for A. salina. Penicillium brevicompactum Dierckx, isolated from sausages, was found to be HT, mainly due to the presence of ochratoxin A and two other unidentified metabolites. PMID:17592895

  2. Comparative toxicity assessment of ozone and activated carbon treated sewage effluents using an in vivo test battery.

    PubMed

    Stalter, Daniel; Magdeburg, Axel; Oehlmann, Jörg

    2010-04-01

    Wastewater treatment plants do not eliminate micropollutants completely and are thus important point sources for these substances. Ozonation and activated carbon treatment might be beneficial for ecosystem health as these techniques provide effective barriers to organic contaminants. However, a toxicity evaluation is required to investigate toxicity reduction and to assess the potential formation of toxic oxidation byproducts during ozonation. Therefore a comparative toxicity evaluation of different treated wastewater effluents was performed on site at a half scale treatment plant equipped with an ozonation step and an activated carbon treatment step in parallel subsequent to conventional activated sludge treatment. For this purpose four invertebrate and one higher plant toxicity test were selected to assess potential biological effects on whole organisms. The reproduction test with the mudsnail Potamopyrgus antipodarum exhibited a decreased reproductive output after advanced treatment compared to conventional treatment. This indicates an effective estrogenicity removal by ozonation and activated carbon treatment and is confirmed by results of the yeast estrogen screen with a reduction of in vitro estrogenic activity by >75%. The Lumbriculus variegatus test revealed a significantly enhanced toxicity after ozonation compared to conventional treatment whereas this effect was reduced following subsequent sand filtration. When ozonation was applied, a significantly increased genotoxicity was observed, detected with the comet assay using haemolymph of the zebra mussel. Again, this effect was removed by subsequent sand filtration to the level of conventional treatment. Activated carbon treatment even resulted in a significant reduction of genotoxicity. Adverse effects after the ozone reactor are possibly a result of the formation of toxic oxidation byproducts. Biologically active sand filtration obviously is an effective barrier to such compounds.

  3. Structure activity relationship of phenolic acid inhibitors of α-synuclein fibril formation and toxicity

    PubMed Central

    Ardah, Mustafa T.; Paleologou, Katerina E.; Lv, Guohua; Abul Khair, Salema B.; Kazim, Abdulla S.; Minhas, Saeed T.; Al-Tel, Taleb H.; Al-Hayani, Abdulmonem A.; Haque, Mohammed E.; Eliezer, David; El-Agnaf, Omar M. A.

    2014-01-01

    The aggregation of α-synuclein (α-syn) is considered the key pathogenic event in many neurological disorders such as Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy, giving rise to a whole category of neurodegenerative diseases known as synucleinopathies. Although the molecular basis of α-syn toxicity has not been precisely elucidated, a great deal of effort has been put into identifying compounds that could inhibit or even reverse the aggregation process. Previous reports indicated that many phenolic compounds are potent inhibitors of α-syn aggregation. The aim of the present study was to assess the anti-aggregating effect of gallic acid (GA) (3,4,5-trihydroxybenzoic acid), a benzoic acid derivative that belongs to a group of phenolic compounds known as phenolic acids. By employing an array of biophysical and biochemical techniques and a cell-viability assay, GA was shown not only to inhibit α-syn fibrillation and toxicity but also to disaggregate preformed α-syn amyloid fibrils. Interestingly, GA was found to bind to soluble, non-toxic oligomers with no β-sheet content, and to stabilize their structure. The binding of GA to the oligomers may represent a potential mechanism of action. Additionally, by using structure activity relationship data obtained from fourteen structurally similar benzoic acid derivatives, it was determined that the inhibition of α-syn fibrillation by GA is related to the number of hydroxyl moieties and their position on the phenyl ring. GA may represent the starting point for designing new molecules that could be used for the treatment of PD and related disorders. PMID:25140150

  4. [Antiesterase activity and toxicity of O,O-dialkyl-S-ethoxycarbonylbromomethylthiophosphates].

    PubMed

    Makhaeva, G F; Iankovskaia, V L; Kovaleva, N V; Fetisov, V I; Malygin, V V; Torgasheva, N A; Khaskin, B A

    1999-01-01

    The interaction of potential pesticides, O,O-dialkyl S-ethoxycarbonylbromomethylthiophosphates (RO)2P(O)SCH(Br)COOC2H5 (R = Et, i-Pr, n-Pr, n-Bu, n-Am, or n-Hx) with the esterases of warm-blooded animals [acetylcholinesterase (ACE), butyryl cholinesterase (BCE), and carboxyl esterase (CE)] was studied. The acute toxicities of these compounds for mice were determined. All the compounds were non-hydrolyzable by CE and capable of irreversible inhibition of all these esterases with ki (M-1 min-1) of 1.2 x 10(5)-6 x 10(6), 2.0 x 10(6)-1.5 x 10(8), and 2.0 x 10(8), respectively. By using multiple regression analysis, we found that the steric factor plays a significant role in the inhibition of ACE, with the steric hindrances manifesting themselves even at the sorption stage. On the other hand, hydrophobic interactions predominate in the case of BCE, while steric properties of its substituents exert a markedly weaker effect and manifest themselves at the phosphorylation stage. We suggested the presence of an electrophilic region in the active site of ACE, which can interact with the ethoxycarbonyl group of the thiophosphates under study. The decrease in toxicities and the affinities to BCE and CE were found to correlate with an increase in the length of n-alkyl substituents of the compounds studied. This suggests that the unspecific esterases play a significant role as a buffer system in the exhibition of toxic effects by the thiophosphates under consideration.

  5. Levels of toxic arsenic species in native terrestrial plants from soils polluted by former mining activities.

    PubMed

    García-Salgado, Sara; Quijano, M Ángeles

    2014-03-01

    Ten native terrestrial plants from soils polluted by former mining activities (Mónica mine, NW Madrid, Spain), with high total arsenic concentration levels (up to 3500 μg g(-1)), have been studied to determine the fraction of arsenic present as toxic forms (inorganic and methylated species), which present a higher mobility and therefore the potential risk associated with their reintegration into the environment is high. Roots and aboveground parts were analyzed separately to assess possible transformations from translocation processes. Extractions were carried out with deionized water by microwave-assisted extraction at a temperature of 90 °C and three extraction steps of 7.5 min each. Total extracted arsenic concentrations were determined by inductively coupled plasma atomic emission spectrometry, showing extraction percentages from 9 to 39% (calculated as the ratio between total extracted arsenic (Asext) and total arsenic (AsT) concentrations in plants). Speciation studies, performed by high performance liquid chromatography-photo-oxidation-hydride generation-atomic fluorescence spectrometry, showed the main presence of arsenate (As(v)) (up to 350 μg g(-1)), followed by arsenite (As(iii)), in both plant parts. Monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) were also found only in some plants. On the other hand, the use of 0.5 mol L(-1) acetic acid as an extractant led to higher extraction percentages (33-87%), but lower column recoveries, probably due to the extraction of arsenic compounds different to the toxic free ions studied, which may come from biotransformation mechanisms carried out by plants to reduce arsenic toxicity. However, As(v) concentrations increased up to 800 μg g(-1) in acid medium, indicating the probable release of As(v) from organoarsenic compounds and therefore a higher potential risk for the environment.

  6. Levels of toxic arsenic species in native terrestrial plants from soils polluted by former mining activities.

    PubMed

    García-Salgado, Sara; Quijano, M Ángeles

    2014-03-01

    Ten native terrestrial plants from soils polluted by former mining activities (Mónica mine, NW Madrid, Spain), with high total arsenic concentration levels (up to 3500 μg g(-1)), have been studied to determine the fraction of arsenic present as toxic forms (inorganic and methylated species), which present a higher mobility and therefore the potential risk associated with their reintegration into the environment is high. Roots and aboveground parts were analyzed separately to assess possible transformations from translocation processes. Extractions were carried out with deionized water by microwave-assisted extraction at a temperature of 90 °C and three extraction steps of 7.5 min each. Total extracted arsenic concentrations were determined by inductively coupled plasma atomic emission spectrometry, showing extraction percentages from 9 to 39% (calculated as the ratio between total extracted arsenic (Asext) and total arsenic (AsT) concentrations in plants). Speciation studies, performed by high performance liquid chromatography-photo-oxidation-hydride generation-atomic fluorescence spectrometry, showed the main presence of arsenate (As(v)) (up to 350 μg g(-1)), followed by arsenite (As(iii)), in both plant parts. Monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) were also found only in some plants. On the other hand, the use of 0.5 mol L(-1) acetic acid as an extractant led to higher extraction percentages (33-87%), but lower column recoveries, probably due to the extraction of arsenic compounds different to the toxic free ions studied, which may come from biotransformation mechanisms carried out by plants to reduce arsenic toxicity. However, As(v) concentrations increased up to 800 μg g(-1) in acid medium, indicating the probable release of As(v) from organoarsenic compounds and therefore a higher potential risk for the environment. PMID:24513726

  7. Toxicity mitigation and solidification of municipal solid waste incinerator fly ash using alkaline activated coal ash

    SciTech Connect

    Ivan Diaz-Loya, E.; Allouche, Erez N.; Eklund, Sven; Joshi, Anupam R.; Kupwade-Patil, Kunal

    2012-08-15

    Highlights: Black-Right-Pointing-Pointer Incinerator fly ash (IFA) is added to an alkali activated coal fly ash (CFA) matrix. Black-Right-Pointing-Pointer Means of stabilizing the incinerator ash for use in construction applications. Black-Right-Pointing-Pointer Concrete made from IFA, CFA and IFA-CFA mixes was chemically characterized. Black-Right-Pointing-Pointer Environmentally friendly solution to IFA disposal by reducing its toxicity levels. - Abstract: Municipal solid waste (MSW) incineration is a common and effective practice to reduce the volume of solid waste in urban areas. However, the byproduct of this process is a fly ash (IFA), which contains large quantities of toxic contaminants. The purpose of this research study was to analyze the chemical, physical and mechanical behaviors resulting from the gradual introduction of IFA to an alkaline activated coal fly ash (CFA) matrix, as a mean of stabilizing the incinerator ash for use in industrial construction applications, where human exposure potential is limited. IFA and CFA were analyzed via X-ray fluorescence (XRF), X-ray diffraction (XRD) and Inductive coupled plasma (ICP) to obtain a full chemical analysis of the samples, its crystallographic characteristics and a detailed count of the eight heavy metals contemplated in US Title 40 of the Code of Federal Regulations (40 CFR). The particle size distribution of IFA and CFA was also recorded. EPA's Toxicity Characteristic Leaching Procedure (TCLP) was followed to monitor the leachability of the contaminants before and after the activation. Also images obtained via Scanning Electron Microscopy (SEM), before and after the activation, are presented. Concrete made from IFA, CFA and IFA-CFA mixes was subjected to a full mechanical characterization; tests include compressive strength, flexural strength, elastic modulus, Poisson's ratio and setting time. The leachable heavy metal contents (except for Se) were below the maximum allowable limits and in many cases

  8. Gas chromatography-mass spectroscopy analysis of bioactive petalostigma extracts: Toxicity, antibacterial and antiviral activities

    PubMed Central

    Kalt, F. R.; Cock, I. E.

    2014-01-01

    Background: Petalostigma pubescens and Petalostigma triloculare were common components of pharmacopeia's of multiple Australian Aboriginal tribal groupings which traditionally inhabited the areas in which they grow. Among these groups, they had a myriad of medicinal uses in treating a wide variety of bacterial, fungal and viral infections. This study was undertaken to test P. pubescens and P. triloculare leaf and fruit extracts for the ability to inhibit bacterial and viral growth and thus validate Australian Aboriginal usage of these plants in treating bacterial and fungal diseases. Materials and Methods: P. pubescens, and P. triloculare leaves and fruit were extracted and tested for antimicrobial, antiviral activity and toxicity. The bioactive extracts were further examined by RP-HPLC and GC-MS to identify the component compounds. Results: The methanol, water and ethyl acetate leaf and fruit extracts of displayed potent antibacterial activity. The methanol and ethyl acetate extracts displayed the broadest specificity, inhibiting the growth of 10 of the 14 bacteria tested (71%) for the leaf extract and 9 of the 14 bacteria tested (64%) for the fruit extracts. The water extracts also had broad spectrum antibacterial activity, inhibiting the growth of 8 (57%) and 7 (50%) of the 14 bacteria tested, respectively. All antibacterial extracts were approximately equally effective against Gram-positive and Gram-negative bacteria, inhibiting the growth of 50-75% of the bacteria tested. The methanol, water and ethyl acetate extracts also displayed antiviral activity in the MS2 plaque reduction assay. The methanol and water extracts inhibited 26.6-49.0% and 85.4-97.2% of MS2 plaque formation, respectively, with the fruit extracts being more potent inhibitors. All ethyl acetate extracts inhibited 100% of MS2 plaque formation. All extracts were also non-toxic or of low toxicity. Analysis of these extracts by RP-HPLC showed that the P. triloculare ethyl acetate fruit extract was

  9. In vivo monitoring of toxic metals: assessment of neutron activation and x-ray fluorescence techniques

    SciTech Connect

    Ellis, K.J.

    1986-01-01

    To date, cadmium, lead, aluminum, and mercury have been measured in vivo in humans. The possibilities of monitoring other toxic metals have also been demonstrated, but no human studies have been performed. Neutron activation analysis appears to be most suitable for Cd and Al measurements, while x-ray fluorescence is ideally suited for measurement of lead in superficial bone. Filtered neutron beams and polarized x-ray sources are being developed which will improve in vivo detection limits. Even so, several of the current facilities are already suitable for use in epidemiological studies of selected populations with suspected long-term low-level ''environmental'' exposures. Evaluation and diagnosis of patients presenting with general clinical symptoms attributable to possible toxic metal exposure may be assisted by in vivo examination. Continued in vivo monitoring of industrial workers, especially follow-up measurements, will provide the first direct assessment of changes in body burden and a direct measure of the biological life-times of these metals in humans. 50 refs., 4 figs., 2 tabs.

  10. Antibacterial activity of neem nanoemulsion and its toxicity assessment on human lymphocytes in vitro.

    PubMed

    Jerobin, Jayakumar; Makwana, Pooja; Suresh Kumar, R S; Sundaramoorthy, Rajiv; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2015-01-01

    Neem (Azadirachta indica) is recognized as a medicinal plant well known for its antibacterial, antimalarial, antiviral, and antifungal properties. Neem nanoemulsion (NE) (O/W) is formulated using neem oil, Tween 20, and water by high-energy ultrasonication. The formulated neem NE showed antibacterial activity against the bacterial pathogen Vibrio vulnificus by disrupting the integrity of the bacterial cell membrane. Despite the use of neem NE in various biomedical applications, the toxicity studies on human cells are still lacking. The neem NE showed a decrease in cellular viability in human lymphocytes after 24 hours of exposure. The neem NE at lower concentration (0.7-1 mg/mL) is found to be nontoxic while it is toxic at higher concentrations (1.2-2 mg/mL). The oxidative stress induced by the neem NE is evidenced by the depletion of catalase, SOD, and GSH levels in human lymphocytes. Neem NE showed a significant increase in DNA damage when compared to control in human lymphocytes (P<0.05). The NE is an effective antibacterial agent against the bacterial pathogen V. vulnificus, and it was found to be nontoxic at lower concentrations to human lymphocytes.

  11. Antibacterial activity of neem nanoemulsion and its toxicity assessment on human lymphocytes in vitro

    PubMed Central

    Jerobin, Jayakumar; Makwana, Pooja; Suresh Kumar, RS; Sundaramoorthy, Rajiv; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2015-01-01

    Neem (Azadirachta indica) is recognized as a medicinal plant well known for its antibacterial, antimalarial, antiviral, and antifungal properties. Neem nanoemulsion (NE) (O/W) is formulated using neem oil, Tween 20, and water by high-energy ultrasonication. The formulated neem NE showed antibacterial activity against the bacterial pathogen Vibrio vulnificus by disrupting the integrity of the bacterial cell membrane. Despite the use of neem NE in various biomedical applications, the toxicity studies on human cells are still lacking. The neem NE showed a decrease in cellular viability in human lymphocytes after 24 hours of exposure. The neem NE at lower concentration (0.7–1 mg/mL) is found to be nontoxic while it is toxic at higher concentrations (1.2–2 mg/mL). The oxidative stress induced by the neem NE is evidenced by the depletion of catalase, SOD, and GSH levels in human lymphocytes. Neem NE showed a significant increase in DNA damage when compared to control in human lymphocytes (P<0.05). The NE is an effective antibacterial agent against the bacterial pathogen V. vulnificus, and it was found to be nontoxic at lower concentrations to human lymphocytes. PMID:26491309

  12. Antibacterial activity of neem nanoemulsion and its toxicity assessment on human lymphocytes in vitro.

    PubMed

    Jerobin, Jayakumar; Makwana, Pooja; Suresh Kumar, R S; Sundaramoorthy, Rajiv; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2015-01-01

    Neem (Azadirachta indica) is recognized as a medicinal plant well known for its antibacterial, antimalarial, antiviral, and antifungal properties. Neem nanoemulsion (NE) (O/W) is formulated using neem oil, Tween 20, and water by high-energy ultrasonication. The formulated neem NE showed antibacterial activity against the bacterial pathogen Vibrio vulnificus by disrupting the integrity of the bacterial cell membrane. Despite the use of neem NE in various biomedical applications, the toxicity studies on human cells are still lacking. The neem NE showed a decrease in cellular viability in human lymphocytes after 24 hours of exposure. The neem NE at lower concentration (0.7-1 mg/mL) is found to be nontoxic while it is toxic at higher concentrations (1.2-2 mg/mL). The oxidative stress induced by the neem NE is evidenced by the depletion of catalase, SOD, and GSH levels in human lymphocytes. Neem NE showed a significant increase in DNA damage when compared to control in human lymphocytes (P<0.05). The NE is an effective antibacterial agent against the bacterial pathogen V. vulnificus, and it was found to be nontoxic at lower concentrations to human lymphocytes. PMID:26491309

  13. Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells.

    PubMed

    Gray, Lachlan R; On, Hung; Roberts, Emma; Lu, Hao K; Moso, Michael A; Raison, Jacqueline A; Papaioannou, Catherine; Cheng, Wan-Jung; Ellett, Anne M; Jacobson, Jonathan C; Purcell, Damian F J; Wesselingh, Steve L; Gorry, Paul R; Lewin, Sharon R; Churchill, Melissa J

    2016-08-01

    Despite the success of combination antiretroviral therapy (cART), HIV persists in long lived latently infected cells in the blood and tissue, and treatment is required lifelong. Recent clinical studies have trialed latency-reversing agents (LRA) as a method to eliminate latently infected cells; however, the effects of LRA on the central nervous system (CNS), a well-known site of virus persistence on cART, are unknown. In this study, we evaluated the toxicity and potency of a panel of commonly used and well-known LRA (panobinostat, romidepsin, vorinostat, chaetocin, disulfiram, hexamethylene bisacetamide [HMBA], and JQ-1) in primary fetal astrocytes (PFA) as well as monocyte-derived macrophages as a cellular model for brain perivascular macrophages. We show that most LRA are non-toxic in these cells at therapeutic concentrations. Additionally, romidepsin, JQ-1, and panobinostat were the most potent at inducing viral transcription, with greater magnitude observed in PFA. In contrast, vorinostat, chaetocin, disulfiram, and HMBA all demonstrated little or no induction of viral transcription. Together, these data suggest that some LRA could potentially activate transcription in latently infected cells in the CNS. We recommend that future trials of LRA also examine the effects of these agents on the CNS via examination of cerebrospinal fluid.

  14. Toxicity of perfluorooctanoic acid towards earthworm and enzymatic activities in soil.

    PubMed

    He, Wenxiang; Megharaj, Mallavarapu; Naidu, Ravi

    2016-07-01

    Perfluorooctanoic acid (PFOA) is a widespread persistent organic contaminant in the environment that has recently raised much of regulatory and public concern. Therefore, assessment of its ecological risk is a top priority research. Hence, this study investigated the toxicity of PFOA to beneficial microbial processes in the soil such as activities of dehydrogenase, urease and potential nitrification in addition to earthworm survival, weight loss and PFOA bioaccumulation in two contrasting soils. In general, PFOA caused inhibition of all the measured microbial processes in a dose-dependent manner and the inhibition was higher in Williamtown (WT) soil than Edinburgh (EB) soil. Thus, WT soil being sandy in nature with low clay content showed higher PFOA bioavailability and hence showed higher toxicity. There was no mortality in earthworms exposed up to 100 mg PFOA/kilogram soil in both the soils; however, there was a significant weight loss from 25 mg/kg onwards. This study clearly demonstrates that soil contamination of PFOA can lead to adverse effects on soil health. PMID:27329475

  15. Anti-Oxidant and Hepatoprotective Activities of Ziziphus mucronata Fruit Extract Against Dimethoate-Induced Toxicity

    PubMed Central

    Kwape, Tebogo Elvis; Chaturvedi, Padmaja; Kamau, Macharia; Majinda, Runner

    2013-01-01

    Objective: The study was carried out to evaluate the hepatoprotective and antioxidant potential of Ziziphus mucronata (ZM) fruit extract. Methods: The different types of fruit extract were prepared by soaking the dry powdered fruit in different solvents followed by rotary evaporation. Each extract was tested for its phenol content and antioxidant activities. An in vivo study was performed in Sprague- Dawley (SD) rats. Thirty adult male SD rats (aged 21 weeks) were divided into six groups of five rats each and treated as follows: The normal control (NC) received distilled water while the dimethoate control (DC) received 6 mg/kg.bw.day-1 dimethoate dissolved in distilled water. The experimental groups E1, E2, E3, and E0 received dimethoate (6 mg/kg.bw) + ZMFM (100 mg/kg.bw-1), dimethoate (6 mg/kg.bw) + ZMFM (200 mg/kg.bw-1), dimethoate (6 mg/kg.bw) + ZMFM (300 mg/kg.bw-1), and ZMFM (300 mg/kg.bw-1) only. Both the normal control and the dimethoate control groups were used to compare the results. After 90 days, rats were sacrificed, blood was collected for biochemical assays, and livers were harvested for histological study. Results: High phenol content was estimated, and 2, 2- diphenyl-1-picryl hydrazyl radical (DPPH) spectrophotometric, thin layer chromatography (TLC) and 2, 2-Azobis-3-ethyl benzothiazoline-6-sulphonic acid (ABTS) assays showed a high antioxidant activity among the extracts. The preventive effects observed in the E1, E2 and E3 groups proved that the extract could prevent dimethoate toxicity by maintaining normal reduced glutathione (GSH), vitamin C and E, superoxide dismutase, catalase, cholineasterase and lipid profiles. The preventive effect was observed to be dose dependent. The EO group showed no extractinduced toxicity. Histological observations agreed with the results obtained in the biochemical studies. Conclusion: The study demonstrated that ZM methanol fruit extract is capable of attenuating dimethoate-induced toxicity because of its high

  16. Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

    NASA Astrophysics Data System (ADS)

    Carpenter, Laurie Jean

    When administered intravenously or intratracheally to rats, rabbits and sheep, phorbol myristate acetate (PMA) produces changes in lung morphology and function are similar to those seen in humans with the adult respiratory distress syndrome (ARDS). Therefore, it is thought that information about the mechanism of ARDS development can be gained from experiments using PMA-treated animals. Currently, the mechanisms by which PMA causes pneumotoxicity are unknown. Results from other studies in rabbits and in isolated, perfused rabbit lungs suggest that PMA-induced lung injury is mediated by active oxygen species from neutrophils (PMN), whereas studies in sheep and rats suggest that PMN are not required for the toxic response. The role of PMN, active oxygen metabolites and thromboxane (TxA_2) in PMA-induced injury to isolated, perfused rat lungs (IPLs) was examined in this thesis. To determine whether PMN were required for PMA to produce toxicity to the IPL, lungs were perfused for 30 min with buffer containing various concentrations of PMA (in the presence or absence of PMN). When concentrations >=q57 ng/ml were added to medium devoid of added PMN, perfusion pressure and lung weight increased. When a concentration of PMA (14-28 ng/ml) that did not by itself cause lungs to accumulate fluid was added to the perfusion medium containing PMN (1 x 10 ^8), perfusion pressure increased, and lungs accumulated fluid. These results indicate that high concentrations of PMA produce lung injury which is independent of PMN, whereas injury induced by lower concentrations is PMN-dependent. To examine whether active oxygen species were involved in mediating lung injury induced by PMA and PMN, lungs were coperfused with the oxygen radical scavengers SOD and/or catalase. Coperfusion with either or both of these enzymes totally protected lungs against injury caused by PMN and PMA. These results suggest that active oxygen species (the hydroxyl radical in particular), mediate lung injury in

  17. Toxicity and Residual Activity of Insecticides Against Tamarixia triozae (Hymenoptera: Eulophidae), a Parasitoid of Bactericera cockerelli (Hemiptera: Triozidae).

    PubMed

    Luna-Cruz, Alfonso; Rodríguez-Leyva, Esteban; Lomeli-Flores, J Refugio; Ortega-Arenas, Laura D; Bautista-Martínez, Néstor; Pineda, Samuel

    2015-10-01

    Bactericera cockerelli (Sulc) (Hemiptera: Triozidae) is one of the most economically important pests of potato, tomato, and peppers in Central America, Mexico, the United States, and New Zealand. Its control is based on the use of insecticides; however, recently, the potential of the eulophid parasitoid Tamarixia triozae (Burks) (Hymenoptera: Eulophidae) for population regulation has been studied. Because T. triozae is likely to be exposed to insecticides on crops, the objective of this study was to explore the compatibility of eight insecticides with this parasitoid. The toxicity and residual activity (persistence) of spirotetramat, spiromesifen, beta-cyfluthrin, pymetrozine, azadirachtin, imidacloprid, abamectin, and spinosad against T. triozae adults were assessed using a method based on the residual contact activity of each insecticide on tomato leaf discs collected from treated plants growing under greenhouse conditions. All eight insecticides were toxic to T. triozae. Following the classification of the International Organization of Biological Control, the most toxic were abamectin and spinosad, which could be placed in toxicity categories 3 and 4, respectively. The least toxic were azadirachtin, pymetrozine, spirotetramat, spiromesifen, imidacloprid, and beta-cyfluthrin, which could be placed in toxicity category 2. In terms of persistence, by day 5, 6, 9, 11, 13, 24, and 41 after application, spirotetramat, azadirachtin, spiromesifen, pymetrozine, imidacloprid, beta-cyfluthrin, abamectin, and spinosad could be considered harmless, that is, placed in toxicity category 1 (<25% mortality of adults). The toxicity and residual activity of some of these insecticides allow them to be considered within integrated pest management programs that include T. triozae. PMID:26453717

  18. Reduced mutant yield at high doses in the Salmonella/activation assay: the cause is not always toxicity.

    PubMed

    McGregor, D; Prentice, R D; McConville, M; Lee, Y J; Caspary, W J

    1984-01-01

    In the Salmonella/activation assay developed by Ames et al [1973, 1975] toxicity is not measured, though it is recognized by the loss of a cloudy appearance on the plate. One approach to the measurement of toxicity is described here and uses a microscope-linked automated colony counter to estimate the number of microcolonies formed by histidine auxotrophs that stop growing after the depletion of histidine. This technique was used to evaluate the effect of toxicity on the revertant count for 16 mutagens, most of which were chosen because, from previous experience, their dose-response curves manifested a maximum at an intermediate dose tested. One of the sixteen, 2-nitrofluorene, was not toxic up to the maximum dose tested. The relationship between mutation and toxicity for the remaining fifteen allowed them to be grouped into two categories: (1) compounds that induced decreases in survival at the same dose at which the number of mutants decreased, and (2) compounds that induced toxicity, but survival was reduced at dose levels higher than those required to reduce the number of mutants. Possible explanations for this reduction of mutant counts occurring with little apparent concomitant increase in toxicity are examined. These results may be significant for attempts to estimate mutagenic potency and, to a lesser extent, construct mathematical models of the Ames test. PMID:6381041

  19. Pharmacological assessment of the medicinal potential of Acacia mearnsii De Wild.: antimicrobial and toxicity activities.

    PubMed

    Olajuyigbe, Olufunmiso O; Afolayan, Anthony J

    2012-01-01

    Acacia mearnsii De Wild. (Fabaceae) is a medicinal plant used in the treatment of microbial infections in South Africa without scientific validation of its bioactivity and toxicity. The antimicrobial activity of the crude acetone extract was evaluated by both agar diffusion and macrobroth dilution methods while its cytotoxicity effect was assessed with brine shrimp lethality assay. The study showed that both bacterial and fungal isolates were highly inhibited by the crude extract. The MIC values for the gram-positive bacteria (78.1-312.5) μg/mL, gram-negative bacteria (39.1-625) μg/mL and fungal isolates (625-5000) μg/mL differ significantly. The bacteria were more susceptible than the fungal strains tested. The antibiosis determination showed that the extract was more (75%) bactericidal than bacteriostatic (25%) and more fungicidal (66.67%) than fungistatic (33.33%). The cytotoxic activity of the extract was observed between 31.25 μg/mL and 500 μg/mL and the LC(50) value (112.36 μg/mL) indicates that the extract was nontoxic in the brine shrimp lethality assay (LC(50) > 100 μg/mL). These results support the use of A. mearnsii in traditional medicine for treatment of microbial infections. The extract exhibiting significant broad spectrum antimicrobial activity and nontoxic effects has potential to yield active antimicrobial compounds. PMID:22605976

  20. Pharmacological Assessment of the Medicinal Potential of Acacia mearnsii De Wild.: Antimicrobial and Toxicity Activities

    PubMed Central

    Olajuyigbe, Olufunmiso O.; Afolayan, Anthony J.

    2012-01-01

    Acacia mearnsii De Wild. (Fabaceae) is a medicinal plant used in the treatment of microbial infections in South Africa without scientific validation of its bioactivity and toxicity. The antimicrobial activity of the crude acetone extract was evaluated by both agar diffusion and macrobroth dilution methods while its cytotoxicity effect was assessed with brine shrimp lethality assay. The study showed that both bacterial and fungal isolates were highly inhibited by the crude extract. The MIC values for the gram-positive bacteria (78.1–312.5) μg/mL, gram-negative bacteria (39.1–625) μg/mL and fungal isolates (625–5000) μg/mL differ significantly. The bacteria were more susceptible than the fungal strains tested. The antibiosis determination showed that the extract was more (75%) bactericidal than bacteriostatic (25%) and more fungicidal (66.67%) than fungistatic (33.33%). The cytotoxic activity of the extract was observed between 31.25 μg/mL and 500 μg/mL and the LC50 value (112.36 μg/mL) indicates that the extract was nontoxic in the brine shrimp lethality assay (LC50 > 100 μg/mL). These results support the use of A. mearnsii in traditional medicine for treatment of microbial infections. The extract exhibiting significant broad spectrum antimicrobial activity and nontoxic effects has potential to yield active antimicrobial compounds. PMID:22605976

  1. Impact of lead sub-chronic toxicity on recognition memory and motor activity of Wistar rat.

    PubMed

    Azzaoui, F Z; Ahami, A O T; Khadmaoui, A

    2009-01-15

    The aim of this research was to investigate the impact of lead nitrate administered in drinking water during 90 days (sub-chronic toxicity), on body weight gain, motor activity, brain lead accumulation and especially on recognition memory of Wistar rats. Two groups of young female Wistar rats were used. Treated rats received 20 mg L(-1) of lead nitrate diluted in drinking water, while control rats received drinking water only, for 3 months. An evolution of body weight, motor activity, object recognition memory and measure of brain lead levels has been evaluated. The body weight was taken weekly, whereas the memory abilities and the motor activity are measured once every fortnight alternatively, by submitting rats to the Open Field (OF) test and to the Novel Object Recognizing (NOR) memory test. The results have shown a non significant effect in gain of body weight. However, a high significance was shown for horizontal activity (p<0.01), long memory term (p<0.01), at the end of testing period and for brain lead levels (p<0.05) between studied groups.

  2. Mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia.

    PubMed

    Ali, Shimaa E; Thoen, Even; Evensen, Øystein; Wiik-Nielsen, Jannicke; Gamil, Amr A A; Skaar, Ida

    2014-01-01

    There has been a significant increase in the incidence of Saprolegnia infections over the past decades, especially after the banning of malachite green. Very often these infections are associated with high economic losses in salmonid farms and hatcheries. The use of boric acid to control the disease has been investigated recently both under in vitro and in vivo conditions, however its possible mode of action against fish pathogenic Saprolegnia is not known. In this study, we have explored the transformation in Saprolegnia spores/hyphae after exposure to boric acid (1 g/L) over a period 4-24 h post treatment. Using transmission electron microscopy (TEM), early changes in Saprolegnia spores were detected. Mitochondrial degeneration was the most obvious sign observed following 4 h treatment in about 20% of randomly selected spores. We also investigated the effect of the treatment on nuclear division, mitochondrial activity and function using confocal laser scanning microscopy (CLSM). Fluorescence microscopy was also used to test the effect of treatment on mitochondrial membrane potential and formation of reactive oxygen species. Additionally, the viability and proliferation of treated spores that correlated to mitochondrial enzymatic activity were tested using an MTS assay. All obtained data pointed towards changes in the mitochondrial structure, membrane potential and enzymatic activity following treatment. We have found that boric acid has no effect on the integrity of membranes of Saprolegnia spores at concentrations tested. It is therefore likely that mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia spp.

  3. Antifungal activity, toxicity and chemical composition of the essential oil of Coriandrum sativum L. fruits.

    PubMed

    Soares, Bruna V; Morais, Selene M; dos Santos Fontenelle, Raquel Oliveira; Queiroz, Vanessa A; Vila-Nova, Nadja S; Pereira, Christiana M C; Brito, Edy S; Neto, Manoel A S; Brito, Erika H S; Cavalcante, Carolina S P; Castelo-Branco, Débora S C M; Rocha, Marcos F G

    2012-01-01

    The aims of this study were to test the antifungal activity, toxicity and chemical composition of essential oil from C. sativum L. fruits. The essential oil, obtained by hydro-distillation, was analyzed by gas chromatography/mass spectroscopy. Linalool was the main constituent (58.22%). The oil was considered bioactive, showing an LC₅₀ value of 23 μg/mL in the Artemia salina lethality test. The antifungal activity was evaluated against Microsporum canis and Candida spp. by the agar-well diffusion method and the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were established by the broth microdilution method. The essential oil induced growth inhibition zones of 28 ± 5.42 and 9.25 ± 0.5 for M. canis and Candida spp. respectively. The MICs and MFCs for M. canis strains ranged from 78 to 620 and 150 to 1,250 μg/mL, and the MICs and MFCs for Candida spp strains ranged from 310 to 620 and 620 to 1,250 μg/mL, respectively. C. sativum essential oil is active in vitro against M. canis and Candida spp. demonstrating good antifungal activity.

  4. Evaluation of Antioxidant Activity and Acute Toxicity of Clausena excavata Leaves Extract

    PubMed Central

    Albaayit, Shaymaa Fadhel Abbas; Abdullah, Rasedee

    2014-01-01

    Clausena excavata (Lour.), locally known as “Kemantu hitam,” is a common plant in Malaysian folklore medicine. This study evaluated the antioxidant properties of the solvent extracts of C. excavata leaves and determined the acute toxicity of methanolic extract C. excavata (MECE) leaves in Sprague-Dawley rats. Harvested leaves were dried and subjected to solvent extraction using petroleum ether, chloroform, ethyl acetate and methanol in succession. The antioxidant activity of each extract was determined using the ferric-reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryl dihydrazyl (DPPH) radical scavenging activity. The total phenolic content (TPC) and total flavonoids content (TFC) were estimated by Folin-Ciocalteu and ethanolic aluminium chloride method, respectively. The chloroform extract was found to be highest in flavonoid content, while the methanolic extract showed the highest TPC and antioxidant activity. There was no mortality in rats treated with MECE leaves even at a high dose of 5000 mg/kg body weight. However, the MECE leaves produced mild to moderate pathological changes in the liver and kidneys, shown by mild degenerative changes and leucocyte infiltration. The extract did not affect the haematological parameters or relative weights of the liver or kidneys. Overall, the MECE leaves have potent antioxidant activity and are presumed safe to be used orally as health-promoting product at low to moderate doses. PMID:25610488

  5. Instrumental neutron activation analysis of mass fractions of toxic metals in plastic.

    PubMed

    Park, Kwangwon; Kang, Namgoo

    2007-10-15

    It is very challenging to decompose a plastic product for the purpose of analysis of hazardous elements contained. To circumvent such technical problem, it is imperative that an analyst employ a nondestructive analytical method free of any pretreatments. The analytical results of the concentrations of toxic metals such as Cd and Cr in polypropylene for seven samples at two different levels were obtained using the instrumental neutron activation analysis. This work was intended ultimately to establish certified reference materials (CRMs) of these metals in the polypropylene, traceable to the SI. The uncertainties associated with the analytical procedures were estimated in accordance with the ISO guideline. The results were subsequently validated by a comparison with those for CRM-680 and -681 of the Bureau Communautaire de Reference (BCR), which demonstrated acceptable agreement within their uncertainty ranges.

  6. Lability of potentially toxic elements in soils affected by smelting activities.

    PubMed

    Popescu, I; Biasioli, M; Ajmone-Marsan, F; Stănescu, R

    2013-01-01

    Determination of total concentration of potentially toxic elements (PTEs) in soil is not a reliable tool for evaluating potential exposure risk for humans. PTE lability (EDTA, SBET and solution extraction) and chemical speciation (BCR sequential extraction) were investigated for Pb, Cd, Cu, and Zn, as well as how these could be affected by flooding in soils polluted by smelting activities. The flooding experiment was performed in pots from which soil solution was extracted at different time intervals using Rhizon Moisture Samplers. After experiments, the soil was again subjected to the previous extractions (EDTA, SBET, and BCR) in order to reveal the changes which occurred during anoxia. From the results we can conclude that PTE lability is very high and flooding caused the increase in their mobility up to 100% (for bioaccessible Pb). The experiment demonstrated that temporary reducing conditions can increase the risk of contaminants passing to other environmental compartments and the food chain.

  7. Lability of potentially toxic elements in soils affected by smelting activities.

    PubMed

    Popescu, I; Biasioli, M; Ajmone-Marsan, F; Stănescu, R

    2013-01-01

    Determination of total concentration of potentially toxic elements (PTEs) in soil is not a reliable tool for evaluating potential exposure risk for humans. PTE lability (EDTA, SBET and solution extraction) and chemical speciation (BCR sequential extraction) were investigated for Pb, Cd, Cu, and Zn, as well as how these could be affected by flooding in soils polluted by smelting activities. The flooding experiment was performed in pots from which soil solution was extracted at different time intervals using Rhizon Moisture Samplers. After experiments, the soil was again subjected to the previous extractions (EDTA, SBET, and BCR) in order to reveal the changes which occurred during anoxia. From the results we can conclude that PTE lability is very high and flooding caused the increase in their mobility up to 100% (for bioaccessible Pb). The experiment demonstrated that temporary reducing conditions can increase the risk of contaminants passing to other environmental compartments and the food chain. PMID:23127724

  8. Quantitative structure-activity relationship modelling of oral acute toxicity and cytotoxic activity of fragrance materials in rodents.

    PubMed

    Papa, E; Luini, M; Gramatica, P

    2009-10-01

    Fragrance materials are used as ingredients in many consumer and personal care products. The wide and daily use of these substances, as well as their mainly uncontrolled discharge through domestic sewage, make fragrance materials both potential indoor and outdoor air pollutants which are also connected to possible toxic effects on humans (asthma, allergies, headaches). Unfortunately, little is known about the environmental fate and toxicity of these substances. However, the use of alternative, predictive approaches, such as quantitative structure-activity relationships (QSARs), can help in filling the data gap and in the characterization of the environmental and toxicological profile of these substances. In the proposed study, ordinary least squares regression-based QSAR models were developed for three toxicological endpoints: mouse oral LD(50), inhibition of NADH-oxidase (EC(50) NADH-Ox) and the effect on mitochondrial membrane potential (EC(50) DeltaPsim). Theoretical molecular descriptors were calculated by using DRAGON software, and the best QSAR models were developed according to the principles defined by the Organization for Economic Co-operation and Development.

  9. Activity-guided chemo toxic profiling of Cassia occidentalis (CO) seeds: detection of toxic compounds in body fluids of CO-exposed patients and experimental rats.

    PubMed

    Panigrahi, Gati Krushna; Ch, Ratnasekhar; Mudiam, Mohana K R; Vashishtha, Vipin M; Raisuddin, S; Das, Mukul

    2015-06-15

    Our prior studies have shown an association between the deaths of children and consumption of Cassia occidentalis (CO) seeds. However, the chemicals responsible for the CO poisoning are not known. Therefore, the present study was designed to identify the key moieties in CO seeds and their cytotoxicity in rat primary hepatocytes and HepG2 cells. Activity-guided sequential extraction and fractionation of the seeds followed by GC-MS analysis identified the toxic compounds in the CO seeds. These identified compounds were subsequently detected and quantified in blood and urine samples from CO-exposed rats and CO poisoning human study cases. GC-MS analysis of different fractions of methanol extracts of CO seeds revealed the presence of five anthraquinones (AQs), viz. physcion, emodin, rhein, aloe-emodin, and chrysophanol. Interestingly, these AQs were detected in serum and urine samples from the study cases and CO-exposed rats. Cytotoxicity analysis of the above AQs in rat primary hepatocytes and HepG2 cells revealed that rhein is the most toxic moiety, followed by emodin, aloe-emodin, physcion, and chrysophanol. These studies indicate that AQ aglycones are responsible for producing toxicity, which may be associated with symptoms of hepatomyoencephalopathy in CO poisoning cases.

  10. Efficacy of activated diatomaceous clay in reducing the toxicity of zearalenone in rats and piglets.

    PubMed

    Denli, M; Blandon, J C; Guynot, M E; Salado, S; Pérez, J F

    2015-02-01

    Two experiments were conducted to evaluate the efficacy of an activated diatomaceous clay (ADC) in reducing the toxic effects of zearalenone (ZEA) in the diet of rats and piglets. In the rat experiment, 90 Sprague-Dawley female weanling rats with an initial BW of 45 ± 1.0 g were assigned to 1 of 6 dietary treatments for 28 d in a completely randomized design (CRD) with a 2 × 3 factorial arrangement (0 or 6 mg ZEA/kg feed and 0, 1, and 5 g ADC/kg feed). In the piglet experiment, 64 female piglets ([Large White × Landrace] × Pietrain with an initial BW of 14.9 ± 1.65 kg) were fed 1 of 8 experimental diets for 26 d in a CRD design with a 2 × 4 factorial arrangement (0 or 0.8 mg ZEA/kg feed and 0, 1, 2, and 5 g ADC/kg feed). The ADFI, ADG, and G:F were determined at the end of each experiment. At the conclusion of studies, serum samples were collected and rats and piglets were euthanized to determine visceral organ weights. The diet contaminated with ZEA did not alter the growth of rats and the relative weight of liver and kidneys. However, ZEA increased ( < 0.05) the relative weight of uterus, ovaries, and spleen and decreased ( < 0.05) the serum activities of alkaline phosphatase and alanine aminotransferase compared to the control group. Supplementation of ADC in the rat diets counteracted ( < 0.05) the observed toxic effects of ZEA on the uterus and ovaries weight. The diet contaminated with ZEA (0.8 mg/kg feed) increased ( < 0.05) the weight of the uterus and ovaries in piglets but did not modify the serum biochemical variables or the relative weight of other visceral organs. The addition of 5 g ADC/kg to the contaminated feed reduced the toxic effects of ZEA on uterus and ovary weights to that of the control group. Zearalenone (10.5 μg/kg bile) and α-zearalenol (5.6 μg/kg bile) residues were detected in the bile of piglets fed the ZEA treatment. Supplementation of ADC to diets contaminated with ZEA reduced ( = 0.001) ZEA content in bile compared to the

  11. Antimicrobial activity and cellular toxicity of nanoparticle-polymyxin B conjugates

    NASA Astrophysics Data System (ADS)

    Park, Soonhyang; Chibli, Hicham; Wong, Jody; Nadeau, Jay L.

    2011-05-01

    We investigate the antimicrobial activity and cytotoxicity to mammalian cells of conjugates of the peptide antibiotic polymyxin B (PMB) to Au nanoparticles and CdTe quantum dots. Au nanoparticles fully covered with PMB are identical in antimicrobial activity to the free drug alone, whereas partially-conjugated Au particles show decreased effectiveness in proportion to the concentration of Au. CdTe-PMB conjugates are more toxic to Escherichia coli than PMB alone, resulting in a flattening of the steep PMB dose-response curve. The effect is most pronounced at low concentrations of PMB, with a greater effect on the concentration required to reduce growth by half (IC50) than on the concentration needed to inhibit all growth (minimum inhibitory concentration, MIC). The Gram positive organism Staphylococcus aureus is resistant to both PMB and CdTe, showing minimal increased sensitivity when the two are conjugated. Measurement of reactive oxygen species (ROS) generation shows a significant reduction in photo-generated hydroxyl and superoxide radicals with CdTe-PMB as compared with bare CdTe. There is a corresponding reduction in toxicity of QD-PMB versus bare CdTe to mammalian cells, with nearly 100% survival in fibroblasts exposed to bactericidal concentrations of QD-PMB. The situation in bacteria is more complex: photoexcitation of the CdTe particles plays a small role in IC50 but has a significant effect on the MIC, suggesting that at least two different mechanisms are responsible for the antimicrobial action seen. These results show that it is possible to create antimicrobial agents using concentrations of CdTe quantum dots that do not harm mammalian cells.

  12. A relational learning approach to Structure-Activity Relationships in drug design toxicity studies.

    PubMed

    Camacho, Rui; Pereira, Max; Costa, Vítor Santos; Fonseca, Nuno A; Adriano, Carlos; Simões, Carlos J V; Brito, Rui M M

    2011-09-16

    It has been recognized that the development of new therapeutic drugs is a complex and expensive process. A large number of factors affect the activity in vivo of putative candidate molecules and the propensity for causing adverse and toxic effects is recognized as one of the major hurdles behind the current "target-rich, lead-poor" scenario. Structure-Activity Relationship (SAR) studies, using relational Machine Learning (ML) algorithms, have already been shown to be very useful in the complex process of rational drug design. Despite the ML successes, human expertise is still of the utmost importance in the drug development process. An iterative process and tight integration between the models developed by ML algorithms and the know-how of medicinal chemistry experts would be a very useful symbiotic approach. In this paper we describe a software tool that achieves that goal--iLogCHEM. The tool allows the use of Relational Learners in the task of identifying molecules or molecular fragments with potential to produce toxic effects, and thus help in stream-lining drug design in silico. It also allows the expert to guide the search for useful molecules without the need to know the details of the algorithms used. The models produced by the algorithms may be visualized using a graphical interface, that is of common use amongst researchers in structural biology and medicinal chemistry. The graphical interface enables the expert to provide feedback to the learning system. The developed tool has also facilities to handle the similarity bias typical of large chemical databases. For that purpose the user can filter out similar compounds when assembling a data set. Additionally, we propose ways of providing background knowledge for Relational Learners using the results of Graph Mining algorithms.

  13. Chemical composition, toxicity and larvicidal and antifungal activities of Persea americana (avocado) seed extracts.

    PubMed

    Leite, João Jaime Giffoni; Brito, Erika Helena Salles; Cordeiro, Rossana Aguiar; Brilhante, Raimunda Sâmia Nogueira; Sidrim, José Júlio Costa; Bertini, Luciana Medeiros; Morais, Selene Maia de; Rocha, Marcos Fábio Gadelha

    2009-01-01

    The present study had the aim of testing the hexane and methanol extracts of avocado seeds, in order to determine their toxicity towards Artemia salina, evaluate their larvicidal activity towards Aedes aegypti and investigate their in vitro antifungal potential against strains of Candida spp, Cryptococcus neoformans and Malassezia pachydermatis through the microdilution technique. In toxicity tests on Artemia salina, the hexane and methanol extracts from avocado seeds showed LC50 values of 2.37 and 24.13 mg mL-1 respectively. Against Aedes aegypti larvae, the LC50 results obtained were 16.7 mg mL-1 for hexane extract and 8.87 mg mL-1 for methanol extract from avocado seeds. The extracts tested were also active against all the yeast strains tested in vitro, with differing results such that the minimum inhibitory concentration of the hexane extract ranged from 0.625 to 1.25mg L-(1), from 0.312 to 0.625 mg mL-1 and from 0.031 to 0.625 mg mL-1, for the strains of Candida spp, Cryptococcus neoformans and Malassezia pachydermatis, respectively. The minimal inhibitory concentration for the methanol extract ranged from 0.125 to 0.625 mg mL-1, from 0.08 to 0.156 mg mL-1 and from 0.312 to 0.625 mg mL-1, for the strains of Candida spp., Cryptococcus neoformans and Malassezia pachydermatis, respectively.

  14. Chemical toxicity to environmental bacteria: Quantitative structure activity relationships and interspecies correlations and comparisons (Volumes I and II)

    SciTech Connect

    Blum, D.J.W.

