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Sample records for 7-ethoxyresorufin o-deethylase activity

  1. Ability of fractionated petroleum refinery effluent to elicit cyto- and photocytotoxic responses and to induce 7-ethoxyresorufin-O-deethylase activity in fish cell lines.

    PubMed

    Schirmer, K; Tom, D J; Bols, N C; Sherry, J P

    2001-04-23

    The ability of fractionated petroleum refinery effluent to cause cellular responses in fish cell lines was evaluated. The cellular responses, which included direct and indirect cytotoxicity, photocytotoxicity and induction of 7-ethoxyresorufin-O-deethylase (EROD) activity, may potentially be linked to sublethal effects observed in effluent-exposed fish and fish larvae. In order to be able to quantify cellular responses rapidly, microtitre plates were used along with fluorescent probes. For the quantification of cyto- and photocytotoxicity, the fluorescent probes were alamar Blue and carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM), which monitor metabolic activity and cell membrane integrity, respectively. EROD activity was measured as the rate of conversion by EROD of the substrate 7-ethoxyresorufin to its fluorescent product, resorufin. Effluent from an Ontario refinery was fractionated into aqueous and particulate phase. As well, a solid phase extract (SPE) was used to prepare concentrated effluent for testing in the cell lines. The effluent was able to elicit all of the responses of interest although significant cyto- and photocytotoxicity required effluent equivalent concentrations above 100% effluent and could only be revealed upon exposure of cells to the SPE concentrated effluent. Based on their retention on C18, the cytotoxicants are likely to be non-polar to moderately polar chemicals. The presence of polar compounds affecting cellular metabolism was indicated by the responses of exposed cells to a 90% aqueous phase effluent. In contrast to cyto- and photocytotoxicity, EROD induction occurred at effluent equivalent concentrations well below 100% effluent and was elicited by the SPE and the particulate fraction thereby suggesting that most EROD-inducers were particle-bound. Among other applications, the described techniques could help to determine the source of causative agents of sublethal effects in the refining process.

  2. Stage-dependent ethoxyresorufin-O-deethylase (EROD) in vivo activity in medaka (Oryzias latipes) embryos.

    PubMed

    González-Doncel, Miguel; Carbonell, Gregoria; San Segundo, Laura; Sastre, Salvador; Beltrán, Eulalia M; Fernández-Torija, Carlos

    2015-09-01

    Using medaka (Oryzias latipes) embryos, this study aimed to quantitatively characterize the stage-dependent in vivo ethoxyresorufin-O-deethylase (EROD) as indicator of cytochrome P4501A (CYP1A) activity. Embryos were challenged for 24-h to an agonist (β-naphthoflavone [BNF], 2.5, 5, 10, and 20 μg L(-1)) or to its combination (2.5 μg L(-1)) with an antagonist (α-naphthoflavone [ANF], 25, 50, 100, and 200 μg L(-1)), initiated at four different developmental time points (1, 3, 6, and 9 d post-fertilization [dpf]). Respective induction and competitive inhibition were evaluated over fluorescent images of whole embryo (nonorgan-specific [NOS] EROD activity) and gallbladder (organ-specific [OS] EROD activity). Both flavonoids showed signs of stability in solution. Generally speaking, the mean fluorescence intensity (MFI) values for NOS EROD increased with BNF concentration and exposure challenge. BNF co-exposure with ⩾50 μg ANF L(-1) during the 1-2 and 3-4 dpf challenges lowered NOS EROD to undetectably induced levels. Significant increments in MFIs for OS-EROD were seen from exposures to ⩾2.5 μg BNF L(-1), peaking during the 6-7 dpf challenge regardless of BNF concentration. The simultaneous BNF/ANF incubation showed competitive inhibition for OS EROD activity, although levels were generally detectably induced during all challenges and at all ANF concentrations. The morphometric in vivo gallbladder analysis indicated significant dilation in the 10 dpf-old embryos co-exposed to BNF and 200 μg ANF L(-1). This quantitative approach can be used successfully at 4 dpf at the NOS-EROD or OS-EROD levels, although the NOS-EROD response was sensitive enough to induction or inhibition, even at 2 dpf.

  3. Hepatic ethoxyresorufin-O-deethylase activity and inducibility in wild populations of double-crested cormorants (Phalacrocorax auritus)

    SciTech Connect

    Davis, J.A.; Fry, D.M.; Wilson, B.W.

    1997-07-01

    Microplate fluorometric techniques were used to measure ethoxyresorufin O-deethylase (EROD) activity in hepatic microsomes and primary hepatocyte cultures from individual wild double-crested cormorant (Phalacrocorax auritus) embryos. Embryos were collected in 1993 and 1994 from Humboldt Bay and San Francisco Bay (CA, USA) and a reference site in coastal Oregon (USA). Median microsomal EROD activities in embryos collected from San Francisco Bay (in both 1993 and 1994) and from Humboldt Bay (1994) were four- to eightfold higher than the reference site median. This degree of induction suggests that cormorant embryos in the two California locations were exposed to concentrations of dioxin-like compounds that are at the threshold for toxic effects in this species. Substantial variation in the EROD response in cultured hepatocytes was observed between individuals, populations, and the two bird species tested (cormorants and chickens [Gallus gallus]). Although most of the cormorant individuals displayed a consistent dose-response profile, a few individuals were uninducible, showing no appreciable increase over basal activity with increasing dose of inducer. Composite dose-response curves for two cormorant colonies appeared to be divergent in spite of small sample sizes, indicating that inducibility can also vary at the population level. These observations suggest that considerable variability in pollutant metabolism and sensitivity associated with single enzyme systems may exist within wild populations and species.