    1989-01-01

    Toxicity data were collected for four groups of bacteria and a fish. These data were collected for four groups of bacteria and a fish. These data were used to compare and correlate the toxicities to different organisms, and to develop Quantitative Structure Activity Relationships (QSARs) correlating chemical structure with toxicity. Chemical toxicity to aerobic heterotrophic bacteria, Nitrosomonas, and methanogens were measured using serum bottle techniques in order to determine the concentration of chemical which caused 50% inhibition in microorganism's activity. Toxicity to Photobacteria phosphoreum (Microtox bacteria) and fathead minnows was also tested or data collected from the literature. Toxicants included chlorinated and other substituted benzenes and phenols, chlorinated alkanes, and a variety of additional compounds covering a range of chemical structures. Data were obtained for 50 to 130 chemicals per species. The sensitivity of the organism fell into two groups with Microtox bacteria, Nitrosomonas, and fathead minnows showing significantly greater sensitivity than aerobic heterotrophs and methanogens. Highly successful interspecies correlations were found between Microtox and each of the other species.

  15. Effect of light intensity on the degree of ammonia toxicity on PSII activity of Arthrospira platensis and Chlorella vulgaris.

    PubMed

    Markou, Giorgos; Muylaert, Koenraad

    2016-09-01

    Herein the effect of increasing light intensity on the degree of ammonia toxicity and its impact on the photosynthetic performance of Arthrospira and Chlorella was investigated using Chl fluorescence as a technique to characterize their photosystem II (PSII) activity. The results revealed that the increase of light intensity amplifies the ammonia toxicity on PSII. Chl fluorescence transients shown that at a given free ammonia (FA) concentration (100mg-N/L), the photochemistry potential decreased by increasing light intensity. The inhibition of the PSII was not reversible either by re-incubating the cells under dark or under decreased FA concentration. Moreover, the decrease of photochemical and non-photochemical quenching (NPQ) of fluorescence suggest that ammonia toxicity decreases the open available PSII centers, as well the inability of PSII to transfer the generated electrons beyond QA. The collapse of NPQ suggests that ammonia toxicity inhibits the photoprotection mechanism(s) and hence renders PSII more sensitive to photoinhibition. PMID:27262720

  16. Methylmercury-induced toxicity is mediated by enhanced intracellular calcium through activation of phosphatidylcholine-specific phospholipase C

    SciTech Connect

    Kang, Mi Sun; Jeong, Ju Yeon; Seo, Ji Heui; Jeon, Hyung Jun; Jung, Kwang Mook; Chin, Mi-Reyoung; Moon, Chang-Kiu; Bonventre, Joseph V.; Jung, Sung Yun; Kim, Dae Kyong . E-mail: proteinlab@hanmail.net

    2006-10-15

    Methylmercury (MeHg) is a ubiquitous environmental toxicant to which humans can be exposed by ingestion of contaminated food. MeHg has been suggested to exert its toxicity through its high reactivity to thiols, generation of arachidonic acid and reactive oxygen species (ROS), and elevation of free intracellular Ca{sup 2+} levels ([Ca{sup 2+}]{sub i}). However, the precise mechanism has not been fully defined. Here we show that phosphatidylcholine-specific phospholipase C (PC-PLC) is a critical pathway for MeHg-induced toxicity in MDCK cells. D609, an inhibitor of PC-PLC, significantly reversed the toxicity in a time- and dose-dependent manner with concomitant inhibition of the diacylglycerol (DAG) generation and the phosphatidylcholine (PC)-breakdown. MeHg activated the group IV cytosolic phospholipase A{sub 2} (cPLA{sub 2}) and acidic form of sphingomyelinase (A-SMase) downstream of PC-PLC, but these enzymes as well as protein kinase C (PKC) were not linked to the toxicity by MeHg. Furthermore, MeHg produced ROS, which did not affect the toxicity. Addition of EGTA to culture media resulted in partial decrease of [Ca{sup 2+}]{sub i} and partially blocked the toxicity. In contrast, when the cells were treated with MeHg in the presence of Ca{sup 2+} in the culture media, D609 completely prevented cell death with parallel decrease in [Ca{sup 2+}]{sub i}. Our results demonstrated that MeHg-induced toxicity was linked to elevation of [Ca{sup 2+}]{sub i} through activation of PC-PLC, but not attributable to the signaling pathways such as cPLA{sub 2}, A-SMase, and PKC, or to the generation of ROS.

  17. Mechanistic quantitative structure-activity relationship model for the photoinduced toxicity of polycyclic aromatic hydrocarbons. 2: An empirical model for the toxicity of 16 polycyclic aromatic hydrocarbons to the duckweed Lemna gibba L. G-3

    SciTech Connect

    Huang, X.D.; Krylov, S.N.; Ren, L.; McConkey, B.J.; Dixon, D.G.; Greenberg, B.M.

    1997-11-01

    Photoinduced toxicity of polycyclic aromatic hydrocarbons (PAHs) occurs via photosensitization reactions (e.g., generation of singlet-state oxygen) and by photomodification (photooxidation and/or photolysis) of the chemicals to more toxic species. The quantitative structure-activity relationship (QSAR) described in the companion paper predicted, in theory, that photosensitization and photomodification additively contribute to toxicity. To substantiate this QSAR modeling exercise it was necessary to show that toxicity can be described by empirically derived parameters. The toxicity of 16 PAHs to the duckweed Lemna gibba was measured as inhibition of leaf production in simulated solar radiation (a light source with a spectrum similar to that of sunlight). A predictive model for toxicity was generated based on the theoretical model developed in the companion paper. The photophysical descriptors required of each PAH for modeling were efficiency of photon absorbance, relative uptake, quantum yield for triplet-state formation, and the rate of photomodification. The photomodification rates of the PAHs showed a moderate correlation to toxicity, whereas a derived photosensitization factor (PSF; based on absorbance, triplet-state quantum yield, and uptake) for each PAH showed only a weak, complex correlation to toxicity. However, summing the rate of photomodification and the PSF resulted in a strong correlation to toxicity that had predictive value. When the PSF and a derived photomodification factor (PMF; based on the photomodification rate and toxicity of the photomodified PAHs) were summed, an excellent explanatory model of toxicity was produced, substantiating the additive contributions of the two factors.

  18. Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules.

    PubMed

    Nobre, Lígia S; Jeremias, Hélia; Romão, Carlos C; Saraiva, Lígia M

    2016-01-28

    Transition metal carbonyl complexes used as CO-releasing molecules (CORMs) for biological and therapeutic applications may exhibit interesting antimicrobial activity. However, understanding the chemical traits and mechanisms of action that rule this activity is required to establish a rationale for the development of CORMs into useful antibiotics. In this work the bactericidal activity, the toxicity to eukaryotic cells, and the ability of CORMs to deliver CO to bacterial and eukaryotic cells were analysed for a set of seven CORMs that differ in the transition metal, ancillary ligands and the CO release profile. Most of these CORMs exhibited bactericidal properties that decrease in the following order: CORM-2 > CORM-3 > ALF062 > ALF850 > ALF186 > ALF153 > [Fe(SBPy3)(CO)](BF4)2. A similar yet not entirely coincident decreasing order was found for their induction of intracellular reactive oxygen species (ROS) in E. coli. In contrast, studies in model animal cells showed that for any given CORM, the level of intracellular ROS generated was negligible when compared with that measured inside bacteria. Importantly, these CORMs were in general not toxic to eukaryotic cells, namely murine macrophages, kidney LLC-PK1 epithelial cells, and liver cell line HepG2. CORM-2 and CORM-3 delivered CO to the intracellular space of both E. coli and the two types of tested eukaryotic cells, yet toxicity was only elicited in the case of E. coli. CO delivered by ALF186 into the intercellular space did not enter E. coli cells and the compound was not toxic to either bacteria or to eukaryotic cells. The Fe(ii) carbonyl complex [Fe(SBPy3)(CO)](2+) had the reverse, undesirable toxicity profile, being unexpectedly toxic to eukaryotic cells and non-toxic to E. coli. ALF153, the most stable complex in the whole set, was essentially devoid of toxicity or ROS induction ability in all cells. These results suggest that CORMs have a relevant therapeutic potential as antimicrobial drugs since (i) they

  19. A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

    PubMed Central

    Rabanal, Francesc; Grau-Campistany, Ariadna; Vila-Farrés, Xavier; Gonzalez-Linares, Javier; Borràs, Miquel; Vila, Jordi; Manresa, Angeles; Cajal, Yolanda

    2015-01-01

    Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain. PMID:26024044

  20. Hepatoprotective activity of Tephrosia purpurea against arsenic induced toxicity in rats

    PubMed Central

    Gora, Ravuri Halley; Baxla, Sushma Lalita; Kerketta, Priscilla; Patnaik, Subhasree; Roy, Birendra Kumar

    2014-01-01

    Aim: The present study was conducted to evaluate the hepatoprotective activity of Tephrosia purpurea (TP) against sodium arsenite (NaAsO2) induced sub-acute toxicity in rats. Materials and Methods: Twenty four wistar albino rats of either sex were randomly divided into three groups. Group II and III were orally administered with sodium arsenite (10 mg/kg) daily in drinking water for 28 days. Additionally Group III was orally treated with hydro-alcoholic extract of Tephrosia purpurea (TP) @ 500 mg/kg daily for the same time period, whereas only deionized water was given to Group I (control). Serum biomarker levels, oxidative stress parameters and arsenic concentration were assessed in liver. Histopathology was also conducted. Results: It has been seen that TPE (500 mg/kg) significantly (P < 0.01) reduced serum ALT, AST, ALP activity and increased total protein and reduced necrosis and inflammation in liver of group III compared to group II. A significantly (P < 0.01) higher LPO and lower GSH levels without change in SOD activity in liver was also observed in group II compared to group III, though there was no significant difference in arsenic accumulation between them. The plant extract also protects the animals of group III from significant (P < 0.01) reduction in body weight. Conclusion: Our study shows that supplementation of Tephrosia purpurea extract (500 mg/kg) could ameliorate the hepatotoxic action of arsenic. PMID:24741193

  1. Toxicity of ionic liquids: eco(cyto)activity as complicated, but unavoidable parameter for task-specific optimization.

    PubMed

    Egorova, Ksenia S; Ananikov, Valentine P

    2014-02-01

    Rapid progress in the field of ionic liquids in recent decades led to the development of many outstanding energy-conversion processes, catalytic systems, synthetic procedures, and important practical applications. Task-specific optimization emerged as a sharpening stone for the fine-tuning of structure of ionic liquids, which resulted in unprecedented efficiency at the molecular level. Ionic-liquid systems showed promising opportunities in the development of green and sustainable technologies; however, the chemical nature of ionic liquids is not intrinsically green. Many ionic liquids were found to be toxic or even highly toxic towards cells and living organisms. In this Review, we show that biological activity and cytotoxicity of ionic liquids dramatically depend on the nature of a biological system. An ionic liquid may be not toxic for particular cells or organisms, but may demonstrate high toxicity towards another target present in the environment. Thus, a careful selection of biological activity data is a must for the correct assessment of chemical technologies involving ionic liquids. In addition to the direct biological activity (immediate response), several indirect effects and aftereffects are of primary importance. The following principal factors were revealed to modulate toxicity of ionic liquids: i) length of an alkyl chain in the cation; ii) degree of functionalization in the side chain of the cation; iii) anion nature; iv) cation nature; and v) mutual influence of anion and cation.

  2. The pathogenic activation of calpain: a marker and mediator of cellular toxicity and disease states

    PubMed Central

    Vanderklish, Peter W; Bahr, Ben A

    2000-01-01

    Over-activation of calpain, a ubiquitous calcium-sensitive protease, has been linked to a variety of degenerative conditions in the brain and several other tissues. Dozens of substrates for calpain have been identified and several of these have been used to measure activation of the protease in the context of experimentally induced and naturally occurring pathologies. Calpain-mediated cleavage of the cytoskeletal protein spectrin, in particular, results in a set of large breakdown products (BDPs) that are unique in that they are unusually stable. Over the last 15 years, measurements of BDPs in experimental models of stroke-type excitotoxicity, hypoxia/ischemia, vasospasm, epilepsy, toxin exposure, brain injury, kidney malfunction, and genetic defects, have established that calpain activation is an early and causal event in the degeneration that ensues from acute, definable insults. The BDPs also have been found to increase with normal ageing and in patients with Alzheimer's disease, and the calpain activity may be involved in related apoptotic processes in conjunction with the caspase family of proteases. Thus, it has become increasingly clear that regardless of the mode of disturbance in calcium homeostasis or the cell type involved, calpain is critical to the development of pathology and therefore a distinct and powerful therapeutic target. The recent development of antibodies that recognize the site at which spectrin is cleaved has greatly facilitated the temporal and spatial resolution of calpain activation in situ. Accordingly, sensitive spectrin breakdown assays now are utilized to identify potential toxic side-effects of compounds and to develop calpain inhibitors for a wide range of indications including stroke, cerebral vasospasm, and kidney failure. PMID:11168679

  3. Palladium Nanoparticle Incorporated Porous Activated Carbon: Electrochemical Detection of Toxic Metal Ions.

    PubMed

    Veerakumar, Pitchaimani; Veeramani, Vediyappan; Chen, Shen-Ming; Madhu, Rajesh; Liu, Shang-Bin

    2016-01-20

    A facile method has been developed for fabricating selective and sensitive electrochemical sensors for the detection of toxic metal ions, which invokes incorporation of palladium nanoparticles (Pd NPs) on porous activated carbons (PACs). The PACs, which were derived from waste biomass feedstock (fruit peels), possess desirable textural properties and porosities favorable for dispersion of Pd NPs (ca. 3-4 nm) on the graphitic PAC substrate. The Pd/PAC composite materials so fabricated were characterized by a variety of different techniques, such as X-ray diffraction, field-emission transmission electron microscopy, gas physisorption/chemisorption, thermogravimetric analysis, and Raman, Fourier-transform infrared, and X-ray photon spectroscopies. The Pd/PAC-modified glassy carbon electrodes (GCEs) were exploited as electrochemical sensors for the detection of toxic heavy metal ions, viz., Cd(2+), Pb(2+), Cu(2+), and Hg(2+), which showed superior performances for both individual as well as simultaneous detections. For simultaneous detection of Cd(2+), Pb(2+), Cu(2+), and Hg(2+), a linear response in the ion concentration range of 0.5-5.5, 0.5-8.9, 0.5-5.0, and 0.24-7.5 μM, with sensitivity of 66.7, 53.8, 41.1, and 50.3 μA μM(-1) cm(-2), and detection limit of 41, 50, 66, and 54 nM, respectively, was observed. Moreover, the Pd/PAC-modified GCEs also show perspective applications in detection of metal ions in real samples, as illustrated in this study for a milk sample.

  4. Evaluation of Antimalarial Activity and Toxicity of a New Primaquine Prodrug

    PubMed Central

    Davanço, Marcelo Gomes; Aguiar, Anna Caroline Campos; dos Santos, Leandro Alves; Padilha, Elias Carvalho; Campos, Michel Leandro; de Andrade, Cleverton Roberto; da Fonseca, Luiz Marcos; dos Santos, Jean Leandro; Chin, Chung Man; Krettli, Antoniana Ursine; Peccinini, Rosangela Gonçalves

    2014-01-01

    Plasmodium vivax is the most prevalent of the five species causing malaria in humans. The current available treatment for P. vivax malaria is limited and unsatisfactory due to at least two drawbacks: the undesirable side effects of primaquine (PQ) and drug resistance to chloroquine. Phenylalanine-alanine-PQ (Phe-Ala-PQ) is a PQ prodrug with a more favorable pharmacokinetic profile compared to PQ. The toxicity of this prodrug was evaluated in in vitro assays using a human hepatoma cell line (HepG2), a monkey kidney cell line (BGM), and human red blood cells deficient in the enzyme glucose-6-phosphate-dehydrogenase (G6PD). In addition, in vivo toxicity assays were performed with rats that received multiple doses of Phe-Ala-PQ to evaluate biochemical, hematological, and histopathological parameters. The activity was assessed by the inhibition of the sporogonic cycle using a chicken malaria parasite. Phe-Ala-PQ blocked malaria transmission in Aedes mosquitoes. When compared with PQ, it was less cytotoxic to BGM and HepG2 cells and caused less hemolysis of G6PD-deficient red blood cells at similar concentrations. The prodrug caused less alteration in the biochemical parameters than did PQ. Histopathological analysis of the liver and kidney did show differences between the control and Phe-Ala-PQ-treated groups, but they were not statistically significant. Taken together, the results highlight the prodrug as a novel lead compound candidate for the treatment of P. vivax malaria and as a blocker of malaria transmission. PMID:25133630

  5. Toxicity mitigation and solidification of municipal solid waste incinerator fly ash using alkaline activated coal ash.

    PubMed

    Diaz-Loya, E Ivan; Allouche, Erez N; Eklund, Sven; Joshi, Anupam R; Kupwade-Patil, Kunal

    2012-08-01

    Municipal solid waste (MSW) incineration is a common and effective practice to reduce the volume of solid waste in urban areas. However, the byproduct of this process is a fly ash (IFA), which contains large quantities of toxic contaminants. The purpose of this research study was to analyze the chemical, physical and mechanical behaviors resulting from the gradual introduction of IFA to an alkaline activated coal fly ash (CFA) matrix, as a mean of stabilizing the incinerator ash for use in industrial construction applications, where human exposure potential is limited. IFA and CFA were analyzed via X-ray fluorescence (XRF), X-ray diffraction (XRD) and Inductive coupled plasma (ICP) to obtain a full chemical analysis of the samples, its crystallographic characteristics and a detailed count of the eight heavy metals contemplated in US Title 40 of the Code of Federal Regulations (40 CFR). The particle size distribution of IFA and CFA was also recorded. EPA's Toxicity Characteristic Leaching Procedure (TCLP) was followed to monitor the leachability of the contaminants before and after the activation. Also images obtained via Scanning Electron Microscopy (SEM), before and after the activation, are presented. Concrete made from IFA, CFA and IFA-CFA mixes was subjected to a full mechanical characterization; tests include compressive strength, flexural strength, elastic modulus, Poisson's ratio and setting time. The leachable heavy metal contents (except for Se) were below the maximum allowable limits and in many cases even below the reporting limit. The leachable Chromium was reduced from 0.153 down to 0.0045 mg/L, Arsenic from 0.256 down to 0.132 mg/L, Selenium from 1.05 down to 0.29 mg/L, Silver from 0.011 down to .001 mg/L, Barium from 2.06 down to 0.314 mg/L and Mercury from 0.007 down to 0.001 mg/L. Although the leachable Cd exhibited an increase from 0.49 up to 0.805 mg/L and Pd from 0.002 up to 0.029 mg/L, these were well below the maximum limits of 1.00 and 5

  6. Antioxidant enzymes activities of Burkholderia spp. strains-oxidative responses to Ni toxicity.

    PubMed

    Dourado, M N; Franco, M R; Peters, L P; Martins, P F; Souza, L A; Piotto, F A; Azevedo, R A

    2015-12-01

    Increased agriculture production associated with intense application of herbicides, pesticides, and fungicides leads to soil contamination worldwide. Nickel (Ni), due to its high mobility in soils and groundwater, constitutes one of the greatest problems in terms of environmental pollution. Metals, including Ni, in high concentrations are toxic to cells by imposing a condition of oxidative stress due to the induction of reactive oxygen species (ROS), which damage lipids, proteins, and DNA. This study aimed to characterize the Ni antioxidant response of two tolerant Burkholderia strains (one isolated from noncontaminated soil, SNMS32, and the other from contaminated soil, SCMS54), by measuring superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione S-transferase (GST) activities. Ni accumulation and bacterial growth in the presence of the metal were also analyzed. The results showed that both strains exhibited different trends of Ni accumulation and distinct antioxidant enzymes responses. The strain from contaminated soil (SCMS54) exhibited a higher Ni biosorption and exhibited an increase in SOD and GST activities after 5 and 12 h of Ni exposure. The analysis of SOD, CAT, and GR by nondenaturing PAGE revealed the appearance of an extra isoenzyme in strain SCMS54 for each enzyme. The results suggest that the strain SCMS54 isolated from contaminated soil present more plasticity with potential to be used in soil and water bioremediation.

  7. Antioxidant enzymes activities of Burkholderia spp. strains-oxidative responses to Ni toxicity.

    PubMed

    Dourado, M N; Franco, M R; Peters, L P; Martins, P F; Souza, L A; Piotto, F A; Azevedo, R A

    2015-12-01

    Increased agriculture production associated with intense application of herbicides, pesticides, and fungicides leads to soil contamination worldwide. Nickel (Ni), due to its high mobility in soils and groundwater, constitutes one of the greatest problems in terms of environmental pollution. Metals, including Ni, in high concentrations are toxic to cells by imposing a condition of oxidative stress due to the induction of reactive oxygen species (ROS), which damage lipids, proteins, and DNA. This study aimed to characterize the Ni antioxidant response of two tolerant Burkholderia strains (one isolated from noncontaminated soil, SNMS32, and the other from contaminated soil, SCMS54), by measuring superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione S-transferase (GST) activities. Ni accumulation and bacterial growth in the presence of the metal were also analyzed. The results showed that both strains exhibited different trends of Ni accumulation and distinct antioxidant enzymes responses. The strain from contaminated soil (SCMS54) exhibited a higher Ni biosorption and exhibited an increase in SOD and GST activities after 5 and 12 h of Ni exposure. The analysis of SOD, CAT, and GR by nondenaturing PAGE revealed the appearance of an extra isoenzyme in strain SCMS54 for each enzyme. The results suggest that the strain SCMS54 isolated from contaminated soil present more plasticity with potential to be used in soil and water bioremediation. PMID:26289332

  8. Evaluation of Antidiabetic Activity and Associated Toxicity of Artemisia afra Aqueous Extract in Wistar Rats

    PubMed Central

    Sunmonu, Taofik O.; Afolayan, Anthony J.

    2013-01-01

    Artemisia afra Jacq. ex Willd. is a widely used medicinal plant in South Africa for the treatment of diabetes. This study aimed to evaluate the hypoglycemic activity and possible toxicity effect of aqueous leaf extract of the herb administered at different dosages for 15 days in streptozotocin-induced diabetic rats. Administration of the extract at 50, 100, and 200 mg/kg body weight significantly (P < 0.05) increased body weight, decreased blood glucose levels, increased glucose tolerance, and improved imbalance in lipid metabolism in diabetic rats. These are indications of antidiabetic property of A. afra with 200 mg/kg body weight of the extract showing the best hypoglycemic action by comparing favourably well with glibenclamide, a standard hypoglycemic drug. The extract at all dosages tested also restored liver function indices and haematological parameters to normal control levels in the diabetic rats, whereas the kidney function indices were only normalized in the diabetic animals administered with 50 mg/kg body weight of the extract. This investigation clearly showed that in addition to its hypoglycemic activity, A. afra may also protect the liver and blood against impairment due to diabetes. However, some kidney functions may be compromised at high dosages of the extract. PMID:23861717

  9. Analgesic activity and acute toxicity study of Semecarpus anacardium stem bark extracts using mice

    PubMed Central

    Lingaraju, G. M.; Hoskeri, H. Joy; Krishna, V.; Babu, P. Suresh

    2011-01-01

    Background: The analgesic activity of petroleum ether, chloroform and methanol extracts of Semecarpus anacardium was investigated by tail flicking and writhing method using acetyl salicylic acid as the standard reference. Materials and Methods: The staircase method was adopted for the determination of the acute toxicity. LD50 of the petroleum ether extract and the chloroform extract was 700 mg/kg; however, the LD50 for the methanol extract was 500 mg/kg. After 1 h of oral administration of the extracts, 0.6% acetic acid was administered intraperitoneally and the analgesic activity was evaluated. Results: The number of writhing observed in the control group was 73.33 writhes. The methanol extract showed a significant analgesic activity, with 28.33 writhes, than the petroleum ether extract and the chloroform extract. But, all the extracts showed proved to be less potent than the standard drug which showed 2.33 writhes. Animals pretreated with saline did not show a signify cant effect on the latent period of tail-flick response. The analgesic effect of the petroleum ether extract was comparatively less evident. The maximum possible analgesia (MPA) increased up to 9.1% which remained elevated above the basal levels throughout the observation period. The MPA calculated for the chloroform extract increased to 14.03%. However, the analgesic effect of the methanol extract was also observed at 0.5 h following oral administration and the effect remained significant throughout the 3 h observation period, and was increased to 20.43%. Conclusion: Consistent analgesic activity of all the three S. anacardium extracts was observed by both the methods. The methanol extract was more potent than the petroleum ether and chloroform extracts but was less effective than the standard drug. This investigation supported the ethnomedicinal claims of S. anacardium. PMID:21731397

  10. Toxicity of essential oil of Satureja khuzistanica: in vitro cytotoxicity and anti-microbial activity.

    PubMed

    Yousefzadi, Morteza; Riahi-Madvar, Ali; Hadian, Javad; Rezaee, Fatemeh; Rafiee, Roya; Biniaz, Mehdi

    2014-01-01

    In nature, essential oils play an important role in the protection of the plants by exerting anti-bacterial, -viral, -fungal, -oxidative, -genotoxic, and free radical scavenging properties, as well as in some cases acting as insecticides. Several Satureja species are used in traditional medicine due to recognized therapeutic properties, namely anti-microbial and cytotoxic activities. The purpose of the present work was to determine the biologic activity of the essential oil of S. khuzistanica Jamzad (Lamiaceae) against four human cancer cell lines, as well as its inhibitory effects against a wide array (i.e. n = 11) of pathogenic bacteria and fungi. The essential oil was isolated by hydro-distillation and analyzed by GC-FID and GC-MS. Carvacrol (92.87%) and limonene (1.2%) were found to be the main components of the isolated oil. Anti-microbial activity of the essential oil was assessed using a disc diffusion method; an MTT cytotoxicity assay was employed to test effects of the oil on each cancer cell line. The oil exhibited considerable anti-microbial activity against the majority of the tested bacteria and fungi. The test oil also significantly reduced cell viability of Vero, SW480, MCF7, and JET 3 cells in a dose-dependent manner, with the IC50 values calculated for each cell type being, respectively, 31.2, 62.5, 125, and 125 μg/ml. Based on the findings, it is concluded that the essential oil of S. khuzistanica and its major constituents have a potential for further use in anti-bacterial and anti-cancer applications, pending far more extensive testing of toxicities in normal (i.e. primary) cells. PMID:23662744

  11. A fluorescence-based hydrolytic enzyme activity assay for quantifying toxic effects of Roundup® to Daphnia magna.

    PubMed

    Ørsted, Michael; Roslev, Peter

    2015-08-01

    Daphnia magna is a widely used model organism for aquatic toxicity testing. In the present study, the authors investigated the hydrolytic enzyme activity of D. magna after exposure to toxicant stress. In vivo enzyme activity was quantified using 15 fluorogenic enzyme probes based on 4-methylumbelliferyl or 7-amino-4-methylcoumarin. Probing D. magna enzyme activity was evaluated using short-term exposure (24-48 h) to the reference chemical K2 Cr2 O7 or the herbicide formulation Roundup®. Toxicant-induced changes in hydrolytic enzyme activity were compared with changes in mobility (International Organization for Standardization standard 6341). The results showed that hydrolytic enzyme activity was quantifiable as a combination of whole body fluorescence of D. magna and the fluorescence of the surrounding water. Exposure of D. magna to lethal and sublethal concentrations of Roundup resulted in loss of whole body enzyme activity and release of cell constituents, including enzymes and DNA. Roundup caused comparable inhibition of mobility and alkaline phosphatase activity with median effective concentration values at 20 °C of 8.7 mg active ingredient (a.i.)/L to 11.7 mg a.i./L. Inhibition of alkaline phosphatase activity by Roundup was lowest at 14 °C and greater at 20 °C and 26 °C. The results suggest that the fluorescence-based hydrolytic enzyme activity assay (FLEA assay) can be used as an index of D. magna stress. Combining enzyme activity with fluorescence measurements may be applied as a simple and quantitative supplement for toxicity testing with D. magna.

  12. Acetylcholinesterase inhibition, antioxidant activity and toxicity of Peumus boldus water extracts on HeLa and Caco-2 cell lines.

    PubMed

    Falé, P L; Amaral, F; Amorim Madeira, P J; Sousa Silva, M; Florêncio, M H; Frazão, F N; Serralheiro, M L M

    2012-08-01

    This work aimed to study the inhibition on acetylcholinesterase activity (AChE), the antioxidant activity and the toxicity towards Caco-2 and HeLa cells of aqueous extracts of Peumus Boldus. An IC(50) value of 0.93 mg/mL, for AChE inhibition, and EC(50) of 18.7 μg/mL, for the antioxidant activity, was determined. This activity can be attributed to glycosylated flavonoid derivatives detected, which were the main compounds, although boldine and other aporphine derivatives were also present. No changes in the chemical composition or the biochemical activities were found after gastrointestinal digestion. Toxicity of P. boldus decoction gave an IC(50) value 0.66 mg/mL for HeLa cells, which caused significant changes in the cell proteome profile. PMID:22617353

  13. Evaluation of the antinociceptive activity and acute oral toxicity of standardized ethanolic extract of the rhizome of Curcuma xanthorrhiza Roxb.

    PubMed

    Devaraj, Sutha; Esfahani, Azadeh Sabetghadam; Ismail, Sabariah; Ramanathan, Surash; Yam, Mun Fei

    2010-04-22

    Ethanolic extract of Curcuma xanthorrhiza was used to evaluate the analgesic and toxicity effects in vivo. The extract was standardized using GC-MS, which showed that 1 mg of Curcuma xanthorrhiza ethanolic extract contains 0.1238 mg of xanthorrhizol. The analgesic activity was studied in rats using three different models, namely the hot plate test, tail flick test and formalin-induced pain test. The acute oral toxicity was examined by the oral administration of standardized Curcuma xanthorrhiza ethanolic extract in mice at doses ranging from 300-5,000 mg/kg and observation for 14 days. Standardized Curcuma xanthorrhiza ethanolic extract did not show significant analgesic effect in the hot plate and tail flick tests. However, in the formalin-induced pain test, Curcuma xanthorrhiza ethanolic extract significantly (P < 0.05) suppressed the paw licking time of rats in both early and late phases at doses 200 and 400 mg/kg of the extract, respectively. In the acute oral toxicity study, Curcuma xanthorrhiza ethanolic extract did not show any toxic effects in mice at 5 g/kg. These experimental results suggest that the standardized Curcuma xanthorrhiza ethanolic extract showed peripheral and central antinociceptive activity associated with neurogenic pain as well as a relative absence of toxic effects which could compromise the medicinal use of this plant in folk medicine.

  14. QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP (QSAR) MODELS TO PREDICT CHEMICAL TOXICITY FOR VARIOUS HEALTH ENDPOINTS

    EPA Science Inventory

    Although ranking schemes based on exposure and toxicity have been developed to aid in the prioritization of research funds for identifying chemicals of regulatory concern, there are significant gaps in the availability of experimental toxicity data for most health endpoints. Pred...

  15. In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

    PubMed Central

    Mopuri, Ramgopal; Meriga, Balaji

    2014-01-01

    Objective To ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata (T. paniculata) ethanolic extract in Sprague Dawley rats. Methods The solvent extracts (hexane, ethyl acetate and ethanol) of T. paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed. The oral acute toxicity was evaluated using ethanolic extract of T. paniculata. Results Ethyl acetate and ethanolic extracts showed more phytochemicals, whereas highest DPPH scavenging activity was found in ethanolic extract. In an acute toxicity study, T. paniculata ethanolic extract was orally administered (1 000 mg/kg body weight) to rats and observed for 72 h for any toxic symptoms and the dose was continued up to 14 d. On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters. We did not observe any behavioral changes in test groups in comparison with their controls. Also, there were no significant alterations in biochemical, hematological (hemoglobin content and blood cells count) and liver function parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total proteins, albumin and bilirubin levels between T. paniculata ethanolic extract treated and normal control groups. Conclusions Together our results demonstrated that T. paniculata ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy. PMID:25182554

  16. An Experimental Comparison of Two Different Technetium Source Activities Which Can Imitate Thyroid Scintigraphy in Case of Thyroid Toxic Nodule

    PubMed Central

    Miftari, Ramë; Fejza, Ferki; Bicaj, Xhavit; Nura, Adem; Topciu, Valdete; Bajrami, Ismet

    2014-01-01

    Purpose: In cases of thyroid toxic autonomous nodule, anterior projection of Tc-99m pertechnetate image shows a hot nodule that occupies most, or the entire thyroid lobe with near-total or total suppression of the contra lateral lobe. In this case is very difficult to distinguish toxic nodule from lobe agenesis. Our interest was to estimate and determinate the rate of radioactivity when the source with high activity can make total suppression of the second source with low activity in same conditions with thyroid scintigraphy procedures. Material and methodology: Thyroid scintigraphy was performed with Technetium 99 meta stable pertechnetate. A parallel high resolution low energy collimator was used as an energy setting of 140 KeV photo peak for T-99m. Images are acquired at 200 Kilo Counts in the anterior projection with the collimator positioned as close as the patient’s extended neck (approximately in distance of 18 cm). The scintigraphy of thyroid gland was performed 15 minutes after intravenous administration of 1.5 mCi Tc-99m pertechnetate. Technetium 99 meta stable radioactive sources with different activity were used for two scintigraphies studies, performed in same thyroid scintigraphy acquisition procedures. In the first study, were compared the standard source with high activity A=11.2 mCi with sources with variable activities B=1.33 mCi; 1.03 mCi; 0.7 mCi; 0.36 mCi; and 0.16mCi) in distance of 1.5cm from each other sources, which is approximately same with distance between two thyroid lobes. In the second study were compared the sources with low activity in proportion 70:1(source A = 1.5 mCi and source B=0.021mCi). As clinical studies we preferred two different patents with different thyroid disorders. There were one patient with thyroid toxic nodule in the right lobe, therefore the second patient was with left thyroid nodule agenesis. Results: During our examination, we accurately determined that two radioactive sources in proportion 70:1 will be

  17. In vitro antibacterial activity and acute toxicity studies of aqueous-methanol extract of Sida rhombifolia Linn. (Malvaceae)

    PubMed Central

    2010-01-01

    Background Many bacteria among the Enterobacteria family are involved in infectious diseases and diarrhoea. Most of these bacteria become resistant to the most commonly used synthetic drugs in Cameroon. Natural substances seem to be an alternative to this problem. Thus the aim of this research was to investigate the in vitro antibacterial activity of the methanol and aqueous-methanol extracts of Sida rhombifolia Linn (Malvaceae) against seven pathogenic bacteria involved in diarrhoea. Acute toxicity of the most active extract was determined and major bioactive components were screened. Methods The agar disc diffusion and the agar dilution method were used for the determination of inhibition diameters and the Minimum Inhibitory Concentration (MICs) respectively. The acute toxicity study was performed according WHO protocol. Results The aqueous-methanol extract (1v:4v) was the most active with diameters of inhibition zones ranging from 8.7 - 23.6 mm, however at 200 μg/dic this activity was relatively weak compared to gentamycin. The MICs of the aqueous-methanol extract (1v:4v) varied from 49.40 to 78.30 μg/ml. Salmonella dysenteriae was the most sensitive (49.40 μg/ml). For the acute toxicity study, no deaths of rats were recorded. However, significant increase of some biochemical parameters such as aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and creatinine (CRT) were found. The phytochemical analysis of the aqueous methanol extract indicated the presence of tannins, polyphenols, alkaloids, glycosides, flavonoids and saponins Conclusion The results showed that the aqueous-methanol extract of S. rhombifolia exhibited moderate antibacterial activity. Some toxic effects were found when rats received more than 8 g/kg bw of extract. Antibacterial; Enterobacteria; Acute toxicity; Phytochemical analysis PMID:20663208

  18. [Effect of Arnica montana tincture on some hydrolytic enzyme activities of rat liver in experimental toxic hepatitis].

    PubMed

    Iaremiĭ, I M; Meshchyshen, I F; Hrihor'ieva, N P; Kostiuk, L S

    1998-01-01

    Effects of tinctura arnica on arginase, adenosine triphosphatase, glucose-6-phosphatase and 5'-nucleotidase activities of rats liver in case of experimental toxic hepatitis have been studied. Toxic hepatitis was caused by 2 times interstomach administration of 0.25 ml oil solution of carbon tetrachloride per 100 g of animal weight. 20 mkl/100 g of tinctura arnica was administered every day per os for 14 days. The enzyme activities have been investigated at 3, 7 and 17 days. A significant demention of a studied hydrolytic enzyme activities in rats liver at intoxication of the body by CCI4 has been shown. It has been established that tinctura arnica administered per os to intoxicated animals sped up the normalization of hydrolytic enzyme activities in rat liver.

  19. The activated sludge metabolic characteristics changing sole carbon source from readily biodegradable acetate to toxic phenol.

    PubMed

    Wu, Changyong; Zhou, Yuexi; Song, Jiamei

    2016-01-01

    A sequencing batch reactor was used to investigate the effect of carbon sources on the metabolism of activated sludge. Acetate and phenol, with the chemical oxygen demand (COD) of 330-350 mg L(-1), was used as the carbon source in Periods I and II, respectively. Acetate decreased in the initial 120 min with the intracellular storage materials (XSTO), extracellular polymeric substances (EPS), and the soluble microbial products (SMP) accumulating to 131.0 mg L(-1), 347.5 mg L(-1), and 35.5 mg L(-1), respectively. Then, XSTO and EPS decreased to 124.5 mg L(-1) and 340.0 mg L(-1), respectively, in the following 120 min. When acetate was replaced by phenol, it could not be used at the beginning due to its toxicity. The XSTO decreased from 142 mg L(-1) to 54.6 mg L(-1) during the aeration period. The EPS had a significant increase, with the highest value of 618.1 mg L(-1), which then decreased to 245.6 mg L(-1) at 240 min. The phenol was gradually degraded with the acclimation and it can be fully degraded 18 d later. Meanwhile, the usage ratio of the internal carbon source decreased. The effluent SMP in Period II was 1.7 times that in Period I. PMID:27191552

  20. Toxicity assessment of inorganic nanoparticles to acetoclastic and hydrogenotrophic methanogenic activity in anaerobic granular sludge.

    PubMed

    Gonzalez-Estrella, Jorge; Sierra-Alvarez, Reyes; Field, James A

    2013-09-15

    Release of engineered nanoparticles (NPs) to municipal wastewater from industrial and residential sources could impact biological systems in wastewater treatment plants. Methanogenic inhibition can cause failure of anaerobic waste(water) treatment. This study investigated the inhibitory effect of a wide array of inorganic NPs (Ag(0), Al₂O₃, CeO₂, Cu(0), CuO, Fe(0), Fe₂O₃, Mn₂O₃, SiO₂, TiO₂, and ZnO supplied up to 1500 mgL(-1)) to acetoclastic and hydrogenotrophic methanogenic activity of anaerobic granular sludge. Of all the NPs tested, only Cu(0) and ZnO caused severe methanogenic inhibition. The 50% inhibiting concentrations determined towards acetoclastic and hydrogenotrophic methanogens were 62 and 68 mgL(-1) for Cu(0) NP; and 87 and 250 mgL(-1) for ZnO NP, respectively. CuO NPs also caused inhibition of acetoclastic methanogens. Cu(2+) and Zn(2+) salts caused similar levels of inhibition as Cu(0) and ZnO NPs based on equilibrium soluble metal concentrations measured during the assays, suggesting that the toxicity was due to the release of metal ions by NP-corrosion. A commercial dispersant, Dispex, intended to increase NP stability did not affect the inhibitory impact of the NPs. The results taken as a whole suggest that Zn- and Cu-containing NPs can release metal ions that are inhibitory for methanogenesis.

  1. Sulforaphane protects Microcystin-LR-induced toxicity through activation of the Nrf2-mediated defensive response

    SciTech Connect

    Gan Nanqin; Mi Lixin; Sun Xiaoyun; Dai Guofei; Chung Funglung; Song Lirong

    2010-09-01

    Microcystins (MCs), a cyclic heptapeptide hepatotoxins, are mainly produced by the bloom-forming cyanobacerium Microcystis, which has become an environmental hazard worldwide. Long term consumption of MC-contaminated water may induce liver damage, liver cancer, and even human death. Therefore, in addition to removal of MCs in drinking water, novel strategies that prevent health damages are urgently needed. Sulforaphane (SFN), a natural-occurring isothiocyanate from cruciferous vegetables, has been reported to reduce and eliminate toxicities from xenobiotics and carcinogens. The purpose of the present study was to provide mechanistic insights into the SFN-induced antioxidative defense system against MC-LR-induced cytotoxicity. We performed cell viability assays, including MTS assay, colony formation assay and apoptotic cell sorting, to study MC-LR-induced cellular damage and the protective effects by SFN. The results showed that SFN protected MC-LR-induced damages at a nontoxic and physiological relevant dose in HepG2, BRL-3A and NIH 3 T3 cells. The protection was Nrf2-mediated as evident by transactivation of Nrf2 and activation of its downstream genes, including NQO1 and HO-1, and elevated intracellular GSH level. Results of our studies indicate that pretreatment of cells with 10 {mu}M SFN for 12 h significantly protected cells from MC-LR-induced damage. SFN-induced protective response was mediated through Nrf2 pathway.

  2. Insect-gene-activity detection system for chemical and biological warfare agents and toxic industrial chemicals

    NASA Astrophysics Data System (ADS)

    Mackie, Ryan S.; Schilling, Amanda S.; Lopez, Arturo M.; Rayms-Keller, Alfredo

    2002-02-01

    Detection of multiple chemical and biological weapons (CBW) agents and/or complex mixtures of toxic industrial chemicals (TIC) is imperative for both the commercial and military sectors. In a military scenario, a multi-CBW attack would create confusion, thereby delaying decontamination and therapeutic efforts. In the commercial sector, polluted sites invariably contain a mixture of TIC. Novel detection systems capable of detecting CBW and TIC are sorely needed. While it may be impossible to build a detector capable of discriminating all the possible combinations of CBW, a detection system capable of statistically predicting the most likely composition of a given mixture is within the reach of current emerging technologies. Aquatic insect-gene activity may prove to be a sensitive, discriminating, and elegant paradigm for the detection of CBW and TIC. We propose to systematically establish the expression patterns of selected protein markers in insects exposed to specific mixtures of chemical and biological warfare agents to generate a library of biosignatures of exposure. The predicting capabilities of an operational library of biosignatures of exposures will allow the detection of emerging novel or genetically engineered agents, as well as complex mixtures of chemical and biological weapons agents. CBW and TIC are discussed in the context of war, terrorism, and pollution.

  3. The activated sludge metabolic characteristics changing sole carbon source from readily biodegradable acetate to toxic phenol.

    PubMed

    Wu, Changyong; Zhou, Yuexi; Song, Jiamei

    2016-01-01

    A sequencing batch reactor was used to investigate the effect of carbon sources on the metabolism of activated sludge. Acetate and phenol, with the chemical oxygen demand (COD) of 330-350 mg L(-1), was used as the carbon source in Periods I and II, respectively. Acetate decreased in the initial 120 min with the intracellular storage materials (XSTO), extracellular polymeric substances (EPS), and the soluble microbial products (SMP) accumulating to 131.0 mg L(-1), 347.5 mg L(-1), and 35.5 mg L(-1), respectively. Then, XSTO and EPS decreased to 124.5 mg L(-1) and 340.0 mg L(-1), respectively, in the following 120 min. When acetate was replaced by phenol, it could not be used at the beginning due to its toxicity. The XSTO decreased from 142 mg L(-1) to 54.6 mg L(-1) during the aeration period. The EPS had a significant increase, with the highest value of 618.1 mg L(-1), which then decreased to 245.6 mg L(-1) at 240 min. The phenol was gradually degraded with the acclimation and it can be fully degraded 18 d later. Meanwhile, the usage ratio of the internal carbon source decreased. The effluent SMP in Period II was 1.7 times that in Period I.

  4. The toxic effects of diethyl phthalate on the activity of glutamine synthetase in greater duckweed (Spirodela polyrhiza L.).

    PubMed

    Cheng, Tai-Sheng

    2012-11-15

    The toxic effects of diethyl phthalate (DEP), a potent allelochemical, on the enzyme activity and polypeptide accumulation of glutamine synthetase (GS) in greater duckweed were investigated. In our previous studies, DEP induced oxidative responses at concentrations from 0.5 to 2 mM in greater duckweed and the antioxidant enzymes played important roles in the defense strategy against DEP stress. In this study, DAB-H(2)O(2) and NBT stain for superoxide radicals (O(2)(·-)), lipid peroxidation, HSP70, and ammonia accumulation in DEP-treated duckweed tissues revealed adverse effect of DEP in plant growth. Biochemical analysis and physiological methods were combined to investigate GS activity and polypeptide accumulation under DEP-induced stress. The results showed that GS activity was reduced with the increasing concentration of DEP, indicative of enhanced toxic effect. Immunoblot analysis with chloroplast soluble fractions indicated that the chloroplastic GS (GS2) polypeptide from greater duckweed was degraded under DEP stress conditions. The response of GS2 to the DEP stress may be modulated by means of redox change in plant tissues, chloroplasts, and chloroplast lysates. The results suggest that DEP is toxic to the greater duckweed by inhibition of the GS isoenzymes in nitrogen assimilation and the GS2 plays important roles in the adaptation strategy against DEP toxicity.

  5. Rate of biodegradiation of toxic organic compounds while in contact with organics which are actively composting. Final report

    SciTech Connect

    Not Available

    1982-03-01

    Results are presented of a study to biodegrade toxic organic wastes and to determine the degree of breakdown of compounds while in contact with high-rate composting. An artificial compost mixture consisting of shredded newspaper, manure, wastewater treatment plant sludge, sawdust, peat moss, soil, powdered milk, and fertilizer was prepared. Toxic organic chemicals were mixed with this actively composting mixture to obtain a concentration of about 500 mg/kg. Samples were analyzed after seven days of composting and again after 30 days. Thirty-two of the 59 chemicals tested were found to be moderately to highly susceptible to biodegradation. The potential for success is shown to be very high for using high-rate composting to degrade organic wastes. The possibility of accelerating the decomposition of toxic wastes in soils is suggested.

  6. Ecotoxicity quantitative structure-activity relationships for alcohol ethoxylate mixtures based on substance-specific toxicity predictions.

    PubMed

    Boeije, G M; Cano, M L; Marshall, S J; Belanger, S E; Van Compernolle, R; Dorn, P B; Gümbel, H; Toy, R; Wind, T

    2006-05-01

    Traditionally, ecotoxicity quantitative structure-activity relationships (QSARs) for alcohol ethoxylate (AE) surfactants have been developed by assigning the measured ecotoxicity for commercial products to the average structures (alkyl chain length and ethoxylate chain length) of these materials. Acute Daphnia magna toxicity tests for binary mixtures indicate that mixtures are more toxic than the individual AE substances corresponding with their average structures (due to the nonlinear relation of toxicity with structure). Consequently, the ecotoxicity value (expressed as effects concentration) attributed to the average structures that are used to develop the existing QSARs is expected to be too low. A new QSAR technique for complex substances, which interprets the mixture toxicity with regard to the "ethoxymers" distribution (i.e., the individual AE components) rather than the average structure, was developed. This new technique was then applied to develop new AE ecotoxicity QSARs for invertebrates, fish, and mesocosms. Despite the higher complexity, the fit and accuracy of the new QSARs are at least as good as those for the existing QSARs based on the same data set. As expected from typical ethoxymer distributions of commercial AEs, the new QSAR generally predicts less toxicity than the QSARs based on average structure. PMID:16256196

  7. Quantifying the toxic and mutagenic activity of complex mixtures with Salmonella typhimurium

    SciTech Connect

    Somani, S.M.; Schaeffer, D.J.; Mack, J.O.

    1981-03-01

    The toxicity and mutagenicity of 11 compounds individually and in mixtures were quantified in Salmonella typhimurium strains TA98, TA100, and TA1537 by a modification of the Ames spot test. The distance (millimeters) from the center of the petri dish to the bacterial growth front represented the toxic response. When mutagenicity occurred, the distance from the inner radius to the outer radius of the mutagenic growth represented the mutagenic response. Multiple regression analysis was used to quantify the toxicity and mutagenicity of individual compounds in the mixtures. The results indicate that the effects of compounds in mixtures are generally additive.

  8. Oxidative toxicity of perfluorinated chemicals in green mussel and bioaccumulation factor dependent quantitative structure-activity relationship.

    PubMed

    Liu, Changhui; Chang, Victor W C; Gin, Karina Y H

    2014-10-01

    Concerns regarding perfluorinated chemicals (PFCs) have risen in recent years because of their ubiquitous presence and high persistency. However, data on the environmental impacts of PFCs on marine organisms are very limited. Oxidative toxicity has been suggested to be one of the major toxic pathways for PFCs to induce adverse effects on organisms. To investigate PFC-induced oxidative stress and oxidative toxicity, a series of antioxidant enzyme activities and oxidative damage biomarkers were examined to assess the adverse effects of the following 4 commonly detected compounds: perfluoro-octanesulfonate, perfluoro-ocanoic acid, perfluorononanoic acid, and perfluorodecanoic acid, on green mussel (Perna viridis). Quantitative structure-activity relationship (QSAR) models were also established. The results showed that all the tested PFCs are able to induce antioxidant response and oxidative damage on green mussels in a dose-dependent manner. At low exposure levels (0 µg/L-100 µg/L), activation of antioxidant enzymes (catalase [CAT] and superoxide dismutase [SOD]) was observed, which is an adaptive response to the excessive reactive oxygen species induced by PFCs, while at high exposure levels (100 µg/L-10 000 µg/L), PFCs were found to inhibit some enzyme activity (glutathione S-transferase and SOD) where the organism's ability to respond in an adaptive manner was compromised. The oxidative stress under high PFC exposure concentration also led to lipid and DNA damage. PFC-induced oxidative toxicity was found to be correlated with the bioaccumulation potential of PFCs. Based on this relationship, QSAR models were established using the bioaccumulation factor (BAF) as the molecular descriptor for the first time. Compared with previous octanol-water partition coefficient-dependent QSAR models, the BAF-dependent QSAR model is more suitable for the impact assessment of PFCs and thus provides a more accurate description of the toxic behavior of these compounds.

  9. Aquatic toxicity of acrylates and methacrylates: quantitative structure-activity relationships based on Kow and LC50

    SciTech Connect

    Reinert, K.H.

    1987-12-01

    Recent EPA scrutiny of acrylate and methacrylate monomers has resulted in restrictive consent orders and Significant New Use Rules under the Toxic Substances Control Act, based on structure-activity relationships using mouse skin painting studies. The concern is centered on human health issues regarding worker and consumer exposure. Environmental issues, such as aquatic toxicity, are still of concern. Understanding the relationships and environmental risks to aquatic organisms may improve the understanding of the potential risks to human health. This study evaluates the quantitative structure-activity relationships from measured log Kow's and log LC50's for Pimephales promelas (fathead minnow) and Carassius auratus (goldfish). Scientific support of the current regulations is also addressed. Two monomer classes were designated: acrylates and methacrylates. Spearman rank correlation and linear regression were run. Based on this study, an ecotoxicological difference exists between acrylates and methacrylates. Regulatory activities and scientific study should reflect this difference.

  10. A comparative study on the relationship between acetylcholinesterase activity and acute toxicity in Daphnia magna exposed to anticholinesterase insecticides.

    PubMed

    Printes, Liane Biehl; Callaghan, Amanda

    2004-05-01

    Acetylcholinesterase (AChE) activity was measured in Daphnia magna that had been exposed to four organophosphates (OPs; parathion, chlorpyrifos, malathion, and acephate) and one carbamate (propoxur) for 48 h. These results were related to acute toxicity (median effective concentration [EC50] for immobility). For the four OPs, the EC50s were 7.03 pM, 3.17 pM, 10.56 pM, and 309.82 microM, respectively. The EC50 for propoxur was 449.90 pM. Reduction in AChE activity was directly related to an increase in immobility in all chemicals tested. However, the ratio between the EC50 and the AChE median inhibiting concentration ranged from 0.31 to 0.90. A 50% reduction in AChE activity generally was associated with detrimental effects on mobility. However, for acephate, high levels of AChE inhibition (70%) were observed in very low concentrations and were not associated with immobility. In addition, increasing the concentration of acephate further had a slight negative effect on AChE activity but a strong detrimental effect on mobility. Binding sites other than AChE possibly are involved in acephate toxicity to D. magna. Our findings demonstrate different associations between AChE inhibition and toxicity when different chemicals are compared. Therefore, the value of using AChE activity as a biomarker in D. magna will be dependent on the chemical tested.

  11. Essential Oil from Flowers and Leaves of Elaeagnus Angustifolia (Elaeagnaceae): Composition, Radical Scavenging and General Toxicity Activities

    PubMed Central

    Torbati, Mohammadali; Asnaashari, Solmaz; Heshmati Afshar, Fariba

    2016-01-01

    Purpose: The aim of this work was to identify the chemical composition of the essential oils obtained from the flowers and leaves of Elaeagnus angostifolia (Elaeagnaceae) along with evaluate the radical scavenging and general toxicity activities. Methods: A combination of GC-MS and GC-FID were utilized for analyzing the chemical profile of the essential oils extracted by hydro-distillation from the leaves and flowers of E. angustifolia. The essential oils were subjected to general toxicity and radical scavenging assays using brine shrimp lethality test and DPPH method, respectively. Results: In total, 53 and 25 components were identified and quantified in the essential oils of flowers and leaves, accounting for 96.59% and 98.97% of the oil, respectively. The both oils were observed to be rich in ester compounds. The most abundant components of the oil from flowers were E-ethyl cinnamate (60.00%), hexahydrofarnesyl acetone (9.99%), palmitic acid (5.20%) and phytol (3.29%). The major constituents of the oil from leaves were E-ethyl cinnamate (37.27%), phytol (12.08%), nonanal (10.74%) and Z-3-hexenyl benzoate (7.65%). Both oils showed moderate activity in DPPH assay; however, they exhibited potent tocixity in brine shrimp lethality test. Conclusion: The remarkable toxicity effects of the oils are worthy to further investigation to find the probable mechanisms of action accountable for the noticeable toxic effect of these essential oils. PMID:27478777

  12. Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity

    PubMed Central

    Johnson, W.D.; Morrissey, R.L.; Usborne, A.L.; Kapetanovic, I.; Crowell, J.A.; Muzzio, M.; McCormick, D.L.

    2011-01-01

    To characterize the subchronic oral toxicity of resveratrol, CD rats received daily gavage doses of 0, 200, 400, or 1000 mg resveratrol/kg/day, and beagle dogs received daily capsule doses of 0, 200, 600, or 1200 mg resveratrol/kg/day for 90 days. Resveratrol induced only minimal toxicity, consisting of dose-related reductions in body weight gain in female rats and both sexes of dogs, and a statistically significant increase in bilirubin levels in rats at the 1000 mg/kg/day dose. Clinical observations, hematology, ophthalmology, neurotoxicity evaluations (functional observational batteries), organ weights, and gross pathology provided no biologically significant evidence of resveratrol toxicity in either species. In rats, the high dose of resveratrol reduced the incidence of cardiomyopathy; no other microscopic changes were seen. Histopathologic changes in dogs were limited to minimal inflammatory infiltrates in the kidney and urinary bladder, which were not considered toxicologically significant. A cardiovascular safety pharmacology (telemetry) study in dogs revealed no evidence of resveratrol toxicity. Based on body weight effects, the No Observed Adverse Effect Level (NOAEL) for resveratrol was 200 mg/kg/day in rats and 600 mg/kg/day in dogs. The apparent cardioprotective activity of resveratrol in rats demonstrates that its potentially beneficial activities may extend beyond efficacy in cancer prevention. PMID:21939727

  13. Using quantitative structure-activity relationship modeling to quantitatively predict the developmental toxicity of halogenated azole compounds.

    PubMed

    Craig, Evisabel A; Wang, Nina Ching; Zhao, Q Jay

    2014-07-01

    Developmental toxicity is a relevant endpoint for the comprehensive assessment of human health risk from chemical exposure. However, animal developmental toxicity data remain unavailable for many environmental contaminants due to the complexity and cost of these types of analyses. Here we describe an approach that uses quantitative structure-activity relationship modeling as an alternative methodology to fill data gaps in the developmental toxicity profile of certain halogenated compounds. Chemical information was obtained and curated using the OECD Quantitative Structure-Activity Relationship Toolbox, version 3.0. Data from 35 curated compounds were analyzed via linear regression to build the predictive model, which has an R(2) of 0.79 and a Q(2) of 0.77. The applicability domain (AD) was defined by chemical category and structural similarity. Seven halogenated chemicals that fit the AD but are not part of the training set were employed for external validation purposes. Our model predicted lowest observed adverse effect level values with a maximal threefold deviation from the observed experimental values for all chemicals that fit the AD. The good predictability of our model suggests that this method may be applicable to the analysis of qualifying compounds whenever developmental toxicity information is lacking or incomplete for risk assessment considerations.

  14. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals

    PubMed Central

    Chandra, Phool; Sachan, Neetu; Kishore, Kamal; Ghosh, Ashoke Kumar

    2012-01-01

    Sooktyn (SKN), mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD50 may be greater than 2 000 mg/kg (orally) for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity. PMID:22837960

  15. Aberrant Activation of p38 MAP Kinase-Dependent Innate Immune Responses Is Toxic to Caenorhabditis elegans.

    PubMed

    Cheesman, Hilary K; Feinbaum, Rhonda L; Thekkiniath, Jose; Dowen, Robert H; Conery, Annie L; Pukkila-Worley, Read

    2016-03-01

    Inappropriate activation of innate immune responses in intestinal epithelial cells underlies the pathophysiology of inflammatory disorders of the intestine. Here we examine the physiological effects of immune hyperactivation in the intestine of the nematode Caenorhabditis elegans. We previously identified an immunostimulatory xenobiotic that protects C. elegans from bacterial infection by inducing immune effector expression via the conserved p38 MAP kinase pathway, but was toxic to nematodes developing in the absence of pathogen. To investigate a possible connection between the toxicity and immunostimulatory properties of this xenobiotic, we conducted a forward genetic screen for C. elegans mutants that are resistant to the deleterious effects of the compound, and identified five toxicity suppressors. These strains contained hypomorphic mutations in each of the known components of the p38 MAP kinase cassette (tir-1, nsy-1, sek-1, and pmk-1), demonstrating that hyperstimulation of the p38 MAPK pathway is toxic to animals. To explore mechanisms of immune pathway regulation in C. elegans, we conducted another genetic screen for dominant activators of the p38 MAPK pathway, and identified a single allele that had a gain-of-function (gf) mutation in nsy-1, the MAP kinase kinase kinase that acts upstream of p38 MAPK pmk-1. The nsy-1(gf) allele caused hyperinduction of p38 MAPK PMK-1-dependent immune effectors, had greater levels of phosphorylated p38 MAPK, and was more resistant to killing by the bacterial pathogen Pseudomonas aeruginosa compared to wild-type controls. In addition, the nsy-1(gf) mutation was toxic to developing animals. Together, these data suggest that the activity of the MAPKKK NSY-1 is tightly regulated as part of a physiological mechanism to control p38 MAPK-mediated innate immune hyperactivation, and ensure cellular homeostasis in C. elegans. PMID:26818074

  16. Cytokine gene expression and activation of NF-{kappa}B in aniline-induced splenic toxicity

    SciTech Connect

    Wang Jianling; Kannan, Subburaj; Li Hui; Firoze Khan, M. . E-mail: mfkhan@utmb.edu

    2005-02-15

    Exposure to aniline results in selective toxicity to the spleen, leading to a variety of sarcomas on chronic exposure in rats, and fibrosis appears to be an important initiating preneoplastic lesion of the spleen. However, the molecular mechanism(s) by which aniline leads to fibrogenic response is not well understood. Previously, we have shown that aniline exposure leads to iron overload and induction of oxidative stress in the spleen. We hypothesized that aniline-induced oxidative stress in the spleen causes transcriptional up-regulation of fibrogenic cytokines via activation of redox-sensitive transcription factor, nuclear factor-kappa B (NF-{kappa}B). To test this hypothesis, male SD rats were treated with 0.5 mmol/kg/day aniline hydrochloride via drinking water for 30 days. Cytokine mRNAs were measured by real-time quantitative PCR, while cytokine release was determined in the supernatants of the cultured splenocytes using specific ELISAs. IL-1{alpha}, IL-6, and TNF-{alpha} mRNA levels showed 6.9-, 2.9-, and 2.6-fold increases, respectively, in the spleens of aniline-treated rats in comparison to the controls. The increases in mRNA levels were associated with enhanced secretion of these cytokines in the splenocyte culture supernatants. NF-{kappa}B p65 level in the nuclear extracts of cultured splenocytes of aniline-treated rats showed a 2-fold increase in comparison to the controls as quantitated by NF-{kappa}B p65-specific ELISA. The binding activity of NF-{kappa}B, determined by electrophoretic mobility shift assay (EMSA), also showed an increase in NF-{kappa}B binding in the nuclear extracts of the splenocytes from aniline-treated rats. The specificity of NF-{kappa}B binding was further confirmed by supershift assays. The results indicate that aniline exposure causes enhanced expression of IL-1{alpha}, IL-6, and TNF-{alpha}, both at mRNA and protein levels, suggesting their role in splenic fibrosis. Also, the increased NF-{kappa}B binding activity suggests

  17. Toxicity of substituted anilines to Pseudokirchneriella subcapitata and quantitative structure-activity relationship analysis for polar narcotics.

    PubMed

    Chen, Chung-Yuan; Ko, Chia-Wen; Lee, Po-I

    2007-06-01

    This study evaluated the toxic effects of substituted anilines on Pseudokirchneriella subcapitata with the use of a closed algal toxicity testing technique with no headspace. Two response endpoints (i.e., dissolved oxygen production [DO] and algal growth rate) were used to evaluate the toxicity of anilines. Both DO and growth rate endpoints revealed similar sensitivity to the effects of anilines. However, trichloroanilines showed stronger inhibitory effects on microalgal photosynthetic reactions than that on algal growth. For various aquatic organisms, the relative sensitivity relationship for anilines is Daphnia magna > luminescent bacteria (Microtox) > or = Pocelia reticulata > or = Pseudokirchneriella subcapitata > or = fathead minnow > Tetrahymena pyriformis. The susceptibility of P. subcapitata to anilines is similar to fish, but P. subcapitata is apparently less sensitive than the water flea. The lack of correlation between the toxicity revealed by different aquatic organisms (microalgae, D. magna, luminescent bacteria, and P. reticulata) suggests that anilines might have different metabolic routes in these organisms. Both hydrogen bonding donor capacity (the lowest unoccupied molecular orbital energy, Elumo) and hydrophobicity (1-octanol:water partition coefficient, Kow) were found to provide satisfactory descriptions for the toxicity of polar narcotics (substituted anilines and chlorophenols). Quantitative structure-activity relationships (QSARs) based on Elumo, log Kow, or both values were established with r2 values varying from 0.75 to 0.92. The predictive power for the QSAR models were found to be satisfactory through leave-one-out cross-validation. Such relationships could provide useful information for the estimation of toxicity for other polar narcotic compounds.

  18. The enhancement of the subacute repeat dose toxicity test OECD TG 407 for the detection of endocrine active chemicals: comparison with toxicity tests of longer duration.

    PubMed

    Gelbke, Heinz-Peter; Hofmann, Andreas; Owens, J William; Freyberger, Alexius

    2007-04-01

    The OECD conventional 28-day repeat dose toxicity test (OECD TG 407) is widely employed in the initial hazard identification and characterization for commercial chemicals. The OECD has recently undertaken an international effort to "enhance" the conventional 28-day repeat dose toxicity test (OECD TG 407) in order to ensure that chemicals acting through (anti)estrogenic, (anti)androgenic, and (anti)thyroid mechanisms are identified. The enhancements include additional parameters based on the respective target organs from the male and female reproductive tracts, the thyroid, and circulating hormone levels. Ten chemicals with known endocrine modes of action and different potencies were administered using the "enhanced TG 407" test protocol to investigate the performance of this procedure. In the present evaluation, these "enhanced TG 407" protocol results, drawn from a report of the OECD validation studies, are compared to studies of the same or similar chemicals with longer and/or in utero exposures in order to evaluate the capability of the this "enhanced TG 407" in identifying the chemicals' mode of action. The major conclusions that can be drawn from these comparisons are: 1. The "enhanced TG 407" will reliably identify chemicals with a strong to moderate potential to act through endocrine modes of action on the gonads and the thyroid. In addition, this test method gives a first indication for the dose-related potency. 2. Substances with a low potency for an endocrine mode of action, i.e., having only marginal effects in the most comprehensive in vivo studies such as multi-generation studies, may not elicit clear endocrine-related effects in the "enhanced TG 407". In these cases, the primary or principal effects observed will be driven by other toxic actions of the test materials in the "enhanced TG 407". 3. It may be concluded from the present database that prolongation of exposure from 28 days up to 90 days is unlikely to improve the chance of detecting an

  19. Induction of lcc2 expression and activity by Agaricus bisporus provides defence against Trichoderma aggressivum toxic extracts

    PubMed Central

    Sjaarda, Calvin P; Abubaker, Kamal S; Castle, Alan J

    2015-01-01

    Laccases are used by fungi for several functions including defence responses to stresses associated with attack by other fungi. Laccase activity changes and the induction of two laccase genes, lcc1 and lcc2, in Agaricus bisporus were measured in response to toxic extracts of medium in which Trichoderma aggressivum, the cause of green mould disease, was grown. A strain of A. bisporus that shows resistance to the extracts showed higher basal levels and greater enzymatic activity after extract exposure than did a sensitive strain. Furthermore, pre-incubation of T. aggressivum extract with laccases reduced toxicity. Faster induction and greater numbers of lcc2 transcripts in response to the extract were noted in the resistant strain than in the sensitive strain. The timing and increase in lcc2 transcript abundance mirrored changes in total laccase activity. No correlation between resistance and lcc1 transcription was apparent. Transcript abundance in transformants with a siRNA construct homologous to both genes varied widely. A strong negative correlation between transcript abundance and sensitivity of the transformant to toxic extract was observed in plate assays. These results indicated that laccase activity and in particular that encoded by lcc2 contributes to toxin metabolism and by extension green mould disease resistance. PMID:25824278

  20. Induction of lcc2 expression and activity by Agaricus bisporus provides defence against Trichoderma aggressivum toxic extracts.

    PubMed

    Sjaarda, Calvin P; Abubaker, Kamal S; Castle, Alan J

    2015-11-01

    Laccases are used by fungi for several functions including defence responses to stresses associated with attack by other fungi. Laccase activity changes and the induction of two laccase genes, lcc1 and lcc2, in Agaricus bisporus were measured in response to toxic extracts of medium in which Trichoderma aggressivum, the cause of green mould disease, was grown. A strain of A. bisporus that shows resistance to the extracts showed higher basal levels and greater enzymatic activity after extract exposure than did a sensitive strain. Furthermore, pre-incubation of T. aggressivum extract with laccases reduced toxicity. Faster induction and greater numbers of lcc2 transcripts in response to the extract were noted in the resistant strain than in the sensitive strain. The timing and increase in lcc2 transcript abundance mirrored changes in total laccase activity. No correlation between resistance and lcc1 transcription was apparent. Transcript abundance in transformants with a siRNA construct homologous to both genes varied widely. A strong negative correlation between transcript abundance and sensitivity of the transformant to toxic extract was observed in plate assays. These results indicated that laccase activity and in particular that encoded by lcc2 contributes to toxin metabolism and by extension green mould disease resistance.

  1. Active foraging for toxic prey during gestation in a snake with maternal provisioning of sequestered chemical defences

    PubMed Central

    Kojima, Yosuke; Mori, Akira

    2015-01-01

    Many animals sequester dietary defensive compounds and incorporate them into the offspring, which protects the young against predation. One possible but poorly investigated question is whether females of such species actively prey upon toxic diets. The snake Rhabdophis tigrinus sequesters defensive steroids from toads consumed as prey; it also feeds on other amphibians. Females produce chemically armed offspring in direct proportion to their own level of toad-derived toxins by provisioning the toxins to their eggs. Our field observations of movements and stomach contents of radio-tracked R. tigrinus showed that gravid snakes preyed upon toads by actively foraging in the habitat of toads, even though toads were a scarce resource and toad-searching may incur potential costs. Our Y-maze experiments demonstrated that gravid females were more likely to trail the chemical cues of toads than were males or non-gravid females. These results showed behavioural switching in females and active foraging for scarce, toxic prey during gestation. Because exploitation of toads by gravid females results in their offspring being more richly endowed with prey-derived toxins, active foraging for toxic prey is expected to be an adaptive antipredator trait, which may enhance chemical defence in offspring. PMID:25392472

  2. Toxicity of ammonia nitrogen to ciliated protozoa Stentor coeruleus and Coleps hirtus isolated from activated sludge of wastewater treatment plants.

    PubMed

    Klimek, Beata; Fyda, Janusz; Pajdak-Stós, Agnieszka; Kocerba, Wioleta; Fiałkowska, Edyta; Sobczyk, Mateusz

    2012-11-01

    We assessed the toxicity of ammonia ions to Stentor coeruleus and Coleps hirtus (Protozoa) isolated from activated sludge taken from two municipal wastewater treatment plants in southern Poland. Stentor coeruleus is a rarely occurring species in activated sludge, unlike the widespread Coleps hirtus. The mean LC50 values (concentration causing 50 % mortality) calculated for the 24 h tests differed hugely between the tested species: 43.03 mg NH(4+) dm(-3) for Stentor coeruleus and 441.12 mg NH(4+) dm(-3) for Coleps hirtus. The ammonia ion concentration apparently is an important factor in the occurrence of these protozoan species in activated sludge. PMID:22976439

  3. Effect of H+ ion activity and Ca2+ on the toxicity of metals in the environment.

    PubMed Central

    Hutchinson, T C; Collins, F W

    1978-01-01

    The role of acidity in determining and restricting plant distribution and performance is discussed. In soils especially, a key effect of H+ ion concentration is on the solubility of potentially toxic heavy metals such as aluminum, managenese, zinc, iron, copper, and nickel. Al has been reported from many studies since the 1920's as the key determining toxic factor in acid soils. Some acid-tolerant species have been shown to be especially tolerant of Al, and mechanisms of tolerance have been suggested. Mn is also a commonly toxic factor at soil pH less than 5.0. Calcium has been shown to alleviate Mn toxicity. Low pH soils are also generally low in Ca, K, Na, and P; all essential major elements for plant growth. In lakes and marine situations acidic waters are uncommon as the waters are buffered. Calcium is again ameliorative of metal toxicities. The pH, redox, and valency state are critical in determining nutrient availability and metal speciation. Recent increases in the H+ ion content of precipitation have caused increased acidities of freshwater lakes in Scandinavia and eastern North America, which have depleted biota, including fish populations. PMID:31277

  4. Fumigant Toxicity and Repellence Activity of Camphor Essential Oil from Cinnamonum camphora Siebold Against Solenopsis invicta Workers (Hymenoptera:Formicidae)

    PubMed Central

    Fu, J. T.; Tang, L.; Li, W. S.; Wang, K.; Cheng, D. M.; Zhang, Z. X.

    2015-01-01

    The red imported fire ant (RIFA) Solenopsis invicta Buren causes severe damage to humans and animals as well as the environment. Chemical treatment is the main strategy of RIFA management, which also is potentially toxic to the environment. Plant essential oils (EOs) are considered as potential substance that can be used to control insects. This study aimed to identify the chemical composition of camphor EO and investigate the insecticidal activity on RIFAs. The chemical composition of the EO was analyzed by gas chromatography/mass spectrometry and gas chromatography with flame ionization detection. Results revealed that 36.61% camphor and 30.05% cineole were the major components. The insecticidal activity of camphor EO was assessed against RIFA workers by conducting two different bioassays: fumigant toxicity and repellence. Fumigant toxicity assay results showed that the lethal dose (LC50) of the EO at 24 h was 1.67 and 4.28 μg/ml for minor and major workers, respectively; knockdown time (KT50) was 10.82 and 14.73 h. At 2.55 μg/ml, the highest average mortality of the ants was 84.89% after 72 h. Camphor EO exhibited fumigant toxicity against minor and major workers as indicated by the effects on attacking, feeding, and climbing behaviors. This EO was also strongly repellent to the two size workers of the colony as observed in their behavior against Tenebrio molitor treated with 5 µl EO. The fumigant toxicity and repellence of camphor EO against RIFA indicated that this substance could be a potential alternative for the development of eco-friendly products used to control pests. PMID:26392574

  5. Fumigant Toxicity and Repellence Activity of Camphor Essential Oil from Cinnamonum camphora Siebold Against Solenopsis invicta Workers (Hymenoptera:Formicidae).

    PubMed

    Fu, J T; Tang, L; Li, W S; Wang, K; Cheng, D M; Zhang, Z X

    2015-01-01

    The red imported fire ant (RIFA) Solenopsis invicta Buren causes severe damage to humans and animals as well as the environment. Chemical treatment is the main strategy of RIFA management, which also is potentially toxic to the environment. Plant essential oils (EOs) are considered as potential substance that can be used to control insects. This study aimed to identify the chemical composition of camphor EO and investigate the insecticidal activity on RIFAs. The chemical composition of the EO was analyzed by gas chromatography/mass spectrometry and gas chromatography with flame ionization detection. Results revealed that 36.61% camphor and 30.05% cineole were the major components. The insecticidal activity of camphor EO was assessed against RIFA workers by conducting two different bioassays: fumigant toxicity and repellence. Fumigant toxicity assay results showed that the lethal dose (LC50) of the EO at 24 h was 1.67 and 4.28 μg/ml for minor and major workers, respectively; knockdown time (KT50) was 10.82 and 14.73 h. At 2.55 μg/ml, the highest average mortality of the ants was 84.89% after 72 h. Camphor EO exhibited fumigant toxicity against minor and major workers as indicated by the effects on attacking, feeding, and climbing behaviors. This EO was also strongly repellent to the two size workers of the colony as observed in their behavior against Tenebrio molitor treated with 5 µl EO. The fumigant toxicity and repellence of camphor EO against RIFA indicated that this substance could be a potential alternative for the development of eco-friendly products used to control pests. PMID:26392574

  6. Search for factors affecting antibacterial activity and toxicity of 1,2,4-triazole-ciprofloxacin hybrids.

    PubMed

    Plech, Tomasz; Kaproń, Barbara; Paneth, Agata; Kosikowska, Urszula; Malm, Anna; Strzelczyk, Aleksandra; Stączek, Paweł; Świątek, Łukasz; Rajtar, Barbara; Polz-Dacewicz, Małgorzata

    2015-06-01

    A series of 1,2,4-triazole-based compounds was designed as potential antibacterial agents using molecular hybridization approach. The target compounds (23-44) were synthesized by Mannich reaction of 1,2,4-triazole-3-thione derivatives with ciprofloxacin (CPX) and formaldehyde. Their potent antibacterial effect on Gram-positive bacteria was accompanied by similarly strong activity against Gram-negative strains. The toxicity of the CPX-triazole hybrids for bacterial cells was even up to 18930 times higher than the toxicity for human cells. The results of enzymatic studies showed that the antibacterial activity of the CPX-triazole hybrids is not dependent solely on the degree of their affinity to DNA gyrase and topoisomerase IV. PMID:25951434

  7. Effect of metals and other inorganic ions on soil microbial activity: soil dehydrogenase assay as a simple toxicity test

    SciTech Connect

    Rogers, J.E.; Li, S.W.

    1985-06-01

    The purpose of this report is to illustrate the utility of the soil dehydrogenase assay as an effective primary test for assessing the potential toxicity of chemicals to soil microbial activity. In this manuscript the authors describe their use of the soil dehydrogenase assay in determining the effects of a number of potential toxic inorganic ions on soil microbial activity. The ions include Cu/sup 2 +/, Mg/sup 2 +/, Ni/sup 2 +/, Zn/sup 2 +/, NH/sub 4//sup +/, Cd/sup 2 +/, Cr/sup 32/, F/sup -/, AsO/sub 4//sup 3 -/, BO/sub 3//sup 3 -/, and SO/sub 4//sup 2 -/.

  8. Removal potential of toxic 2378-substituted PCDD/F from incinerator flue gases by waste-derived activated carbons

    SciTech Connect

    Hajizadeh, Yaghoub; Onwudili, Jude A.; Williams, Paul T.

    2011-06-15

    The application of activated carbons has become a commonly used emission control protocol for the removal or adsorption of persistent organic pollutants from the flue gas streams of waste incinerators. In this study, the 2378-substituted PCDD/F removal efficiency of three types of activated carbons derived from the pyrolysis of refuse derived fuel, textile waste and scrap tyre was investigated and compared with that of a commercial carbon. Experiments were carried out in a laboratory scale fixed-bed reactor under a simulated flue gas at 275 deg. C with a reaction period of four days. The PCDD/F in the solid matrices and exhaust gas, were analyzed using gas chromatography coupled with a triple quadrupole mass spectrometer. In the absence of activated carbon adsorbent, there was a significant increase in the concentration of toxic PCDD/F produced in the reacted flyash, reaching up to 6.6 times higher than in the raw flyash. In addition, there was a substantial release of PCDD/F into the gas phase, which was found in the flue gas trapping system. By application of the different commercial, refuse derived fuel, textile and tyre activated carbons the total PCDD/F toxic equivalent removal efficiencies in the exhaust gas stream were 58%, 57%, 64% and 52%, respectively. In general, the removal of the PCDDs was much higher with an average of 85% compared to PCDFs at 41%. Analysis of the reacted activated carbons showed that there was some formation of PCDD/F, for instance, a total of 60.6 {mu}g I-TEQ kg{sup -1} toxic PCDD/F was formed in the refuse derived fuel activated carbon compared to 34 {mu}g I-TEQ kg{sup -1} in the commercial activated carbon. The activated carbons derived from the pyrolysis of waste, therefore, showed good potential as a control material for PCDD/F emissions in waste incinerator flue gases.

  9. Recombinant murine toxin from Yersinia pestis shows high toxicity and β-adrenergic blocking activity in mice.

    PubMed

    Fan, Yanxiao; Zhou, Yazhou; Feng, Na; Wang, Qiong; Tian, Guang; Wu, Xiaohong; Liu, Zizhong; Bi, Yujing; Yang, Ruifu; Wang, Xiaoyi

    2016-05-01

    Yersinia pestis murine toxin (Ymt) encoded on pMT1 is a 61-kDa protein, a member of the phospholipase D superfamily, which is found in all the domains of life. It is considered to be an intracellular protein required for the survival of Y. pestis in the midgut of the flea, but the exact role of Ymt in the pathogenesis of Y. pestis has not been clarified. Purified Ymt is highly toxic to mice and rats, but the exact mechanism of the animals' death is unclear. Here, we prepared a recombinant Ymt in Escherichia coli BL21 cells, and determined its toxicity and activity. We demonstrated that recombinant Ymt was as toxic to mice as the native protein when administered via the intraperitoneal or intravenous route, and inhibited the elevation of blood sugar caused by adrenaline. We also demonstrated that recombinant Ymt was highly toxic to mice when administered via the muscular or subcutaneous route. We also show that the multiple organ congestion or hemorrhage caused by Ymt poisoning may explain the death of the mice. PMID:26774329

  10. Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors

    PubMed Central

    Zuhl, Andrea M.; Nolan, Charles E.; Brodney, Michael A.; Niessen, Sherry; Atchison, Kevin; Houle, Christopher; Karanian, David A.; Ambroise, Claude; Brulet, Jeffrey W.; Beck, Elizabeth M.; Doran, Shawn D.; O'Neill, Brian T.; am Ende, Christopher W.; Chang, Cheng; Geoghegan, Kieran F.; West, Graham M.; Judkins, Joshua C.; Hou, Xinjun; Riddell, David R.; Johnson, Douglas S.

    2016-01-01

    Inhibition of β-secretase BACE1 is considered one of the most promising approaches for treating Alzheimer's disease. Several structurally distinct BACE1 inhibitors have been withdrawn from development after inducing ocular toxicity in animal models, but the target mediating this toxicity has not been identified. Here we use a clickable photoaffinity probe to identify cathepsin D (CatD) as a principal off-target of BACE1 inhibitors in human cells. We find that several BACE1 inhibitors blocked CatD activity in cells with much greater potency than that displayed in cell-free assays with purified protein. Through a series of exploratory toxicology studies, we show that quantifying CatD target engagement in cells with the probe is predictive of ocular toxicity in vivo. Taken together, our findings designate off-target inhibition of CatD as a principal driver of ocular toxicity for BACE1 inhibitors and more generally underscore the power of chemical proteomics for discerning mechanisms of drug action. PMID:27727204

  11. Toxicant content, physical properties and biological activity of waterpipe tobacco smoke and its tobacco-free alternatives

    PubMed Central

    Shihadeh, Alan; Schubert, Jens; Klaiany, Joanne; El Sabban, Marwan; Luch, Andreas; Saliba, Najat A

    2015-01-01

    Objectives Waterpipe smoking using sweetened, flavoured tobacco products has become a widespread global phenomenon. In this paper, we review chemical, physical and biological properties of waterpipe smoke. Data sources Peer-reviewed publications indexed in major databases between 1991 and 2014. Search keywords included a combination of: waterpipe, narghile, hookah, shisha along with names of chemical compounds and classes of compounds, in addition to terms commonly used in cellular biology and aerosol sizing. Study selection The search was limited to articles published in English which reported novel data on waterpipe tobacco smoke (WTS) toxicant content, biological activity or particle size and which met various criteria for analytical rigour including: method specificity and selectivity, precision, accuracy and recovery, linearity, range, and stability. Data extraction Multiple researchers reviewed the reports and collectively agreed on which data were pertinent for inclusion. Data synthesis Waterpipe smoke contains significant concentrations of toxicants thought to cause dependence, heart disease, lung disease and cancer in cigarette smokers, and includes 27 known or suspected carcinogens. Waterpipe smoke is a respirable aerosol that induces cellular responses associated with pulmonary and arterial diseases. Except nicotine, smoke generated using tobacco-free preparations marketed for ‘health conscious’ users contains the same or greater doses of toxicants, with the same cellular effects as conventional products. Toxicant yield data from the analytical laboratory are consistent with studies of exposure biomarkers in waterpipe users. Conclusions A sufficient evidence base exists to support public health interventions that highlight the fact that WTS presents a serious inhalation hazard. PMID:25666550

  12. Granular activated carbon for simultaneous adsorption and biodegradation of toxic oil sands process-affected water organic compounds.

    PubMed

    Islam, Md Shahinoor; Zhang, Yanyan; McPhedran, Kerry N; Liu, Yang; Gamal El-Din, Mohamed

    2015-04-01

    Naphthenic acids (NAs) released into oil sands process-affected water (OSPW) during bitumen processing in Northern Alberta are problematic for oil sands industries due to their toxicity in the environment and resistance to degradation during conventional wastewater treatment processes. Granular activated carbon (GAC) has shown to be an effective media in removing biopersistent organics from wastewater using a combination of adsorption and biodegradation removal mechanisms. A simultaneous GAC (0.4 g GAC/L) adsorption and biodegradation (combined treatment) study was used for the treatment of raw and ozonated OSPW. After 28 days of batch treatment, classical and oxidized NAs removals for raw OSPW were 93.3% and 73.7%, and for ozonated OSPW were 96.2% and 77.1%, respectively. Synergetic effects of the combined treatment process were observed in removals of COD, the acid extractable fraction, and oxidized NAs, which indicated enhanced biodegradation and bioregeneration in GAC biofilms. A bacteria copy number >10(8) copies/g GAC on GAC surfaces was found using quantitative real time polymerase chain reaction after treatment for both raw and ozonated OSPW. A Microtox(®) acute toxicity test (Vibrio fischeri) showed effective toxicity removal (>95.3%) for the combined treatments. Therefore, the simultaneous GAC adsorption and biodegradation treatment process is a promising technology for the elimination of toxic OSPW NAs.

  13. QSTR modeling for predicting aquatic toxicity of pharmacological active compounds in multiple test species for regulatory purpose.

    PubMed

    Singh, Kunwar P; Gupta, Shikha; Basant, Nikita

    2015-02-01

    High concentrations of pharmacological active compounds (PACs) detected in global drinking water resources and their toxicological implications in aquatic life has become a matter of concern compelling for the development of reliable QSTRs (qualitative/quantitative structure-toxicity relationships) for their risk assessment. Robust QSTRs, such as decision treeboost (DTB) and decision tree forest (DTF) models implementing stochastic gradient boosting and bagging algorithms were established by experimental toxicity data of structurally diverse PACs in daphnia using molecular descriptors for predicting toxicity of new untested compounds in multiple test species. Developed models were rigorously validated using OECD recommended internal and external validation procedures and predictive power tested with external data of different trophic level test species (algae and fish). Classification QSTRs (DTB, DTF) rendered accuracy of 98.73% and 97.47%, respectively in daphnia and 84.38%, 85.94% (algae), 78.46% and 79.23% (fish). On the other hand, the regression QSTRs (DTB, DTF) yielded squared correlation coefficient values of 0.831, 0.852 (daphnia), 0.534, 0.556 (algae) and 0.620, 0.637 (fish). QSTRs developed in this study passed the OECD validation criteria and performed better than reported earlier for predicting toxicity of PACs, and can be used for screening the new untested compounds for regulatory purpose.

  14. Evaluation of Toxicity and Antimicrobial Activity of an Ethanolic Extract from Leaves of Morus alba L. (Moraceae)

    PubMed Central

    de Oliveira, Alisson Macário; Mesquita, Matheus da Silva; da Silva, Gabriela Cavalcante; de Oliveira Lima, Edeltrudes; de Medeiros, Paloma Lys; Paiva, Patrícia Maria Guedes; de Souza, Ivone Antônia; Napoleão, Thiago Henrique

    2015-01-01

    This work evaluated an ethanolic extract from Morus alba leaves for toxicity to Artemia salina, oral toxicity to mice, and antimicrobial activity. Phytochemical analysis revealed the presence of coumarins, flavonoids, tannins, and triterpenes in the extract, which did not show toxicity to A. salina nauplii. No mortality and behavioral alterations were detected for mice treated with the extract (300 and 2000 mg/kg b.w.) for 14 days. However, animals that received the highest dose showed reduced MCV and MCHC as well as increased serum alkaline phosphatase activity. In treatments with the extract at both 300 and 2000 mg/kg, there was a reduction in number of leukocytes, with decrease in percentage of lymphocytes and increase in proportion of segmented cells. Histopathological analysis of organs from mice treated with the extract at 2000 mg/kg revealed turgidity of contorted tubules in kidneys, presence of leukocyte infiltration around the liver centrilobular vein, and high dispersion of the spleen white pulp. The extract showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida krusei, Candida tropicalis, and Aspergillus flavus. In conclusion, the extract contains antimicrobial agents and was not lethal for mice when ingested; however, its use requires caution because it promoted biochemical, hematological, and histopathological alterations. PMID:26246840

  15. Evaluation of Toxicity and Antimicrobial Activity of an Ethanolic Extract from Leaves of Morus alba L. (Moraceae).

    PubMed

    de Oliveira, Alisson Macário; Mesquita, Matheus da Silva; da Silva, Gabriela Cavalcante; de Oliveira Lima, Edeltrudes; de Medeiros, Paloma Lys; Paiva, Patrícia Maria Guedes; de Souza, Ivone Antônia; Napoleão, Thiago Henrique

    2015-01-01

    This work evaluated an ethanolic extract from Morus alba leaves for toxicity to Artemia salina, oral toxicity to mice, and antimicrobial activity. Phytochemical analysis revealed the presence of coumarins, flavonoids, tannins, and triterpenes in the extract, which did not show toxicity to A. salina nauplii. No mortality and behavioral alterations were detected for mice treated with the extract (300 and 2000 mg/kg b.w.) for 14 days. However, animals that received the highest dose showed reduced MCV and MCHC as well as increased serum alkaline phosphatase activity. In treatments with the extract at both 300 and 2000 mg/kg, there was a reduction in number of leukocytes, with decrease in percentage of lymphocytes and increase in proportion of segmented cells. Histopathological analysis of organs from mice treated with the extract at 2000 mg/kg revealed turgidity of contorted tubules in kidneys, presence of leukocyte infiltration around the liver centrilobular vein, and high dispersion of the spleen white pulp. The extract showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida krusei, Candida tropicalis, and Aspergillus flavus. In conclusion, the extract contains antimicrobial agents and was not lethal for mice when ingested; however, its use requires caution because it promoted biochemical, hematological, and histopathological alterations.

  16. Toxicity effect of dichlorvos on loach (Misgurnus anguillicaudatus) assessed by micronucleus test, hepatase activity analysis and comet assay.

    PubMed

    Nan, Ping; Yan, Shuaiguo; Li, Li; Chen, Jianjun; Du, Qiyan; Chang, Zhongjie

    2015-06-01

    Pesticides and other chemicals at environmental concentrations often have detrimental effects. Many aquatic species are particularly threatened because of their susceptibility and also because water environment are often polluted. This study preliminarily evaluated the toxicity effect of dichlorvos (DDVP) on loach (Misgurnus anguillicaudatus) using the methods of micronucleus (MN) test, hepatase activity and comet assay. The tested results showed that indeed very little DDVP had strong toxicity effect on loach and its 50% lethal concentration (LC50) at 24 h, 48 h and 96 h was 8.38 μg l(-1), 7.168 μg l(-1) and 6.411 μg l(-1), respectively; The glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) activity of loach liver decreased; meanwhile, the GPT and GOT activity of loach serum, the MN rate (‰) and three comet parameters of tested fish increased with the increase in the treatment concentration and treatment time of DDVP, and there was significant difference between control group and each treatment group (p < 0.05). These results suggested that DDVP residues might become toxic chemical contaminant in environment and would threaten aquatic and other organisms.

  17. Antiproliferative Activity and in Vivo Toxicity of Double-Point Modified Analogs of 1,25-Dihydroxyergocalciferol

    PubMed Central

    Trynda, Justyna; Turlej, Eliza; Milczarek, Magdalena; Pietraszek, Anita; Chodyński, Michał; Kutner, Andrzej; Wietrzyk, Joanna

    2015-01-01

    Analogs of 1,25-dihydroxyergocalciferol, modified in the side-chain and in the A-ring, were tested for their antiproliferative activity against a series of human cancer cell lines in vitro and in vivo toxicity. The proliferation inhibition caused by the analogs was higher than that of the parent compounds, while the toxicity, measured as the serum calcium level, was lower. All analogs were able to induce, in HL-60 and MV4-11 leukemic cells, G0/G1 cell cycle arrest and differentiation expressed as morphological signs typical for monocytes. The analogs also induced the expression of CD11b and/or CD14 cell-differentiation markers. The most potent analogs, PRI-5105, PRI-5106, PRI-5201 and PRI-5202, were also able to induce vitamin D receptor (VDR) protein expression, mainly in the cytoplasmic fraction of HL-60 or MV4-11 cells. The most active analogs were the 19-nor ones with an extended and rigidified side-chain (PRI-5201 and PRI-5202), as in the former analogs PRI-1906 and PRI-1907. Epimerization at C-24 (PRI-5101) or introduction of an additional hydroxyl at C-23 (PRI-5104) reduced the toxicity of the analog with retained antiproliferative activity. PMID:26492238

  18. Effect of Environmental Conditions and Toxic Compounds on the Locomotor Activity of Pediculus humanus capitis (Phthiraptera: Pediculidae).

    PubMed

    Ortega-Insaurralde, I; Toloza, A C; Gonzalez-Audino, P; Mougabure-Cueto, G A; Alvarez-Costa, A; Roca-Acevedo, G; Picollo, M I

    2015-09-01

    In this work, we evaluated the effect of environmental variables such as temperature, humidity, and light on the locomotor activity of Pediculus humanus capitis. In addition, we used selected conditions of temperature, humidity, and light to study the effects of cypermethrin and N,N-diethyl-3-methylbenzamide (DEET) on the locomotor activity of head lice. Head lice increased their locomotor activity in an arena at 30°C compared with activity at 20°C. When we tested the influence of the humidity level, the locomotor activity of head lice showed no significant differences related to humidity level, both at 30°C and 20°C. Concerning light influence, we observed that the higher the intensity of light, the slower the movement of head lice. We also demonstrated that sublethal doses of toxics may alter locomotor activity in adults of head lice. Sublethal doses of cypermethrin induced hyperactivated responses in adult head lice. Sublethal doses of DEET evocated hypoactivated responses in head lice. The observation of stereotyped behavior in head lice elicited by toxic compounds proved that measuring locomotor activity in an experimental set-up where environmental conditions are controlled would be appropriate to evaluate compounds of biological importance, such as molecules involved in the host-parasite interaction and intraspecific relationships. PMID:26336260

  19. Effect of Environmental Conditions and Toxic Compounds on the Locomotor Activity of Pediculus humanus capitis (Phthiraptera: Pediculidae).

    PubMed

    Ortega-Insaurralde, I; Toloza, A C; Gonzalez-Audino, P; Mougabure-Cueto, G A; Alvarez-Costa, A; Roca-Acevedo, G; Picollo, M I

    2015-09-01

    In this work, we evaluated the effect of environmental variables such as temperature, humidity, and light on the locomotor activity of Pediculus humanus capitis. In addition, we used selected conditions of temperature, humidity, and light to study the effects of cypermethrin and N,N-diethyl-3-methylbenzamide (DEET) on the locomotor activity of head lice. Head lice increased their locomotor activity in an arena at 30°C compared with activity at 20°C. When we tested the influence of the humidity level, the locomotor activity of head lice showed no significant differences related to humidity level, both at 30°C and 20°C. Concerning light influence, we observed that the higher the intensity of light, the slower the movement of head lice. We also demonstrated that sublethal doses of toxics may alter locomotor activity in adults of head lice. Sublethal doses of cypermethrin induced hyperactivated responses in adult head lice. Sublethal doses of DEET evocated hypoactivated responses in head lice. The observation of stereotyped behavior in head lice elicited by toxic compounds proved that measuring locomotor activity in an experimental set-up where environmental conditions are controlled would be appropriate to evaluate compounds of biological importance, such as molecules involved in the host-parasite interaction and intraspecific relationships.

  20. Toxic megacolon

    MedlinePlus

    ... disease - toxic megacolon; Crohn disease - toxic megacolon; Ulcerative colitis - toxic megacolon ... people with an inflamed colon due to: Ulcerative colitis , or Crohn disease that is not well controlled ...

  1. Toxicity Estimation Software Tool (TEST)

    EPA Science Inventory

    The Toxicity Estimation Software Tool (TEST) was developed to allow users to easily estimate the toxicity of chemicals using Quantitative Structure Activity Relationships (QSARs) methodologies. QSARs are mathematical models used to predict measures of toxicity from the physical c...

  2. Mechanisms of perfluoroalkyl acid (PFAA) toxicity: Involvement of peroxisome proliferator activator receptor alpha (PPAR) molecular signals.

    EPA Science Inventory

    Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of a family of environmentally persistent perfluorinated compounds and are found in the serum of wildlife and humans. PFOS and PFOA are developmentally toxic in rats and mice. Exposure in utero reduces...

  3. In-silico structure activity relationship study of toxicity endpoints by QSAR modeling (SOT)

    EPA Science Inventory

    Several thousand chemicals were tested in 700 toxicity-related in-vitro HTS bioassays through the EPA’s ToxCast and Tox21 projects. This chemical set only covers a portion of the chemical space of interest for environmental exposure, leading to a need to fill data gaps with alter...

  4. Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels.

    PubMed

    Defarge, Nicolas; Takács, Eszter; Lozano, Verónica Laura; Mesnage, Robin; Spiroux de Vendômois, Joël; Séralini, Gilles-Eric; Székács, András

    2016-03-01

    Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine-POEA and alkyl polyglucoside-APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone. PMID:26927151

  5. Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels

    PubMed Central

    Defarge, Nicolas; Takács, Eszter; Lozano, Verónica Laura; Mesnage, Robin; Spiroux de Vendômois, Joël; Séralini, Gilles-Eric; Székács, András

    2016-01-01

    Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18–2000 times for co-formulants, 8–141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone. PMID:26927151

  6. Mitochondrial Toxicity Studied with the PBMC of Children from the Chinese National Pediatric Highly Active Antiretroviral Therapy Cohort

    PubMed Central

    Liu, Daojie; Yin, Jiming; Qiao, Luxin; Shi, Ying; Dong, Yaowu; Li, Ning; Zhang, Fujie; Chen, Dexi

    2013-01-01

    As the backbone of highly active antiretroviral therapy (HAART), nucleoside reverse transcriptase inhibitors (NRTIs) have effectively improved outcomes for HIV-infected patients. However, long-term treatment with NRTIs can cause a series of pathologies associated with mitochondrial toxicity. To date, the status and mechanism of mitochondrial toxicity induced by NRTIs are still not clear, especially in HIV-infected children. As part of the national pediatric HAART program in China, our study focused on mitochondrial toxicity and its potential mechanism in HIV-1-infected children who were divided into two groups based on their duration of treatment with NRTIs: one group received treatment for less than 36 months and one group was treated for 36 to 72 months. The control group comprised age-matched non-HIV-infected children. Blood lactic acid and ATP levels in peripheral blood mononuclear cells (PBMCs) were measured to evaluate mitochondrial function, and mtDNA copies and mutations in PBMCs were determined for detecting mtDNA lesions. Simultaneously, TK2 and P53R2 gene expression in PBMC was measured. As compared with the control group, blood lactic acid levels in both NRTI treatment groups were significantly higher, whereas ATP levels and mtDNA mutation rates in PBMCs did not differ between the control and the two NRTI treatment groups. Both NRTI treatment groups exhibited significant mtDNA loss. N Moreover, we found that P53R2 mRNA expression and protein levels were significantly reduced in both treatment groups and that TK2 mRNA expression and protein levels were induced in the long-term NRTI treatment group. These results suggest that mitochondrial toxicity occurs in long-term HAART patients and that P53R2 and TK2 levels in PBMCs are useful biomarkers for detecting mitochondrial toxicity in patients on long-term treatment with NRTIs. PMID:23468942

  7. Assessment of quantitative structure-activity relationship of toxicity prediction models for Korean chemical substance control legislation

    PubMed Central

    Kim, Kwang-Yon; Shin, Seong Eun; No, Kyoung Tai

    2015-01-01

    Objectives For successful adoption of legislation controlling registration and assessment of chemical substances, it is important to obtain sufficient toxicological experimental evidence and other related information. It is also essential to obtain a sufficient number of predicted risk and toxicity results. Particularly, methods used in predicting toxicities of chemical substances during acquisition of required data, ultimately become an economic method for future dealings with new substances. Although the need for such methods is gradually increasing, the-required information about reliability and applicability range has not been systematically provided. Methods There are various representative environmental and human toxicity models based on quantitative structure-activity relationships (QSAR). Here, we secured the 10 representative QSAR-based prediction models and its information that can make predictions about substances that are expected to be regulated. We used models that predict and confirm usability of the information expected to be collected and submitted according to the legislation. After collecting and evaluating each predictive model and relevant data, we prepared methods quantifying the scientific validity and reliability, which are essential conditions for using predictive models. Results We calculated predicted values for the models. Furthermore, we deduced and compared adequacies of the models using the Alternative non-testing method assessed for Registration, Evaluation, Authorization, and Restriction of Chemicals Substances scoring system, and deduced the applicability domains for each model. Additionally, we calculated and compared inclusion rates of substances expected to be regulated, to confirm the applicability. Conclusions We evaluated and compared the data, adequacy, and applicability of our selected QSAR-based toxicity prediction models, and included them in a database. Based on this data, we aimed to construct a system that can be used

  8. The fate and toxicity of Raman-active silica-gold nanoparticles in mice.

    PubMed

    Thakor, Avnesh S; Luong, Richard; Paulmurugan, Ramasamy; Lin, Frank I; Kempen, Paul; Zavaleta, Cristina; Chu, Pauline; Massoud, Tarik F; Sinclair, Robert; Gambhir, Sanjiv S

    2011-04-20

    Raman spectroscopy is an optical imaging method that is based on the Raman effect, the inelastic scattering of a photon when energy is absorbed from light by a surface. Although Raman spectroscopy is widely used for chemical and molecular analysis, its clinical application has been hindered by the inherently weak nature of the Raman effect. Raman-silica-gold-nanoparticles (R-Si-Au-NPs) overcome this limitation by producing larger Raman signals through surface-enhanced Raman scattering. Because we are developing these particles for use as targeted molecular imaging agents, we examined the acute toxicity and biodistribution of core polyethylene glycol (PEG)-ylated R-Si-Au-NPs after different routes of administration in mice. After intravenous administration, PEG-R-Si-Au-NPs were removed from the circulation by macrophages in the liver and spleen (that is, the reticuloendothelial system). At 24 hours, PEG-R-Si-Au-NPs elicited a mild inflammatory response and an increase in oxidative stress in the liver, which subsided by 2 weeks after administration. No evidence of significant toxicity was observed by measuring clinical, histological, biochemical, or cardiovascular parameters for 2 weeks. Because we are designing targeted PEG-R-Si-Au-NPs (for example, PEG-R-Si-Au-NPs labeled with an affibody that binds specifically to the epidermal growth factor receptor) to detect colorectal cancer after administration into the bowel lumen, we tested the toxicity of the core nanoparticle after administration per rectum. We observed no significant bowel or systemic toxicity, and no PEG-R-Si-Au-NPs were detected systemically. Although additional studies are required to investigate the long-term effects of PEG-R-Si-Au-NPs and their toxicity when carrying the targeting moiety, the results presented here support the idea that PEG-R-Si-Au-NPs can be safely used in living subjects, especially when administered rectally.

  9. A Comparison of the Antimicrobial Activity and Toxicity of Six Combretum and Two Terminalia Species from Southern Africa

    PubMed Central

    Cock, I. E.; Van Vuuren, S.F.

    2015-01-01

    Background: Plants of the family Combretaceae are amongst the most widely used plants for traditional medicinal purposes in southern Africa. In particular, many species of Combretum and Terminalia are used for their antibacterial, antifungal, antiprotozoal, antiviral, antidiarrhoeal, analgesic, antimalarial, antioxidant, anti-inflammatory and anticancer activities, yet their antimicrobial potential has not been rigorously studied and compared. Materials and Methods: A survey of antimicrobial activity was undertaken on selected South African Combretum and Terminalia species. Sixteen extracts from 6 Combretum and 2 Terminalia plant species with a history of medicinal usage were investigated by disc diffusion assay against a panel of bacteria and fungi and their MIC values were determined. Toxicity was determined using the Artemia franciscana nauplii bioassay. Results: All extracts tested displayed broad spectrum antibacterial activity, inhibiting the growth of 12-16 (75-100%) of the bacteria tested, with Gram-positive and Gram-negative bacteria being approximately equally susceptible. Potent antibacterial activities (generally in the range 200-5000 μg/ml) were evident for all Combretaceae extracts against both Gram-positive and Gram-negative bacteria. Similarly, the extracts also displayed good antifungal activity, inhibiting the growth of 2-3 (66.7-100%) of the fungal species tested, with fungal growth inhibition activities generally in the range 200–4000 μg/ml. In general, the Terminalia extracts had better efficacies than the Combretum extracts. Furthermore, the methanol extracts were generally better antimicrobial agents than the water extracts. All extracts were also shown to be non-toxic in the Artemia nauplii bioassay. Conclusion: The lack of toxicity of these extracts and their inhibitory bioactivity against a panel of bacteria and fungi indicate their potential as medicinal agents and partially validate their usage in multiple South African traditional

  10. Clone- and age-dependent toxicity of a glyphosate commercial formulation and its active ingredient in Daphnia magna.

    PubMed

    Cuhra, Marek; Traavik, Terje; Bøhn, Thomas

    2013-03-01

    Low levels of glyphosate based herbicide induced significant negative effects on the aquatic invertebrate Daphnia magna. Glyphosate herbicides such as brands of Roundup, are known to be toxic to daphnids. However, published findings on acute toxicity show significant discrepancies and variation across several orders of magnitude. To test the acute effects of both glyphosate and a commercial formulation of Roundup (hereafter Roundup), we conducted a series of exposure experiments with different clones and age-classes of D. magna. The results demonstrated EC(50) (48) values in the low ppm-range for Roundup as well as for the active ingredient (a.i.) isopropylamine salt of glyphosate (glyphosate IPA) alone. Roundup showed slightly lower acute toxicity than glyphosate IPA alone, i.e. EC(50) values of 3.7-10.6 mg a.i./l, as compared to 1.4-7.2 mg a.i./l for glyphosate IPA. However, in chronic toxicity tests spanning the whole life-cycle, Roundup was more toxic. D. magna was exposed to sublethal nominal concentrations of 0.05, 0.15, 0.45, 1.35 and 4.05 mg a.i./l for 55 days. Significant reduction of juvenile size was observed even in the lowest test concentrations of 0.05 mg a.i./l, for both glyphosate and Roundup. At 0.45 mg a.i./l, growth, fecundity and abortion rate was affected, but only in animals exposed to Roundup. At 1.35 and 4.05 mg a.i./l of both glyphosate and Roundup, significant negative effects were seen on most tested parameters, including mortality. D. magna was adversely affected by a near 100 % abortion rate of eggs and embryonic stages at 1.35 mg a.i./l of Roundup. The results indicate that aquatic invertebrate ecology can be adversely affected by relevant ambient concentrations of this major herbicide. We conclude that glyphosate and Roundup toxicity to aquatic invertebrates have been underestimated and that current European Commission and US EPA toxicity classification of these chemicals need to be revised.

  11. A conjugate of the lytic peptide Hecate and gallic acid: structure, activity against cervical cancer, and toxicity.

    PubMed

    Sanches, Paulo R S; Carneiro, Bruno M; Batista, Mariana N; Braga, Ana Cláudia S; Lorenzón, Esteban N; Rahal, Paula; Cilli, Eduardo Maffud

    2015-07-01

    Conjugate compounds constitute a new class of molecules of important biological interest mainly for the treatment of diseases such as cancer. The N-terminus region of cationic peptides has been described as important for their biological activity. The aim of this study was to evaluate the lytic peptide Hecate (FALALKALKKALKKLKKALKKAL) and the effect of conjugating this macromolecule with gallic acid (C7H6O5) in terms of structure, anti-cancer activity, and toxicity. An N-terminus GA-Hecate peptide conjugate was synthesized to provide information regarding the relationship between the amino-terminal region and its charge and the secondary structure and biological activity of the peptide; and the effects of gallic acid on these parameters. Peptide secondary structure was confirmed using circular dichroism (CD). The CD measurements showed that the peptide has a high incidence of α-helical structures in the presence of SDS and LPC, while GA-Hecate presented lower incidence of α-helical structures in the same chemical environment. An evaluation of the anti-cancer activity in HeLa cancer cells indicated that both peptides are active, but that coupling gallic acid at the N-terminus decreased the activity of the free peptide. GA-Hecate showed lower activity in non-tumor keratinocyte cells but higher hemolytic activity. Our findings suggest that the N-terminus of Hecate plays an important role in its activity against cervical cancer by affecting it secondary structure, toxicity, and hemolytic activity. This study highlights the importance of the N-terminus in antitumor activity and could provide an important tool for developing new anti-cancer drugs.

  12. Topological study on the toxicity of ionic liquids on Vibrio fischeri by the quantitative structure-activity relationship method.

    PubMed

    Yan, Fangyou; Shang, Qiaoyan; Xia, Shuqian; Wang, Qiang; Ma, Peisheng

    2015-04-01

    As environmentally friendly solvents, ionic liquids (ILs) are unlikely to act as air contaminants or inhalation toxins resulting from their negligible vapor pressure and excellent thermal stability. However, they can be potential water contaminants because of their considerable solubility in water; therefore, a proper toxicological assessment of ILs is essential. The environmental fate of ILs is studied by quantitative structure-activity relationship (QSAR) method. A multiple linear regression (MLR) model is obtained by topological method using toxicity data of 157 ILs on Vibrio fischeri, which are composed of 74 cations and 22 anions. The topological index developed in our research group is used for predicting the V. fischeri toxicity for the first time. The MLR model is precise for estimating LogEC50 of ILs on V. fischeri with square of correlation coefficient (R(2)) = 0.908 and the average absolute error (AAE) = 0.278.

  13. Haem peroxidase activity in Daphnia magna: a biomarker for sub-lethal toxicity assessments of kerosene-contaminated groundwater.

    PubMed

    Connon, Richard; Dewhurst, Rachel E; Crane, Mark; Callaghan, Amanda

    2003-10-01

    A novel biomarker was developed in Daphnia magna to detect organic pollution in groundwater. The haem peroxidase assay, which is an indirect means of measuring oxidase activity, was particularly sensitive to kerosene contamination. Exposure to sub-lethal concentrations of kerosene-contaminated groundwater resulted in a haem peroxidase activity increase by dose with a two-fold activity peak at 25%. Reproduction in D. magna remained unimpaired when exposed to concentrations below 25% for 21 days, and a decline in fecundity was only observed at concentrations above the peak in enzyme activity. The measurement of haem peroxidase activity in D. magna detected sublethal effects of kerosene in just 24 h, whilst offering information on the health status of the organisms. The biomarker may be useful in determining concentrations above which detrimental effects would occur from long-term exposure for fuel hydrocarbons. Moreover, this novel assay detects exposure to chemicals in samples that would normally be classified as non-toxic by acute toxicity tests.

  14. Mimic of superoxide dismutase activity protects Chlorella sorokiniana against the toxicity of sulfite

    SciTech Connect

    Rabinowitch, H.D.; Rosen, G.M.; Fridovich, I.

    1989-01-01

    The spin-trapping agent 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) has been used to demonstrate the light-dependent production of O/sub 2/- by Chlorella sorokiniana. In the presence of SO/sub 3/= a light-dependent production of the sulfur trioxy anion radical (SO/sub 3/-.) could also be seen. A complex prepared by reacting desferrioxamine with MnO/sub 2/, which catalyzes the dismutation of O/sub 2/-, protected the alga against the toxicity of sulfite. The data suggest that SO/sub 2/ toxicity is at least partially due to the effects of sulfoxy-free radicals generated by the oxidation of SO3= by O/sub 2/-.

  15. Mechanisms of olfactory toxicity of the herbicide 2,6-dichlorobenzonitrile: Essential roles of CYP2A5 and target-tissue metabolic activation

    SciTech Connect

    Xie Fang; Zhou Xin; Behr, Melissa; Fang Cheng; Horii, Yuichi; Gu Jun; Kannan, Kurunthachalam; Ding Xinxin

    2010-11-15

    The herbicide 2,6-dichlorobenzonitril (DCBN) is a potent and tissue-specific toxicant to the olfactory mucosa (OM). The toxicity of DCBN is mediated by cytochrome P450 (P450)-catalyzed bioactivation; however, it is not known whether target-tissue metabolic activation is essential for toxicity. CYP2A5, expressed abundantly in both liver and OM, was previously found to be one of the P450 enzymes active in DCBN bioactivation in vitro. The aims of this study were to determine the role of CYP2A5 in DCBN toxicity in vivo, by comparing the extents of DCBN toxicity between Cyp2a5-null and wild-type (WT) mice, and to determine whether hepatic microsomal P450 enzymes (including CYP2A5) are essential for the DCBN toxicity, by comparing the extents of DCBN toxicity between liver-Cpr-null (LCN) mice, which have little P450 activity in hepatocytes, and WT mice. We show that the loss of CYP2A5 expression did not alter systemic clearance of DCBN (at 25 mg/kg); but it did inhibit DCBN-induced non-protein thiol depletion and cytotoxicity in the OM. Thus, CYP2A5 plays an essential role in mediating DCBN toxicity in the OM. In contrast to the results seen in the Cyp2a5-null mice, the rates of systemic DCBN clearance were substantially reduced, while the extents of DCBN-induced nasal toxicity were increased, rather than decreased, in the LCN mice, compared to WT mice. Therefore, hepatic P450 enzymes, although essential for DCBN clearance, are not necessary for DCBN-induced OM toxicity. Our findings form the basis for a mechanism-based approach to assessing the potential risks of DCBN nasal toxicity in humans.

  16. Protective activity of hesperidin and lipoic acid against sodium arsenite acute toxicity in mice.

    PubMed

    das Neves, Ricardo N Pires; Carvalho, Félix; Carvalho, Márcia; Fernandes, Eduarda; Soares, Elisa; de Bastos, Maria Lourdes; de Pereira, Maria Lourdes

    2004-01-01

    The objective of the present work was to evaluate the toxic effects of sodium arsenite, As(III), in mice and the protective effect of 2 antioxidants, hesperidin and lipoic acid, against the observed As(III)-induced toxicity. In each study, mice were assigned to 1 of 4 groups: control, antioxidant, antioxidant + arsenite, and arsenite. Animals were first injected with the vehicle or 25 mg antioxidant/kg BW. After 30 minutes they received an injection of 10 mg arsenite/kg BW or 0.9% NaCl. Two hours after the first injection, the liver, kidney, and testis were collected for histological evaluation. Liver samples were also taken for quantification of arsenic. In mice exposed only to As(III), various histopathological effects were observed in the liver, kidneys, and testes. In mice pretreated with either hesperidin or lipoic acid, a reduction of histopathologic effects on the liver and kidneys was observed. No protective effects were observed in the testes for either of the 2 studied antioxidants. In conclusion, hesperidin and lipoic acid provided protective effects against As(III)-induced acute toxicity in the liver and kidneys of mice. These compounds may potentially play an important role in the protection of populations chronically exposed to arsenic.

  17. Rifampicin-activated human pregnane X receptor and CYP3A4 induction enhance acetaminophen-induced toxicity.

    PubMed

    Cheng, Jie; Ma, Xiaochao; Krausz, Kristopher W; Idle, Jeffrey R; Gonzalez, Frank J

    2009-08-01

    Acetaminophen (APAP) is safe at therapeutic levels but causes hepatotoxicity via N-acetyl-p-benzoquinone imine-induced oxidative stress upon overdose. To determine the effect of human (h) pregnane X receptor (PXR) activation and CYP3A4 induction on APAP-induced hepatotoxicity, mice humanized for PXR and CYP3A4 (TgCYP3A4/hPXR) were treated with APAP and rifampicin. Human PXR activation and CYP3A4 induction enhanced APAP-induced hepatotoxicity as revealed by hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities elevated in serum, and hepatic necrosis after coadministration of rifampicin and APAP, compared with APAP administration alone. In contrast, hPXR mice, wild-type mice, and Pxr-null mice exhibited significantly lower ALT/AST levels compared with TgCYP3A4/hPXR mice after APAP administration. Toxicity was coincident with depletion of hepatic glutathione and increased production of hydrogen peroxide, suggesting increased oxidative stress upon hPXR activation. Moreover, mRNA analysis demonstrated that CYP3A4 and other PXR target genes were significantly induced by rifampicin treatment. Urinary metabolomic analysis indicated that cysteine-APAP and its metabolite S-(5-acetylamino-2-hydroxyphenyl)mercaptopyruvic acid were the major contributors to the toxic phenotype. Quantification of plasma APAP metabolites indicated that the APAP dimer formed coincident with increased oxidative stress. In addition, serum metabolomics revealed reduction of lysophosphatidylcholine in the APAP-treated groups. These findings demonstrated that human PXR is involved in regulation of APAP-induced toxicity through CYP3A4-mediated hepatic metabolism of APAP in the presence of PXR ligands.

  18. Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity

    SciTech Connect

    Okawa, Hiromi; Motohashi, Hozumi; Kobayashi, Akira; Aburatani, Hiroyuki; Kensler, Thomas W.; Yamamoto, Masayuki . E-mail: masi@tara.tsukuba.ac.jp

    2006-01-06

    Nrf2 is a key regulator of many detoxifying enzyme genes, and cytoplasmic protein Keap1 represses the Nrf2 activity under quiescent conditions. Germ line deletion of the keap1 gene results in constitutive activation of Nrf2, but the pups unexpectedly died before weaning. To investigate how constitutive activation of Nrf2 influences the detoxification system in adult mice, we generated mice bearing a hepatocyte-specific disruption of the keap1 gene. Homozygous mice were viable and their livers displayed no apparent abnormalities, but nuclear accumulation of Nrf2 is elevated. Microarray analysis revealed that, while many detoxifying enzyme genes are highly expressed, some of the typical Nrf2-dependent genes are only marginally increased in the Keap1-deficient liver. The mutant mice were significantly more resistant to toxic doses of acetaminophen than control animals. These results demonstrate that chronic activation of Nrf2 confers animals with resistance to xenobiotics without affecting the morphological and physiological integrity of hepatocytes.

  19. The antioxidant, general toxicity and insecticidal activities of Nepeta scrophularioides Rech. f. extracts in different developmental stages.

    PubMed

    Gharbani, Parvin; Javazi, Hamideh

    2015-09-01

    The essence of the present study is to focus on the antioxidant, general toxicity and insecticidal properties of the extracts of Nepeta scrophularioides Rech.f. during different developmental (vegetative, flowering, post-flowering) stages. The samples were subjected to screening for their possible antioxidant activities by using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The extracts of the flowering and the post-flowering stages showed higher antioxidant activity than those from the vegetative stage. The MeOH extracts of N. scrophularioides in different development stages were tested for cytotoxicity by brine shrimp toxicity assay. The result obtained for the bio assay was found to be significantly lethality. Among the samples, the extracts of flowering stage were found to be the most active with a LC50 value of 0.078 mg/mL. All three extracts showed significant insecticidal activity at the concentration of 20 mg/mL dose of test sample after 24 h. The extracts of vegetative and post-flowering were the most potent samples. PMID:26525034

  20. Antitumor activities and on-target toxicities mediated by a TRAIL receptor agonist following cotreatment with panobinostat.

    PubMed

    Martin, Ben P; Frew, Ailsa J; Bots, Michael; Fox, Stephen; Long, Fenella; Takeda, Kazuyoshi; Yagita, Hideo; Atadja, Peter; Smyth, Mark J; Johnstone, Ricky W

    2011-06-01

    The recent development of novel targeted anticancer therapeutics such as histone deacetylase inhibitors (HDACi) and activators of the TRAIL pathway provide opportunities for the introduction of new treatment regimens in oncology. HDACi and recombinant TRAIL or agonistic anti-TRAIL receptor antibodies have been shown to induce synergistic tumor cell apoptosis and some therapeutic activity in vivo. Herein, we have used syngeneic preclinical models of human solid cancers to demonstrate that the HDACi panobinostat can sensitize tumor cells to apoptosis mediated by the anti-mouse TRAIL receptor antibody MD5-1. We demonstrate that the combination of panobinostat and MD5-1 can eradicate tumors grown subcutaneously and orthotopically in immunocompetent mice, while single agent treatment has minimal effect. However, escalation of the dose of panobinostat to enhance antitumor activity resulted in on-target MD5-1-mediated gastrointestinal toxicities that were fatal to the treated mice. Studies performed in mice with knockout of the TRAIL receptor showed that these mice could tolerate doses of the panobinostat/MD5-1 combination that were lethal in wild type mice resulting in superior tumor clearance. Given that clinical studies using HDACi and activators of the TRAIL pathway have been initiated, our preclinical data highlight the potential toxicities that could limit the use of such a treatment regimen. Our studies also demonstrate the power of using syngeneic in vivo tumor models as physiologically relevant preclinical systems to test the antitumor effects and identify potential side effects of novel anticancer regimens.

  1. The antioxidant, general toxicity and insecticidal activities of Nepeta scrophularioides Rech. f. extracts in different developmental stages.

    PubMed

    Gharbani, Parvin; Javazi, Hamideh

    2015-09-01

    The essence of the present study is to focus on the antioxidant, general toxicity and insecticidal properties of the extracts of Nepeta scrophularioides Rech.f. during different developmental (vegetative, flowering, post-flowering) stages. The samples were subjected to screening for their possible antioxidant activities by using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The extracts of the flowering and the post-flowering stages showed higher antioxidant activity than those from the vegetative stage. The MeOH extracts of N. scrophularioides in different development stages were tested for cytotoxicity by brine shrimp toxicity assay. The result obtained for the bio assay was found to be significantly lethality. Among the samples, the extracts of flowering stage were found to be the most active with a LC50 value of 0.078 mg/mL. All three extracts showed significant insecticidal activity at the concentration of 20 mg/mL dose of test sample after 24 h. The extracts of vegetative and post-flowering were the most potent samples.

  2. Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling.

    PubMed

    Yost, Erin E; Stanek, John; DeWoskin, Robert S; Burgoon, Lyle D

    2016-07-19

    The United States Environmental Protection Agency (EPA) identified 1173 chemicals associated with hydraulic fracturing fluids, flowback, or produced water, of which 1026 (87%) lack chronic oral toxicity values for human health assessments. To facilitate the ranking and prioritization of chemicals that lack toxicity values, it may be useful to employ toxicity estimates from quantitative structure-activity relationship (QSAR) models. Here we describe an approach for applying the results of a QSAR model from the TOPKAT program suite, which provides estimates of the rat chronic oral lowest-observed-adverse-effect level (LOAEL). Of the 1173 chemicals, TOPKAT was able to generate LOAEL estimates for 515 (44%). To address the uncertainty associated with these estimates, we assigned qualitative confidence scores (high, medium, or low) to each TOPKAT LOAEL estimate, and found 481 to be high-confidence. For 48 chemicals that had both a high-confidence TOPKAT LOAEL estimate and a chronic oral reference dose from EPA's Integrated Risk Information System (IRIS) database, Spearman rank correlation identified 68% agreement between the two values (permutation p-value =1 × 10(-11)). These results provide support for the use of TOPKAT LOAEL estimates in identifying and prioritizing potentially hazardous chemicals. High-confidence TOPKAT LOAEL estimates were available for 389 of 1026 hydraulic fracturing-related chemicals that lack chronic oral RfVs and OSFs from EPA-identified sources, including a subset of chemicals that are frequently used in hydraulic fracturing fluids. PMID:27172125

  3. Sorption and toxicity reduction of pharmaceutically active compounds and endocrine disrupting chemicals in the presence of colloidal humic acid.

    PubMed

    Kim, Injeong; Kim, Hyo-Dong; Jeong, Tae-Yong; Kim, Sang Don

    2016-01-01

    This study investigated the toxicity changes and sorption of pharmaceuticals and endocrine disrupters in the presence of humic acid (HA). For the sorption experiment, a dead end filtration (DEF) system was used to separate bound and free-form target compounds. An algae growth inhibition test and E-screen assay were conducted to estimate the toxic effect of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs), respectively. The permeate concentration was confirmed using liquid chromatography-mass spectrometry. In the sorption test, we observed significant sorption of PhACs and EDCs on colloidal HA, except for sulfamethoxazole (SMX). The values of log KCOC derived from DEF determinations ranged from 4.40 to 5.03. The removal efficiency varied with the HA concentration and the target chemical properties. Tetracycline and 4-octylphenol showed the highest sorption or removal efficiency (≈50%), even at 5 mg C/L HA. The algal growth inhibition of PhACs and the estrogenic effects of EDCs were significantly decreased in proportion to HA concentrations, except for SMX. In addition, the chemical analysis results showed a positive relationship with the bioassay results. Consequently, the sorption of PhACs and EDCs onto colloidal HA should be emphasized in natural environments because it significantly reduces bioavailable concentrations and toxicity to aquatic organisms. PMID:27533865

  4. Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling.

    PubMed

    Yost, Erin E; Stanek, John; DeWoskin, Robert S; Burgoon, Lyle D

    2016-07-19

    The United States Environmental Protection Agency (EPA) identified 1173 chemicals associated with hydraulic fracturing fluids, flowback, or produced water, of which 1026 (87%) lack chronic oral toxicity values for human health assessments. To facilitate the ranking and prioritization of chemicals that lack toxicity values, it may be useful to employ toxicity estimates from quantitative structure-activity relationship (QSAR) models. Here we describe an approach for applying the results of a QSAR model from the TOPKAT program suite, which provides estimates of the rat chronic oral lowest-observed-adverse-effect level (LOAEL). Of the 1173 chemicals, TOPKAT was able to generate LOAEL estimates for 515 (44%). To address the uncertainty associated with these estimates, we assigned qualitative confidence scores (high, medium, or low) to each TOPKAT LOAEL estimate, and found 481 to be high-confidence. For 48 chemicals that had both a high-confidence TOPKAT LOAEL estimate and a chronic oral reference dose from EPA's Integrated Risk Information System (IRIS) database, Spearman rank correlation identified 68% agreement between the two values (permutation p-value =1 × 10(-11)). These results provide support for the use of TOPKAT LOAEL estimates in identifying and prioritizing potentially hazardous chemicals. High-confidence TOPKAT LOAEL estimates were available for 389 of 1026 hydraulic fracturing-related chemicals that lack chronic oral RfVs and OSFs from EPA-identified sources, including a subset of chemicals that are frequently used in hydraulic fracturing fluids.

  5. Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity

    NASA Astrophysics Data System (ADS)

    Aramwit, Pornanong; Porasuphatana, Supatra; Srichana, Teerapol; Nakpheng, Titpawan

    2015-03-01

    In the previous study, we have found that the cordycepin which was extracted from Cordyceps mycelia produced by growing Cordyceps militaris on the dead larva of Bombyx mori silkworms showed the anti-proliferative effect toward lung cancer cells without toxicity to non-cancer cells. In this work, the cordycepin was tested for its in vitro mutagenicity and in vivo toxicity. From the Ames test and subacute toxicity test using oral administration in a rat model, the cordycepin was proved to be a non-mutagenic and non-toxic compound. The hematology and blood chemistry as well as the microanatomical characteristic of the tissues of rats fed with cordycepin every day for consecutive 30 days were comparable to those of the normal ones. Then, the cordycepin was incorporated in gelatin type A (GA) and gelatin type B (GB) nanoparticles aimed to sustain its release and activity. The cordycepin incorporated in both GA and GB nanoparticles showed the sustained release profiles. GA nanoparticles could encapsulate cordycepin at higher encapsulation efficiency due to the attractive electrostatic interaction between the positive-charged GA and the negative-charged cordycepin. However, GA nanoparticles released cordycepin at the higher amount possibly because of the large surface area of small size nanoparticles. Comparing to GB nanoparticles, the higher amount of cordycepin released from GA nanoparticles showed the higher anti-proliferative and anti-migratory effects on A549 lung cancer cells. In conclusion, GA nanoparticles were suggested as a suitable carrier for the sustained release of cordycepin. The GA nanoparticles releasing cordycepin could be an effective and non-invasive material for the treatment of lung cancer cells.

  6. Thresholds of arsenic toxicity to Eisenia fetida in field-collected agricultural soils exposed to copper mining activities in Chile.

    PubMed

    Bustos, Víctor; Mondaca, Pedro; Verdejo, José; Sauvé, Sébastien; Gaete, Hernán; Celis-Diez, Juan L; Neaman, Alexander

    2015-12-01

    Several previous studies highlighted the importance of using field-collected soils-and not artificially-contaminated soils-for ecotoxicity tests. However, the use of field-collected soils presents several difficulties for interpretation of results, due to the presence of various contaminants and unavoidable differences in the physicochemical properties of the tested soils. The objective of this study was to estimate thresholds of metal toxicity in topsoils of 24 agricultural areas historically contaminated by mining activities in Chile. We performed standardized earthworm reproduction tests (OECD 222 and ISO 11268-2) with Eisenia fetida. Total soil concentrations of Cu, As, Zn, and Pb were in the ranges of 82-1295 mg kg(-1), 7-41 mg kg(-1), 86-345 mg kg(-1), and 25-97 mg kg(-1), respectively. In order to differentiate between the effects of different metals, we used regression analysis between soil metal concentrations and earthworm responses, as well as between metal concentrations in earthworm tissues and earthworm responses. Based on regression analysis, we concluded that As was a metal of prime concern for Eisenia fetida in soils affected by Cu mining activities, while Cu exhibited a secondary effect. In contrast, the effects of Zn and Pb were not significant. Soil electrical conductivity was another significant contributor to reproduction toxicity in the studied soils, forcing its integration in the interpretation of the results. By using soils with electrical conductivity ≤ 0.29 dS m(-1) (which corresponds to EC50 of salt toxicity to Eisenia fetida), it was possible to isolate the effect of soil salinity on earthworm reproduction. Despite the confounding effects of Cu, it was possible to determine EC10, EC25 and EC50 values for total soil As at 8 mg kg(-1), 14 mg kg(-1) and 22 mg kg(-1), respectively, for the response of the cocoon production. However, it was not possible to determine these threshold values for juvenile production. Likewise, we were able to

  7. Thresholds of arsenic toxicity to Eisenia fetida in field-collected agricultural soils exposed to copper mining activities in Chile.

    PubMed

    Bustos, Víctor; Mondaca, Pedro; Verdejo, José; Sauvé, Sébastien; Gaete, Hernán; Celis-Diez, Juan L; Neaman, Alexander

    2015-12-01

    Several previous studies highlighted the importance of using field-collected soils-and not artificially-contaminated soils-for ecotoxicity tests. However, the use of field-collected soils presents several difficulties for interpretation of results, due to the presence of various contaminants and unavoidable differences in the physicochemical properties of the tested soils. The objective of this study was to estimate thresholds of metal toxicity in topsoils of 24 agricultural areas historically contaminated by mining activities in Chile. We performed standardized earthworm reproduction tests (OECD 222 and ISO 11268-2) with Eisenia fetida. Total soil concentrations of Cu, As, Zn, and Pb were in the ranges of 82-1295 mg kg(-1), 7-41 mg kg(-1), 86-345 mg kg(-1), and 25-97 mg kg(-1), respectively. In order to differentiate between the effects of different metals, we used regression analysis between soil metal concentrations and earthworm responses, as well as between metal concentrations in earthworm tissues and earthworm responses. Based on regression analysis, we concluded that As was a metal of prime concern for Eisenia fetida in soils affected by Cu mining activities, while Cu exhibited a secondary effect. In contrast, the effects of Zn and Pb were not significant. Soil electrical conductivity was another significant contributor to reproduction toxicity in the studied soils, forcing its integration in the interpretation of the results. By using soils with electrical conductivity ≤ 0.29 dS m(-1) (which corresponds to EC50 of salt toxicity to Eisenia fetida), it was possible to isolate the effect of soil salinity on earthworm reproduction. Despite the confounding effects of Cu, it was possible to determine EC10, EC25 and EC50 values for total soil As at 8 mg kg(-1), 14 mg kg(-1) and 22 mg kg(-1), respectively, for the response of the cocoon production. However, it was not possible to determine these threshold values for juvenile production. Likewise, we were able to

  8. Modification of Lipid A Biosynthesis in Neisseria meningitidis lpxL Mutants: Influence on Lipopolysaccharide Structure, Toxicity, and Adjuvant Activity

    PubMed Central

    van der Ley, Peter; Steeghs, Liana; Hamstra, Hendrik Jan; ten Hove, Jan; Zomer, Bert; van Alphen, Loek

    2001-01-01

    Two genes homologous to lpxL and lpxM from Escherichia coli and other gram-negative bacteria, which are involved in lipid A acyloxyacylation, were identified in Neisseria meningitidis strain H44/76 and insertionally inactivated. Analysis by tandem mass spectrometry showed that one of the resulting mutants, termed lpxL1, makes lipopolysaccharide (LPS) with penta- instead of hexa-acylated lipid A, in which the secondary lauroyl chain is specifically missing from the nonreducing end of the GlcN disaccharide. Insertional inactivation of the other (lpxL2) gene was not possible in wild-type strain H44/76 expressing full-length immunotype L3 lipopolysaccharide (LPS) but could be readily achieved in a galE mutant expressing a truncated oligosaccharide chain. Structural analysis of lpxL2 mutant lipid A showed a major tetra-acylated species lacking both secondary lauroyl chains and a minor penta-acylated species. The lpxL1 mutant LPS has retained adjuvant activity similar to wild-type meningococcal LPS when used for immunization of mice in combination with LPS-deficient outer membrane complexes from N. meningitidis but has reduced toxicity as measured in a tumor necrosis factor alpha induction assay with whole bacteria. In contrast, both adjuvant activity and toxicity of the lpxL2 mutant LPS are strongly reduced. As the combination of reduced toxicity and retained adjuvant activity has not been reported before for either lpxL or lpxM mutants from other bacterial species, our results demonstrate that modification of meningococcal lipid A biosynthesis can lead to novel LPS species more suitable for inclusion in human vaccines. PMID:11553534

  9. Life stage toxicity and residual activity of insecticides to codling moth and oriental fruit moth (Lepidoptera: Tortricidae).

    PubMed

    Magalhaes, Leonardo C; Walgenbach, James F

    2011-12-01

    The codling moth, Cydia pomonella (L.), and oriental fruit moth, Grapholita molesta (Busck), are two key pests of apple (Malus domestica Borkh.) in North Carolina. Growers extensively relied on organophosphate insecticides, primarily azinphosmethyl, for > 40 yr to manage these pests. Because of organophosphate resistance development and regulatory actions, growers are transitioning to management programs that use new, reduced-risk, and OP-replacement insecticides. This study evaluated the toxicity of a diversity of replacement insecticides to eggs, larvae, and adults, as well as an assessment of their residual activity, to codling moth and oriental fruit moth. Laboratory-susceptible strains of both species were used for all bioassays. Fresh field-harvested apples were used as a media for assessing the ovicidal activity of insecticides. For larval studies, insecticides were topically applied to the surface of lima bean-based diet, onto which neonates were placed. Toxicity was based on two measures of mortality; 5-d mortality and development to adult stage. Ovicidal bioassays showed that oriental fruit moth eggs were generally more tolerant than codling moth eggs to insecticides, with novaluron, acetamiprid, and azinphoshmethyl having the highest levels of toxicity to eggs of both species. In contrast, codling moth larvae generally were more tolerant than oriental fruit moth to most insecticides. Methoxyfenozide and pyriproxyfen were the only insecticides with lower LC50 values against codling moth than oriental fruit moth neonates. Moreover, a number of insecticides, particularly the IGRs methoxyfenozide and novaluron, the anthranilic diamide chlorantriliprole, and the spinosyn spinetoram, provided equal or longer residual activity against codling moth compared with azinphosmethyl in field studies. Results are discussed in relation to their use in devising field use patterns of insecticides and for insecticide resistance monitoring programs.

  10. Metabolites from Aspergillus fumigatus, an endophytic fungus associated with Melia azedarach, and their antifungal, antifeedant, and toxic activities.

    PubMed

    Li, Xiao-Jun; Zhang, Qiang; Zhang, An-Ling; Gao, Jin-Ming

    2012-04-01

    Thirty-nine fungal metabolites 1-39, including two new alkaloids, 12β-hydroxy-13α-methoxyverruculogen TR-2 (6) and 3-hydroxyfumiquinazoline A (16), were isolated from the fermentation broth of Aspergillus fumigatus LN-4, an endophytic fungus isolated from the stem bark of Melia azedarach. Their structures were elucidated on the basis of detailed spectroscopic analysis (mass spectrometry and one- and two-dimensional NMR experiments) and by comparison of their NMR data with those reported in the literature. These isolated compounds were evaluated for in vitro antifungal activities against some phytopathogenic fungi, toxicity against brine shrimps, and antifeedant activities against armyworm larvae (Mythimna separata Walker). Among them, sixteen compounds showed potent antifungal activities against phytopathogenic fungi (Botrytis cinerea, Alternaria solani, Alternaria alternata, Colletotrichum gloeosporioides, Fusarium solani, Fusarium oxysporum f. sp. niveum, Fusarium oxysporum f. sp. vasinfectum, and Gibberella saubinettii), and four of them, 12β-hydroxy-13α-methoxyverruculogen TR-2 (6), fumitremorgin B (7), verruculogen (8), and helvolic acid (39), exhibited antifungal activities with MIC values of 6.25-50 μg/mL, which were comparable to the two positive controls carbendazim and hymexazol. In addition, of eighteen that exerted moderate lethality toward brine shrimps, compounds 7 and 8 both showed significant toxicities with median lethal concentration (LC(50)) values of 13.6 and 15.8 μg/mL, respectively. Furthermore, among nine metabolites that were found to possess antifeedant activity against armyworm larvae, compounds 7 and 8 gave the best activity with antifeedant indexes (AFI) of 50.0% and 55.0%, respectively. Structure-activity relationships of the metabolites were also discussed. PMID:22409377

  11. ERK1/2 activation modulates pyocyanin-induced toxicity in A549 respiratory epithelial cells.

    PubMed

    Forbes, Amanda; Davey, Andrew K; Perkins, Anthony V; Grant, Gary D; McFarland, Amelia J; McDermott, Catherine M; Anoopkumar-Dukie, Shailendra

    2014-02-01

    Pyocyanin (PCN), a virulence factor produced by Pseudomonas aeruginosa, has many damaging effects on mammalian cells. Several lines of evidence suggest that this damage is primarily mediated by its ability to generate oxidative stress. However mechanisms underlying PCN-induced oxidative injury remain unclear. Although oxidative stress and subsequent MAPK signaling has been shown to modulate cell death in other models, its role in PCN-induced cytotoxicity remains unknown. Therefore the aim of this study was to investigate the role of redox-sensitive MAPK in PCN-induced toxicity in A549 cells. Here we show that PCN (50μM) rapidly increased ERK1/2 phosphorylation after 5min. Pre-treatment of A549 cells with the MEK1/2 inhibitor U0126 (10μM) decreased PCN-induced ERK1/2 phosphorylation and protected cells against apoptosis and cell injury suggesting a role for ERK signalling. In contrast, JNK and p38 MAPK phosphorylation remained unchanged following exposure to PCN and pretreatment with either the JNK or p38 MAPK inhibitors (10μM SP600125 and 10μM SB203580, respectively) did not afford protection against PCN toxicity. This would suggest that PCN-induced cytotoxicity appears to occur independently of JNK and p38 MAPK signaling pathways. Finally, although we confirm that oxidative stress contributes to PCN-induced toxicity, our data suggest the contribution of oxidative stress is independent of ERK1/2 signaling. These findings may provide insight for novel targeted therapies to reduce PCN-mediated lung injury in patients with chronic P. aeruginosa respiratory infections.

  12. THE FATE AND TOXICITY OF RAMAN ACTIVE SILICA-GOLD NANOPARTICLES IN MICE

    PubMed Central

    THAKOR, AVNESH S; LUONG, RICHARD; PAULMURUGAN, RAMASAMY; LIN, FRANK I; KEMPEN, PAUL; ZAVALETA, CRISTINA; CHU, PAULINE; MASSOUD, TARIK F; SINCLAIR, ROBERT; GAMBHIR, SANJIV S

    2013-01-01

    Raman spectroscopy is an optical imaging modality which analyses the Raman effect in which energy is exchanged between light and matter. Although Raman spectroscopy has been widely used for chemical and molecular analysis, its use in clinical applications has been hindered by the inherently weak nature of the Raman effect. Raman-silica-gold-nanoparticles (R-Si-Au-NPs) overcome this limitation by producing high Raman signals via Surface Enhanced Raman Scattering. Targeted polyethylene glycol (PEG)-ylated R-Si-Au-NPs (e.g. PEG-R-Si-Au-NPs labeled with an affibody which binds specifically to the epidermal growth factor receptor) are currently being designed to detect colorectal cancer after administration into the bowel lumen. With this approach, PEG-R-Si-Au-NPs are not expected to enter the systemic circulation and would be removed from the body via defecation. We examined the acute toxicity and biodistribution of core PEG-R-Si-Au-NPs after different routes of administration in mice. After intravenous administration, PEG-R-Si-Au-NPs were removed from the circulation by marcophages in the liver and spleen (i.e. the reticuloendothelial system). At 24 hours, PEG-R-Si-Au-NPs elicited a mild inflammatory response and an increase in oxidative stress in the liver, which subsided by 2 weeks. No evidence of significant toxicity was observed by measuring clinical, histological, biochemical or cardiovascular parameters for 2 weeks. Notably, after administration per rectum, we observed no significant bowel or systemic toxicity and no PEG-R-Si-Au-NPs were detected systemically. Although additional studies are required to investigate the long-term effects of PEG-R-Si-Au-NPs, these initial results support the idea that they can be safely used in living subjects, especially when administered rectally. PMID:21508310

  13. [Use of biologically active substances in preventing the toxic action of some heavy metals].

    PubMed

    Degtiareva, T D; Katsnel'son, B A; Pirvalova, L I; Beresneva, O Iu; Gurvich, V B; Kuz'min, S V; Malykh, O L

    2001-01-01

    The paper presents experimental and theoretical rationales for some methods and means of biological prevention of the toxic effects of a number of heavy metals (lead, chromium, arsenic, cadmium) that pollute the environment. Subchronic experiments were made on laboratory animals exposed to the above substances in combination with various biological agents (sodium glutaminate, the adaptogen saparal, pectin-containing enterosorbent, calcium, the multivitamin-multimineral preparation Pikovit, etc.). They have indicated that the complex use of preparations is more beneficial than they are used alone. The results of controlled trials of biologically preventive preparations on children residing in an area exposed to industrial pollution are presented.

  14. Oxidative Stress and Mitochondrial Activation as the Main Mechanisms Underlying Graphene Toxicity against Human Cancer Cells

    PubMed Central

    Jarosz, Anna; Skoda, Marta; Dudek, Ilona; Szukiewicz, Dariusz

    2016-01-01

    Due to the development of nanotechnology graphene and graphene-based nanomaterials have attracted the most attention owing to their unique physical, chemical, and mechanical properties. Graphene can be applied in many fields among which biomedical applications especially diagnostics, cancer therapy, and drug delivery have been arousing a lot of interest. Therefore it is essential to understand better the graphene-cell interactions, especially toxicity and underlying mechanisms for proper use and development. This review presents the recent knowledge concerning graphene cytotoxicity and influence on different cancer cell lines. PMID:26649139

  15. Lunar Dust and Lunar Simulant Activation, Monitoring, Solution and Cellular Toxicity Properties

    NASA Technical Reports Server (NTRS)

    Jeevarajan, A.S.; Wallace, W.T.

    2009-01-01

    During the Apollo missions, many undesirable situations were encountered that must be mitigated prior to returning humans to the moon. Lunar dust (that part of the lunar regolith less than 20 m in diameter) was found to produce several problems with astronaut s suits and helmets, mechanical seals and equipment, and could have conceivably produced harmful physiological effects for the astronauts. For instance, the abrasive nature of the dust was found to cause malfunctions of various joints and seals of the spacecraft and suits. Additionally, though efforts were made to exclude lunar dust from the cabin of the lunar module, a significant amount of material nonetheless found its way inside. With the loss of gravity correlated with ascent of the lunar module from the lunar surface to rendezvous with the command module, much of the major portions of the contaminating soil and dust began to float, irritating the astronaut s eyes and being inhaled into their lungs. Our goal has been to understand some of the properties of lunar dust that could lead to possible hazards for humans. Due to the lack of an atmosphere, there is nothing to protect the lunar soil from ultraviolet radiation, solar wind, and meteorite impacts. These processes could all serve to activate the soil, or produce reactive surface species. In order to understand the possible toxic effects of the reactive dust, it is necessary to reactivate the dust, as samples returned during the Apollo missions were exposed to the atmosphere of the Earth. We have used grinding and UV exposure to mimic some of the processes occurring on the Moon. The level of activation has been monitored using two methods: fluorescence spectroscopy and electron paramagnetic resonance spectroscopy (EPR). These techniques allow the monitoring of hydroxyl radical production in solution. We have found that grinding of lunar dust produces 2-3 times the concentration of hydroxyl radicals as lunar simulant and 10 times that of quartz. Exposure

  16. Toxic impact of aldrin on acid and alkaline phosphatase activity of penaeid prawn, Metapenaeus monoceros: In vitro study

    SciTech Connect

    Reddy, M.S.; Jayaprada, P.; Rao, K.V.R. )

    1991-03-01

    The increasing contamination of the aquatic environment by the indiscriminate and widespread use of different kinds of pesticides is a serious problem for environmental biologists. Organochlorine insecticides are more hazardous since they are not only more toxic but also leave residues in nature. The deleterious effects of aldrin on several crustaceans have been studied. But studies concerning the impact of aldrin on biochemical aspects of crustaceans are very much limited. The present study is aimed at probing the in vitro effects of aldrin on the acid and alkaline phosphatase activity levels in selected tissues of penaeid prawn, Metapenaeus monoceros (Fabricius).

  17. Developmental exposures to ethanol or dimethylsulfoxide at low concentrations alter locomotor activity in larval zebrafish: implications for behavioral toxicity bioassays.

    PubMed

    Chen, Te-Hao; Wang, Yen-Hsin; Wu, Yu-Hwan

    2011-04-01

    Ethanol and dimethylsulfoxide (DMSO) are commonly used as carrier solvents for lipophilic chemicals in aquatic toxicity bioassays. However, very little information has been reported on the behavioral effects of these solvents. In this study, we examined the effects of ethanol and DMSO on development and locomotor activity by a zebrafish embryo-larval bioassay. The zebrafish were exposed to different concentrations (control, 0.01, 0.1, and 1%) of ethanol or DMSO from blastula stage to 144 hour-post-fertilization (hpf). Hatchability, survival, and abnormalities were monitored every 12h, and locomotor activity of the larvae was analyzed at 144 hpf. Hatchability was not affected by the ethanol or DMSO treatments. No effect on survival was observed except the 1% ethanol group suffered 89% mortality during 108-120 hpf. No developmental defects were observed in any of the solvents at the 0.01 and 0.1% concentrations, but significantly higher deformity rates occurred with 1% ethanol and DMSO groups. Hyperactivity and less tortuous swimming paths were observed in all ethanol and DMSO concentrations. Based on this study, we suggest that data of behavioral toxicity bioassays using ethanol or DMSO as carrier solvents should be interpreted cautiously, because the solvents at low concentrations could alter locomotor activity of larval zebrafish without causing any observable developmental defects. PMID:21356178

  18. Loss of Frataxin induces iron toxicity, sphingolipid synthesis, and Pdk1/Mef2 activation, leading to neurodegeneration

    PubMed Central

    Chen, Kuchuan; Lin, Guang; Haelterman, Nele A; Ho, Tammy Szu-Yu; Li, Tongchao; Li, Zhihong; Duraine, Lita; Graham, Brett H; Jaiswal, Manish; Yamamoto, Shinya; Rasband, Matthew N; Bellen, Hugo J

    2016-01-01

    Mutations in Frataxin (FXN) cause Friedreich’s ataxia (FRDA), a recessive neurodegenerative disorder. Previous studies have proposed that loss of FXN causes mitochondrial dysfunction, which triggers elevated reactive oxygen species (ROS) and leads to the demise of neurons. Here we describe a ROS independent mechanism that contributes to neurodegeneration in fly FXN mutants. We show that loss of frataxin homolog (fh) in Drosophila leads to iron toxicity, which in turn induces sphingolipid synthesis and ectopically activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2). Dampening iron toxicity, inhibiting sphingolipid synthesis by Myriocin, or reducing Pdk1 or Mef2 levels, all effectively suppress neurodegeneration in fh mutants. Moreover, increasing dihydrosphingosine activates Mef2 activity through PDK1 in mammalian neuronal cell line suggesting that the mechanisms are evolutionarily conserved. Our results indicate that an iron/sphingolipid/Pdk1/Mef2 pathway may play a role in FRDA. DOI: http://dx.doi.org/10.7554/eLife.16043.001 PMID:27343351

  19. Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in guinea-pig

    PubMed Central

    Kasali, Félicien Mushagalusa; Kadima, Justin Ntokamunda; Mpiana, Pius Tshimankinda; Ngbolua, Koto-te-Nyiwa; Tshibangu, Damien Sha-Tshibey

    2013-01-01

    Objective To verify the antidiabetic activity of leaf extracts from Physalis peruviana L. popularly used in the Eastern part of the Democratic Republic of the Congo and to point out the possible toxicity. Method Aqueous decoctions prepared from dried leaves powder were administrated to guinea pigs at the dose range of 100 mg/kg to 3.2 g/kg of body weight. The hypoglycemic activity was evaluated by glucose tolerance test, loading animals with glucose 4 g/kg and measuring blood glucose concentrations at various times. The effect was compared to the control and glibenclamide as antidiabetic reference drug. Acute toxicity was evaluated by recording mortality rate, changes on blood biomarkers and damage caused to vital organs. Results At a dose of 100 mg/kg, the aqueous extract induced a significant reduction of peak concentration at 30 min after glucose loading as compared with control or reference (P<0.05). At doses greater than 400 mg, some alterations on blood, kidney and liver markers were observed. Upper 800 mg/kg, mortality was observed with LD50 estimated at about 1 280 mg/kg. At the autopsy, vital organs were in haemorrhage and swelling state. Conclusion The crude aqueous extracts from the leaves of Physalis peruviana L. present hypoglycemic activity in animal model, but at high doses the plant may cause severe intoxication.

  20. Determination of the acute toxicities of physicochemical pretreatment and advanced oxidation processes applied to dairy effluents on activated sludge.

    PubMed

    Sivrioğlu, Özge; Yonar, Taner

    2015-04-01

    In this study, the acute toxicities of raw, physicochemical pre-treated, ozonated, and Fenton reagent applied samples of dairy wastewater toward activated sludge microorganisms, evaluated using the International Organization for Standardization's respiration inhibition test (ISO 8192), are presented. Five-day biological oxygen demand (BOD5) was measured to determine the biodegradability of physicochemical treatment, ozonation, Fenton oxidation or no treatment (raw samples) of dairy wastewater. Chemical pretreatment positively affected biodegradability, and the inhibition exhibited by activated sludge was removed to a considerable degree. Ozonation and the Fenton process exhibited good chemical oxygen demand removal (61%) and removal of toxins. Low sludge production was observed for the Fenton process applied to dairy effluents. We did not determine the inhibitory effect of the Fenton-process on the activated sludge mixture. The pollutant-removal efficiencies of the applied processes and their associated operating costs were determined.

  1. Toxicity Profiles In Vivo in Mice and Antitumour Activity in Tumour-Bearing Mice of Di- and Triorganotin Compounds

    PubMed Central

    Willem, R.; Dalil, H.; de Vos, D.; Kuiper, C. M.; Peters, G. J.

    1998-01-01

    The in vivo toxicity profiles in mice and the antitumour activity in tumour bearing mice were screened for four di-n-butyltin and five triorganotin carboxylates, di-n-butyltin diterebate (5), bis(phenylacetate) (6), bis(deoxycholate) (7), bis(lithocholate) (8), tri-n-butyltin terebate (9), cinnamate (10), and triphenyltin terebate (11). At their maximum tolerated dosis (MTD), no antitumour effect (T/C ~1) was observed for the compounds 5, 7, 9, 10 and 11. The compounds 6 (T/C = 0.51) and 8 (T/C = 0.42) showed clear antitumour activity after single dose administration and might therefore be of interest for further antitumour activity studies. PMID:18475827

  2. Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats.

    PubMed

    Reddy, Y Amarnath; Chalamaiah, M; Ramesh, B; Balaji, G; Indira, P

    2014-05-01

    Lead poisoning has been known to be associated with structural and functional abnormalities of multiple organ systems of human body. The aim of this investigation was to study the renal protective effects of ginger (Zingiber officinale) extract in lead induced toxicity rats. In this study renal glutathione (GSH) level, glutathione peroxidase (GPX), glutathione-s-transferase (GST), and catalase enzymes were measured in lead nitrate (300 mg/kg BW), and lead nitrate plus ginger extract (150 mg/kg BW) treated rat groups for 1 week and 3 weeks respectively. The glutathione level and GSH dependent antioxidant enzymes such as glutathione peroxidase, glutathione-s-transferase, and catalase significantly (P < 0.05) increased in ginger extract treated rat groups. In addition, histological studies showed lesser renal changes in lead plus ginger extract treated rat groups than that of lead alone treated rat groups. These results indicate that ginger extract alleviated lead toxic effects by enhancing the levels of glutathione, glutathione peroxidase, glutathione-s-transferase and catalase.

  3. Anti-inflammatory, Antioxidant and Antimicrobial Activity Characterization and Toxicity Studies of Flowers of "Jarilla", a Medicinal Shrub from Argentina.

    PubMed

    Moreno, Alejandra; Nuño, Gabriela; Cuello, Soledad; Sayago, Jorge E; Alberto, María Rosa; Zampini, Catiana; Isla, María Inés

    2015-06-01

    Zuccagnia punctata Cav. (Fabaceae) is an Argentine medicinal aromatic shrub (jarilla pispito, puspus, lata and jarilla macho). The chalcones were identified as pigments responsible for the yellow color of the flowers. Hydroethanolic extracts were obtained both from fresh flowers and from flowers dried by lyophilization. The extracts were standardized by their phenolic and flavonoids content. Their fingerprints by HPLC-DAD indicated the presence of two chalcones as major compounds (2',4'-dihydroxychalcone and 2',4'-dihydroxy-3'-methoxychalcone). Both extracts showed the same total phenolic, non-flavonoid phenolic and flavonoid phenolic content and their phenolic profiles were similar. The polyphenolic extracts exhibited antioxidant (free radical scavenging and inhibitory activity on lipoperoxidation) and anti-inflammatory (inhibition of lipoxygenase and cyclooxygenase enzymes) activities. The flower extracts were active against six Candida species with MIC values between 60 and 120 μg GAE x mL(-1) and were also active on methicillin-resistant Staphylococcus aureus (MIC: 250 μg GAE x mL(-1)) and Enterococcus faecalis (MIC: 500 μg GAE x mL(-1)). The extracts were neither toxic (Artemia salina test) nor mutagenic (Ames test). Jarilla flowers could be considered as a new dietary supplement that could help to prevent pathologies associated with oxidative stress and the polyphenolic extract obtained from them could be considered as a standardized phytotherapeutic product with antimicrobial, antioxidant and anti-inflammatory activities. The aim of this work was to determine the pigments responsible for the yellow color of the flowers of Z. punctata and to evaluate the functional properties of the polyphenolic extract of the flowers. The toxicity (Artemia salina) and mutagenic activity (Ames test) of the extract were also evaluated.

  4. Induction of nitric oxide synthase activity by toxic shock syndrome toxin 1 in a macrophage-monocyte cell line.

    PubMed Central

    Zembowicz, A; Vane, J R

    1992-01-01

    Toxic shock syndrome toxin 1 (TSST-1) is a Mr 22,000 protein produced by Staphylococcus aureus. It is thought to be the cause of toxic shock syndrome. We investigated the hypothesis that TSST-1 induces nitric oxide (NO) synthase and that the NO formed may be involved in the pathogenesis of toxic shock syndrome. We used the murine monocyte-macrophage cell line J744.2 that responds to TSST-1 and also expresses NO synthase activity upon immunological stimulation. J774.2 macrophages stimulated with TSST-1 (10-100 nM) generated nitrite, a breakdown product of NO, and induced concentration-dependent elevations of cGMP in the pig kidney epithelial cell line (LLC-PK1). This latter effect was due to the generation of L-arginine-derived NO for it was (i) abolished by oxyhemoglobin (10 microM), a scavenger of NO, or by methylene blue (10 microM), an inhibitor of NO-activated guanylate cyclase; (ii) potentiated by superoxide dismutase (100 units/ml), which prolongs the life of NO; (iii) inhibited by NG-monomethyl-L-arginine (0.3 mM), an inhibitor of NO synthase; (iv) significantly decreased when L-arginine (0.4 mM) in the medium was replaced by D-arginine (0.4 mM). Moreover, TSST-1 (100 nM) enhanced the activity of cytosolic NO synthase in J774.2 cells. Hydrocortisone (1 microM) but not indomethacin (5 micrograms/ml) or salicylic acid (5 micrograms/ml) prevented the generation of NO2- and the increases in cGMP levels in LLC-PK1 cells induced by J774.2 cells stimulated with TSST-1. The effects of hydrocortisone were partially reversed by coincubation with RU 486 (1 microM), an antagonist of glucocorticoid receptors. Thus, TSST-1 and perhaps other exotoxins produced by Gram-positive bacteria induce NO synthase and the increased NO formation may contribute to toxic shock syndrome and possibly to changes in the immune responses that accompany infection. PMID:1372433

  5. Tacrine-Trolox Hybrids: A Novel Class of Centrally Active, Nonhepatotoxic Multi-Target-Directed Ligands Exerting Anticholinesterase and Antioxidant Activities with Low In Vivo Toxicity.

    PubMed

    Nepovimova, Eugenie; Korabecny, Jan; Dolezal, Rafael; Babkova, Katerina; Ondrejicek, Ales; Jun, Daniel; Sepsova, Vendula; Horova, Anna; Hrabinova, Martina; Soukup, Ondrej; Bukum, Neslihan; Jost, Petr; Muckova, Lubica; Kassa, Jiri; Malinak, David; Andrs, Martin; Kuca, Kamil

    2015-11-25

    Coupling of two distinct pharmacophores, tacrine and trolox, endowed with different biological properties, afforded 21 hybrid compounds as novel multifunctional candidates against Alzheimer's disease. Several of them showed improved inhibitory properties toward acetylcholinesterase (AChE) in relation to tacrine. These hybrids also scavenged free radicals. Molecular modeling studies in tandem with kinetic analysis exhibited that these hybrids target both catalytic active site as well as peripheral anionic site of AChE. In addition, incorporation of the moiety bearing antioxidant abilities displayed negligible toxicity on human hepatic cells. This striking effect was explained by formation of nontoxic metabolites after 1 h incubation in human liver microsomes system. Finally, tacrine-trolox hybrids exhibited low in vivo toxicity after im administration in rats and potential to penetrate across blood-brain barrier. All of these outstanding in vitro results in combination with promising in vivo outcomes highlighted derivative 7u as the lead structure worthy of further investigation.

  6. 19-Substituted Benzoquinone Ansamycin Heat Shock Protein-90 Inhibitors: Biological Activity and Decreased Off-Target Toxicity

    PubMed Central

    Chang, Chuan-Hsin; Drechsel, Derek A.; Kitson, Russell R. A.; Siegel, David; You, Qiang; Backos, Donald S.; Ju, Cynthia; Moody, Christopher J.

    2014-01-01

    The benzoquinone ansamycins (BQAs) are a valuable class of antitumor agents that serve as inhibitors of heat shock protein (Hsp)-90. However, clinical use of BQAs has resulted in off-target toxicities, including concerns of hepatotoxicity. Mechanisms underlying the toxicity of quinones include their ability to redox cycle and/or arylate cellular nucleophiles. We have therefore designed 19-substituted BQAs to prevent glutathione conjugation and nonspecific interactions with protein thiols to minimize off-target effects and reduce hepatotoxicity. 19-Phenyl– and 19-methyl–substituted versions of geldanamycin and its derivatives, 17-allylamino-17-demethoxygeldanamycin and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), did not react with glutathione, whereas marked reactivity was observed using parent BQAs. Importantly, although 17-DMAG induced cell death in primary and cultured mouse hepatocytes, 19-phenyl and 19-methyl DMAG showed reduced toxicity, validating the overall approach. Furthermore, our data suggest that arylation reactions, rather than redox cycling, are a major mechanism contributing to BQA hepatotoxicity. 19-Phenyl BQAs inhibited purified Hsp90 in a NAD(P)H:quinone oxidoreductase 1 (NQO1)–dependent manner, demonstrating increased efficacy of the hydroquinone ansamycin relative to its parent quinone. Molecular modeling supported increased stability of the hydroquinone form of 19-phenyl-DMAG in the active site of human Hsp90. In human breast cancer cells, 19-phenyl BQAs induced growth inhibition also dependent upon metabolism via NQO1 with decreased expression of client proteins and compensatory induction of Hsp70. These data demonstrate that 19-substituted BQAs are unreactive with thiols, display reduced hepatotoxicity, and retain Hsp90 and growth-inhibitory activity in human breast cancer cells, although with diminished potency relative to parent BQAs. PMID:24682466

  7. Joint toxicity of sediment-associated permethrin and cadmium to Chironomus dilutus: The role of bioavailability and enzymatic activities.

    PubMed

    Chen, Xin; Li, Huizhen; You, Jing

    2015-12-01

    Pyrethroid insecticides and metals commonly co-occurred in sediment and caused toxicity to benthic organisms jointly. To improve accuracy in assessing risk of the sediments contaminated by insecticides and metals, it is of great importance to understand interaction between the contaminants and reasons for the interaction. In the current study, permethrin and cadmium were chosen as representative contaminants to study joint toxicity of pyrethroids and metals to a benthic invertebrate Chironomus dilutus. A median effect/combination index-isobologram was applied to evaluate the interaction between sediment-bound permethrin and cadmium at three dose ratios. Antagonistic interaction was observed in the midges for all treatments. Comparatively, cadmium-dominated group (the ratio of toxicity contribution from permethrin and cadmium was 1:3) showed stronger antagonism than equitoxicity (1:1) and permethrin-dominated groups (3:1). The reasons for the observed antagonism were elucidated from two aspects, including bioavailability and enzymatic activity. The bioavailability of permethrin, expressed as the freely dissolved concentrations in sediment porewater and measured by solid phase microextraction, was not altered by the addition of cadmium, suggesting the change in permethrin bioavailability was not the reason for the antagonism. On the other hand, the activities of metabolic enzymes, glutathione S-transferase and carboxylesterase in the midges which were exposed to mixtures of permethrin and cadmium were significantly higher than those in the midges exposed to permethrin solely. Cadmium considerably enhanced the detoxifying processes of permethrin in the midges, which largely explained the observed antagonistic interaction between permethrin and cadmium.

  8. Analytical applications of microbial fuel cells. Part II: Toxicity, microbial activity and quantification, single analyte detection and other uses.

    PubMed

    Abrevaya, Ximena C; Sacco, Natalia J; Bonetto, Maria C; Hilding-Ohlsson, Astrid; Cortón, Eduardo

    2015-01-15

    Microbial fuel cells were rediscovered twenty years ago and now are a very active research area. The reasons behind this new activity are the relatively recent discovery of electrogenic or electroactive bacteria and the vision of two important practical applications, as wastewater treatment coupled with clean energy production and power supply systems for isolated low-power sensor devices. Although some analytical applications of MFCs were proposed earlier (as biochemical oxygen demand sensing) only lately a myriad of new uses of this technology are being presented by research groups around the world, which combine both biological-microbiological and electroanalytical expertises. This is the second part of a review of MFC applications in the area of analytical sciences. In Part I a general introduction to biological-based analytical methods including bioassays, biosensors, MFCs design, operating principles, as well as, perhaps the main and earlier presented application, the use as a BOD sensor was reviewed. In Part II, other proposed uses are presented and discussed. As other microbially based analytical systems, MFCs are satisfactory systems to measure and integrate complex parameters that are difficult or impossible to measure otherwise, such as water toxicity (where the toxic effect to aquatic organisms needed to be integrated). We explore here the methods proposed to measure toxicity, microbial metabolism, and, being of special interest to space exploration, life sensors. Also, some methods with higher specificity, proposed to detect a single analyte, are presented. Different possibilities to increase selectivity and sensitivity, by using molecular biology or other modern techniques are also discussed here.

  9. In vitro and in vivo acaricidal activity and residual toxicity of spinosad to the poultry red mite, Dermanyssus gallinae.

    PubMed

    George, D R; Shiel, R S; Appleby, W G C; Knox, A; Guy, J H

    2010-10-29

    This paper describes two experiments conducted to examine the acaricidal potential of spinosad against the poultry red mite, Dermanyssus gallinae (De Geer), a serious ectoparasitic pest of laying hens. Spinosad is a natural product derived from the fermentation of the micro-organism Saccharopolyspora spinosa. In vitro testing confirmed that, when applied to a galvanised metal plate to the point of run-off, spinosad was toxic to adult female D. gallinae and suggested that at an application rate of 3.88 g/L a significant residual toxicity of spinosad could be achieved for up to 21 days. A subsequent in vivo experiment in a conventional cage housing system for laying hens demonstrated the acaricidal activity and residual toxicity to D. gallinae of a single application of spinosad when applied at either 1.94 or 3.88 g/L. Residual toxicity of spinosad at both of these application rates was maintained throughout the course of the 28 day post-spray study period, with a peak in product efficacy seen 14 days after spraying. The results suggest that the greater the D. gallinae population the greater will be the toxic effect of spinosad. Although the exact reasons for this are unclear, it can be speculated that conspecifics spread the product between each other more efficiently at higher mite population densities. However, further study is warranted to confirm this possibility. Application of spinosad in vivo had no effect on hen bodyweight or egg production parameters (number and weight), suggesting that this product could be used to effectively control D. gallinae infestations whilst birds are in lay. This paper also describes a novel method for effectively and efficiently achieving replication of treatments in a single poultry house, previously unpopulated with D. gallinae. Individual groups of conventional cages were stocked with hens, seeded with D. gallinae and used as replicates. Independence of replicates was achieved by isolating cage groups from one another using a

  10. Synthesis, antibacterial and anti-MRSA activity, in vivo toxicity and a structure-activity relationship study of a quinoline thiourea.

    PubMed

    Dolan, Niamh; Gavin, Declan P; Eshwika, Ahmed; Kavanagh, Kevin; McGinley, John; Stephens, John C

    2016-01-15

    We report the synthesis, antibacterial evaluation of a series of thiourea-containing compounds. 1-(3,5-Bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)-((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea 5, was the most active against a range of Gram-positive and Gram-negative bacteria, and exhibited bacteriostatic activity against methicillin resistant Staphylococcus aureus (MRSA) comparable to that of the well-known antibacterial agent vancomycin. Quinoline thiourea 5 was subjected to a detailed structure-activity relationship study, with 5 and its derivatives evaluated for their bacteriostatic activity against both Gram-negative and Gram-positive bacteria. A number of structural features important for the overall activity of quinoline thiourea 5 have been identified. A selection of compounds, including 5, was also evaluated for their in vivo toxicity using the larvae of the Greater wax moth, Galleria mellonella. Compound 5, and a number of derivatives, were found to be non-toxic to the larvae of Galleria mellonella. A new class of antibiotic can result from the further development of this family of compounds.

  11. Decreasing toxic and mutagenic activity of soils through the application of humic substances

    NASA Astrophysics Data System (ADS)

    Gorova Alla, I.; Pavlichenko Artem, 2.; Klimkina Iryna, 3.

    2009-04-01

    Based on an example of conditions on mining industry land adjacent to the Dnepr River in the Dnepropetrovsk Region (Ukraine), the ecological quality of the soils was evaluated by cytogenetic methods and, in parallel, the efficiency of using humates obtained from brown coal of the Alexandria deposit was also researched. During an ecological monitoring programme from 1997 to 2007, the genetic characteristics of soils at 12 locations in Dnepropetrovsk, and at 33 locations in four other industrial mining areas in the region, was studied. A theoretical basis for the use of humic substances for blocking the migration paths of ecological toxic-matter within a soil-to-plant system was reasoned, namely that introducing natrium humate into the soil would promote a normalization of the cell division processes and a reduction in the chromosome aberration rate in the root meristem of the biological indicators. Laboratory tests involved growing seeds of an indicator plant (Pisum sativum L.) in the different soils, to some of which humic substances had been added. The data showed evidence that the soils of the region display a rather patchy picture in terms of toxic and mutagen features. This was obvious from the variety of levels on the mitotic index, as well as from the increase of 5 to 24 times the frequency of aberrant chromosomes. Introducing 0.01per cent of a Christecol water solution into a substratum for growing the indicator plant apparently reduced (P<0,01) the level of the chromosome aberrations in the meristem cells of the test material. The mutagenic rates of the soils during the test was reduced by 1.5 to 4 times and, at the same time, a reduction of the soil toxic rates was also observed. The reduction in chromosome aberration levels in the cells of the tested materials for the soils in the different city districts, varied from 2.9 to 12.4 times. Importantly, a reliable reduction in the genetic damage under the influence of humic substances was observed in all test

  12. A novel natural Nrf2 activator with PPARγ-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia.

    PubMed

    Hsu, Wei-Hsuan; Lee, Bao-Hong; Chang, Yu-Ying; Hsu, Ya-Wen; Pan, Tzu-Ming

    2013-11-01

    Methylglyoxal (MG) is a toxic-glucose metabolite and a major precursor of advanced glycation endproducts (AGEs). MG has been reported to result in inflammation by activating receptor for AGEs (RAGE). We recently found that Monascus-fermented metabolite monascin acts as a novel natural peroxisome proliferator-activated receptor-γ (PPARγ) agonist that improves insulin sensitivity. We investigated the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats treated with oral administration of monascin or rosiglitazone. Monascin (a novel PPARγ agonist) activated nuclear factor-erythroid 2-related factor 2 (Nrf2) and down-regulated hyperinsulinmia in oral glucose tolerance test (OGTT). Monascin was able to elevate glyoxalase-1 expression via activation of hepatic Nrf2, hence, resulting in MG metabolism to d-lactic acid and protected from AGEs production in MG-treated rats. Rosiglitazone did not activate Nrf2 nor glyoxalase expression to lower serum and hepatic AGEs levels. Monascin acts as a novel natural Nrf2 activator with PPARγ-agonist activity were confirmed by Nrf2 and PPARγ reporter assays in Hep G2 cells. These findings suggest that monascin acts as an anti-diabetic and anti-oxidative stress agent to a greater degree than rosiglitazone and thus may have therapeutic potential for the prevention of diabetes. PMID:23954466

  13. Short KR-12 analogs designed from human cathelicidin LL-37 possessing both antimicrobial and antiendotoxic activities without mammalian cell toxicity.

    PubMed

    Jacob, Binu; Park, Il-Seon; Bang, Jeong-Kyu; Shin, Song Yub

    2013-11-01

    KR-12 (residues 18-29 of LL-37) was known to be the smallest peptide of human cathelicidin LL-37 possessing antimicrobial activity. In order to optimize α-helical short antimicrobial peptides having both antimicrobial and antiendotoxic activities without mammalian cell toxicity, we designed and synthesized a series of KR-12 analogs. Highest hydrophobic analogs KR-12-a5 and KR-12-a6 displayed greater inhibition of lipopolysaccharide (LPS)-stimulated tumor necrosis factor-α production and higher LPS-binding activity. We have observed that antimicrobial activity is independent of charge, but LPS neutralization requires a balance of hydrophobicity and net positive charge. Among KR-12 analogs, KR-12-a2, KR-12-a3 and KR-12-a4 showed much higher cell specificity for bacteria over erythrocytes and retained antiendotoxic activity, relative to parental LL-37. KR-12-a5 displayed the strongest antiendotoxic activity but almost similar cell specificity as compared with LL-37. Also, these KR-12 analogs (KR-12-a2, KR-12-a3, KR-12-a4 and KR-12-a5) exhibited potent antimicrobial activity (minimal inhibitory concentration: 4 μM) against methicillin-resistant Staphylococcus aureus. Taken together, these KR-12 analogs have the potential for future development as a novel class of antimicrobial and anti-inflammatory therapeutic agents.

  14. Study of antisickling and vasorelaxant activities and acute toxicity assessment of crude extracts of leaves of Ficus sycomorus L. (Moraceae).

    PubMed

    Ramdé-Tiendrébéogo, Alphonsine; Tibiri, André; Ouedraogo, Moussa; Ouédraogo, Sylvin; Nacoulma, Odile Germaine; Guissou, Innocent Pierre

    2014-06-01

    The leaves of Ficus sycomorus are used in Burkina Faso folk medicine for the treatment of sickle cell disease. The present comparative study of crude extracts of leaves (decoction, macerated extract and a 95% ethanol extract) was performed with the aim to assess the efficiency of this traditional use and to determine the most active of the three extracts. Antisickling activity was assessed by the Emmel's test. Vasorelaxant effect on rat aortic rings precontracted by phenylephrine with and without N-nitro-L-arginine methyl ester chloride (L-NAME) was also evaluated. The 95% ethanol extract (20 mg mL(-1)) showed the most antisickling activity on sickle erythrocytes, by inhibiting completely sickling of double heterozygote SC cells in 60 min and that of homozygote SS cells in 90 min. On the aorta this extract exhibited a significant (p<0.05) vasorelaxant activity, better than that of the other extracts, with an IC50 value of 6.86±0.13 mg mL(-1) against 18.78±0.38 and 28.56±1.27 mg mL(-1), respectively for the macerated extract and the decoction. When the aortic rings were pretreated with L-NAME, only the ethanolic extract conserved its vasorelaxant activity, up to 73% of relaxation. The acute toxicity of the decoction, assessed by intraperitoneal route and using the Litchfield and Wilcoxon method, led to an LD50 value of 1553.61 mg kg(-1) b.wt. This places the drug among those with low toxicity according to the WHO scale. These results confirm those previously obtained and provide a scientific basis supporting the use of this plant in folk medicine against sickle cell disease. They indicate the importance of Ficus sycomorus in the research of new antisickling molecules. PMID:26035956

  15. Antioxidant activity, delayed aging, and reduced amyloid-β toxicity of methanol extracts of tea seed pomace from Camellia tenuifolia.

    PubMed

    Wei, Chia-Cheng; Yu, Chan-Wei; Yen, Pei-Ling; Lin, Huan-You; Chang, Shang-Tzen; Hsu, Fu-Lan; Liao, Vivian Hsiu-Chuan

    2014-11-01

    There is a growing interest in the exploitation of the residues generated by plants. This study explored the potential beneficial health effects from the main biowaste, tea seed pomace, produced when tea seed is processed. DPPH radical scavenging and total phenolic content assays were performed to evaluate the in vitro activities of the extracts. Caenorhabditis elegans was used as in vivo model to evaluate the beneficial health effects, including antioxidant activity, delayed aging, and reduced amyloid-β toxicity. Among all soluble fractions obtained from the extracts of tea seed pomace from Camellia tenuifolia, the methanol (MeOH)-soluble fraction has the best in vivo antioxidant activities. The MeOH-soluble extraction was further divided into six fractions by chromatography with a Diaion HP-20 column eluted with water/MeOH, and fraction 3 showed the best in vitro and in vivo antioxidant activities. Further analysis in C. elegans showed that the MeOH extract (fraction 3) of tea seed pomace significantly decreased intracellular reactive oxygen species, prolonged C. elegans lifespan, and reduced amyloid-β (Aβ) toxicity in transgenic C. elegans expressing human Aβ. Moreover, bioactivity-guided fractionation yielded two potent constituents from fraction 3 of the MeOH extract, namely, kaempferol 3-O-(2″-glucopyranosyl)-rutinoside and kaempferol 3-O-(2″-xylopyranosyl)-rutinoside, and both compounds exhibited excellent in vivo antioxidant activity. Taken together, MeOH extracts of tea seed pomace from C. tenuifolia have multiple beneficial health effects, suggesting that biowaste might be valuable to be explored for further development as nutraceutical products. Furthermore, the reuse of agricultural byproduct tea seed pomace also fulfills the environmental perspective.

  16. Study of antisickling and vasorelaxant activities and acute toxicity assessment of crude extracts of leaves of Ficus sycomorus L. (Moraceae).

    PubMed

    Ramdé-Tiendrébéogo, Alphonsine; Tibiri, André; Ouedraogo, Moussa; Ouédraogo, Sylvin; Nacoulma, Odile Germaine; Guissou, Innocent Pierre

    2014-06-01

    The leaves of Ficus sycomorus are used in Burkina Faso folk medicine for the treatment of sickle cell disease. The present comparative study of crude extracts of leaves (decoction, macerated extract and a 95% ethanol extract) was performed with the aim to assess the efficiency of this traditional use and to determine the most active of the three extracts. Antisickling activity was assessed by the Emmel's test. Vasorelaxant effect on rat aortic rings precontracted by phenylephrine with and without N-nitro-L-arginine methyl ester chloride (L-NAME) was also evaluated. The 95% ethanol extract (20 mg mL(-1)) showed the most antisickling activity on sickle erythrocytes, by inhibiting completely sickling of double heterozygote SC cells in 60 min and that of homozygote SS cells in 90 min. On the aorta this extract exhibited a significant (p<0.05) vasorelaxant activity, better than that of the other extracts, with an IC50 value of 6.86±0.13 mg mL(-1) against 18.78±0.38 and 28.56±1.27 mg mL(-1), respectively for the macerated extract and the decoction. When the aortic rings were pretreated with L-NAME, only the ethanolic extract conserved its vasorelaxant activity, up to 73% of relaxation. The acute toxicity of the decoction, assessed by intraperitoneal route and using the Litchfield and Wilcoxon method, led to an LD50 value of 1553.61 mg kg(-1) b.wt. This places the drug among those with low toxicity according to the WHO scale. These results confirm those previously obtained and provide a scientific basis supporting the use of this plant in folk medicine against sickle cell disease. They indicate the importance of Ficus sycomorus in the research of new antisickling molecules.

  17. Sitophilus granarius L. (Coleoptera) Toxicity and Biological Activities of the Essential Oils of Tanacetum macrophyllum (Waldst. & Kit.) Schultz Bip.

    PubMed

    Polatoğlu, Kaan; Karakoç, Ömer Cem; Demirci, Betül; Gören, Nezhun; Can Başer, Kemal Hüsnü

    2015-01-01

    Insecticides of the natural origin are an important alternative to the synthetic insecticides that are being employed for the preserving stored products. The volatiles obtained from T. cinerariifolium (=Pyrethrum cinerariifolium) is being used for many types of insecticidal applications; however there is a very little information on the insecticidal activity of the essential oils of other Tanacetum species. The main purpose of the present study is to determine the chemical composition of T. macrophyllum (Waldst. & Kit.) Schultz Bip. essential oils and evaluate their insecticidal activity against S. granarius as well as its other beneficial biological activities. Highest contact toxicity was observed in the leaf oil of (88.93%) against S. granarius. The flower oil showed considerable fumigant toxicity against L. minor at 10 mg/mL application concentration (61.86 %) when compared with other samples at the same concentration. The highest DPPH (2,2-Diphenyl-1-picrylhydrazyl) scavenging activity (47.7%) and phosphomolybdenum reducing activity was observed also for the flower oil of T. macrophyllum at 10 mg/mL concentration. The essential oils were analyzed by GC, GC/MS. The flower and leaf oils were characterized with γ-eudesmol 21.5%, (E)-sesquilavandulol 20.3%, copaborneol 8.5% and copaborneol 14.1%, 1,8-cineole 11%, bornyl acetate 9.6%, borneol 6.3% respectively. AHC analysis of the qualitative and quantitative data obtained from the essential oil composition of the T. macrophyllum essential oil from the present research and previous reports pointed out that two different chemotypes could be proposed with current findings which are p-methyl benzyl alcohol/ cadinene and eudesmane chemotypes.

  18. Sitophilus granarius L. (Coleoptera) Toxicity and Biological Activities of the Essential Oils of Tanacetum macrophyllum (Waldst. & Kit.) Schultz Bip.

    PubMed

    Polatoğlu, Kaan; Karakoç, Ömer Cem; Demirci, Betül; Gören, Nezhun; Can Başer, Kemal Hüsnü

    2015-01-01

    Insecticides of the natural origin are an important alternative to the synthetic insecticides that are being employed for the preserving stored products. The volatiles obtained from T. cinerariifolium (=Pyrethrum cinerariifolium) is being used for many types of insecticidal applications; however there is a very little information on the insecticidal activity of the essential oils of other Tanacetum species. The main purpose of the present study is to determine the chemical composition of T. macrophyllum (Waldst. & Kit.) Schultz Bip. essential oils and evaluate their insecticidal activity against S. granarius as well as its other beneficial biological activities. Highest contact toxicity was observed in the leaf oil of (88.93%) against S. granarius. The flower oil showed considerable fumigant toxicity against L. minor at 10 mg/mL application concentration (61.86 %) when compared with other samples at the same concentration. The highest DPPH (2,2-Diphenyl-1-picrylhydrazyl) scavenging activity (47.7%) and phosphomolybdenum reducing activity was observed also for the flower oil of T. macrophyllum at 10 mg/mL concentration. The essential oils were analyzed by GC, GC/MS. The flower and leaf oils were characterized with γ-eudesmol 21.5%, (E)-sesquilavandulol 20.3%, copaborneol 8.5% and copaborneol 14.1%, 1,8-cineole 11%, bornyl acetate 9.6%, borneol 6.3% respectively. AHC analysis of the qualitative and quantitative data obtained from the essential oil composition of the T. macrophyllum essential oil from the present research and previous reports pointed out that two different chemotypes could be proposed with current findings which are p-methyl benzyl alcohol/ cadinene and eudesmane chemotypes. PMID:26179008

  19. Inhibition of toxic activities of Bothrops asper venom and other crotalid snake venoms by a novel neutralizing mixture.

    PubMed

    Borkow, G; Gutierrez, J M; Ovadia, M

    1997-12-01

    The majority of snake bites in Central America are caused by Bothrops asper, whose venom induce complex local effects such as myonecrosis, edema and especially hemorrhage. These effects are only partially neutralized by the clinically used antivenom, even when administered rapidly after envenomation. Recently we screened 49 substances for antihemorrhagic activity and found that a mixture composed of CaNa2, EDTA, a B. asper serum fraction (natural antidote), and the currently used horse polyvalent antiserum is highly effective in the neutralization of local and systemic hemorrhage developing after B. asper envenomation (Borkow et al., Toxicon 35, 865-877, 1997). In the present study we screened the best six antihemorrhagic compounds for their capacity to neutralize the lethal activity in mice and the proteolytic, hemolytic, and antiattachment activities in vitro of the venom. The compounds tested included the currently used horse antivenom, rabbit antiserum against whole B. asper venom or against heated venom, B. asper and Natrix tessellata serum fractions, and CaNa2 EDTA. The constituents of the antihemorrhagic mixture were also the best inhibitors of the other examined toxic activities. Importantly, the mixture effectively neutralized toxic activities of an additional nine venoms from snakes abundant in Central America. This work suggests that the polyvalent antivenom used in Central America could be enriched with a B. asper serum fraction producing a more effective antivenom. In addition, the local application of CaNa2 EDTA to neutralize hemorrhagic toxins, immediately after a snake bite, may provide rapid inhibition of local damage caused by the venoms. PMID:9439739

  20. Antioxidant activity, delayed aging, and reduced amyloid-β toxicity of methanol extracts of tea seed pomace from Camellia tenuifolia.

    PubMed

    Wei, Chia-Cheng; Yu, Chan-Wei; Yen, Pei-Ling; Lin, Huan-You; Chang, Shang-Tzen; Hsu, Fu-Lan; Liao, Vivian Hsiu-Chuan

    2014-11-01

    There is a growing interest in the exploitation of the residues generated by plants. This study explored the potential beneficial health effects from the main biowaste, tea seed pomace, produced when tea seed is processed. DPPH radical scavenging and total phenolic content assays were performed to evaluate the in vitro activities of the extracts. Caenorhabditis elegans was used as in vivo model to evaluate the beneficial health effects, including antioxidant activity, delayed aging, and reduced amyloid-β toxicity. Among all soluble fractions obtained from the extracts of tea seed pomace from Camellia tenuifolia, the methanol (MeOH)-soluble fraction has the best in vivo antioxidant activities. The MeOH-soluble extraction was further divided into six fractions by chromatography with a Diaion HP-20 column eluted with water/MeOH, and fraction 3 showed the best in vitro and in vivo antioxidant activities. Further analysis in C. elegans showed that the MeOH extract (fraction 3) of tea seed pomace significantly decreased intracellular reactive oxygen species, prolonged C. elegans lifespan, and reduced amyloid-β (Aβ) toxicity in transgenic C. elegans expressing human Aβ. Moreover, bioactivity-guided fractionation yielded two potent constituents from fraction 3 of the MeOH extract, namely, kaempferol 3-O-(2″-glucopyranosyl)-rutinoside and kaempferol 3-O-(2″-xylopyranosyl)-rutinoside, and both compounds exhibited excellent in vivo antioxidant activity. Taken together, MeOH extracts of tea seed pomace from C. tenuifolia have multiple beneficial health effects, suggesting that biowaste might be valuable to be explored for further development as nutraceutical products. Furthermore, the reuse of agricultural byproduct tea seed pomace also fulfills the environmental perspective. PMID:25295856

  1. Evaluation of the antibacterial activity and toxicity of 2 new hydrogels: a pilot study.

    PubMed

    Vandenbulcke, Katia; Horvat, Lada-Ivana Laenen; De Mil, Martine; Slegers, Guido; Beele, Hilde

    2006-06-01

    Wound bed preparation remains a very important issue in wound healing. To promote the production of granulation tissue, it is necessary to remove necrotic tissue and to control infection. Necrotic tissue may be removed using a hydrogel preparation. Flaminal and Flaminal Hydro (Flen Pharma, Belgium) are 2 new hydroactive colloid gel dressings with state antibacterial properties. These properties are attributed to an enzymatic complex in their formulation. In the study described in this report, the antibacterial effects of Flaminal and Flaminal Hydro were confirmed in an in vitro as well as an in vivo setting. It was also demonstrated that Flaminal and Flaminal Hydro are not toxic to keratinocytes in vitro using an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. PMID:16698915

  2. Effect of olive mill wastewaters on the oxygen consumption by activated sludge microorganisms: an acute toxicity test method.

    PubMed

    Paixão, S M; Anselmo, A M

    2002-01-01

    The test for inhibition of oxygen consumption by activated sludge (ISO 8192-1986 (E)) was evaluated as a tool for assessing, the acute toxicity of olive mill wastewaters (OMW). According to the ISO test, information generated by this method may be helpful in estimating the effect of a test material on bacterial communities in the aquatic environment, especially in aerobic biological treatment systems. However, the lack of standardized bioassay methodology for effluents imposed that the test conditions were modified and adapted. The experiments were conducted in the presence or absence of an easily biodegradable carbon source (glucose) with different contact times (20 min and 24 h). The results obtained showed a remarkable stimulatory effect of this effluent to the activated sludge microorganisms. In fact, the oxygen uptake rate values increase with increasing effluent concentrations and contact times up to 0.98 microl O(2) h(-1) mg(-1) dry weight for a 100% OMW sample, 24 h contact time, with blanks exhibiting an oxygen uptake rate of ca. 1/10 of this value (0.07-0.10). It seems that the application of the ISO test as an acute toxicity test for effluents should be reconsidered, with convenient adaptation for its utilization as a method of estimating the effect on bacterial communities present in aerobic biological treatment systems. PMID:12015797

  3. Larvicidal activity of Myrtaceae essential oils and their components against Aedes aegypti, acute toxicity on Daphnia magna, and aqueous residue.

    PubMed

    Park, Hye-Mi; Kim, Junheon; Chang, Kyu-Sik; Kim, Byung-Seok; Yang, Yu-Jung; Kim, Gil-Hah; Shin, Sang-Chul; Park, Il-Kwon

    2011-03-01

    The larvicidal activity of 11 Myrtaceae essential oils and their constituents was evaluated against Aedes aegypti L. Of the 11, Melaleuca linariifolia Sm., Melaleuca dissitiflora F. Muell., Melaleuca quinquenervia (Cav.) S. T. Blake, and Eucalyptus globulus Labill oils at 0.1 mg/ml exhibited > or = 80% larval mortality. At this same concentration, the individual constituents tested, allyl isothiocyanate, alpha-terpinene, p-cymene, (+)-limonene, (-)-limonene, gamma-terpinene, and (E)-nerolidol, resulted in > or = 95% mortality. We also tested the acute toxicity of these four active oils earlier mentioned and their constituents against Daphnia magna Straus. M. linariifolia and allyl isothiocyanate was the most toxic to D. magna. Twodays after treatment, residues of M. dissitiflora, M. linariifolia, M. quinquenervia, and E. globulus oils in water were 55.4, 46.6, 32.4, and 14.8%, respectively. Less than 10% of allyl isothiocyanate, alpha-terpinene, p-cymene, (-)-limonene, (+)-limonene, and gamma-terpinene was detected in the water at 2 d after treatment. Our results indicated that oils and their constituents could easily volatilize in water within a few days after application, thus minimizing their effect on the aqueous ecosystem. Therefore, Myrtaceae essential oils and their constituents could be developed as control agents against mosquito larvae. PMID:21485381

  4. Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies.

    PubMed

    Skibinski, Gaia; Nakamura, Ken; Cookson, Mark R; Finkbeiner, Steven

    2014-01-01

    By combining experimental neuron models and mathematical tools, we developed a "systems" approach to deconvolve cellular mechanisms of neurodegeneration underlying the most common known cause of Parkinson's disease (PD), mutations in leucine-rich repeat kinase 2 (LRRK2). Neurons ectopically expressing mutant LRRK2 formed inclusion bodies (IBs), retracted neurites, accumulated synuclein, and died prematurely, recapitulating key features of PD. Degeneration was predicted from the levels of diffuse mutant LRRK2 that each neuron contained, but IB formation was neither necessary nor sufficient for death. Genetic or pharmacological blockade of its kinase activity destabilized LRRK2 and lowered its levels enough to account for the moderate reduction in LRRK2 toxicity that ensued. By contrast, targeting synuclein, including neurons made from PD patient-derived induced pluripotent cells, dramatically reduced LRRK2-dependent neurodegeneration and LRRK2 levels. These findings suggest that LRRK2 levels are more important than kinase activity per se in predicting toxicity and implicate synuclein as a major mediator of LRRK2-induced neurodegeneration.

  5. Predicting competitive adsorption behavior of major toxic anionic elements onto activated alumina: a speciation-based approach.

    PubMed

    Su, Tingzhi; Guan, Xiaohong; Tang, Yulin; Gu, Guowei; Wang, Jianmin

    2010-04-15

    Toxic anionic elements such as arsenic, selenium, and vanadium often co-exist in groundwater. These elements may impact each other when adsorption methods are used to remove them. In this study, we investigated the competitive adsorption behavior of As(V), Se(IV), and V(V) onto activated alumina under different pH and surface loading conditions. Results indicated that these anionic elements interfered with each other during adsorption. A speciation-based model was developed to quantify the competitive adsorption behavior of these elements. This model could predict the adsorption data well over the pH range of 1.5-12 for various surface loading conditions, using the same set of adsorption constants obtained from single-sorbate systems. This model has great implications in accurately predicting the field capacity of activated alumina under various local water quality conditions when multiple competitive anionic elements are present.

  6. Fumigant toxicity of Oriental sweetgum (Liquidambar orientalis) and valerian (Valeriana wallichii) essential oils and their components, including their acetylcholinesterase inhibitory activity, against Japanese termites (Reticulitermes speratus).

    PubMed

    Park, Il-Kwon

    2014-01-01

    This study investigated the fumigant toxicity of oriental sweetgum (Liquidambar orientalis) and valerian (Valeriana wallichii) essential oils and their components against the Japanese termite (Reticulitermes speratus). The fumigant toxicity of oriental sweetgum and valerian oil differed significantly according to exposure time. Oriental sweetgum showed toxicity at short exposure times (2 days), and the toxicity of valerian oil was high 7 days after treatment. The main constituents of oriental sweetgum and valerian oils were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, benzyl alcohol, acetophenone, 1-phenyl-1-ethanol, hydrocinnamyl alcohol, trans-cinnamyl aldehyde, trans-cinnamyl alcohol, cis-asarone, styrene, and cis-ocimene showed toxicity against Japanese termites 7 days after treatment. Hydrocinnamyl alcohol and trans-cinnamyl alcohol were found to be the major contributors to the fumigant antitermitic toxicity of oriental sweetgum oil. The acetylcholinesterase (AChE) inhibition activity of two oils and their constituents was tested to determine their mode of action. Only cis-ocimene showed strong AChE inhibition activity with an IC50 value of 0.131 mg/mL. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control. PMID:25153870

  7. Fumigant toxicity of Oriental sweetgum (Liquidambar orientalis) and valerian (Valeriana wallichii) essential oils and their components, including their acetylcholinesterase inhibitory activity, against Japanese termites (Reticulitermes speratus).

    PubMed

    Park, Il-Kwon

    2014-08-19

    This study investigated the fumigant toxicity of oriental sweetgum (Liquidambar orientalis) and valerian (Valeriana wallichii) essential oils and their components against the Japanese termite (Reticulitermes speratus). The fumigant toxicity of oriental sweetgum and valerian oil differed significantly according to exposure time. Oriental sweetgum showed toxicity at short exposure times (2 days), and the toxicity of valerian oil was high 7 days after treatment. The main constituents of oriental sweetgum and valerian oils were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, benzyl alcohol, acetophenone, 1-phenyl-1-ethanol, hydrocinnamyl alcohol, trans-cinnamyl aldehyde, trans-cinnamyl alcohol, cis-asarone, styrene, and cis-ocimene showed toxicity against Japanese termites 7 days after treatment. Hydrocinnamyl alcohol and trans-cinnamyl alcohol were found to be the major contributors to the fumigant antitermitic toxicity of oriental sweetgum oil. The acetylcholinesterase (AChE) inhibition activity of two oils and their constituents was tested to determine their mode of action. Only cis-ocimene showed strong AChE inhibition activity with an IC50 value of 0.131 mg/mL. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control.

  8. A predictive quantitative structure-activity relationship model for the photoinduced toxicity of polycyclic aromatic hydrocarbons to Daphnia magna with the use of factors for photosensitization and photomodification.

    PubMed

    Lampi, Mark A; Gurska, Jolanta; Huang, Xiao-Dong; Dixon, D George; Greenberg, Bruce M

    2007-03-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants that readily absorb environmentally relevant solar ultraviolet radiation. On absorption of a photon, photoinduced toxicity of PAHs is manifested through photosensitization and photomodification. Both of these processes occur under environmentally relevant levels of actinic radiation. An empirical quantitative structure-activity relationship model previously developed was explanatory of photoinduced toxicity of 16 PAHs in Lemna gibba (duckweed). This model was found to be predictive of toxicity to Vibrio fischeri. The L. gibba quantitative structure-activity relationship showed that a photosensitization factor and a photomodification factor could be combined to describe photoinduced toxicity. To further examine this model, we assessed whether it could be applied to Daphnia magna (water flea), a key bioindicator species in aquatic ecosystems. Toxicity was assessed as median effective concentration and median effective time for immobility. As with L. gibba and V. fischeri, neither the photosensitization factor nor the photomodification factor alone correlated to toxicity in D. magna. However, a photosensitization factor modified for D. magna exhibited a correlation to toxicity (r2 = 0.86), which was modestly improved when summed with a modified photomodification factor (r2 = 0.92). The greatest correlation was observed with median effective concentration data. This research provides evidence that models incorporating factors for photosensitization and photomodification have interspecies applicability. PMID:17373503

  9. A predictive quantitative structure-activity relationship model for the photoinduced toxicity of polycyclic aromatic hydrocarbons to Daphnia magna with the use of factors for photosensitization and photomodification.

    PubMed

    Lampi, Mark A; Gurska, Jolanta; Huang, Xiao-Dong; Dixon, D George; Greenberg, Bruce M

    2007-03-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants that readily absorb environmentally relevant solar ultraviolet radiation. On absorption of a photon, photoinduced toxicity of PAHs is manifested through photosensitization and photomodification. Both of these processes occur under environmentally relevant levels of actinic radiation. An empirical quantitative structure-activity relationship model previously developed was explanatory of photoinduced toxicity of 16 PAHs in Lemna gibba (duckweed). This model was found to be predictive of toxicity to Vibrio fischeri. The L. gibba quantitative structure-activity relationship showed that a photosensitization factor and a photomodification factor could be combined to describe photoinduced toxicity. To further examine this model, we assessed whether it could be applied to Daphnia magna (water flea), a key bioindicator species in aquatic ecosystems. Toxicity was assessed as median effective concentration and median effective time for immobility. As with L. gibba and V. fischeri, neither the photosensitization factor nor the photomodification factor alone correlated to toxicity in D. magna. However, a photosensitization factor modified for D. magna exhibited a correlation to toxicity (r2 = 0.86), which was modestly improved when summed with a modified photomodification factor (r2 = 0.92). The greatest correlation was observed with median effective concentration data. This research provides evidence that models incorporating factors for photosensitization and photomodification have interspecies applicability.

  10. Activation of Hedgehog signaling by the environmental toxicant arsenic may contribute to the etiology of arsenic-induced tumors.

    PubMed

    Fei, Dennis Liang; Li, Hua; Kozul, Courtney D; Black, Kendall E; Singh, Samer; Gosse, Julie A; DiRenzo, James; Martin, Kathleen A; Wang, Baolin; Hamilton, Joshua W; Karagas, Margaret R; Robbins, David J

    2010-03-01

    Exposure to the environmental toxicant arsenic, through both contaminated water and food, contributes to significant health problems worldwide. In particular, arsenic exposure is thought to function as a carcinogen for lung, skin, and bladder cancer via mechanisms that remain largely unknown. More recently, the Hedgehog signaling pathway has also been implicated in the progression and maintenance of these same cancers. Based on these similarities, we tested the hypothesis that arsenic may act in part through activating Hedgehog signaling. Here, we show that arsenic is able to activate Hedgehog signaling in several primary and established tissue culture cells as well as in vivo. Arsenic activates Hedgehog signaling by decreasing the stability of the repressor form of GLI3, one of the transcription factors that ultimately regulate Hedgehog activity. We also show, using tumor samples from a cohort of bladder cancer patients, that high levels of arsenic exposure are associated with high levels of Hedgehog activity. Given the important role Hedgehog signaling plays in the maintenance and progression of a variety of tumors, including bladder cancer, these results suggest that arsenic exposure may in part promote cancer through the activation of Hedgehog signaling. Thus, we provide an important insight into the etiology of arsenic-induced human carcinogenesis, which may be relevant to millions of people exposed to high levels of arsenic worldwide.

  11. First Evidence of Altererythrobacter sp. LY02 with Indirect Algicidal Activity on the Toxic Dinoflagellate, Alexandrium tamarense.

    PubMed

    Li, Yi; Liu, Lei; Xu, Yanting; Guan, Chengwei; Lei, Xueqian; Zheng, Wei; Wang, Hailei; Zheng, Tianling

    2016-10-01

    Alexandrium tamarense is a toxic harmful algal blooms (HABs) causing species, which poses great threat to human health and marine economy. In this study, we isolated an algicidal bacterium Altererythrobacter sp. LY02 towards to A. tamarense and later investigated the algicidal activity, algicidal mode, characteristics of algicidal active substance and algicidal procedure. The results indicated that the cell-free filtrate of strain LY02 showed high algicidal effect on algal growth, however, bacterial cells almost lost algicidal activity. The algicidal active substance was temperature- and pH-stability, and its molecular weight was less than 1000 Da, and was a non-proteinaceous material or non-polysaccharide, mid-polar substance. Under the algicidal effect of active substance, the morphology and structure of A. tamarense cells were seriously damaged as well as organelles. Our study confirmed that the algicidal active substance could be used as an excellent bio-agent for controlling HABs caused by A. tamarense. PMID:27422436

  12. Toxic Hazards Research Unit

    NASA Technical Reports Server (NTRS)

    Macewen, J. D.; Vernot, E. H.

    1971-01-01

    The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1970 through May 1971 reviewed. Modification of the animal exposure facilities primarily for improved human safety but also for experimental integrity and continuity are discussed. Acute toxicity experiments were conducted on hydrogen fluoride (HF), hydrogen chloride (HCl), nitrogen dioxide (NO2), and hydrogen cyanide (HCN) both singly and in combination with carbon dioxide (CO). Additional acute toxicity experiments were conducted on oxygen difluoride (OF2) and chlorine pentafluoride (ClF5). Subacute toxicity studies were conducted on methylisobutylketone and dichloromethane (methylene dichloride). The interim results of further chronic toxicity experiments on monomethylhydrazine (MMH) are also described.

  13. Target Organ Specific Activity of Drosophila MRP (ABCC1) Moderates Developmental Toxicity of Methylmercury

    PubMed Central

    Prince, Lisa; Korbas, Malgorzata; Davidson, Philip; Broberg, Karin; Rand, Matthew Dearborn

    2014-01-01

    Methylmercury (MeHg) is a ubiquitous and persistent neurotoxin that poses a risk to human health. Although the mechanisms of MeHg toxicity are not fully understood, factors that contribute to susceptibility are even less well known. Studies of human gene polymorphisms have identified a potential role for the multidrug resistance-like protein (MRP/ABCC) family, ATP-dependent transporters, in MeHg susceptibility. MRP transporters have been shown to be important for MeHg excretion in adult mouse models, but their role in moderating MeHg toxicity during development has not been explored. We therefore investigated effects of manipulating expression levels of MRP using a Drosophila development assay. Drosophila MRP (dMRP) is homologous to human MRP1–4 (ABCC1–4), sharing 50% identity and 67% similarity with MRP1. A greater susceptibility to MeHg is seen in dMRP mutant flies, demonstrated by reduced rates of eclosion on MeHg-containing food. Furthermore, targeted knockdown of dMRP expression using GAL4>UAS RNAi methods demonstrates a tissue-specific function for dMRP in gut, Malpighian tubules, and the nervous system in moderating developmental susceptibility to MeHg. Using X-ray synchrotron fluorescence imaging, these same tissues were also identified as the highest Hg-accumulating tissues in fly larvae. Moreover, higher levels of Hg are seen in dMRP mutant larvae compared with a control strain fed an equivalent dose of MeHg. In sum, these data demonstrate that dMRP expression, both globally and within Hg-targeted organs, has a profound effect on susceptibility to MeHg in developing flies. Our findings point to a potentially novel and specific role for dMRP in neurons in the protection against MeHg. Finally, this experimental system provides a tractable model to evaluate human polymorphic variants of MRP and other gene variants relevant to genetic studies of mercury-exposed populations. PMID:24863968

  14. Modulators of γ-Secretase Activity Can Facilitate the Toxic Side-Effects and Pathogenesis of Alzheimer's Disease

    PubMed Central

    Svedružić, Željko M.; Popović, Katarina; Šendula-Jengić, Vesna

    2013-01-01

    Background Selective modulation of different Aβ products of an intramembrane protease γ-secretase, could be the most promising strategy for development of effective therapies for Alzheimer's disease. We describe how different drug-candidates can modulate γ-secretase activity in cells, by studying how DAPT affects changes in γ-secretase activity caused by gradual increase in Aβ metabolism. Results Aβ 1–40 secretion in the presence of DAPT shows biphasic activation-inhibition dose-response curves. The biphasic mechanism is a result of modulation of γ-secretase activity by multiple substrate and inhibitor molecules that can bind to the enzyme simultaneously. The activation is due to an increase in γ-secretase's kinetic affinity for its substrate, which can make the enzyme increasingly more saturated with otherwise sub-saturating substrate. The noncompetitive inhibition that prevails at the saturating substrate can decrease the maximal activity. The synergistic activation-inhibition effects can drastically reduce γ-secretase's capacity to process its physiological substrates. This reduction makes the biphasic inhibitors exceptionally prone to the toxic side-effects and potentially pathogenic. Without the modulation, γ-secretase activity on it physiological substrate in cells is only 14% of its maximal activity, and far below the saturation. Significance Presented mechanism can explain why moderate inhibition of γ-secretase cannot lead to effective therapies, the pharmacodynamics of Aβ-rebound phenomenon, and recent failures of the major drug-candidates such as semagacestat. Novel improved drug-candidates can be prepared from competitive inhibitors that can bind to different sites on γ-secretase simultaneously. Our quantitative analysis of the catalytic capacity can facilitate the future studies of the therapeutic potential of γ-secretase and the pathogenic changes in Aβ metabolism. PMID:23308095

  15. Minding the Calcium Store: Ryanodine Receptor Activation as a Convergent Mechanism of PCB Toxicity

    PubMed Central

    Pessah, Isaac N.; Cherednichenko, Gennady; Lein, Pamela J.

    2009-01-01

    Chronic low level polychlorinated biphenyls (PCB) exposures remain a significant public health concern since results from epidemiological studies indicate PCB burden is associated with immune system dysfunction, cardiovascular disease, and impairment of the developing nervous system. Of these various adverse health effects, developmental neurotoxicity has emerged as a particularly vulnerable endpoint in PCB toxicity. Arguably the most pervasive biological effects of PCBs could be mediated by their ability to alter the spatial and temporal fidelity of Ca2+ signals through one or more receptor mediated processes. This review will focus on our current knowledge of the structure and function of ryanodine receptors (RyRs) in muscle and nerve cells and how PCBs and related non-coplanar structures alter these functions. The molecular and cellular mechanisms by which non-coplanar PCBs and related structures alter local and global Ca2+ signaling properties and the possible short and long-term consequences of these perturbations on neurodevelopment and neurodegeneration are reviewed. PMID:19931307

  16. Structure-Activity Relationship Studies on the Mosquito Toxicity and Biting Deterrency of Callicarpenal Derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Callicarpenal (13,14,15,16-tetranor-3-cleroden-12-al) has previously demonstrated significant mosquito bite-deterring activity against Aedes aegypti and Anopheles stephensi in addition to repellent activity against host-seeking nymphs of the blacklegged tick, Ixodes scapularis. In the present study...

  17. Developmental toxicity of perfluorononanoic acid is dependent on peroxisome proliferator activated receptor-alpha.

    EPA Science Inventory

    Perfluorononanoic acid (PFNA) is one of the predominant perfluoroalkyl acids in the environment and in tissues of humans and wildlife. PFNA strongly activates the mouse and human peroxisome proliferator-activated receptor-alpha (PPARα) in vitro and negatively impacts development ...

  18. Using Quantitative Structure-Activity Relationship Modeling to Quantitatively Predict the Developmental Toxicity of Halogenated Azole compounds

    EPA Science Inventory

    Developmental toxicity is a relevant endpoint for the comprehensive assessment of human health risk from chemical exposure. However, animal developmental toxicity studies remain unavailable for many environmental contaminants due to the complexity and cost of these types of analy...

  19. A Quantitative Structure Activity Relationship for acute oral toxicity of pesticides on rats: Validation, domain of application and prediction.

    PubMed

    Hamadache, Mabrouk; Benkortbi, Othmane; Hanini, Salah; Amrane, Abdeltif; Khaouane, Latifa; Si Moussa, Cherif

    2016-02-13

    Quantitative Structure Activity Relationship (QSAR) models are expected to play an important role in the risk assessment of chemicals on humans and the environment. In this study, we developed a validated QSAR model to predict acute oral toxicity of 329 pesticides to rats because a few QSAR models have been devoted to predict the Lethal Dose 50 (LD50) of pesticides on rats. This QSAR model is based on 17 molecular descriptors, and is robust, externally predictive and characterized by a good applicability domain. The best results were obtained with a 17/9/1 Artificial Neural Network model trained with the Quasi Newton back propagation (BFGS) algorithm. The prediction accuracy for the external validation set was estimated by the Q(2)ext and the root mean square error (RMS) which are equal to 0.948 and 0.201, respectively. 98.6% of external validation set is correctly predicted and the present model proved to be superior to models previously published. Accordingly, the model developed in this study provides excellent predictions and can be used to predict the acute oral toxicity of pesticides, particularly for those that have not been tested as well as new pesticides.

  20. Removal of toxic zinc from water/wastewater using eucalyptus seeds activated carbon: non-linear regression analysis.

    PubMed

    Senthil Kumar, Ponnusamy; Saravanan, Anbalagan; Anish Kumar, Kodyingil; Yashwanth, Ramesh; Visvesh, Sridharan

    2016-08-01

    In the present study, a novel activated carbon was prepared from low-cost eucalyptus seeds, which was utilised for the effectively removal of toxic zinc from the water/wastewater. The prepared adsorbent was studied by Fourier transform infrared spectroscopy and scanning electron microscopic characterisation studies. Adsorption process was experimentally performed for optimising the influencing factors such as adsorbent dosage, solution pH, contact time, initial zinc concentration, and temperature for the maximum removal of zinc from aqueous solution. Adsorption isotherm of zinc removal was ensued Freundlich model, and the kinetic model ensued pseudo-second order model. Langmuir monolayer adsorption capacity of the adsorbent for zinc removal was evaluated as 80.37 mg/g. The results of the thermodynamic studies suggested that the adsorption process was exothermic, thermodynamically feasible and impulsive process. Finally, a batch adsorber was planned to remove zinc from known volume and known concentration of wastewater using best obeyed model such as Freundlich. The experimental details showed the newly prepared material can be effectively utilised as a cheap material for the adsorption of toxic metal ions from the contaminated water. PMID:27463796

  1. Quantitative structure-activity relationships and mixture toxicity of organic chemicals in Photobacterium phosphoreum: the Microtox test

    SciTech Connect

    Hermens, J.; Busser, F.; Leeuwangh, P.; Musch, A.

    1985-02-01

    Quantitative structure-activity relationships were calculated for the inhibition of bioluminescence of Photobacterium phosphoreum by 22 nonreactive organic chemicals. The inhibition was measured using the Microtox test and correlated with the partition coefficient between n-octanol and water (Poct), molar refractivity (MR), and molar volume (MW/d). At log Poct less than 1 and greater than 3, deviations from linearity were observed. Introduction of MR and MW/d improved the quality of the relationships. The influences of MR or MW/d may be related with an interaction of the tested chemicals to the enzyme system which produces the light emission. The sensitivity of the Microtox test to the 22 tested compounds is comparable to a 14-day acute mortality test with guppies for chemicals with log Poct less than 4. The inhibition of bioluminescence by a mixture of the tested compounds was slightly less than was expected in case of concentration addition. The Microtox test can give a good estimate of the total aspecific minimum toxicity of polluted waters. When rather lipophilic compounds or pollutants with more specific modes of action are present, this test will underestimate the toxicity to other aquatic life.

  2. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats

    PubMed Central

    Prado-Ochoa, María Guadalupe; Gutiérrez-Amezquita, Ricardo Alfonso; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate) with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P < 0.05) and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg) of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity. PMID:24883331

  3. Designing quantitative structure activity relationships to predict specific toxic endpoints for polybrominated diphenyl ethers in mammalian cells.

    PubMed

    Rawat, S; Bruce, E D

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are known as effective flame retardants and have vast industrial application in products like plastics, building materials and textiles. They are found to be structurally similar to thyroid hormones that are responsible for regulating metabolism in the body. Structural similarity with the hormones poses a threat to human health because, once in the system, PBDEs have the potential to affect thyroid hormone transport and metabolism. This study was aimed at designing quantitative structure-activity relationship (QSAR) models for predicting toxic endpoints, namely cell viability and apoptosis, elicited by PBDEs in mammalian cells. Cell viability was evaluated quantitatively using a general cytotoxicity bioassay using Janus Green dye and apoptosis was evaluated using a caspase assay. This study has thus modelled the overall cytotoxic influence of PBDEs at an early and a late endpoint by the Genetic Function Approximation method. This research was a twofold process including running in vitro bioassays to collect data on the toxic endpoints and modeling the evaluated endpoints using QSARs. Cell viability and apoptosis responses for Hep G2 cells exposed to PBDEs were successfully modelled with an r(2) of 0.97 and 0.94, respectively. PMID:24738916

  4. Stability and toxicity of tris-tolyl bismuth(V) dicarboxylates and their biological activity towards Leishmania major.

    PubMed

    Ong, Yih Ching; Blair, Victoria L; Kedzierski, Lukasz; Tuck, Kellie L; Andrews, Philip C

    2015-11-01

    A series of 29 tris-tolyl bismuth(v) di-carboxylato complexes of composition [Bi(Tol)3(O2CR)2] involving either ortho, meta or para substituted tolyl ligands have been synthesized and characterised. Of these 15 were assessed for their toxicity towards Leishmania promastigotes and human fibroblast cells, with ten then being subsequently assessed against parasite amastigotes. The carboxylate ligands are drawn from a series of substituted and biologically relevant benzoic acids which allow a comparison with earlier studies on [BiPh3(O2CR)2] and analogous Sb(v) [SbAr3(O2CR)2] (Ar = Ph and Tol) complexes. Twelve complexes have been structurally characterized by single crystal X-ray diffraction and shown to adopt a typical trigonal bipyramidal geometry in which the three tolyl ligands occupy the equatorial plane. NMR studies on two illustrative examples indicate that the complexes are stable in D2O and DMSO but only have a half-life of 1.2 hours in culture medium, with glucose being a contributing factor in decomposition and reduction to Bi(Tol)3. Despite their short lifetime many complexes show significant toxicity towards promastigotes at low concentration (<6 μM) and at that concentration provide for good selectivity indices (parasite vs. mammalian cells), for example 114 for [Bi(o-Tol)3(O2CC6H3(2-OH,5-C6H3(2,4-F2)))2] and 838 for [Bi(m-Tol)3(O2CC6H4(2-OAc))2]. Best activity and selectivity is observed with complexes containing o- and m-tolyl ligands, and it appears the primary influence on fibroblast toxicity is the Ar ligand while the carboxylate influences promastigote toxicity. The complexes are less effective in vitro against the parasite amastigotes, where longer incubation times and harsher chemical and biological environments are encountered in the assay. Nevertheless, there were some statistically relevant differences at 1 μM against the positive controls with the best performing complexes being [Bi(o-Tol)3(O2CC6H4(2-EtO))2] and [Bi(m-Tol)3(O2CC6H4(2-OAc))2

  5. A novel natural Nrf2 activator with PPARγ-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia

    SciTech Connect

    Hsu, Wei-Hsuan; Lee, Bao-Hong; Chang, Yu-Ying; Hsu, Ya-Wen; Pan, Tzu-Ming

    2013-11-01

    Methylglyoxal (MG) is a toxic-glucose metabolite and a major precursor of advanced glycation endproducts (AGEs). MG has been reported to result in inflammation by activating receptor for AGEs (RAGE). We recently found that Monascus-fermented metabolite monascin acts as a novel natural peroxisome proliferator-activated receptor-γ (PPARγ) agonist that improves insulin sensitivity. We investigated the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats treated with oral administration of monascin or rosiglitazone. Monascin (a novel PPARγ agonist) activated nuclear factor-erythroid 2-related factor 2 (Nrf2) and down-regulated hyperinsulinmia in oral glucose tolerance test (OGTT). Monascin was able to elevate glyoxalase-1 expression via activation of hepatic Nrf2, hence, resulting in MG metabolism to D-lactic acid and protected from AGEs production in MG-treated rats. Rosiglitazone did not activate Nrf2 nor glyoxalase expression to lower serum and hepatic AGEs levels. Monascin acts as a novel natural Nrf2 activator with PPARγ-agonist activity were confirmed by Nrf2 and PPARγ reporter assays in Hep G2 cells. These findings suggest that monascin acts as an anti-diabetic and anti-oxidative stress agent to a greater degree than rosiglitazone and thus may have therapeutic potential for the prevention of diabetes. - Highlights: • Monascin acts as a PPARgamma agonist. • Monascin activates Nrf2 and AMPK. • Monascin promotes MG metabolism into D-lactic acid. • Monascin attenuates inflammation and diabetes in vivo.

  6. Effects of zinc, copper, and lead toxicity on. cap alpha. -aminolevulinic acid dehydratase activity. [Rats

    SciTech Connect

    Shafiq-ur-Rehman

    1984-07-01

    The distribution of lead, zinc and copper in the human environment has been recognized as a major toxicological factor. Lead ions have been shown to inhibit the activity of delta-aminolevulinic acid dehydratase (delta-ALAD), which is involved in the biosynthesis of heme. Copper also has its inhibitory effect on delta-ALAD activity. A study has shown that the delta-ALAD was activated by zinc ions at physiological concentrations. In view of these reports, it was considered worthwhile to study the poisoning effects of lead, zinc and copper on delta-ALAD activity along with the concentrations of these metal ions in the blood. A possible role of Zn/sup + +/, Cu/sup + +/, and Pb/sup + +/ interaction and their influence on delta-ALAD has been explored in the present paper.

  7. Toxic responses and antioxidative enzymes activity of Scenedesmus obliquus exposed to fenhexamid and atrazine, alone and in mixture.

    PubMed

    Mofeed, Jelan; Mosleh, Yahia Y

    2013-09-01

    Laboratory studies were conducted to determine the effects of different concentrations of fenhexamid and atrazine (25, 50 and 100 µg L(-1)) on growth and oxidative stress on Scenedesmus obliquus (microalgae) after exposure for 24, 48, and 96 h. In addition, residues of fenhexamid and atrazine were determined in the culture medium after 96 h; 52%, 44% and 43% of fenhexamid remained in the medium for the lowest, middle and highest concentrations, respectively. Atrazine concentration decreased significantly in the medium with time. The reduction was faster with the lowest concentration (-53%), than in the highest concentration (-46%), while it was intermediate with 50 µg L(-1) (-47%). The antioxidative enzyme activities were used as biomarkers to evaluate the toxic effects of fenhexamid and atrazine on the microalgae. Enzymatic activities were measured in the presence of each compound alone after 24, 48 and 96 h and also in mixture after 24h exposure. The results showed that fenhexamid and atrazine induced antioxidative enzyme activities (GST, CAT and GR) at different concentrations. Catalase activities (CAT) in both pesticides treated-algae were significantly increased. Additionally, an increase in gulathione-S-transferase (GST) was observed in algae after 24, 48 and 96 h of exposure to both fenhexamid and atrazine. Antioxidative enzymes in fenhexamid and atrazine mixture treatment showed an antagonistic interaction after 24h of exposure in algae.

  8. Species differences in avian serum B esterases revealed by chromatofocusing and possible relationships of esterase activity to pesticide toxicity.

    PubMed

    Thompson, H M; Mackness, M I; Walker, C H; Hardy, A R

    1991-04-15

    Serum cholinesterase (BChE) and carboxylesterase (CbE) activities were investigated in ten species of birds. Multiple forms of serum BChE and CbE were also separated by chromatofocusing. Higher CbE activity and a wider range of CbE and BChE forms were present in the sera of omnivorous/herbivorous birds than carnivores. Omnivores/herbivores studied were the starling, house sparrow, tree sparrow, pigeon, partridge and magpie. Serum CbE activities of these species ranged from 0.46 to 2.93 mumol/min/mL with 2-6 forms separated by chromatofocusing. 0-6 forms of BChE were separated by the same method. The serum CbE activities of the little owl, tawny owl, barn owl and razorbill ranged from 0.19 to 0.58 mumoles/min/mL with 0-2 forms separated by chromatofocusing. No ChE forms were present within the pH gradient. These results may be significant in contributing to the understanding of the selective toxicity of organophosphorus and carbamate pesticides.

  9. Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida.

    PubMed

    Wang, Kai; Qi, Suzhen; Mu, Xiyan; Chai, Tingting; Yang, Yang; Wang, Dandan; Li, Dongzhi; Che, Wunan; Wang, Chengju

    2015-10-01

    Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms was assessed using an artificial soil medium. The median lethal concentration (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect concentration of imidacloprid about hatchability, growth, AChE activity and DNA damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively.

  10. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    PubMed

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

  11. Evaluation of a two-generation reproduction toxicity study adding endpoints to detect endocrine disrupting activity using lindane.

    PubMed

    Matsuura, Ikuo; Saitoh, Tetsuji; Tani, Einosuke; Wako, Yumi; Iwata, Hiroshi; Toyota, Naoto; Ishizuka, Yoshihito; Namiki, Masato; Hoshino, Nobuhito; Tsuchitani, Minoru; Ikeda, Yasuo

    2005-12-01

    A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using lindane by dietary administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). F1 offspring were examined for emotionality (open field test), motor coordination (rotarod test), as well as learning and memory (pole-climbing test). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed general toxicological effects on parental animals, influence on reproductive function, and altered development of offspring; however, they did not demonstrate any distinct changes in the extra endpoints for detection of endocrine disrupting activity. Adult toxicity was observed in both F0 and F1 animals, including suppressed body weight gain and reduced food consumption in both sexes, and deaths of females at 300 ppm. Convulsions and irritability were observed during the perinatal period in pregnant F1 females given 300 ppm. Pathological examination revealed increased liver weights and centrilobular hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and above; in addition, increased kidney weights and increased hyaline droplets in the proximal tubule epithelium, and basophilic renal tubules in males were noted at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1 males and females and adrenal weights were increased in F1 males and females at 300 ppm; however, no histological changes were observed, and manifestations suggesting endocrine disrupting activity related to these changes were lacking. Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in F1 males at 60 and 300 ppm, and decreases

  12. Modulation of cupric ion activity by pH and fulvic acid as determinants of toxicity in Xenopus laevis embryos and larvae

    SciTech Connect

    Buchwalter, D.B. |; Linder, G.; Curtis, L.R.

    1996-04-01

    An ion-specific electrode measured cupric ion activity modulated by fulvic acid (FA) and pH in a series of modified Frog Embryo Teratogenesis Assay--Xenopus (FETAX) toxicity assays. Hydrogen ion concentration was the primary determinant of cupric ion activity, while FA played a smaller but significant role. Fulvic acid was a weak copper complexing agent at pH 5.50. At pH 5.50 there was slight reduction of ionic activity and a subsequent attenuation of copper toxicity with 5.0 mg/L FA. At pH 7.50, FA also had a mild attenuating effect on copper toxicity. At pH 6.50, copper was strongly complexed by FA at total copper (TCu) concentrations below its pH-dependent solubility limit. At TCu concentrations above the solubility limit FA enhanced toxicity. There was more cupric ion activity measured in the presence of 0.5 and 5.0 mg/L FA than without it at TCu concentrations above the solubility limit. The proposed mechanism for this behavior was FA action as a nucleation inhibitor. Under the chemical conditions of the pH 6.50 experiments, a stable supersaturation of copper was formed, resulting in a more toxic aqueous matrix.

  13. Toxicity of aryl- and benzylhalides to Daphnia magna and classification of their mode of action based on quantitative structure-activity relationship

    SciTech Connect

    Marchini, S.; Passerini, L.; Hoglund, M.D.; Pino, A.; Nendza, M.

    1999-12-01

    The acute toxicity of aryl- and benzylhalides to Daphnia magna was investigated to test the validity of existing classification schemes for chemicals by mode of action, mainly based on fish studies, and the applicability of predictive quantitative structure-activity relationship (QSAR) models. Halobenzenes and halotoluenes are generally agreed to be unambiguous baseline toxicants (class 1) with the major exception of the benzylic structures, which are reactive in fish tests (class 3). Eighty-nine percent of the arylhalides tested in this study match a log P{sub ow}-dependent QSAR, including fluorinated, chlorinated, brominated, and iodinated derivatives, thereby confirming the validity of the baseline models also for variously halogenated compounds (other than only-chloro compounds). The toxicities of the benzylhalides relative to baseline QSARs clearly indicate that these compounds belong to two classes of mode of action, i.e., they either act as narcotic toxicants (class 1) or reveal excess toxicity due to unspecific reactivity (class 3). On some occasions, the assignment to the two classes of F. magna deviates from the structural rules derived from fish, i.e., iodinated compounds as well as {alpha},{alpha}-Cl{sub 2}-toluene's lack reactive excess toxicity but behave as nonpolar nonspecific toxicants. The QSARs derived during this study reveal lower slopes and higher intercepts than typical baseline models and, together with the analysis of mixture toxicity studies, behavioral studies, and critical body burden, advocate the hypothesis that there are several different ways to produce baseline toxicity. Most halobenzenes and halotoluenes are actually baseline chemicals with some extra reactivity and as such form a subgroup, whose limits still have to be defined. Different primary sites of action could explain why the chemicals are discriminated by different classification systems, but still they must have some rate-limiting interaction in common as they fit the

  14. Hepatoprotective and Antioxidant Activity of Dunaliella salina in Paracetamol-induced Acute Toxicity in Rats

    PubMed Central

    Madkour, Fedekar F.; Abdel-Daim, M. M.

    2013-01-01

    Paracetamol has a reasonable safety profile when taken in therapeutic doses. However, it could induce hepatotoxicity and even more severe fatal acute hepatic damage when taken in an overdose. The green alga, Dunaliella salina was investigated for hepatoprotective and antioxidant activity against paracetamol-induced liver damage in rats. Male albino Wistar rats overdosed with paracetamol showed liver damage and oxidative stress as indicated by significantly (P<0.05) increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide. At the same time, there were decreased activities of serum superoxide dismutase and total antioxidant capacity compared with the control group. Treatment with D. salina methanol extract at doses of 500 and 1000 mg/kg body weight or silymarin could significantly (P<0.05) decrease the liver damage marker enzymes, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide levels and increase the activities of superoxide dismutase and total antioxidant capacity in serum when compared with paracetamol intoxicated group. Liver histopathology also showed that D. salina reduced the centrilobular necrosis, congestion and inflammatory cell infiltration evoked by paracetamol overdose. These results suggest that D. salina exhibits a potent hepatoprotective effect on paracetamol-induced liver damage in rats, which may be due to both the increase of antioxidant enzymes activity and inhibition of lipid peroxidation. PMID:24591738

  15. Surface Water Impacted by Rural Activities Induces Genetic Toxicity Related to Recombinagenic Events in Vivo

    PubMed Central

    Soares Neto, José Lopes; de Carli, Raíne Fogliati; Kotzal, Queila Susana Gambim; Latroni, Francine Bolico; Lehmann, Mauricio; Dias, Johnny Ferraz; de Souza, Cláudia Telles; Niekraszewicz, Liana Appel Boufleur; da Silva, Fernanda Rabaioli; da Silva, Juliana; Dihl, Rafael Rodrigues

    2016-01-01

    This investigation assessed the interaction of surface water samples with DNA to quantitatively and qualitatively characterize their mutagenic and/or recombinagenic activity. Samples were obtained at three different sites along the Tocantins River (Tocantins State, Brazil). The area has withstood the impact mainly of rural activities, which release different chemical compounds in the environment. The Drosophila melanogaster Somatic Mutation and Recombination Test (SMART) was performed in standard (ST) and high bioactivation (HB) crosses. SMART is useful for the detection of mutational and recombinational events induced by genotoxins of direct and indirect action. Results demonstrated that samples collected in both seasons were able to induce increments on the mutant spot frequencies in the larvae of the HB cross. Genotoxicity was related to a massive recombinagenic activity. The positive responses ascribed to only the HB cross means that it is linked to pro-genotoxins requiring metabolic activation. The SMART wing test in Drosophila melanogaster was shown to be highly sensitive to detect genotoxic agents present in the aquatic environment impacted by agriculture. PMID:27537904

  16. Hepatoprotective and Antioxidant Activity of Dunaliella salina in Paracetamol-induced Acute Toxicity in Rats.

    PubMed

    Madkour, Fedekar F; Abdel-Daim, M M

    2013-11-01

    Paracetamol has a reasonable safety profile when taken in therapeutic doses. However, it could induce hepatotoxicity and even more severe fatal acute hepatic damage when taken in an overdose. The green alga, Dunaliella salina was investigated for hepatoprotective and antioxidant activity against paracetamol-induced liver damage in rats. Male albino Wistar rats overdosed with paracetamol showed liver damage and oxidative stress as indicated by significantly (P<0.05) increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide. At the same time, there were decreased activities of serum superoxide dismutase and total antioxidant capacity compared with the control group. Treatment with D. salina methanol extract at doses of 500 and 1000 mg/kg body weight or silymarin could significantly (P<0.05) decrease the liver damage marker enzymes, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide levels and increase the activities of superoxide dismutase and total antioxidant capacity in serum when compared with paracetamol intoxicated group. Liver histopathology also showed that D. salina reduced the centrilobular necrosis, congestion and inflammatory cell infiltration evoked by paracetamol overdose. These results suggest that D. salina exhibits a potent hepatoprotective effect on paracetamol-induced liver damage in rats, which may be due to both the increase of antioxidant enzymes activity and inhibition of lipid peroxidation.

  17. Surface Water Impacted by Rural Activities Induces Genetic Toxicity Related to Recombinagenic Events in Vivo.

    PubMed

    Soares Neto, José Lopes; de Carli, Raíne Fogliati; Kotzal, Queila Susana Gambim; Latroni, Francine Bolico; Lehmann, Mauricio; Dias, Johnny Ferraz; de Souza, Cláudia Telles; Niekraszewicz, Liana Appel Boufleur; da Silva, Fernanda Rabaioli; da Silva, Juliana; Dihl, Rafael Rodrigues

    2016-01-01

    This investigation assessed the interaction of surface water samples with DNA to quantitatively and qualitatively characterize their mutagenic and/or recombinagenic activity. Samples were obtained at three different sites along the Tocantins River (Tocantins State, Brazil). The area has withstood the impact mainly of rural activities, which release different chemical compounds in the environment. The Drosophila melanogaster Somatic Mutation and Recombination Test (SMART) was performed in standard (ST) and high bioactivation (HB) crosses. SMART is useful for the detection of mutational and recombinational events induced by genotoxins of direct and indirect action. Results demonstrated that samples collected in both seasons were able to induce increments on the mutant spot frequencies in the larvae of the HB cross. Genotoxicity was related to a massive recombinagenic activity. The positive responses ascribed to only the HB cross means that it is linked to pro-genotoxins requiring metabolic activation. The SMART wing test in Drosophila melanogaster was shown to be highly sensitive to detect genotoxic agents present in the aquatic environment impacted by agriculture. PMID:27537904

  18. Tecoma sambucifolia: anti-inflammatory and antinociceptive activities, and 'in vitro' toxicity of extracts of the 'huarumo' of peruvian incas.

    PubMed

    Alguacil, L F; Galán de Mera, A; Gómez, J; Llinares, F; Morales, L; Muñoz-Mingarro, M D; Pozuelo, J M; Vicente Orellana, J A

    2000-06-01

    Aqueous and alcoholic extracts of pods and flowers of Tecoma sambucifolia H.B.K. (Bignoniaceae) ('huarumo') were analysed to determine their anti-inflammatory activity (carrageenan-induced edema test), antinociceptive activity (acetic acid writhing test) and 'in vitro' toxicity in Chinese hamster ovary cells, human hepatome cells and human larynx epidermal carcinoma cells. The cytotoxic effects of both extracts were evaluated by two endpoint systems: neutral red uptake assay and tetrazolium assay. The results showed that all extracts have anti-inflammatory and antinociceptive activity, but the highest potency is that of the alcoholic extracts. There were significant differences in cytotoxicity between extracts and among the response of cells to them. The highest cytotoxicity was noted with the alcoholic extract, and the human hepatome cell line was the most sensitive, especially to the alcoholic extract of flowers. The aqueous pod extract appeared to have the best pharmaco-toxicological profile, since it provided a significant reduction of both pain and inflammation together with the lowest cytotoxicity.

  19. Activation of transcription factor AP-1 and mitogen-activated protein kinases in aniline-induced splenic toxicity

    SciTech Connect

    Khan, M. Firoze . E-mail: mfkhan@utmb.edu; Kannan, Subburaj; Wang Jianling

    2006-01-15

    Signaling mechanisms in aniline-induced fibrogenic and/or tumorigenic response in the spleen are not known. Previous studies have shown that aniline exposure leads to iron accumulation and oxidative stress in the spleen, which may cause activation of redox-sensitive transcription factors and regulate the transcription of genes involved in fibrosis and/or tumorigenesis. To test this, male SD rats were treated with 0.5 mmol/kg/day aniline via drinking water for 30 days, and activation of transcription factor AP-1 was determined in the splenocyte nuclear extracts (NEs). AP-1 DNA-binding activity in the NEs of freshly isolated splenocytes from aniline-treated rats increased in comparison to the controls, as determined by electrophoretic mobility shift assay (EMSA). AP-1 binding was also determined in the NEs of cultured splenocytes (2 h and 24 h), which showed even a greater increase in binding activity at 2 h. The specificity of AP-1 binding for relevant DNA motifs was confirmed by competition EMSA and by supershift EMSA using antibodies specific to c-Jun and c-Fos. To further explore the signaling mechanisms in the AP-1 activation, phosphorylation patterns of mitogen-activated protein kinases (MAPKs) were pursued. Aniline exposure induced increases in the phosphorylation of the three classes of MAPKs: extracellular-signal-regulated kinase (ERK 1/2), c-Jun N-terminal kinase (JNK 1/2), and p38 MAPKs. Furthermore, TGF-{beta}1 mRNA expression showed a 3-fold increase in the spleens of aniline-treated rats. These observations suggest a strong association among MAPK phosphorylation, AP-1 activation, and enhanced TGF-{beta}1 gene expression. The observed sequence of events subsequent to aniline exposure could regulate genes that lead to fibrogenic and/or tumorigenic response in the spleen.

  20. In vitro anticancer activity, toxicity and structure-activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii

    SciTech Connect

    Le Calve, Benjamin; Lallemand, Benjamin; Perrone, Carmen; Lenglet, Gaelle; Depauw, Sabine; Van Goietsenoven, Gwendoline; Bury, Marina; Vurro, Maurizio; Herphelin, Francoise; Andolfi, Anna; Zonno, Maria Chiara; Mathieu, Veronique; Dufrasne, Francois; Van Antwerpen, Pierre; Poumay, Yves

    2011-07-01

    The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.

  1. Effects of Croton rhamnifolioides essential oil on Aedes aegypti oviposition, larval toxicity and trypsin activity.

    PubMed

    Santos, Geanne K N; Dutra, Kamilla A; Lira, Camila S; Lima, Bheatriz N; Napoleão, Thiago H; Paiva, Patrícia M G; Maranhão, Claudia A; Brandão, Sofia S F; Navarro, Daniela M A F

    2014-01-01

    Although numerous reports are available concerning the larvicidal potential of essential oils, very few investigations have focused on their mechanisms of action. In the present study, we have investigated the chemical composition of the leaf oil of Croton rhamnifolioides during storage and its effects on oviposition and survival of larvae of the dengue fever mosquito Aedes aegypti. In addition, we have established a possible mechanism of action for the larvicidal activity of the essential oil. GC-MS analyses revealed marked differences in the composition of oil that had been freshly isolated and that of a sample that had been stored in a sealed amber-glass vial under refrigeration for three years. However, both fresh and stored oil exhibited substantial larvicidal activities with LC50 values of 122.35 and 89.03 ppm, respectively, and oviposition deterrent effects against gravid females at concentrations of 50 and 100 µg·mL-1. These results demonstrate that the larvicidal effect of the essential oil was unchanged during three years of storage even though its chemical composition altered. Hence, the essential oil could be used in the preparation of commercial products. In addition, we observed that the trypsin-like activity of mosquito larvae was inhibited in vitro by the essential oil of C. rhamnifolioides, suggesting that the larvicidal effect may be associated with inhibition of this enzyme.

  2. Effects of Croton rhamnifolioides essential oil on Aedes aegypti oviposition, larval toxicity and trypsin activity.

    PubMed

    Santos, Geanne K N; Dutra, Kamilla A; Lira, Camila S; Lima, Bheatriz N; Napoleão, Thiago H; Paiva, Patrícia M G; Maranhão, Claudia A; Brandão, Sofia S F; Navarro, Daniela M A F

    2014-01-01

    Although numerous reports are available concerning the larvicidal potential of essential oils, very few investigations have focused on their mechanisms of action. In the present study, we have investigated the chemical composition of the leaf oil of Croton rhamnifolioides during storage and its effects on oviposition and survival of larvae of the dengue fever mosquito Aedes aegypti. In addition, we have established a possible mechanism of action for the larvicidal activity of the essential oil. GC-MS analyses revealed marked differences in the composition of oil that had been freshly isolated and that of a sample that had been stored in a sealed amber-glass vial under refrigeration for three years. However, both fresh and stored oil exhibited substantial larvicidal activities with LC50 values of 122.35 and 89.03 ppm, respectively, and oviposition deterrent effects against gravid females at concentrations of 50 and 100 µg·mL-1. These results demonstrate that the larvicidal effect of the essential oil was unchanged during three years of storage even though its chemical composition altered. Hence, the essential oil could be used in the preparation of commercial products. In addition, we observed that the trypsin-like activity of mosquito larvae was inhibited in vitro by the essential oil of C. rhamnifolioides, suggesting that the larvicidal effect may be associated with inhibition of this enzyme. PMID:25317582

  3. Acute toxic and genotoxic activities of widely used cytostatic drugs in higher plants: Possible impact on the environment.

    PubMed

    Mišík, Miroslav; Pichler, Clemens; Rainer, Bernhard; Filipic, Metka; Nersesyan, Armen; Knasmueller, Siegfried

    2014-11-01

    Cytostatic drugs are highly toxic pharmaceuticals and it was repeatedly postulated that they may cause adverse effects in ecosystems. The acute toxic and genotoxic properties of these drugs have not been adequately investigated in higher plants so far; therefore, we studied the most widely used drugs (5-flurouracil, 5FU; etoposide, Et; cisplatin, CisPt; carboplatin, CaPt; vincristine sulfate, VinS and cyclophosphamide monohydrate, CP) in micronucleus (MN) assays with meiotic pollen tetrad cells of Tradescantia and with root cells from Allium cepa. MNi are formed as a consequence of chromosome breaks and aneuploidy. We monitored also the acute toxic properties of the drugs, i.e. inhibition of cell division (mitotic indices and retardation of root growth) in the latter species. All compounds caused in both indicator plants genotoxic effects. The order of genotoxic potencies expressed as NOELs in µM was CisPt (0.1)≥ Et (0.5)>CP (1.0)>CaPt (10)>5FU (30)>VinS (100) in Tradescantia. A similar order was seen in Allium MN but Et was less active (5.0µM). Four compounds caused alterations of the mitotic indices under the present conditions namely CisPt (0.5), Et (10.0), 5FU (10.0) and VinS (100). Inhibition of root growth decreased in the order CisPt (0.5)>Et (1.0)≥VinS (1.0)>5FU (5.0)>CaPt (33.0)>CP (>1000). Comparisons of the NOELs with the predicted environmental concentrations (PEC) show that the latter values are at least 5 orders of magnitude lower and indicate that it is unlikely that their release in the environment may cause adverse effects in higher plants. However, it is notable that the levels of both platinum compounds and of 5FU in hospital effluents may reach levels which may induce damage of the genetic material.

  4. Preparation, In Vivo Administration, Dose-Limiting Toxicities, and Antineoplastic Activity of Cytochalasin B

    PubMed Central

    Trendowski, Matthew; Zoino, Joseph N.; Christen, Timothy D.; Acquafondata, Christopher; Fondy, Thomas P.

    2015-01-01

    An effective and inexpensive protocol for producing cytochalasins A and B is being disclosed to propose a viable method by which to examine the in vivo antineoplastic activity of these congeners in preclinical tumor-bearing mammalian models. In addition, we determine the maximum tolerated doses of cytochalasin B using multiple routes and formulations, characterize the tissue distribution of intravenous bolus cytochalasin B, and assess the in vivo antineoplastic activity of cytochalasin B in comparison in doxorubicin in Balb/c mice challenged intradermally with M109 murine lung carcinoma. We also examine the effects of cytochalasin B against several other murine neoplastic cell lines (Lewis lung, LA4, B16F10, and M5076). Finally, we examine a potential mechanism of the antimetastatic activity of cytochalasin B by observing the effects of the agent on the secretion of N-acetylglucosaminidase (GlcNACase) by B16BL6 and B16F10 murine melanomas in vitro. The results of the study can be summarized as follows: 1) Cytochalasin B can be safely administered intravenously, intraperitoneally, and subcutaneously in murine models, with the maximum tolerated dose of all routes of administration being increased by liposome encapsulation. 2) Cytochalasin B can significantly inhibit the growth of tumors in mice challenged with M109, Lewis lung, LA4, B16F10, or M5076, producing long-term survival against lung carcinomas and adenocarcinomas (M109, Lewis lung, and LA4) and B16F10 melanoma, but not M5076 sarcoma. These effects were comparable to intraperitoneally administered doxorubicin. 4) Low concentrations of cytochalasin B inhibit the secretion of GlcNACase, indicating that cytochalasin B may inhibit metastatic progression by mechanisms not directly associated with its influence on cell adhesion and motility. PMID:26310377

  5. Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity.

    PubMed

    Judenherc-Haouzi, Annick; Zhang, Xue-Qian; Sonobe, Takashi; Song, Jianliang; Rannals, Matthew D; Wang, JuFang; Tubbs, Nicole; Cheung, Joseph Y; Haouzi, Philippe

    2016-06-01

    We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H2S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H2S on cardiac function, as well as the numerous properties of MB, the nature of this interaction, if any, remains uncertain. The aim of this study was to clarify 1) the effects of MB on H2S-induced cardiac toxicity and 2) whether L-type Ca(2+) channels, one of the targets of H2S, could transduce some of the counteracting effects of MB. In sedated rats, H2S infused at a rate that would be lethal within 5 min (24 μM·kg(-1)·min(-1)), produced a rapid fall in left ventricle ejection fraction, determined by echocardiography, leading to a pulseless electrical activity. Blood concentrations of gaseous H2S reached 7.09 ± 3.53 μM when cardiac contractility started to decrease. Two to three injections of MB (4 mg/kg) transiently restored cardiac contractility, blood pressure, and V̇o2, allowing the animals to stay alive until the end of H2S infusion. MB also delayed PEA by several minutes following H2S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H2S (100 μM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca(2+)]i) transient amplitudes, and L-type Ca(2+) currents (ICa) within 3 min of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca(2+)]i) transient, and ICa The present results offer a new approach for counteracting H2S toxicity and potentially other conditions associated with acute inhibition of L-type Ca(2+) channels. PMID:26962024

  6. Development of acute toxicity quantitative structure activity relationships (QSAR) and their use in linear alkylbenzene sulfonate species sensitivity distributions.

    PubMed

    Belanger, Scott E; Brill, Jessica L; Rawlings, Jane M; Price, Brad B

    2016-07-01

    Linear Alkylbenzene Sulfonate (LAS) is high tonnage and widely dispersed anionic surfactant used by the consumer products sector. A range of homologous structures are used in laundry applications that differ primarily on the length of the hydrophobic alkyl chain. This research summarizes the development of a set of acute toxicity QSARs (Quantitative Structure Activity Relationships) for fathead minnows (Pimephales promelas) and daphnids (Daphnia magna, Ceriodaphnia dubia) using accepted test guideline approaches. A series of studies on pure chain length LAS from C10 to C14 were used to develop the QSARs and the robustness of the QSARs was tested by evaluation of two technical mixtures of differing compositions. All QSARs were high quality (R(2) were 0.965-0.997, p < 0.0001). Toxicity normalization employing QSARs is used to interpret a broader array of tests on LAS chain length materials to a diverse group of test organisms with the objective of developing Species Sensitivity Distributions (SSDs) for various chain lengths of interest. Mixtures include environmental distributions measured from exposure monitoring surveys of wastewater effluents, various commercial mixtures, or specific chain lengths. SSD 5th percentile hazardous concentrations (HC5s) ranged from 0.129 to 0.254 mg/L for wastewater effluents containing an average of 11.26-12 alkyl carbons. The SSDs are considered highly robust given the breadth of species (n = 19), use of most sensitive endpoints from true chronic studies and the quality of the underlying statistical properties of the SSD itself. The data continue to indicate a low hazard to the environment relative to expected environmental concentrations.

  7. Development of acute toxicity quantitative structure activity relationships (QSAR) and their use in linear alkylbenzene sulfonate species sensitivity distributions.

    PubMed

    Belanger, Scott E; Brill, Jessica L; Rawlings, Jane M; Price, Brad B

    2016-07-01

    Linear Alkylbenzene Sulfonate (LAS) is high tonnage and widely dispersed anionic surfactant used by the consumer products sector. A range of homologous structures are used in laundry applications that differ primarily on the length of the hydrophobic alkyl chain. This research summarizes the development of a set of acute toxicity QSARs (Quantitative Structure Activity Relationships) for fathead minnows (Pimephales promelas) and daphnids (Daphnia magna, Ceriodaphnia dubia) using accepted test guideline approaches. A series of studies on pure chain length LAS from C10 to C14 were used to develop the QSARs and the robustness of the QSARs was tested by evaluation of two technical mixtures of differing compositions. All QSARs were high quality (R(2) were 0.965-0.997, p < 0.0001). Toxicity normalization employing QSARs is used to interpret a broader array of tests on LAS chain length materials to a diverse group of test organisms with the objective of developing Species Sensitivity Distributions (SSDs) for various chain lengths of interest. Mixtures include environmental distributions measured from exposure monitoring surveys of wastewater effluents, various commercial mixtures, or specific chain lengths. SSD 5th percentile hazardous concentrations (HC5s) ranged from 0.129 to 0.254 mg/L for wastewater effluents containing an average of 11.26-12 alkyl carbons. The SSDs are considered highly robust given the breadth of species (n = 19), use of most sensitive endpoints from true chronic studies and the quality of the underlying statistical properties of the SSD itself. The data continue to indicate a low hazard to the environment relative to expected environmental concentrations. PMID:27105149

  8. Acute toxicity and genotoxic activity of avocado seed extract (Persea americana Mill., c.v. Hass).

    PubMed

    Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

    2013-01-01

    The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test. PMID:24298206

  9. Acute toxicity and genotoxic activity of avocado seed extract (Persea americana Mill., c.v. Hass).

    PubMed

    Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

    2013-01-01

    The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test.

  10. Acute Toxicity and Genotoxic Activity of Avocado Seed Extract (Persea americana Mill., c.v. Hass)

    PubMed Central

    Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

    2013-01-01

    The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test. PMID:24298206

  11. Protective activity of Bacopa monniera Linn. on nicotine-induced toxicity in mice.

    PubMed

    Vijayan, Viji; Helen, A

    2007-04-01

    Nicotine, a pharmacologically active component of cigarettes smoke causes devastating effects in important biomolecules of the cell through generation of free radicals leading to genomic instability. Bacopa monniera is a reputed drug in Ayurveda known for its hepatoprotective and DNA protective effects. In this study, an aqueous extract of Bacopa monniera (BAE, 50 mg/kg i.p.) was investigated for its ability to reduce nicotine-induced lipid peroxidation (LPO) and confer genoprotection in Swiss mice. Genoprotective effect was assayed using micronucleus (MN) assay. LPO status was studied by evaluating MDA levels and antioxidant status. Nicotine altered hepatic function as evident by increased ALP and GST levels and decreased SOD, catalase and GPx activities. BAE treatment restored antioxidant enzymes such as SOD, catalase and GPx in liver. BAE treatment also significantly reduced the frequency of micronuclei induced by nicotine by decreasing the incidence of micronucleated polychromatic erythrocytes (MN-PCE). Hepatic GSH, ALP and GST levels were brought to normal values indicating protection. The results of the present study suggest that BAE exerts protective effects by modulating the extent of lipid peroxidation and enhancing the antioxidant status. PMID:17236174

  12. Different toxic mechanisms are activated by emission PM depending on combustion efficiency

    NASA Astrophysics Data System (ADS)

    Uski, O.; Jalava, P. I.; Happo, M. S.; Leskinen, J.; Sippula, O.; Tissari, J.; Mäki-Paakkanen, J.; Jokiniemi, J.; Hirvonen, M.-R.

    2014-06-01

    Ambient air levels of fine particulate matter (PM ≤ 2.5 μm) are associated with mortality and morbidity. In addition to traffic, large quantities of fine and ultrafine particles (UFPs ≤ 100 nm) are emitted by residential wood combustion. Polycyclic aromatic hydrocarbon (PAH) and soot-rich emissions from small scale heating appliances have been linked with a plethora of toxicological effects. Recently, new technology appliances have been introduced into use although there are several uncertainties related to the toxicological properties of those emissions. In this study, PM1 (PM ≤ 1 μm) emissions from three different biomass combustion situations were compared. PM samples were produced in a novel adjustable biomass combustion reactor to avoid the problems encountered if one uses different appliances to generate the desired combustion conditions. The combustion conditions represented efficient, intermediate and smoldering situations. The concentration related effects of the particles (15, 50,150 and 300 μg ml-1) were investigated in a RAW264.7 macrophage cell line after 24 h' exposure. We analyzed cellular metabolic activity, cell cycle, and indicators of genotoxicty, oxidative stress and proinflammatory responses. Interestingly, the particles collected from smoldering and intermediate combustion conditions decreased cellular metabolic activity less than those from efficient combustion (10-fold difference). However, the samples from intermediate and smoldering combustion evoked greater DNA damage in the comet assay (2.5-fold difference). In contrast, only the particulate samples from efficient combustion triggered G2-cell cycle arrest and oxidative stress in the macrophages. These results indicate that ash rich PM emissions from appliances with almost complete combustion may still exert health impacts. However, particulate emissions from efficient combustion were small when compared to the two other situations. Thus, even with their faults and the obvious

  13. Hepatoprotective activity of Tribulus terrestris extract against acetaminophen-induced toxicity in a freshwater fish (Oreochromis mossambicus).

    PubMed

    Kavitha, P; Ramesh, R; Bupesh, G; Stalin, A; Subramanian, P

    2011-12-01

    The potential protective role of Tribulus terrestris in acetaminophen-induced hepatotoxicity in Oreochromis mossambicus was investigated. The effect of oral exposure of acetaminophen (500 mg/kg) in O. mossambicus at 24-h duration was evaluated. The plant extract (250 mg/kg) showed a remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity. It was judged from the tissue-damaging level and antioxidant levels in liver, gill, muscle and kidney tissues. Further acetaminophen impact induced a significant rise in the tissue-damaging level, and the antioxidant level was discernible from the enzyme activity modulations such as glutamate oxaloacetic transaminase, glutamate pyruvic transaminase, alkaline phosphatase, acid phosphatase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, lipid peroxidase and reduced glutathione. The levels of all these enzymes have significantly (p < 0.05) increased in acetaminophen-treated fish tissues. The elevated levels of these enzymes were significantly controlled by the treatment of T. terrestris extract (250 kg/mg). Histopathological changes of liver, gill and muscle samples were compared with respective controls. The results of the present study specify the hepatoprotective and antioxidant properties of T. terrestris against acetaminophen-induced toxicity in freshwater fish, O. mossambicus.

  14. Sorption and modeling of mass transfer of toxic chemical vapors in activated-carbon fiber-cloth adsorbers

    USGS Publications Warehouse

    Lordgooei, M.; Sagen, J.; Rood, M.J.; Rostam-Abadi, M.

    1998-01-01

    A new activated-carbon fiber-cloth (ACFC) adsorber coupled with an electrothermal regenerator and a cryogenic condenser was designed and developed to efficiently capture and recover toxic chemical vapors (TCVs) from simulated industrial gas streams. The system was characterized for adsorption by ACFC, electrothermal desorption, and cryogenic condensation to separate acetone and methyl ethyl ketone from gas streams. Adsorption dynamics are numerically modeled to predict system characteristics during scale-up and optimization of the process in the future. The model requires diffusivities of TCVs into an activated-carbon fiber (ACF) as an input. Effective diffusivities of TCVs into ACFs were modeled as a function of temperature, concentration, and pore size distribution. Effective diffusivities for acetone at 65 ??C and 30-60 ppmv were measured using a chromatography method. The energy factor for surface diffusion was determined from comparison between the experimental and modeled effective diffusivities. The modeled effective diffusivities were used in a dispersive computational model to predict mass transfer zones of TCVs in fixed beds of ACFC under realistic conditions for industrial applications.

  15. Jasmonic Acid Modulates the Physio-Biochemical Attributes, Antioxidant Enzyme Activity, and Gene Expression in Glycine max under Nickel Toxicity.

    PubMed

    Sirhindi, Geetika; Mir, Mudaser Ahmad; Abd-Allah, Elsayed Fathi; Ahmad, Parvaiz; Gucel, Salih

    2016-01-01

    In present study, we evaluated the effects of Jasmonic acid (JA) on physio-biochemical attributes, antioxidant enzyme activity, and gene expression in soybean (Glycine max L.) plants subjected to nickel (Ni) stress. Ni stress decreases the shoot and root length and chlorophyll content by 37.23, 38.31, and 39.21%, respectively, over the control. However, application of JA was found to improve the chlorophyll content and length of shoot and root of Ni-fed seedlings. Plants supplemented with JA restores the chlorophyll fluorescence, which was disturbed by Ni stress. The present study demonstrated increase in proline, glycinebetaine, total protein, and total soluble sugar (TSS) by 33.09, 51.26, 22.58, and 49.15%, respectively, under Ni toxicity over the control. Addition of JA to Ni stressed plants further enhanced the above parameters. Ni stress increases hydrogen peroxide (H2O2) by 68.49%, lipid peroxidation (MDA) by 50.57% and NADPH oxidase by 50.92% over the control. Supplementation of JA minimizes the accumulation of H2O2, MDA, and NADPH oxidase, which helps in stabilization of biomolecules. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) increases by 40.04, 28.22, 48.53, and 56.79%, respectively, over the control in Ni treated seedlings and further enhancement in the antioxidant activity was observed by the application of JA. Ni treated soybean seedlings showed increase in expression of Fe-SOD by 77.62, CAT by 15.25, POD by 58.33, and APX by 80.58% over the control. Nevertheless, application of JA further enhanced the expression of the above genes in the present study. Our results signified that Ni stress caused negative impacts on soybean seedlings, but, co-application of JA facilitate the seedlings to combat the detrimental effects of Ni through enhanced osmolytes, activity of antioxidant enzymes and gene expression.

  16. TFP5, a peptide derived from p35, a Cdk5 neuronal activator, rescues cortical neurons from glucose toxicity.

    PubMed

    Binukumar, B K; Zheng, Ya-Li; Shukla, Varsha; Amin, Niranjana D; Grant, Philip; Pant, Harish C

    2014-01-01

    Multiple lines of evidence link the incidence of diabetes to the development of Alzheimer's disease (AD). Patients with diabetes have a 50 to 75% increased risk of developing AD. Cyclin dependent kinase 5 (Cdk5) is a serine/threonine protein kinase, which forms active complexes with p35 or p39, found principally in neurons and in pancreatic β cells. Recent studies suggest that Cdk5 hyperactivity is a possible link between neuropathology seen in AD and diabetes. Previously, we identified P5, a truncated 24-aa peptide derived from the Cdk5 activator p35, later modified as TFP5, so as to penetrate the blood-brain barrier after intraperitoneal injections in AD model mice. This treatment inhibited abnormal Cdk5 hyperactivity and significantly rescued AD pathology in these mice. The present study explores the potential of TFP5 peptide to rescue high glucose (HG)-mediated toxicity in rat embryonic cortical neurons. HG exposure leads to Cdk5-p25 hyperactivity and oxidative stress marked by increased reactive oxygen species production, and decreased glutathione levels and superoxide dismutase activity. It also induces hyperphosphorylation of tau, neuroinflammation as evident from the increased expression of inflammatory cytokines like TNF-α, IL-1β, and IL-6, and apoptosis. Pretreatment of cortical neurons with TFP5 before HG exposure inhibited Cdk5-p25 hyperactivity and significantly attenuated oxidative stress by decreasing reactive oxygen species levels, while increasing superoxide dismutase activity and glutathione. Tau hyperphosphorylation, inflammation, and apoptosis induced by HG were also considerably reduced by pretreatment with TFP5. These results suggest that TFP5 peptide may be a novel candidate for type 2 diabetes therapy. PMID:24326517

  17. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  18. Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances

    PubMed Central

    Auger, Jacques; Eustache, Florence; Rouiller-Fabre, Virginie; Canivenc-Lavier, Marie Chantal; Livera, Gabriel

    2014-01-01

    In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance (EAS) exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action (MOA) of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool (together with the epidemiological approach) for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction. PMID:24369134

  19. Antioxidant enzyme activity in bacterial resistance to nicotine toxicity by reactive oxygen species.

    PubMed

    Shao, Tiejuan; Yuan, Haiping; Yan, Bo; Lü, Zhenmei; Min, Hang

    2009-10-01

    We analyzed superoxide dismutase (SOD), catalase (CAT), and ATPase activities in the highly nicotine-degrading strain Pseudomonas sp. HF-1 and two standard strains Escherichia coli and Bacillus subtilis in an attempt to understand antioxidant enzymes in bacteria are produced in response to nicotine, which increases the virulence of the bacteria. Nicotine had different effects on different antioxidant enzymes of different bacteria. SOD plays a more important role in resistance to nicotine stress in E. coli than it does in CAT. Multiple antioxidant enzymes are involved in combating oxidative stress caused by nicotine in Pseudomonas sp. HF-1. The contribution of a particular antioxidant enzyme for protection from nicotine stress varies with the growth phase involved. The inhibition of ATPase in Pseudomonas sp. HF-1 at the stationary phase was enhanced with increasing nicotine concentration, showing a striking dose-response relationship. Nicotine probably affected the metabolism of ATP to some extent. Furthermore, different bacteria possessed distinct SOD isoforms to cope with oxidative stress caused by nicotine. PMID:19294456

  20. Antidotal activity of Averrhoa carambola (Star fruit) on fluoride induced toxicity in rats

    PubMed Central

    Vasant, Rupal A.

    2014-01-01

    Consumption of fluoride leads to several physiological disturbances in carbohydrate, lipid and antioxidant metabolisms. Averrhoa carambola L. fruit (Star fruit) is a commonly consumed fruit in tropical countries and is an ingredient in folklore medicines. As the fruits have high polyphenolic and antioxidant contents, the present study was undertaken to investigate the potential of star fruit as a dietary supplement in attenuating the fluoride induced hyperglycemia, hypercholesterolemia and oxidative stress in laboratory rats. A four-week exposure to fluoride caused sustained hyperglycemia, hyperlipidemia and oxidative stress and, when the diet was supplemented with star fruit powder, carbohydrate, lipid and antioxidant profiles were restored significantly. It is surmised that the antihyperglycemic, antihypercholesterolemic and antioxidant activities of star fruit in fluoride exposed rats could be due to the presence of polyphenols, flavonoids, saponins, phytosterols, ascorbic acid and fibers in the fruit, which are all well known regulators of carbohydrate, lipid and antioxidant metabolisms. These findings suggest that star fruit can be used as a dietary supplement in fluoride endemic regions to contain fluoride induced hyperglycemia, hyperlipidemia and oxidative stress. PMID:26109886

  1. Biosorption of toxic lead (II) ions using tomato waste (Solanum lycopersicum) activated by NaOH

    NASA Astrophysics Data System (ADS)

    Permatasari, Diah; Heraldy, Eddy; Lestari, Witri Wahyu

    2016-02-01

    This research present to uptake lead (II) ion from aqueous solutions by activated tomato waste. Biosorbent were characterized by applying Fourier Transform Infrared Spectroscopy (FTIR) and Surface Area Analyzer (SAA). The biosorption investigated with parameters including the concentration of NaOH, effects of solution pH, biosorbent dosage, contact time,and initial metal concentration. Experimental data were analyzed in terms of two kinetic model such us the pseudo-first order and pseudo-second order. Langmuir and Freundlich isotherm models were applied todescribe the biosorption process. According to the experiment, the optimum concentration of NaOH was achieved at 0.1 M. The maximum % lead (II) removal was achieved at pH 4 with 94.5%. Optimum biosorbentdosage were found as 0.1 g/25 mL solution while optimum contact time were found at 75 minutes. The results showed that the biosorption processes of Lead (II) followed pseudo-second order kinetics. Langmuir adsorption isotherm was found fit the adsorption data with amaximum capacity of 24.079 mg/g with anadsorption energy of 28.046 kJ/mol.

  2. Oxidative DNA damage contributes to the toxic activity of propylparaben in mammalian cells.

    PubMed

    Pérez Martín, José Manuel; Peropadre, Ana; Herrero, Oscar; Fernández Freire, Paloma; Labrador, Verónica; Hazen, María José

    2010-09-30

    Propyl p-hydroxybenzoate, commonly referred to as propylparaben, is the most frequently used preservative to inhibit microbial growth and extend shelf life of a range of consumer products. The objective of this study was to provide further insight into the toxicological profile of this compound, because of the current discrepancy in the literature with regard to the safety of parabens. The Vero cell line, derived from the kidney of the green monkey, was selected to evaluate the adverse effects of propylparaben by use of a set of mechanistically relevant endpoints for detecting cytotoxicity and genotoxic activities. Our results demonstrate that exposure to the compound for 24h causes changes in cell-proliferation rates rather than in cell viability. A significant and dose-dependent decline in the percentage of mitotic cells was observed at the lowest concentration tested, mainly due to cell-cycle arrest at the G0/G1 phase. Immunodetection techniques revealed that induction of DNA double-strand breaks and oxidative damage underlies the cytostatic effect observed in treated Vero cells. Additional studies are in progress to extend these findings, which define a novel mode of action of propylparaben in cultured mammalian cells.

  3. Antidotal activity of Averrhoa carambola (Star fruit) on fluoride induced toxicity in rats.

    PubMed

    Vasant, Rupal A; Narasimhacharya, A V R L

    2014-06-01

    Consumption of fluoride leads to several physiological disturbances in carbohydrate, lipid and antioxidant metabolisms. Averrhoa carambola L. fruit (Star fruit) is a commonly consumed fruit in tropical countries and is an ingredient in folklore medicines. As the fruits have high polyphenolic and antioxidant contents, the present study was undertaken to investigate the potential of star fruit as a dietary supplement in attenuating the fluoride induced hyperglycemia, hypercholesterolemia and oxidative stress in laboratory rats. A four-week exposure to fluoride caused sustained hyperglycemia, hyperlipidemia and oxidative stress and, when the diet was supplemented with star fruit powder, carbohydrate, lipid and antioxidant profiles were restored significantly. It is surmised that the antihyperglycemic, antihypercholesterolemic and antioxidant activities of star fruit in fluoride exposed rats could be due to the presence of polyphenols, flavonoids, saponins, phytosterols, ascorbic acid and fibers in the fruit, which are all well known regulators of carbohydrate, lipid and antioxidant metabolisms. These findings suggest that star fruit can be used as a dietary supplement in fluoride endemic regions to contain fluoride induced hyperglycemia, hyperlipidemia and oxidative stress.

  4. Asparagus racemosus ameliorates cisplatin induced toxicities and augments its antileishmanial activity by immunomodulation in vivo.

    PubMed

    Sachdeva, Heena; Sehgal, Rakesh; Kaur, Sukhbir

    2014-02-01

    Current drugs for the treatment of visceral leishmaniasis are inadequate and their efficacies are also compromised due to suppression of immune function associated during the course of infection. To overcome this problem, efforts are needed to develop therapies with effective immunomodulatory agents where decrease of parasitic burden and simultaneous enhancement of adaptive immunity can be achieved. In this study we have evaluated a new therapeutic approach based on combination of Asparagus racemosus, an immunomodulatory drug, in combination with cisplatin against Leishmania donovani infected BALB/c mice. We demonstrate that A. racemosus (650 mg/kg b.wt./day for 15 days, orally) in combination with cisplatin (5 mg/kg b.wt./day for 5 days, intraperitoneally) enhanced the clearance of parasites as determined by Giemsa-stained liver impression smears. Besides having better killing activity, this combination group achieved increased production of disease resolving Th-1 response (IFN-gamma, IL-2), heightened DTH (delayed type hypersensitivity) response and augmented levels of IgG2a. Moreover, A. racemosus in combination with cisplatin not only provided enhanced protective immune response but also resulted in remarkable improved kidney and liver function tests as manifested by normal levels of SGOT, SGPT, alkaline phosphatase, creatinine and urea in blood plasma with normal histological observations as compared to only cisplatin treated L. donovani infected BALB/c mice. Through this study we have ascertained that A. racemosus in combination with cisplatin in L. donovani infected BALB/c mice boosted as well as restored both cellular and humoral immunity. Thus in view of severe immunosuppression in visceral leishmaniasis, a better and effective strategy for optimum efficacy of future antileishmanial drugs would direct not only killing of parasite by the drug, but also simultaneous generation of immunity against the disease.

  5. Lunar Dust and Lunar Simulant Activation, Monitoring, Solution and Cellular Toxicity Properties

    NASA Technical Reports Server (NTRS)

    Wallace, William; Jeevarajan, A. S.

    2009-01-01

    During the Apollo missions, many undesirable situations were encountered that must be mitigated prior to returning humans to the moon. Lunar dust (that part of the lunar regolith less than 20 microns in diameter) was found to produce several problems with mechanical equipment and could have conceivably produced harmful physiological effects for the astronauts. For instance, the abrasive nature of the dust was found to cause malfunctions of various joints and seals of the spacecraft and suits. Additionally, though efforts were made to exclude lunar dust from the cabin of the lunar module, a significant amount of material nonetheless found its way inside. With the loss of gravity correlated with ascent from the lunar surface, much of the finer fraction of this dust began to float and was inhaled by the astronauts. The short visits tothe Moon during Apollo lessened exposure to the dust, but the plan for future lunar stays of up to six months demands that methods be developed to minimize the risk of dust inhalation. The guidelines for what constitutes "safe" exposure will guide the development of engineering controls aimed at preventing the presence of dust in the lunar habitat. This work has shown the effects of grinding on the activation level of lunar dust, the changes in dissolution properties of lunar simulant, and the production of cytokines by cellular systems. Grinding of lunar dust leads to the production of radicals in solution and increased dissolution of lunar simulant in buffers of different pH. Additionally, ground lunar simulant has been shown to promote the production of IL-6 and IL-8, pro-inflammatory cytokines, by alveolar epithelial cells. These results provide evidence of the need for further studies on these materials prior to returning to the lunar surface.

  6. Antiviral activity of Quercus persica L.: High efficacy and low toxicity

    PubMed Central

    Karimi, Ali; Moradi, Mohammad-Taghi; Saeedi, Mojtaba; Asgari, Sedigheh; Rafieian-kopaei, Mahmoud

    2013-01-01

    Background: Drug-resistant strain of Herpes simplex virus type 1 (HSV-I) has increased the interest in the use of natural substances. Aims: This study was aimed to determine minimum inhibitory concentration of hydroalchoholic extract of a traditionally used herbal plant, Quercus persica L., on HSV-1 replication on baby hamster kidney (BHK) cells. Setting: The study was conducted in Shahrekord University of Medical Sciences, Iran. Design: This was an experimental study. Materials and Methods: BHK cells were grown in monolayer culture with Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% fetal calf serum and plated onto 48-well culture plates. Fifty percent cytotoxic concentration (CC50%) of Q. persica L. on BHK cells was determined. Subsequently, 50% inhibitory concentration (IC50%) of the extract on replication of HSV-1 both in interacellular and exteracellular cases was assessed. Statistical Analysis: Statistic Probit model was used for statistical analysis. The dose-dependent effect of antiviral activity of the extracts was determined by linear regression. Results: Q. persica L. had no cytotoxic effect on this cell line. There was significant relationship between the concentration of the extract and cell death (P<0.01). IC50s of Q. persica L. on HSV-1, before and after attachment to BHK cells were 1.02 and 0.257 μg/mL, respectively. There was significant relationship between the concentration of this extract and inhibition of cytopathic effect (CPE) (P<0.05). Antioxidant capacity of the extract was 67.5%. Conclusions: The hydroalchoholic extract of Q. persica L. is potentially an appropriate and promising anti herpetic herbal medicine. PMID:24516836

  7. Blood acylpeptide hydrolase activity is a sensitive marker for exposure to some organophosphate toxicants.

    PubMed

    Quistad, Gary B; Klintenberg, Rebecka; Casida, John E

    2005-08-01

    Acylpeptide hydrolase (APH) unblocks N-acetyl peptides. It is a major serine hydrolase in rat blood, brain, and liver detected by derivatization with (3)H-diisopropyl fluorophosphate (DFP) or a biotinylated fluorophosphonate. Although APH does not appear to be a primary target of acute poisoning by organophosphorus (OP) compounds, the inhibitor specificity of this secondary target is largely unknown. This study fills the gap and emphasizes blood APH as a potential marker of OP exposure. The most potent in vitro inhibitors for human erythrocyte and mouse brain APH are DFP (IC(50) 11-17 nM), chlorpyrifos oxon (IC(50) 21-71 nM), dichlorvos (IC(50) 230-560 nM), naled (IC(50) 370-870 nM), and their analogs with modified alkyl substituents. (3)H-diisopropyl fluorophosphate is a potent inhibitor of mouse blood and brain APH in vivo (ED(50) 0.09-0.2 mg/kg and 0.02-0.03 mg/l for ip and vapor exposure, respectively). Mouse blood and brain APH and blood butyrylcholinesterase (BChE) are of similar sensitivity to DFP in vitro and in vivo (ip and vapor exposure), but APH inhibition is much more persistent in vivo (still >80% inhibition after 4 days). The inhibitory potency of OP pesticides in vivo in mice varies from APH selective (dichlorvos, naled, and trichlorfon), to APH and BChE selective (profenofos and tribufos), to ChE selective or nonselective (many commercial insecticides). Sarin administered ip at a lethal dose to guinea pigs inhibits blood acetylcholinesterase and BChE completely but erythrocyte APH only partially. Blood APH activity is therefore a sensitive marker for exposure to some but not all OP pesticides and chemical warfare agents. PMID:15888665

  8. Neurodevelopmental toxicity of prenatal polychlorinated biphenyls (PCBs) by chemical structure and activity: a birth cohort study

    PubMed Central

    2010-01-01

    Background Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxins. Although there is growing evidence to support an association between PCBs and deficits of neurodevelopment, the specific mechanisms are not well understood. The potentially different roles of specific PCB groups defined by chemical structures or hormonal activities e.g., dioxin-like, non-dioxin like, or anti-estrogenic PCBs, remain unclear. Our objective was to examine the association between prenatal exposure to defined subsets of PCBs and neurodevelopment in a cohort of infants in eastern Slovakia enrolled at birth in 2002-2004. Methods Maternal and cord serum samples were collected at delivery, and analyzed for PCBs using high-resolution gas chromatography. The Bayley Scales of Infant Development -II (BSID) were administered at 16 months of age to over 750 children who also had prenatal PCB measurements. Results Based on final multivariate-adjusted linear regression model, maternal mono-ortho-substituted PCBs were significantly associated with lower scores on both the psychomotor (PDI) and mental development indices (MDI). Also a significant association between cord mono-ortho-substituted PCBs and reduced PDI was observed, but the association with MDI was marginal (p = 0.05). Anti-estrogenic and di-ortho-substituted PCBs did not show any statistically significant association with cognitive scores, but a suggestive association between di-ortho-substituted PCBs measured in cord serum and poorer PDI was observed. Conclusion Children with higher prenatal mono-ortho-substituted PCB exposures performed more poorly on the Bayley Scales. Evidence from this and other studies suggests that prenatal dioxin-like PCB exposure, including mono-ortho congeners, may interfere with brain development in utero. Non-dioxin-like di-ortho-substituted PCBs require further investigation. PMID:20731829

  9. A low-cost non-toxic post-growth activation step for CdTe solar cells.

    PubMed

    Major, J D; Treharne, R E; Phillips, L J; Durose, K

    2014-07-17

    Cadmium telluride, CdTe, is now firmly established as the basis for the market-leading thin-film solar-cell technology. With laboratory efficiencies approaching 20 per cent, the research and development targets for CdTe are to reduce the cost of power generation further to less than half a US dollar per watt (ref. 2) and to minimize the environmental impact. A central part of the manufacturing process involves doping the polycrystalline thin-film CdTe with CdCl2. This acts to form the photovoltaic junction at the CdTe/CdS interface and to passivate the grain boundaries, making it essential in achieving high device efficiencies. However, although such doping has been almost ubiquitous since the development of this processing route over 25 years ago, CdCl2 has two severe disadvantages; it is both expensive (about 30 cents per gram) and a water-soluble source of toxic cadmium ions, presenting a risk to both operators and the environment during manufacture. Here we demonstrate that solar cells prepared using MgCl2, which is non-toxic and costs less than a cent per gram, have efficiencies (around 13%) identical to those of a CdCl2-processed control group. They have similar hole densities in the active layer (9 × 10(14) cm(-3)) and comparable impurity profiles for Cl and O, these elements being important p-type dopants for CdTe thin films. Contrary to expectation, CdCl2-processed and MgCl2-processed solar cells contain similar concentrations of Mg; this is because of Mg out-diffusion from the soda-lime glass substrates and is not disadvantageous to device performance. However, treatment with other low-cost chlorides such as NaCl, KCl and MnCl2 leads to the introduction of electrically active impurities that do compromise device performance. Our results demonstrate that CdCl2 may simply be replaced directly with MgCl2 in the existing fabrication process, thus both minimizing the environmental risk and reducing the cost of CdTe solar-cell production.

  10. A low-cost non-toxic post-growth activation step for CdTe solar cells

    NASA Astrophysics Data System (ADS)

    Major, J. D.; Treharne, R. E.; Phillips, L. J.; Durose, K.

    2014-07-01

    Cadmium telluride, CdTe, is now firmly established as the basis for the market-leading thin-film solar-cell technology. With laboratory efficiencies approaching 20 per cent, the research and development targets for CdTe are to reduce the cost of power generation further to less than half a US dollar per watt (ref. 2) and to minimize the environmental impact. A central part of the manufacturing process involves doping the polycrystalline thin-film CdTe with CdCl2. This acts to form the photovoltaic junction at the CdTe/CdS interface and to passivate the grain boundaries, making it essential in achieving high device efficiencies. However, although such doping has been almost ubiquitous since the development of this processing route over 25 years ago, CdCl2 has two severe disadvantages; it is both expensive (about 30 cents per gram) and a water-soluble source of toxic cadmium ions, presenting a risk to both operators and the environment during manufacture. Here we demonstrate that solar cells prepared using MgCl2, which is non-toxic and costs less than a cent per gram, have efficiencies (around 13%) identical to those of a CdCl2-processed control group. They have similar hole densities in the active layer (9 × 1014 cm-3) and comparable impurity profiles for Cl and O, these elements being important p-type dopants for CdTe thin films. Contrary to expectation, CdCl2-processed and MgCl2-processed solar cells contain similar concentrations of Mg; this is because of Mg out-diffusion from the soda-lime glass substrates and is not disadvantageous to device performance. However, treatment with other low-cost chlorides such as NaCl, KCl and MnCl2 leads to the introduction of electrically active impurities that do compromise device performance. Our results demonstrate that CdCl2 may simply be replaced directly with MgCl2 in the existing fabrication process, thus both minimizing the environmental risk and reducing the cost of CdTe solar-cell production.

  11. DEVELOPMENT OF QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS (QSARS) TO PREDICT TOXICITY FOR A VARIETY OF HUMAN AND ECOLOGICAL ENDPOINTS

    EPA Science Inventory

    A web accessible software tool is being developed to predict the toxicity of unknown chemicals for a wide variety of endpoints. The tool will enable a user to easily predict the toxicity of a query compound by simply entering its structure in a 2-dimensional (2-D) chemical sketc...

  12. DEVELOPMENT OF QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS (QSARS) TO PREDICT TOXICITY FOR A VARIETY OF HUMAN AND ECOLOGICAL ENDPOINTS

    EPA Science Inventory

    In general, the accuracy of a predicted toxicity value increases with increase in similarity between the query chemical and the chemicals used to develop a QSAR model. A toxicity estimation methodology employing this finding has been developed. A hierarchical based clustering t...

  13. Corrigendum to "PAHs in the Great Barrier Reef Lagoon reach potentially toxic levels from coal port activities" [Estuar. Coast. Shelf Sci. 144, 39-45

    NASA Astrophysics Data System (ADS)

    Burns, Kathryn A.

    2014-08-01

    Erratum with respect to the paper: Burns, K A, 2014 PAHs in the Great Barrier Reef Lagoon reach potentially toxic levels from coal port activities. Estuarine Coastal and Shelf Science 144, 39-45. DOI 10.1016/j.ecss.2014.04.001.

  14. Balance between herbicidal activity and toxicity effect: a case study of the joint effects of triazine and phenylurea herbicides on Selenastrum capricornutum and Photobacterium phosphoreum.

    PubMed

    Ge, Hongming; Lin, Zhifen; Yao, Zhifeng; Gao, Ya; Cong, Yongping; Yu, Hongxia

    2014-05-01

    The use of herbicide mixtures has become a cost-effective strategy against the evolution of herbicide resistance to protect global food production. Much research has focused on investigating either the herbicidal activities or the toxicity effects of herbicides; however, few of them have investigated both factors. This study investigates the balance between herbicidal activity for Selenastrum capricornutum and toxicity effect toward Photobacterium phosphoreum by determining the joint effects of triazine (simetryn, atrazine, prometon and prometryn) and phenylurea (fenuron, monuron, monolinuron and diuron) herbicides. The results showed that among the four triazines, only simetryn exhibited a unique effect (formation of a pi-sigma bond with the D1 microalga protein and an H-bond with the Luc photobacterial protein); and among 16 triazine-phenylurea binary mixtures, only the mixtures containing simetryn resulted in TU1 values (herbicidal activities of mixtures on S. capricornutum) >TU2 values (toxicity effects of mixtures on P. phosphoreum). However, the other 12 mixtures, which did not contain simetryn, showed the opposite result (TU1activity and toxicity effect, which will encourage thoughtful efforts for how to best combine herbicides in a sustainable way. PMID:24681700

  15. Efficacy of attractive toxic sugar baits (ATSB) against Aedes albopictus with garlic oil encapsulated in beta-Cyclodextrin as the active ingredient

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We tested the efficacy of attractive toxic sugar bait (ATSB) with garlic oil microencapsulated in beta-cyclodextrin as active ingredient against Aedes albopictus in suburban Haifa, Israel. Two three-acre gardens with high numbers of Ae. albopictus were chosen for perimeter spray treatment with ATSB ...

  16. Toxic effects of heavy metals (Cd, Cr and Pb) on seed germination and growth and DPPH-scavenging activity in Brassica rapa var. turnip.

    PubMed

    Siddiqui, Maryam Mehmood; Abbasi, Bilal Haider; Ahmad, Nisar; Ali, Mohammad; Mahmood, Tariq

    2014-04-01

    Toxicity of heavy metal is a wide spread environmental problem affecting all life forms including plants. In the present study the toxic effects of heavy metals, cadmium (Cd), chromium (Cr) and lead (Pb) on seed germination rate (%), germination index (G-index) and growth (mm) of Brassica rapa var. turnip have been investigated. The seeds were soaked either in distilled water (control) or in aqueous solutions of Cd, Cr and Pb (1 g/l, 2.5 g/l and 5 g/l) at 4°C in dark for 24 hours. Prior to inoculation onto MS0 medium, the soaked seeds were either washed with sterile distilled water or inoculated without washing on solidified MS0 medium at 25 ± 2°C with 16/8-hour photoperiod in a growth chamber to germinate in vitro. Such stress conditions revealed that by increasing the concentration of heavy metals, the germination rate (%), G-index value and growth (mm) decreased significantly, suggesting their toxic effect on B. rapa var. turnip. This study further revealed that experiment with seed washing resulted in less toxicity of selected heavy metals on germination and growth of B. rapa var. turnip, as compared to experiment without washing. However, the resulting toxicity order of the selected heavy metals remained the same (Cd > Cr > Pb). Significant decrease has been observed in seed viability and germination potential and finally heavy metals completely ceased further growth and development of plants. The 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging activity revealed that significantly higher activity was observed in control plants without heavy metals treatment. Furthermore, the Cd-treated plants showed decreased antioxidant activity. Cr and Pb were less toxic as compared to Cd (control > Pb > Cr > Cd). This study revealed that selected heavy metals not only affected plant development but also disturbed plant metabolic pathways.

  17. Antioxidant and antiapoptotic activities of Calotropis procera latex on Catfish (Clarias gariepinus) exposed to toxic 4-nonylphenol.

    PubMed

    Sayed, Alaa El-Din H; Mohamed, Nadia H; Ismail, Mady A; Abdel-Mageed, Wael M; Shoreit, Ahmed A M

    2016-06-01

    Calotropis procera L. is known as medicinal plant. The Phytochemical analyzes of its latex revealed that it possessed antioxidants, namely terpenes, phenolic compounds and cardenolides, flavonoids and saponins, while tannins, alkaloids and resin were absent in moderate to high concentration. In the present study, the role of latex of Calotropis procera as antioxidant and antiapoptotic was reported. To carry out this aim, fishes were exposed to 100 µg l(-1) 4-nonylphenol as chemical pollutant. The enzymes, superoxidase dismutase, catalase, acetlycholinstrase (AchE), glutathione s-transferase, cortisol, G6PDH) and apoptotic cells increased significantly (p<0.05) accompanied by irregular disturbance of (Na(+), K(+)) ions in the presence of 4-nonylphenol. On the other hand, these enzymes, ions, and apoptotic cells decreased normally and significantly (p<0.05) in the presence of latex. Total phenol content, total capacity antioxidant, reducing power decrease significantly (p<0.05) in the presence of 4-nonylphenol and increase normally in the presence of latex. Latex was used for the first time to protect catfish after 4-nonylphenol exposure. Our study confirms that crude latex of Calotropis procera possessed antioxidant and antiapoptotic activities against the toxicity of 4-Nonylphenol. PMID:26946283

  18. Study of the analgesic activities, chronic toxicity and addictive potential of Jia-Yuan-Qing pill in rats

    PubMed Central

    TIAN, YE; TENG, LI-RONG; WANG, ZHEN-ZUO; ZHAO, MIN; MENG, QING-FAN; LU, JIA-HUI; TIAN, JIAN-MING; ZHANG, WEI-WEI; ZHENG, XIAOYI; WANG, DI; TENG, LE-SHENG

    2015-01-01

    Jia-Yuan-Qing pill (JYQP) composed of Porcellio laevis Latreille, Corydalis Rhizoma and Radix Cynanchi Paniculati at a ratio of 9:7:7 has been found to be an effective analgesic agent. The present study aimed to evaluate the safety, addictive potential and anti-cancer pain activity of JYQP in a rat model. During the 6-month chronic toxicity test, no significant changes in general behavior, defecation, postural abnormalities, dietary or water intake or blood biochemical parameters were observed in male and female rats. Although a high dose of JYQP (5 g/kg) caused swelling of the liver, spleen and kidney in male and female rats, no pathological changes were observed in all organs examined via hematoxylin and eosin staining. The analgesic effect of JYQP on bone cancer pain was successfully confirmed in a rat model of Walker 256 cell-induced bone cancer. In contrast to morphine, in a physical dependence test, JYQP produced no withdrawal symptoms following chronic administration. The data from this study provide experimental evidence supporting the clinical use of JYQP as an effective, safe and non-addictive agent for the treatment of bone cancer pain. PMID:26136985

  19. Antifungal activity and acute toxicity of stem bark extracts of Drypetes gossweileri S. Moore-euphorbiaceae from Cameroon.

    PubMed

    Ngouana, Vincent; Fokou, Patrick Valère Tsouh; Foudjo, Brice Ulrich Saha; Ngouela, Silvère Augustin; Boyom, Fabrice Fekam; Zollo, Paul Henri Amvam

    2011-01-01

    Drypetes gossweilleri S. Moore is a plant used in traditional medicine in Cameroon. The antifungal properties of its stem-bark crude extract and fractions DG(1), DG(2), DG(3), DG(4), DG(5), DG(6), DG(7), DG(8) and DG(9) were assayed by agar and broth dilution methods on solid and liquid media against C. Krusei, C. albicans, C. glabrata, T. mentagerophytes, M. langeroinii, M. gypeum, M. audouini, T. rubrum, T. soudanense, T. terrestre, A. flavus and A. niger. The results revealed a substantial antifungal effect with minimal inhibitory concentrations ranging respectively from 24.11µg/ml to 1562µg/ml for yeasts and from 3125µg/ml to 12500µg/ml for filamentous fungi. Among the fractions, fraction DG4 exerted the highest antifungal activity. Moreover, no toxic effect was noticed in male and female albinos Wistar rats treated per os with the crude stem bark's extract of Drypetes gossweileri at a dose up to 12g/kg of body weight. The phytochemical screening of the crude extract and fractions showed the presence of alkaloids, phenols, flavonoids, saponins, anthocyanines, anthraquinones, sterols, lipids and essential oils. Therefore, Drypetes gossweileri may be safe as phytomedecine for the treatment of fungal infections. PMID:22468013

  20. Evaluation of immunostimulant activity and chemoprotective effect of mangrove Rhizophora apiculata against cyclophosphamide induced toxicity in BALB/c mice.

    PubMed

    Vinod Prabhu, V; Guruvayoorappan, C

    2012-08-01

    Chemotherapeutic drugs available today are immunosuppressant, cytotoxic and with variety of side effects in cancer chemotherapy. Plant based immunomodulators are often an auxiliary therapy to overcome the repulsive effects of cytotoxic chemotherapeutic agents and to restore immunity with normal health. Mangroves Rhizophora apiculata (R. apiculata) extract was found to protect mice from cyclophosphamide (CTX) induced leukopenia. The leukocyte counts in the R. apiculata extract treated animals was significantly increased (10425 ± 163 mm³) where the control group shows no significant increase (7855 ± 282 mm³). The leukocytes count in CTX induced group treated with R. apiculata extract shows significant increase (5235 ± 303 mm³) when compared with CTX induced group (3416 ± 172 mm³) on the same day. The hemoglobin level of CTX induced group treated with R. apiculata extract shows increase in the level compared with the CTX induced animals. The bone marrow cellularity and α-esterase activity was also significantly higher compared to normal group and CTX induced group. Moreover, R. apiculata extract prevented the loss of organ weight and is increased the organ weight in treated animals. This indicates the efficiency of R. apiculata extract as an effective immunostimulant and better chemoprotectant against CTX induced toxicity in BALB/c mice. PMID:22211366

  1. Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI

    PubMed Central

    Lee, Lawrence Soon-U; Seng, Kok-Yong; Wang, Ling-Zhi; Yong, Wei-Peng; Hee, Kim-Hor; Soh, Thomas I.; Wong, Andrea; Cheong, Pei F.; Soong, Richie; Sapari, Nur S.; Soo, Ross; Fan, Lu; Lee, Soo-Chin; Goh, Boon C.

    2016-01-01

    Background Irinotecan toxicity correlates with UGT1A1 activity. We explored whether phenotyping UGT1A1 using a probe approach works better than current genotyping methods. Methods Twenty-four Asian cancer patients received irinotecan as part of the FOLFIRI regimen. Subjects took raltegravir 400 mg orally and intravenous midazolam 1 mg. Pharmacokinetic analyses were performed using WinNonLin and NONMEM. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1 and CYP3A4/5. Results SN-38G/SN-38 AUC ratio correlated well with Raltegravir glucuronide/ Raltegravir AUC ratio (r = 0.784 p<0.01). Midazolam clearance correlated well with irinotecan clearance (r = 0.563 p<0.01). SN-38 AUC correlated well with Log10Nadir Absolute Neutrophil Count (ANC) (r = -0.397 p<0.05). Significant correlation was found between nadir ANC and formation rate constant of raltegravir glucuronide (r = 0.598, P<0.005), but not UGT1A1 genotype. Conclusion Raltegravir glucuronide formation is a good predictor of nadir ANC, and can predict neutropenia in East Asian patients. Prospective studies with dose adjustments should be done to develop raltegravir as a probe to optimize irinotecan therapy. Trial Registration Clinicaltrials.gov NCT00808184 PMID:26808671

  2. Brain necrosis after permanent low-activity iodine-125 implants: case report and review of toxicity from focal radiation.

    PubMed

    Bampoe, J; Nag, S; Leung, P; Laperriere, N; Bernstein, M

    2000-01-01

    Focal irradiation has emerged as a useful modality in the management of malignant brain tumors. Its main limitation is radiation necrosis. We report on the radiation dose distribution in the cerebellum of a patient who developed imaging and autopsy diagnosis of radiation necrosis after permanent iodine-125 implants for a solitary osseous plasmacytoma of her left occipital condyle. A 55-year-old woman initially presented with neck and occipital pain and a lytic lesion of her left occipital condyle. A cytological diagnosis of solitary osseous plasmacytoma was made by transpharyngeal needle biopsy. After an initial course of external beam radiation, the patient required further treatment with systemic chemotherapy 21 months later for clinical and radiographic progression of her disease. She ultimately required subtotal surgical resection of an anaplastic plasmacytoma with intracranial extension. Permanent low-activity iodine-125 seeds were implanted in the tumor cavity. Satisfactory local control was achieved. However, clinical and imaging signs of radiation damage appeared 28 months after iodine-125 seed implantation. Progressive systemic myeloma led to her death 11 years after presentation and 9 years after seed implantation. Radiation dose distribution is described, with a discussion of toxicity from focal radiation dose escalation.

  3. Immobilized nickel hexacyanoferrate on activated carbons for efficient attenuation of radio toxic Cs(I) from aqueous solutions

    NASA Astrophysics Data System (ADS)

    Lalhmunsiama; Lalhriatpuia, C.; Tiwari, Diwakar; Lee, Seung-Mok

    2014-12-01

    The aim of this study is to immobilize nickel hexacyanoferrate onto the large surface of activated carbons (ACs) precursor to rice hulls and areca nut waste materials. These nickel hexacyanoferrate immobilized materials are then assessed in the effective attenuation of radio logically important cesium ions from aqueous solutions. The solid samples are characterized by the XRD analytical method and surface morphology is obtained from the SEM images. The batch reactor experiments show that an increase in sorptive pH (2.0-10.0) apparently not affecting the high percent uptake of Cs(I). Equilibrium modeling studies suggest that the data are reasonably and relatively fitted well to the Langmuir adsorption isotherm. Kinetic studies show that sorption process is fairly rapid and the kinetic data are fitted well to the pseudo-second order rate model. Increasing the background electrolyte concentration from 0.001 to 0.1 mol/L NaCl causes insignificant decrease in Cs(I) removal which infers the higher selectivity of these materials for Cs(I) from aqueous solutions. Further, the column reactor operations enable to obtain the breakthrough data which are then fitted to the Thomas non-linear equation as to obtain the loading capacity of column for Cs(I). The results show that the modified materials show potential applicability in the attenuation of radio toxic cesium from aqueous solution.

  4. Quantitative structure-activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes).

    PubMed

    Lin, Hongkang; Morandi, Garrett D; Brown, R Stephen; Snieckus, Victor; Rantanen, Toni; Jørgensen, Kåre B; Hodson, Peter V

    2015-02-01

    Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs.

  5. Interspecies quantitative structure-activity relationships (QSARs) for eco-toxicity screening of chemicals: the role of physicochemical properties.

    PubMed

    Furuhama, A; Hasunuma, K; Aoki, Y

    2015-01-01

    In addition to molecular structure profiles, descriptors based on physicochemical properties are useful for explaining the eco-toxicities of chemicals. In a previous study we reported that a criterion based on the difference between the partition coefficient (log POW) and distribution coefficient (log D) values of chemicals enabled us to identify aromatic amines and phenols for which interspecies relationships with strong correlations could be developed for fish-daphnid and algal-daphnid toxicities. The chemicals that met the log D-based criterion were expected to have similar toxicity mechanisms (related to membrane penetration). Here, we investigated the applicability of log D-based criteria to the eco-toxicity of other kinds of chemicals, including aliphatic compounds. At pH 10, use of a log POW - log D > 0 criterion and omission of outliers resulted in the selection of more than 100 chemicals whose acute fish toxicities or algal growth inhibition toxicities were almost equal to their acute daphnid toxicities. The advantage of log D-based criteria is that they allow for simple, rapid screening and prioritizing of chemicals. However, inorganic molecules and chemicals containing certain structural elements cannot be evaluated, because calculated log D values are unavailable.

  6. Lowering the isoelectric point of the Fv portion of recombinant immunotoxins leads to decreased nonspecific animal toxicity without affecting antitumor activity.

    PubMed

    Onda, M; Nagata, S; Tsutsumi, Y; Vincent, J J; Wang, Q; Kreitman, R J; Lee, B; Pastan, I

    2001-07-01

    Recombinant immunotoxins are genetically engineered proteins in which the Fv portion of an antibody is fused to a toxin. Our laboratory uses a 38-kDa form of Pseudomonas exotoxin A termed PE38 for this purpose. Clinical studies with immunotoxins targeting CD25 and CD22 have shown that dose-limiting side effects are attributable to liver damage and other inflammatory toxicities. We recently showed that mutating exposed surface neutral residues to acidic residues in the framework region of the Fv portion of an immunotoxin targeting CD25 [anti-Tac(scFv)-PE38] lowered its isoelectric point (pI) and decreased its toxicity in mice without impairing its cytotoxic or antitumor activities. We have now extended these studies and made mutations that change basic residues to neutral or acidic residues. Initially the pI of the mutant Fv (M1) of anti-Tac(scFv)-PE38 was decreased further. Subsequently, mutations were made in two other immunotoxins, SS1(dsFv)-PE38 targeting ovarian cancer and B3(dsFv)-PE38 targeting colon and breast cancers. We have found that all these mutant molecules fully retained specific target cell cytotoxicity and antitumor activity but were considerably less toxic to mice. Therefore, lowering the pI of the Fv may be a general approach to diminish the nonspecific toxicity of recombinant immunotoxins and other Fv fusion proteins without losing antitumor activity. PMID:11431343

  7. Evidence for effects on the in vivo activity of ribulose-bisphosphate carboxylase/oxygenase during development of Mn toxicity in tobacco. [Nicotiana tabacum L. cv KY14

    SciTech Connect

    Houtz, R.L.; Nable, R.O.; Cheniae, G.M. )

    1988-04-01

    The progressive decrease in net photosynthesis accompanying development of Mn toxicity in young leaves of burley tobacco (Nicotiana tabacum L. cv KY 14) is a result of effects on in vivo activity of ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (rubisco, EC 4.1.1.39). This conclusion is supported by: (a) decrease in rates of CO{sub 2} depletion during measurements of CO{sub 2} compensation, (b) increase in leaf RuBP concentrations, (c) progressive decreases in rate-constants of RuBP loss (light to dark transition analyses) with progressive increases of leaf Mn concentrations, and (d) restoration of diminished rates of net photosynthesis to control rates by elevated CO{sub 2} (5%). Moreover, elevated CO{sub 2} (1100 microliters per liter) during culture of Mn-treated plants decreased elevated RuBP concentrations to control levels and alleviated foliar symptoms of Mn toxicity. These effects of Mn toxicity on in vivo activity of rubisco were not expressed by in vitro kinetic analyses of rubisco prepared under conditions to sequester Mn or to adsorb polyphenols or their oxidation products. Similarly, the in vitro activity of fructose bisphosphatase (EC 3.1.3.11) was unaffected by Mn toxicity.

  8. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    SciTech Connect

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  9. Fumigant toxicity and acetylcholinesterase inhibitory activity of 4 Asteraceae plant essential oils and their constituents against Japanese termite (Reticulitermes speratus Kolbe).

    PubMed

    Seo, Seon-Mi; Kim, Junheon; Kang, Jaesoon; Koh, Sang-Hyun; Ahn, Young-Joon; Kang, Kyu-Suk; Park, Il-Kwon

    2014-07-01

    This study investigated the fumigant toxicity of 4 Asteraceae plant essential oils and their constituents against the Japanese termite Reticulitermes speratus Kolbe. Fumigant toxicity varied with plant essential oils or constituents, exposure time, and concentration. Among the tested essential oils, those from Chamaemelum nobile exhibited the strongest fumigant toxicity, followed by those from Santolina chamaecyparissus, Ormenis multicaulis, and Eriocephalus punctulatus at 2 days after treatment. In all, 15, 24, 19, and 9 compounds were identified in the essential oils from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus, respectively, by using gas chromatography, gas chromatography-mass spectrometry, or open-column chromatography. The identified compounds were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, trans-pinocarveol, caryophyllene oxide, sabinene hydrate, and santolina alcohol showed strong fumigant toxicity against Japanese termites. Acetylcholinesterase (AChE) inhibition activity of the identified compounds from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus essential oils were tested to determine the mode of their action. The IC50 values of (+)-α-pinene, (-)-limonene, (-)-α-pinene, β-pinene, and β-phellandrene against Japanese termite AChE were 0.03, 0.13, 0.41, 0.42, and 0.67mg/mL, respectively. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control.

  10. Jasmonic Acid Modulates the Physio-Biochemical Attributes, Antioxidant Enzyme Activity, and Gene Expression in Glycine max under Nickel Toxicity

    PubMed Central

    Sirhindi, Geetika; Mir, Mudaser Ahmad; Abd-Allah, Elsayed Fathi; Ahmad, Parvaiz; Gucel, Salih

    2016-01-01

    In present study, we evaluated the effects of Jasmonic acid (JA) on physio-biochemical attributes, antioxidant enzyme activity, and gene expression in soybean (Glycine max L.) plants subjected to nickel (Ni) stress. Ni stress decreases the shoot and root length and chlorophyll content by 37.23, 38.31, and 39.21%, respectively, over the control. However, application of JA was found to improve the chlorophyll content and length of shoot and root of Ni-fed seedlings. Plants supplemented with JA restores the chlorophyll fluorescence, which was disturbed by Ni stress. The present study demonstrated increase in proline, glycinebetaine, total protein, and total soluble sugar (TSS) by 33.09, 51.26, 22.58, and 49.15%, respectively, under Ni toxicity over the control. Addition of JA to Ni stressed plants further enhanced the above parameters. Ni stress increases hydrogen peroxide (H2O2) by 68.49%, lipid peroxidation (MDA) by 50.57% and NADPH oxidase by 50.92% over the control. Supplementation of JA minimizes the accumulation of H2O2, MDA, and NADPH oxidase, which helps in stabilization of biomolecules. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) increases by 40.04, 28.22, 48.53, and 56.79%, respectively, over the control in Ni treated seedlings and further enhancement in the antioxidant activity was observed by the application of JA. Ni treated soybean seedlings showed increase in expression of Fe-SOD by 77.62, CAT by 15.25, POD by 58.33, and APX by 80.58% over the control. Nevertheless, application of JA further enhanced the expression of the above genes in the present study. Our results signified that Ni stress caused negative impacts on soybean seedlings, but, co-application of JA facilitate the seedlings to combat the detrimental effects of Ni through enhanced osmolytes, activity of antioxidant enzymes and gene expression. PMID:27242811

  11. Jasmonic Acid Modulates the Physio-Biochemical Attributes, Antioxidant Enzyme Activity, and Gene Expression in Glycine max under Nickel Toxicity.

    PubMed

    Sirhindi, Geetika; Mir, Mudaser Ahmad; Abd-Allah, Elsayed Fathi; Ahmad, Parvaiz; Gucel, Salih

    2016-01-01

    In present study, we evaluated the effects of Jasmonic acid (JA) on physio-biochemical attributes, antioxidant enzyme activity, and gene expression in soybean (Glycine max L.) plants subjected to nickel (Ni) stress. Ni stress decreases the shoot and root length and chlorophyll content by 37.23, 38.31, and 39.21%, respectively, over the control. However, application of JA was found to improve the chlorophyll content and length of shoot and root of Ni-fed seedlings. Plants supplemented with JA restores the chlorophyll fluorescence, which was disturbed by Ni stress. The present study demonstrated increase in proline, glycinebetaine, total protein, and total soluble sugar (TSS) by 33.09, 51.26, 22.58, and 49.15%, respectively, under Ni toxicity over the control. Addition of JA to Ni stressed plants further enhanced the above parameters. Ni stress increases hydrogen peroxide (H2O2) by 68.49%, lipid peroxidation (MDA) by 50.57% and NADPH oxidase by 50.92% over the control. Supplementation of JA minimizes the accumulation of H2O2, MDA, and NADPH oxidase, which helps in stabilization of biomolecules. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) increases by 40.04, 28.22, 48.53, and 56.79%, respectively, over the control in Ni treated seedlings and further enhancement in the antioxidant activity was observed by the application of JA. Ni treated soybean seedlings showed increase in expression of Fe-SOD by 77.62, CAT by 15.25, POD by 58.33, and APX by 80.58% over the control. Nevertheless, application of JA further enhanced the expression of the above genes in the present study. Our results signified that Ni stress caused negative impacts on soybean seedlings, but, co-application of JA facilitate the seedlings to combat the detrimental effects of Ni through enhanced osmolytes, activity of antioxidant enzymes and gene expression. PMID:27242811

  12. Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Quantitative Structure-Activity Relationship (QSAR) toxicity models have become popular tools for identifying potential toxic compounds and prioritizing candidates for animal toxicity tests. However, few QSAR studies have successfully modeled large, diverse mammalian toxicity end...

  13. Quantitative structure-activity relationship (QSAR) prediction of (eco)toxicity of short aliphatic protic ionic liquids.

    PubMed

    Peric, Brezana; Sierra, Jordi; Martí, Esther; Cruañas, Robert; Garau, Maria Antonia

    2015-05-01

    Ionic liquids (ILs) are considered as a group of very promising compounds due to their excellent properties (practical non-volatility, high thermal stability and very good and diverse solving capacity). The ILs have a good prospect of replacing traditional organic solvents in vast variety of applications. However, the complete information on their environmental impact is still not available. There is also an enormous number of possible combinations of anions and cations which can form ILs, the fact that requires a method allowing the prediction of toxicity of existing and potential ILs. In this study, a group contribution QSAR model has been used in order to predict the (eco)toxicity of protic and aprotic ILs for five tests (Microtox®, Pseudokirchneriella subcapitata and Lemna minor growth inhibition test, and Acetylcholinestherase inhibition and Cell viability assay with IPC-81 cells). The predicted and experimental toxicity are well correlated. A prediction of EC50 for these (eco)toxicity tests has also been made for eight representatives of the new family of short aliphatic protic ILs, whose toxicity has not been determined experimentally to date. The QSAR model applied in this study can allow the selection of potentially less toxic ILs amongst the existing ones (e.g. in the case of aprotic ILs), but it can also be very helpful in directing the synthesis efforts toward developing new "greener" ILs respectful with the environment (e.g. short aliphatic protic ILs). PMID:25728357

  14. Quantitative structure-activity relationship (QSAR) prediction of (eco)toxicity of short aliphatic protic ionic liquids.

    PubMed

    Peric, Brezana; Sierra, Jordi; Martí, Esther; Cruañas, Robert; Garau, Maria Antonia

    2015-05-01

    Ionic liquids (ILs) are considered as a group of very promising compounds due to their excellent properties (practical non-volatility, high thermal stability and very good and diverse solving capacity). The ILs have a good prospect of replacing traditional organic solvents in vast variety of applications. However, the complete information on their environmental impact is still not available. There is also an enormous number of possible combinations of anions and cations which can form ILs, the fact that requires a method allowing the prediction of toxicity of existing and potential ILs. In this study, a group contribution QSAR model has been used in order to predict the (eco)toxicity of protic and aprotic ILs for five tests (Microtox®, Pseudokirchneriella subcapitata and Lemna minor growth inhibition test, and Acetylcholinestherase inhibition and Cell viability assay with IPC-81 cells). The predicted and experimental toxicity are well correlated. A prediction of EC50 for these (eco)toxicity tests has also been made for eight representatives of the new family of short aliphatic protic ILs, whose toxicity has not been determined experimentally to date. The QSAR model applied in this study can allow the selection of potentially less toxic ILs amongst the existing ones (e.g. in the case of aprotic ILs), but it can also be very helpful in directing the synthesis efforts toward developing new "greener" ILs respectful with the environment (e.g. short aliphatic protic ILs).

  15. Relative toxicity of para-substituted phenols: log K/sub ow/ and pKa-dependent structure-activity relationships

    SciTech Connect

    Schultz, T.W.

    1987-06-01

    The toxic response of the majority of industrial chemicals which are nonreactive and non -ionic can be quantitatively modeled by the 1-octanol/water partition coefficient (K/sub ow/) in a linear fashion following a log-log transformation of the data. The toxicity of phenols, however does not model by these same quantitative structure-activity relationships (QSAR). Earlier studies have shown that the addition of pKa as a second molecular descriptor improves the predictive capability of log K/sub ow/ QSAR. The predicted toxicity of phenol derivatives, which ionize poorly under the test conditions, is not significantly altered by using models in which pKa is not included. In an effort to systematically explore the extent to which such log K/sub ow/ and, log K/sub ow/ and pKa-dependent QSAR can be used to predict the biological activity of phenols, the first in a series of investigations was conducted using the rapid and inexpensive Tetrahymena population growth impairment assay to determine relative toxicity of 30 para-substituted derivatives.

  16. Cytotoxicity of lymphocytes activated by superantigen toxic-shock-syndrome toxin-1 against colorectal cancer LoVo cells.

    PubMed

    Wang, Wei; Sun, Xuejun; Lu, Le; Zheng, Jian-Bao; Tian, Yong; Wang, Wei

    2013-04-01

    Toxic-shock-syndrome toxin-1 (TSST-1), a superantigen, can stimulate T cell activation and be used for immunotherapy. In this study, we employed the carcinoembryonic antigen (CEA)-positive LoVo cells to test whether retrovirus-mediated TSST-1 expression could activate human T cells and promote cytotoxicity against tumor cells. We first generated plasmids of pLEGFP-N1-5HRE-CEAp-TSST-1-linker-CD80TM containing a fusion gene of the CEA promoter, 5 copies of the hypoxia-response elements (HRE) as an enhancer, the fragments for TSST-1, and the transmembrane domain of CD80 (CD80TM) and control pLEGFP-N1-5HRE-CEAp (without TSST-1) and generated retroviruses of 5HCTC and 5HC, respectively. After infection with 5HC and 5HCTC retroviruses to establish cell lines, the high levels of TSST-1 expression were observed on the membrane and cytoplasm of the 5HCTC-infected LoVo cells, particularly culture under a hypoxic condition, but not on CEA(-) HeLa cells. Furthermore, the TSST-1-expressing LoVo cell lysates, but not the control cell lysates, stimulated human T cell proliferation, and the co-culture of the TSST-1-expressing LoVo, but not control cells, with human peripheral blood mononuclear cells (PBMC) induced a high frequency of TNF-α- and IL-2-secreting T cells in vitro, particularly under hypoxic conditions. More importantly, co-culture of the TSST-1-expressing LoVo cells, particularly under hypoxic conditions, but not control cells, with different numbers of PBMC promoted potent cytotoxicity against LoVo cells in a dose-dependent manner in vitro. These data provide proof of the principle that selective induction of TSST1 expression in CEA(+) colorectal cancer (CRC) cells activates T cells that destroy tumor cells, particularly under a hypoxic condition. Therefore, our findings may aid in the design of new immunotherapy for the intervention of CRC at clinic.

  17. Halogenated ligands and their interactions with amino acids: implications for structure-activity and structure-toxicity relationships.

    PubMed

    Kortagere, Sandhya; Ekins, Sean; Welsh, William J

    2008-09-01

    The properties of chemicals are rooted in their molecular structure. It follows that structural analysis of specific interactions between ligands and biomolecules at the molecular level is invaluable for defining structure-activity relationships (SARs) and structure-toxicity relationships (STRs). This study has elucidated the structural and molecular basis of interactions of biomolecules with alkyl and aryl halides that are extensively used as components in many commercial pesticides, disinfectants, and drugs. We analyzed the protein structures deposited in Protein Data Bank (PDB) for structural information associated with interactions between halogenated ligands and proteins. This analysis revealed distinct patterns with respect to the nature and structural characteristics of halogen interactions with specific types of atoms and groups in proteins. Fluorine had the highest propensity of interactions for glycine, while chlorine for leucine, bromine for arginine, and iodine for lysine. Chlorine, bromine and iodine had the lowest propensity of interactions for cysteine, while fluorine had a lowest propensity for proline. These trends for highest propensity shifted towards the hydrophobic residues for all the halogens when only interactions with the side chain were considered. Halogens had equal propensities of interaction for the halogen bonding partners (nitrogen and oxygen atoms), albeit with different geometries. The optimal angle for interactions with halogens was approximately 120 degrees for oxygen atoms, and approximately 96 degrees for nitrogen atoms. The distance distributions of halogens with various amino acids were mostly bimodal, and the angle distributions were unimodal. Insights gained from this study have implications for the rational design of safer drugs and commercially important chemicals.

  18. Determination of Toxic Activities in Bothrops spp. Snake Venoms Using Animal-Free Approaches: Correlation Between In Vitro Versus In Vivo Assays.

    PubMed

    de Souza, Letícia Lopes; Stransky, Stephanie; Guerra-Duarte, Clara; Flor-Sá, Ana; Schneider, Francisco Santos; Kalapothakis, Evanguedes; Chávez-Olórtegui, Carlos

    2015-10-01

    The main purpose of this study is to investigate the in vitro toxic effects of 5 Bothrops spp. snake venoms, which are part of the antigenic mixture used for the production of Brazilian antivenom, and evaluate their correlation with the in vivo toxic activities of Bothrops spp. venoms. The correlation analysis could be helpful for the replacement of living animals experimentation for in vitro bioassay. Cytotoxicity, L-amino acid oxidase (LAAO), proteolitic (serine and metalloproteinase), hyaluronidase (Hyal), and phospholipase A2 (PLA2) activities were estimated and the correlation coefficient was determined for each activity in relation to lethality, edema, hemorrhage and necrosis induced in live animals by B. jararaca, B. alternatus, B. jararacussu, B. neuwiedi, and B. moojeni venoms. The lethal activity in mice was highly related to Hyal activity (r = 0.94, p < .05), edema related to PLA2 activity (r = 0.94, p < .05), whereas the necrotizing activity showed high correlation with LAAO activity (r = 0.83, p < .05). A very significant correlation between in vitro cytotoxicity and LAAO activities was also observed (r = 0.97, p < .05).

  19. Determination of Toxic Activities in Bothrops spp. Snake Venoms Using Animal-Free Approaches: Correlation Between In Vitro Versus In Vivo Assays.

    PubMed

    de Souza, Letícia Lopes; Stransky, Stephanie; Guerra-Duarte, Clara; Flor-Sá, Ana; Schneider, Francisco Santos; Kalapothakis, Evanguedes; Chávez-Olórtegui, Carlos

    2015-10-01

    The main purpose of this study is to investigate the in vitro toxic effects of 5 Bothrops spp. snake venoms, which are part of the antigenic mixture used for the production of Brazilian antivenom, and evaluate their correlation with the in vivo toxic activities of Bothrops spp. venoms. The correlation analysis could be helpful for the replacement of living animals experimentation for in vitro bioassay. Cytotoxicity, L-amino acid oxidase (LAAO), proteolitic (serine and metalloproteinase), hyaluronidase (Hyal), and phospholipase A2 (PLA2) activities were estimated and the correlation coefficient was determined for each activity in relation to lethality, edema, hemorrhage and necrosis induced in live animals by B. jararaca, B. alternatus, B. jararacussu, B. neuwiedi, and B. moojeni venoms. The lethal activity in mice was highly related to Hyal activity (r = 0.94, p < .05), edema related to PLA2 activity (r = 0.94, p < .05), whereas the necrotizing activity showed high correlation with LAAO activity (r = 0.83, p < .05). A very significant correlation between in vitro cytotoxicity and LAAO activities was also observed (r = 0.97, p < .05). PMID:26160116

  20. Mechanistic quantitative structure-activity relationship model for the photoinduced toxicity of polycyclic aromatic hydrocarbons. 1: Physical model based on chemical kinetics in a two-compartment system

    SciTech Connect

    Krylov, S.N.; Huang, X.D.; Zeiler, L.F.; Dixon, D.G.; Greenberg, B.M.

    1997-11-01

    A quantitative structure-activity relationship model for the photoinduced toxicity of 16 polycyclic aromatic hydrocarbons (PAHs) to duckweed (Lemna gibba) in simulated solar radiation (SSR) was developed. Lemna gibba was chosen for this study because toxicity could be considered in two compartments: water column and leaf tissue. Modeling of photoinduced toxicity was described by photochemical reactions between PAHs and a hypothetical group of endogenous biomolecules (G) required for normal growth, with damage to G by PAHs and/or photomodified PAHs in SSR resulting in impaired growth. The reaction scheme includes photomodification of PAHs, uptake of PAHs into leaves, triplet-state formation of intact PAHs, photosensitization reactions that damage G, and reactions between photomodified PAHs and G. The assumptions used were: the PAH photomodification rate is slower than uptake of chemicals into leaves, the PAH concentration in aqueous solution is nearly constant during a toxicity test, the fluence rate of actinic radiation is lower within leaves than in the aqueous phase, and the toxicity of intact PAHs in the dark is negligible. A series of differential equations describing the reaction kinetics of intact and photomodifed PAHs with G was derived. The resulting equation for PAH toxicity was a function of treatment period, initial PAH concentration, relative absorbance of SSR by each PAH, quantum yield for formation of triplet-state PAH, and rate of PAH photomodification. Data for growth in the presence of intact and photomodified PAHs were used to empirically solve for a photosensitization constant (PSC) and a photomodification constant (PMC) for each of the 16 PAHs tested. For 9 PAHs the PMC dominates and for 7 PAHs the PSC dominates.

  1. Toxic proteins in plants.

    PubMed

    Dang, Liuyi; Van Damme, Els J M

    2015-09-01

    Plants have evolved to synthesize a variety of noxious compounds to cope with unfavorable circumstances, among which a large group of toxic proteins that play a critical role in plant defense against predators and microbes. Up to now, a wide range of harmful proteins have been discovered in different plants, including lectins, ribosome-inactivating proteins, protease inhibitors, ureases, arcelins, antimicrobial peptides and pore-forming toxins. To fulfill their role in plant defense, these proteins exhibit various degrees of toxicity towards animals, insects, bacteria or fungi. Numerous studies have been carried out to investigate the toxic effects and mode of action of these plant proteins in order to explore their possible applications. Indeed, because of their biological activities, toxic plant proteins are also considered as potentially useful tools in crop protection and in biomedical applications, such as cancer treatment. Genes encoding toxic plant proteins have been introduced into crop genomes using genetic engineering technology in order to increase the plant's resistance against pathogens and diseases. Despite the availability of ample information on toxic plant proteins, very few publications have attempted to summarize the research progress made during the last decades. This review focuses on the diversity of toxic plant proteins in view of their toxicity as well as their mode of action. Furthermore, an outlook towards the biological role(s) of these proteins and their potential applications is discussed.

  2. Microplastic Size-Dependent Toxicity, Oxidative Stress Induction, and p-JNK and p-p38 Activation in the Monogonont Rotifer (Brachionus koreanus).

    PubMed

    Jeong, Chang-Bum; Won, Eun-Ji; Kang, Hye-Min; Lee, Min-Chul; Hwang, Dae-Sik; Hwang, Un-Ki; Zhou, Bingsheng; Souissi, Sami; Lee, Su-Jae; Lee, Jae-Seong

    2016-08-16

    In this study, we evaluated accumulation and adverse effects of ingestion of microplastics in the monogonont rotifer (Brachionus koreanus). The dependence of microplastic toxicity on particle size was investigated by measuring several in vivo end points and studying the ingestion and egestion using 0.05-, 0.5-, and 6-μm nonfunctionalized polystyrene microbeads. To identify the defense mechanisms activated in response to microplastic exposure, the activities of several antioxidant-related enzymes and the phosphorylation status of mitogen-activated protein kinases (MAPKs) were determined. Exposure to polystyrene microbeads of all sizes led to significant size-dependent effects, including reduced growth rate, reduced fecundity, decreased lifespan and longer reproduction time. Rotifers exposed to 6-μm fluorescently labeled microbeads exhibited almost no fluorescence after 24 h, while rotifers exposed to 0.05- and 0.5-μm fluorescently labeled microbeads displayed fluorescence until 48 h, suggesting that 6-μm microbeads are more effectively egested from B. koreanus than 0.05- or 0.5-μm microbeads. This observation provides a potential explanation for our findings that microbead toxicity was size-dependent and smaller microbeads were more toxic. In vitro tests revealed that antioxidant-related enzymes and MAPK signaling pathways were significantly activated in response to microplastic exposure in a size-dependent manner.

  3. Microplastic Size-Dependent Toxicity, Oxidative Stress Induction, and p-JNK and p-p38 Activation in the Monogonont Rotifer (Brachionus koreanus).

    PubMed

    Jeong, Chang-Bum; Won, Eun-Ji; Kang, Hye-Min; Lee, Min-Chul; Hwang, Dae-Sik; Hwang, Un-Ki; Zhou, Bingsheng; Souissi, Sami; Lee, Su-Jae; Lee, Jae-Seong

    2016-08-16

    In this study, we evaluated accumulation and adverse effects of ingestion of microplastics in the monogonont rotifer (Brachionus koreanus). The dependence of microplastic toxicity on particle size was investigated by measuring several in vivo end points and studying the ingestion and egestion using 0.05-, 0.5-, and 6-μm nonfunctionalized polystyrene microbeads. To identify the defense mechanisms activated in response to microplastic exposure, the activities of several antioxidant-related enzymes and the phosphorylation status of mitogen-activated protein kinases (MAPKs) were determined. Exposure to polystyrene microbeads of all sizes led to significant size-dependent effects, including reduced growth rate, reduced fecundity, decreased lifespan and longer reproduction time. Rotifers exposed to 6-μm fluorescently labeled microbeads exhibited almost no fluorescence after 24 h, while rotifers exposed to 0.05- and 0.5-μm fluorescently labeled microbeads displayed fluorescence until 48 h, suggesting that 6-μm microbeads are more effectively egested from B. koreanus than 0.05- or 0.5-μm microbeads. This observation provides a potential explanation for our findings that microbead toxicity was size-dependent and smaller microbeads were more toxic. In vitro tests revealed that antioxidant-related enzymes and MAPK signaling pathways were significantly activated in response to microplastic exposure in a size-dependent manner. PMID:27438693

  4. Toxic Encephalopathy

    PubMed Central

    Kim, Jae Woo

    2012-01-01

    This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

  5. TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations.

    PubMed

    Ekstrand-Hammarström, Barbro; Hong, Jaan; Davoodpour, Padideh; Sandholm, Kerstin; Ekdahl, Kristina N; Bucht, Anders; Nilsson, Bo

    2015-05-01

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity.

  6. TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations.

    PubMed

    Ekstrand-Hammarström, Barbro; Hong, Jaan; Davoodpour, Padideh; Sandholm, Kerstin; Ekdahl, Kristina N; Bucht, Anders; Nilsson, Bo

    2015-05-01

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. PMID:25770998

  7. Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity

    SciTech Connect

    Manning, Gillian E.; Mundy, Lukas J.; Crump, Doug; Jones, Stephanie P.; Chiu, Suzanne; Klein, Jeff; Konstantinov, Alex; Potter, Dave; Kennedy, Sean W.

    2013-01-01

    Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complement the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species. -- Highlights: ► The chicken isn't the most sensitive species to CYP1A induction by PCB 105 and 118. ► The relative potency of PCBs differs between avian species. ► EROD activity was correlated with luciferase activity from the LRG assay. ► EROD activity was a better predictor of toxicity than CYP

  8. Amendment in phosphorus levels moderate the chromium toxicity in Raphanus sativus L. as assayed by antioxidant enzymes activities.

    PubMed

    Sayantan, D; Shardendu

    2013-09-01

    Chromium (Z=24), a d-block element, is a potent carcinogen, whereas phosphorus is an essential and limiting nutrient for the plant growth and development. This study undertakes the role of phosphorus in moderating the chromium toxicity in Raphanus sativus L., as both of them compete with each other during the uptake process. Two-factor complete randomized experiment (5 chromium × 5 phosphorus concentrations) was conducted for twenty eight days in green house. The individuals of R. sativus were grown in pots supplied with all essential nutrients. The toxic effects of chromium and the moderation of toxicity due to phosphorus amendment were determined as accumulation of chromium, nitrogen, phosphorus in root tissues and their effects were also examined in the changes in biomass, chlorophyll and antioxidant enzyme levels. Cr and N accumulation were almost doubled at the highest concentration of Cr supply, without any P amendment, whereas at the highest P concentration (125 mM), the accumulation was reduced to almost half. A significant reduction in toxic effects of Cr was determined as there was three-fold increase in total chlorophyll and biomass at the highest P amendment. Antioxidant enzymes like superoxide dismutase, catalase, peroxidase and lipid peroxidation were analyzed at various levels of Cr each amended with five levels of P. It was observed that at highest level of P amendment, the reduction percentage in toxicity was 33, 44, 39 and 44, correspondingly. Conclusively, the phosphorus amendment moderates the toxicity caused by the supplied chromium in R. sativus. This finding can be utilized to develop a novel technology for the amelioration of chromium stressed fields.

  9. Combined Toxic Effects of Polar and Nonpolar Chemicals on Human Hepatocytes (HepG2) Cells by Quantitative Property-Activity Relationship Modeling

    PubMed Central

    Kim, Ki-Woong; Won, Yong Lim; Park, Dong Jin; Kim, Young Sun; Jin, Eun Sil; Lee, Sung Kwang

    2016-01-01

    We determined the toxicity of mixtures of ethyl acetate (EA), isopropyl alcohol (IPA), methyl ethyl ketone (MEK), toluene (TOL) and xylene (XYL) with half-maximal effective concentration (EC50) values obtained using human hepatocytes cells. According to these data, quantitative property-activity relationships (QPAR) models were successfully proposed to predict the toxicity of mixtures by multiple linear regressions (MLR). The leave-one-out cross validation method was used to find the best subsets of descriptors in the learning methods. Significant differences in physico-chemical properties such as boiling point (BP), specific gravity (SG), Reid vapor pressure (rVP) and flash point (FP) were observed between the single substances and the mixtures. The EC50 of the mixture of EA and IPA was significantly lower than that of contained TOL and XYL. The mixture toxicity was related to the mixing ratio of MEK, TOL and XYL (MLR equation EC50 = 3.3081 − 2.5018 × TOL − 3.2595 × XYL − 12.6596 × MEK × XYL), as well as to BP, SG, VP and FP (MLR equation EC50 = 1.3424 + 6.2250 × FP − 7.1198 × SG × FP − 0.03013 × rVP × FP). These results suggest that QPAR-based models could accurately predict the toxicity of polar and nonpolar mixtures used in rotogravure printing industries.

  10. Genes implicated in thiopurine-induced toxicity: Comparing TPMT enzyme activity with clinical phenotype and exome data in a paediatric IBD cohort

    PubMed Central

    Coelho, Tracy; Andreoletti, Gaia; Ashton, James J.; Batra, Akshay; Afzal, Nadeem Ahmad; Gao, Yifang; Williams, Anthony P.; Beattie, Robert M.; Ennis, Sarah

    2016-01-01

    The aim of our study was to assess the utility of next generation sequencing (NGS) for predicting toxicity and clinical response to thiopurine drugs in paediatric patients with inflammatory bowel disease. Exome data for 100 patients were assessed against biochemically measured TPMT enzyme activity, clinical response and adverse effects. The TPMT gene and a panel of 15 other genes implicated in thiopurine toxicity were analysed using a gene based statistical test (SKAT-O test). Nine patients out of 100 (Crohn’s disease- 67, ulcerative colitis- 23 and IBDU-10) had known TPMT mutations associated with deficient enzyme activity. A novel and a highly pathogenic TPMT variant not detectable through standard genotyping, was identified through NGS in an individual intolerant to thiopurines. Of the 14 patients intolerant to thiopurines, NGS identified deleterious TPMT variants in 5 individuals whereas the biochemical test identified 8 individuals as intolerant (sensitivity 35.7% and 57.14%; specificity 93.75% and 50% respectively). SKAT-O test identified a significant association between MOCOS gene and TPMT activity (p = 0.0015), not previously reported. Although NGS has the ability to detect rare or novel variants not otherwise identified through standard genotyping, it demonstrates no clear advantage over the biochemical test in predicting toxicity in our modest cohort. PMID:27703193

  11. DEVELOPMENT OF QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS TO PREDICT TOXICITY FOR A VARIETY OF HUMAN AND ECOLOGICAL ENDPOINTS

    EPA Science Inventory

    The number of chemicals released into the environment has significantly increased over the past few years, leading to increased risk of human exposure through inhalation, ingestion, or dermal uptake. In addition, the risk also increases with increasing toxicity of the chemical. ...

  12. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    SciTech Connect

    Oorschot, Bregje van; Hovingh, Suzanne E.; Moerland, Perry D.; Medema, Jan Paul; Stalpers, Lukas J.A.; Vrieling, Harry; Franken, Nicolaas A.P.

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  13. Digitalis toxicity

    MedlinePlus

    ... may be rapid, or slow and irregular. An ECG is done to check for irregular heartbeats. Blood ... A. Digitalis toxicity. In: Goldberger AL, ed. Clinical Electrocardiography : A Simplified Approach, 8th ed. Philadelphia, PA: Elsevier ...

  14. Antimony Toxicity

    PubMed Central

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically. PMID:21318007

  15. Toxic trauma.

    PubMed

    Moles, T M; Baker, D J

    2001-01-01

    Hazardous materials (HAZMAT) carry many inherent dangers. Such materials are distributed widely in industrial and military sites. Toxic trauma (TT) denotes the complex of systemic and organ injury caused by toxic agents. Often, TT is associated with other injuries that also require the application of life-support techniques. Rapid onset of acute respiratory failure and consequent cardiovascular failure are of primary concern. Management of TT casualties is dependent upon the characteristics of the toxic agents involved and on the demographics surrounding the HAZMAT incident. Agents that can produce TT possess two pairs of salient characteristics: (1) causality (toxicity and latency), and (2) EMS system (persistency and transmissibility). Two characteristics of presentations are important: (1) incident presentation, and (2) casualty presentation. In addition, many of these agents complicate the processes associated with anaesthesia and must be dealt with. Failure of recognition of these factors may result in the development of respiratory distress syndromes and multiorgan system failure, or even death. PMID:11513285

  16. A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model

    PubMed Central

    2012-01-01

    Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich.) Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae), Maytenus senegalensis (Lam.) Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.)Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholerae (clinical isolate), and Klebsiella pneumoniae (clinical isolate) using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole. Both the individual

  17. Evaluation of acute and subacute toxicity and mutagenic activity of the aqueous extract of pecan shells [Carya illinoinensis (Wangenh.) K. Koch].

    PubMed

    Porto, Luiz Carlos Santos; da Silva, Juliana; Ferraz, Alexandre de Barros Falcão; Corrêa, Dione Silva; dos Santos, Marcela Silva; Porto, Caroline Dalla Lana; Picada, Jaqueline Nascimento

    2013-09-01

    The infusion of pecan shells has been used to prevent and control hypercholesterolemia, diabetes and toxicological diseases. The aim of the present study was to evaluate toxicity and mutagenic effects of pecan shells aqueous extract (PSAE). Wistar rats were treated with a single dose of 300 or 2000 mg/kg of PSAE in the acute toxicity test. For the subacute test, the animals received 10 or 100 mg/kg of PSAE for 28 days. The mutagenicity was evaluated using Salmonella/microsome assay in TA1535, TA1537, TA98, TA100 and TA102 S. typhimurium strains in the presence and absence of metabolic activation (S9 mix) and micronucleus test in bone marrow. HPLC analyses indicated the presence of tannins, flavonoids, gallic and ellagic acids. Except for triglycerides, all treated groups presented normal hematological and biochemical parameters. Lower levels of triglycerides and weight loss were observed in the 100 mg/kg group. Mutagenic activities were not detected in S. typhimurium strains and by the micronucleus test. Based on these results, PSAE was not able to induce chromosomal or point mutations, under the conditions tested. The 100mg/kg dose showed significant antihyperlipidemic action, with no severe toxic effects.

  18. Evaluation of acute and subacute toxicity and mutagenic activity of the aqueous extract of pecan shells [Carya illinoinensis (Wangenh.) K. Koch].

    PubMed

    Porto, Luiz Carlos Santos; da Silva, Juliana; Ferraz, Alexandre de Barros Falcão; Corrêa, Dione Silva; dos Santos, Marcela Silva; Porto, Caroline Dalla Lana; Picada, Jaqueline Nascimento

    2013-09-01

    The infusion of pecan shells has been used to prevent and control hypercholesterolemia, diabetes and toxicological diseases. The aim of the present study was to evaluate toxicity and mutagenic effects of pecan shells aqueous extract (PSAE). Wistar rats were treated with a single dose of 300 or 2000 mg/kg of PSAE in the acute toxicity test. For the subacute test, the animals received 10 or 100 mg/kg of PSAE for 28 days. The mutagenicity was evaluated using Salmonella/microsome assay in TA1535, TA1537, TA98, TA100 and TA102 S. typhimurium strains in the presence and absence of metabolic activation (S9 mix) and micronucleus test in bone marrow. HPLC analyses indicated the presence of tannins, flavonoids, gallic and ellagic acids. Except for triglycerides, all treated groups presented normal hematological and biochemical parameters. Lower levels of triglycerides and weight loss were observed in the 100 mg/kg group. Mutagenic activities were not detected in S. typhimurium strains and by the micronucleus test. Based on these results, PSAE was not able to induce chromosomal or point mutations, under the conditions tested. The 100mg/kg dose showed significant antihyperlipidemic action, with no severe toxic effects. PMID:23831307

  19. Acute toxicity and sublethal effects of the mixture glyphosate (Roundup Active) and Cosmo-Flux 411F to anuran embryos and tadpoles of four Colombian species.

    PubMed

    Henao Muñoz, Liliana Marcela; Montes Rojas, Claudia Marsela; Bernal Bautista, Manuel Hernando

    2015-03-01

    Glyphosate is the most widely used herbicide in the world with application in agriculture, forestry, industrial weed control, garden and aquatic environments. However, its use is highly controversial for the possible impact on not-target organisms, such as amphibians, which are vanishing at an alarming and rapid rate. Due to the high solubility in water and ionic nature, the glyphosate requires of surfactants to increase activity. In addition, for the control of coca (Erythroxylum coca) and agricultural weeds in Colombia, formulated glyphosate is mixed and sprayed with the adjuvant Cosmo-Flux 411F to increase the penetration and activity of the herbicide. This study evaluates the acute toxic and sublethal effects (embryonic development, tadpole body size, tadpole swimming performance) of the mixture of the formulated glyphosate Roundup Active and Cosmo-Flux 411F to anuran embryos and tadpoles of four Colombian species under 96h laboratory standard tests and microcosms, which are more similar to field conditions as they include soil, sand and macrophytes. In the laboratory, embryos and tadpoles of Engystomops pustulosus were the most tolerant (LC50 = 3904 microg a.e./L; LC50=2 799 pg a.e./L, respectively), while embryos and tadpoles of Hypsiboas crepitans (LC50=2 203 microg a.e./L; LC50=1424 microgg a.e./L, respectively) were the most sensitive. R. humboldti and R. marina presented an intermediate toxicity. Embryos were significantly more tolerant to the mixture than tadpoles, which could be likely attributed to the exclusion of chemicals by the embryonic membranes and the lack of organs, such as gills, which are sensitive to surfactants. Sublethal effects were observed for the tadpole body size, but not for the embryonic development and tadpole swimming performance. In microcosms, no toxicity (LC50 could not be estimated), or sublethal responses were observed at concentrations up to fourfold (14.76 kg glyphosate a.e./ha) the highest field application rate of 3

  20. A Parkinson's disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity

    PubMed Central

    Dusonchet, Julien; Li, Hu; Guillily, Maria; Liu, Min; Stafa, Klodjan; Derada Troletti, Claudio; Boon, Joon Y.; Saha, Shamol; Glauser, Liliane; Mamais, Adamantios; Citro, Allison; Youmans, Katherine L.; Liu, LiQun; Schneider, Bernard L.; Aebischer, Patrick; Yue, Zhenyu; Bandopadhyay, Rina; Glicksman, Marcie A.; Moore, Darren J.; Collins, James J.; Wolozin, Benjamin

    2014-01-01

    Mutations in LRRK2 are one of the primary genetic causes of Parkinson's disease (PD). LRRK2 contains a kinase and a GTPase domain, and familial PD mutations affect both enzymatic activities. However, the signaling mechanisms regulating LRRK2 and the pathogenic effects of familial mutations remain unknown. Identifying the signaling proteins that regulate LRRK2 function and toxicity remains a critical goal for the development of effective therapeutic strategies. In this study, we apply systems biology tools to human PD brain and blood transcriptomes to reverse-engineer a LRRK2-centered gene regulatory network. This network identifies several putative master regulators of LRRK2 function. In particular, the signaling gene RGS2, which encodes for a GTPase-activating protein (GAP), is a key regulatory hub connecting the familial PD-associated genes DJ-1 and PINK1 with LRRK2 in the network. RGS2 expression levels are reduced in the striata of LRRK2 and sporadic PD patients. We identify RGS2 as a novel interacting partner of LRRK2 in vivo. RGS2 regulates both the GTPase and kinase activities of LRRK2. We show in mammalian neurons that RGS2 regulates LRRK2 function in the control of neuronal process length. RGS2 is also protective against neuronal toxicity of the most prevalent mutation in LRRK2, G2019S. We find that RGS2 regulates LRRK2 function and neuronal toxicity through its effects on kinase activity and independently of GTPase activity, which reveals a novel mode of action for GAP proteins. This work identifies RGS2 as a promising target for interfering with neurodegeneration due to LRRK2 mutations in PD patients. PMID:24794857

  1. Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

    PubMed Central

    Zhang, Li; Wang, Tengteng; Li, Qiang; Huang, Jing; Xu, Hao; Li, Jinlong; Wang, Yongjun; Liang, Qianqian

    2016-01-01

    Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is −35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P<0.01) and had no side effects or toxic effects on the thymus index (P>0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment. PMID:27354796

  2. Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo.

    PubMed

    Zhang, Li; Wang, Tengteng; Li, Qiang; Huang, Jing; Xu, Hao; Li, Jinlong; Wang, Yongjun; Liang, Qianqian

    2016-01-01

    Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is -35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P<0.01) and had no side effects or toxic effects on the thymus index (P>0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment. PMID:27354796

  3. Emulsifying Activity and Stability of a Non-Toxic Bioemulsifier Synthesized by Microbacterium sp. MC3B-10

    PubMed Central

    Camacho-Chab, Juan Carlos; Guézennec, Jean; Chan-Bacab, Manuel Jesús; Ríos-Leal, Elvira; Sinquin, Corinne; Muñiz-Salazar, Raquel; De la Rosa-García, Susana del C.; Reyes-Estebanez, Manuela; Ortega-Morales, Benjamín Otto

    2013-01-01

    A previously reported bacterial bioemulsifier, here termed microbactan, was further analyzed to characterize its lipid component, molecular weight, ionic character and toxicity, along with its bioemulsifying potential for hydrophobic substrates at a range of temperatures, salinities and pH values. Analyses showed that microbactan is a high molecular weight (700 kDa), non-ionic molecule. Gas chromatography of the lipid fraction revealed the presence of palmitic, stearic, and oleic acids; thus microbactan may be considered a glycolipoprotein. Microbactan emulsified aromatic hydrocarbons and oils to various extents; the highest emulsification index was recorded against motor oil (96%). The stability of the microbactan-motor oil emulsion model reached its highest level (94%) at 50 °C, pH 10 and 3.5% NaCl content. It was not toxic to Artemia salina nauplii. Microbactan is, therefore, a non-toxic and non-ionic bioemulsifier of high molecular weight with affinity for a range of oily substrates. Comparative phylogenetic assessment of the 16S rDNA gene of Microbacterium sp. MC3B-10 with genes derived from other marine Microbacterium species suggested that this genus is well represented in coastal zones. The chemical nature and stability of the bioemulsifier suggest its potential application in bioremediation of marine environments and in cosmetics. PMID:24065097

  4. Using metal-ligand binding characteristics to predict metal toxicity: quantitative ion character-activity relationships (QICARs).

    PubMed Central

    Newman, M C; McCloskey, J T; Tatara, C P

    1998-01-01

    Ecological risk assessment can be enhanced with predictive models for metal toxicity. Modelings of published data were done under the simplifying assumption that intermetal trends in toxicity reflect relative metal-ligand complex stabilities. This idea has been invoked successfully since 1904 but has yet to be applied widely in quantitative ecotoxicology. Intermetal trends in toxicity were successfully modeled with ion characteristics reflecting metal binding to ligands for a wide range of effects. Most models were useful for predictive purposes based on an F-ratio criterion and cross-validation, but anomalous predictions did occur if speciation was ignored. In general, models for metals with the same valence (i.e., divalent metals) were better than those combining mono-, di-, and trivalent metals. The softness parameter (sigma p) and the absolute value of the log of the first hydrolysis constant ([symbol: see text] log KOH [symbol: see text]) were especially useful in model construction. Also, delta E0 contributed substantially to several of the two-variable models. In contrast, quantitative attempts to predict metal interactions in binary mixtures based on metal-ligand complex stabilities were not successful. PMID:9860900

  5. Synergistic enhancement of parasiticidal activity of amphotericin B using copaiba oil in nanoemulsified carrier for oral delivery: an approach for non-toxic chemotherapy

    PubMed Central

    Gupta, Pramod K; Jaiswal, Anil K; Asthana, Shalini; Teja B, Venkatesh; Shukla, Prashant; Shukla, Minakshi; Sagar, Neeti; Dube, Anuradha; Rath, Srikanta K; Mishra, Prabhat R

    2015-01-01

    Background and Purpose The aim of this study was to devise a nanoemulsified carrier system (CopNEC) to improve the oral delivery of amphotericin B (AmB) by increasing its oral bioavailability and synergistically enhance its antileishmanial activity with copaiba oil (Cop). Experimental Approach The AmB encapsulated NEC (CopNEC-AmB) comprised of Cop, d-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine was prepared by high-pressure homogenization method. Stability study of CopNEC-AmB was carried out in simulated gastric fluid and simulated intestinal fluid. The CopNEC-AmB and plain AmB were compared as regards their in vitro antileishmanial activity, pharmacokinetics, organ distribution and toxicity. Key Results The optimal CopNEC-AmB had a small globule size, low polydispersity index, high ζ potential and encapsulation efficiency. The high resolution transmission electron microscopy illustrated spherical particle geometry with homogeny in their sizes. The optimal CopNEC-AmB was found to be stable in gastrointestinal fluids showing insignificant changes in globule size and encapsulation efficiency. The AUC0–48 value of CopNEC-AmB in rats was significantly improved showing 7.2-fold higher oral bioavailability than free drug. The in vitro antileishmanial activity of CopNEC-AmB was significantly higher than that of the free drug as Cop synergistically enhanced the antileishmanial effect of AmB by causing drastic changes in the morphology of Leishmania parasite and rupturing its plasma membrane. The CopNEC-AmB showed significantly less haemolytic toxicity and cytotoxicity and did not change the histopathology of kidney tissues as compared with AmB alone. Conclusions and Implications This prototype CopNEC formulation showed improved bioavailability and had a non-toxic synergistic effect on the antileishmanial activity of AmB. PMID:25825339

  6. Quantitative analysis of rat activity in the home cage by infrared monitoring. Application to the acute toxicity testing of acetanilide and phenylmercuric acetate.

    PubMed

    Tamborini, P; Sigg, H; Zbinden, G

    1989-01-01

    A new method for continuous in-cage monitoring of the activity of rats using passive sensors to detect the animals' infrared emissions, and its usefulness for toxicological screening tests is described. In order to obtain baseline values for toxicological tests, the differences between day and night activity, adaptation to changing day/night rhythm, the effects of handling the animals (measurement of body weight, food and water consumption) and the effect on activity patterns of the female estrus cycle were investigated. In two separate experiments, single doses of acetanilide and phenylmercuric acetate were administered. Passive infrared monitoring of motor activity proved to be a sensitive and discriminating method suitable for quantitative and qualitative assessment of acute toxic effects.

  7. Binding of nickel and copper to fish gills predicts toxicity when water hardness varies, but free-ion activity does not

    SciTech Connect

    Meyer, J.S.; Bobbitt, J.P.; Debrey, L.D.; Boese, C.J.; Bergman, H.L.; Santore, R.C.; Paquin, P.R.; Ditoro, D.M.; Allen, H.E.

    1999-03-15

    Based on a biotic-ligand model (BLM), the authors hypothesized that the concentration of a transition metal bound to fish gills ([M{sub gill}]) will be a constant predictor of mortality, whereas a free-ion activity model is generally interpreted to imply that the chemical activity of the aquo (free) ion of the metal will be a constant predictor of mortality. In laboratory tests, measured [Ni{sub gill}] and calculated [Cu{sub gill}] were constant predictors of acute toxicity of Ni and Cu to fathead minnows (Pimephales promelas) when water hardness varied up to 10-fold, whereas total aqueous concentrations and free-ion activities of Ni and Cu were not. Thus, the BLM, which simultaneously accounts for (a) metal speciation in the exposure water and (b) competitive binding of transition-metal ions and other cations to biotic ligands predicts acute toxicity better than does free-ion activity of Ni or Cu. Adopting a biotic-ligand modeling approach could help establish a more defensible, mechanistic basis for regulating aqueous discharges of metals.

  8. Functional characterizations of venom phenotypes in the eastern diamondback rattlesnake (Crotalus adamanteus) and evidence for expression-driven divergence in toxic activities among populations.

    PubMed

    Margres, Mark J; Walls, Robert; Suntravat, Montamas; Lucena, Sara; Sánchez, Elda E; Rokyta, Darin R

    2016-09-01

    Phenotypes frequently vary across and within species. The connection between specific phenotypic effects and function, however, is less understood despite being essential to our understanding of the adaptive process. Snake venoms are ideal for identifying functionally important phenotypic variation because venom variation is common, and venoms can be functionally characterized through simple assays and toxicity measurements. Previous work with the eastern diamondback rattlesnake (Crotalus adamanteus) used multivariate statistical approaches to identify six unique venom phenotypes. We functionally characterized hemolytic, gelatinase, fibrinogenolytic, and coagulant activity for all six phenotypes, as well as one additional venom, to determine if the statistically significant differences in toxin expression levels previously documented corresponded to differences in venom activity. In general, statistical differences in toxin expression predicted the identified functional differences, or lack thereof, in toxic activity, demonstrating that the statistical approach used to characterize C. adamanteus venoms was a fair representation of biologically meaningful differences. Minor differences in activity not accounted for by the statistical model may be the result of amino-acid differences and/or post-translational modifications, but overall we were able to link variation in protein expression levels to variation in function as predicted by multivariate statistical approaches. PMID:27179420

  9. Toxic effects of the joint exposure of decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA) on soil microorganism and enzyme activity.

    PubMed

    Zhang, Wei; Chen, Lei; An, Shuai; Liu, Kou; Lin, Kuangfei; Zhao, Li

    2014-09-01

    Decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA) are the main contaminants at e-waste recycling sites, and their potential toxicological effects have received extensive attention. However, the impact on soil culturable microbial population and enzyme activity of joint exposure to the two chemicals remains almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the eco-toxicological response in the joint presence of BDE209 and TBBPA for the first time. The results have demonstrated some notable toxic effects due to long-term exposure to either or both contaminants. The inhibition ratios of microbial populations increased with incubation time and increasing concentrations of BDE209 or TBBPA following certain dose-response relationships and time-effect trends. The response sensitivity sequence was fungi>bacteria>actinomycete. The influence of the two chemicals on soil enzymes reached peak values on day 7, and highly significant differences (P<0.01) were observed compared to the controls. Urease was more susceptive to the two chemicals than catalase and saccharase activities. Generally, the joint toxicity of both contaminants on soil microbes, catalase or saccharase activities indicated antagonistic effects, while, as for urease activity, addition role was dominant. Such observations have provided the useful information of potential ecological effects of brominated flame retardants contamination in the environment. PMID:25195096

  10. Toxic effects of the joint exposure of decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA) on soil microorganism and enzyme activity.

    PubMed

    Zhang, Wei; Chen, Lei; An, Shuai; Liu, Kou; Lin, Kuangfei; Zhao, Li

    2014-09-01

    Decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA) are the main contaminants at e-waste recycling sites, and their potential toxicological effects have received extensive attention. However, the impact on soil culturable microbial population and enzyme activity of joint exposure to the two chemicals remains almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the eco-toxicological response in the joint presence of BDE209 and TBBPA for the first time. The results have demonstrated some notable toxic effects due to long-term exposure to either or both contaminants. The inhibition ratios of microbial populations increased with incubation time and increasing concentrations of BDE209 or TBBPA following certain dose-response relationships and time-effect trends. The response sensitivity sequence was fungi>bacteria>actinomycete. The influence of the two chemicals on soil enzymes reached peak values on day 7, and highly significant differences (P<0.01) were observed compared to the controls. Urease was more susceptive to the two chemicals than catalase and saccharase activities. Generally, the joint toxicity of both contaminants on soil microbes, catalase or saccharase activities indicated antagonistic effects, while, as for urease activity, addition role was dominant. Such observations have provided the useful information of potential ecological effects of brominated flame retardants contamination in the environment.

  11. Toxic neuropathies.