  4. Ethoxyresorufin-O-deethylase enzyme activities and accumulation of secondary/tertiary lysosomes in rabbitfish Siganus oramin as biomarkers for xenobiotic exposures.

    PubMed

    Fang, James K H; Au, Doris W T; Chan, Alice K Y; So, Leo K Y; Liu, Wenhua; Mok, Helen O L; Yu, Wai-Yin; Wu, Rudolf S S; Shin, Paul K S

    2010-09-15

    The sensitivities of using hepatic and intestinal ethoxyresorufin-O-deethylase (EROD) activities and hepatic accumulation of secondary/tertiary (2 degrees/3 degrees) lysosomes to detect xenobiotic exposures were assessed in the rabbitfish Siganus oramin in a metropolitan harbour, subtropical Hong Kong, over a complete seasonal cycle of one year. Additional information on the body-burden pollutants and physiological indices in S. oramin, and seasonal variables in seawater quality, were extracted from published data and re-analyzed. Under the influences of pollutant cocktail and seasonal factors, neither the hepatic nor intestinal EROD activity was indicative of total polycyclic aromatic hydrocarbons (Sigma PAH), total polychlorinated biphenyls, condition factor and hepatosomatic index (HSI) in S. oramin. However, the relative ratio of hepatic to intestinal EROD activities provided an indication to differentiate the xenobiotic intake route in the fish through diffusion via gills/skin or consumption of contaminated food. In addition, the elevated hepatic accumulation of 2 degrees/3 degrees lysosomes was closely associated with the dominant temporal trends of zinc and Sigma PAH, as well as reduced HSI, in S. oramin. Being minimally influenced by any investigated seasonal factors, the hepatic 2 degrees/3 degrees lysosomes in S. oramin was recommended as an effective biomarker of xenobiotic exposures and toxic effects for use in coastal pollution monitoring programmes.

  5. Human health risk assessment of soil dioxin/furans contamination and dioxin-like activity determined by ethoxyresorufin-O-deethylase bioassay.

    PubMed

    Man, Yu Bon; Chow, Ka Lai; Wang, Hong Sheng; Sun, Xiao Lin; Wu, Sheng Chun; Cai, Zong Wei; Kang, Yuan; Li, Hui; Zheng, Jin Shu; Giesy, John P; Wong, Ming Hung

    2015-04-01

    The major objective of this study was to evaluate the human health risks of agricultural land use conversion to other purposes in Hong Kong, based on the levels of polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran (PCDD/Fs) and determined dioxin-like activity in soil using ethoxyresorufin-O-deethylase (EROD) bioassay. Hazard quotient showed soils of open burning site (OBS) and electronic waste open burning site (EW (OBS)) exert a relatively higher non-cancer risk on adults (50.9 and 8.00) and children (407 and 64.0) via the pathway of accidental ingestion of soil particles than other types of land use. In addition, the levels of 17 PCDD/Fs congeners in OBS and EW (OBS) soils indicated high and moderate (1654 and 260 in one million people) cancer risks through the above pathway. Furthermore, the biologically derived TCDD concentrations (TEQbio) were also significantly correlated to the chemically derived toxic equivalent concentrations of dioxin-like chemicals (TEQcal (sum of chemically derived 2,3,7,8-TeCDD toxic equivalent concentrations (TEQPCDD/F) and chemically derived dioxin-like PAHs toxic equivalent concentrations (TEQPAH)) (r = 0.770, p <0.05). PCDD/Fs (95.4 to 99.9%) were the major stressor to the TEQcal in the soil samples, indicating higher concentrations of PCDD/Fs derived from chemical analyses may reflect a higher potency of inducing EROD activity.

  6. Temporal trends in ethoxyresorufin-o-deethylase activity of brook trout (Salvelinus fontinalis) fed 2,3,7,8-tetrachlorodibenzo-p-dioxin

    SciTech Connect

    Cormier, S.M.; Millward, M.R.; Mueller, C.; Subramanian, B.; Johnson, R.D.; Tietge, J.E.

    2000-02-01

    Changes in ethoxyresorufin-O-deethylase (EROD) activity were monitored through an extended 6-month dietary exposure to determine the relationship between EROD activity and uptake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in brook trout, Salvelinus fontinalis. Brook trout were fed labeled TCDD during a 4-week loading phase and an 11-week maintenance phase to achieve whole-body concentrations of 0, 75, 150, 300, 600, and 1,200 pg TCDD/g fish. A spawning phase followed during which no TCDD was introduced. The TCDD had an extended half-life, with maximal levels detected in the late loading-early maintenance phases and 81 d after TCDD had been removed from the diet. Accumulation in liver increased as whole-body target concentration increased but was generally less than half of anticipated whole-body target concentrations. The EROD activity demonstrated a dose-dependent increase. Positive correlations were observed between EROD activity and TCDD body burdens for both males and females. For males, maximal induction was attained early in the maintenance phase and maintained during latter phases. For females, induction was characterized by a biphasic pattern. Maximal induction was attained during late loading-early maintenance, with an attenuated response observed just before spawning. In addition, the induction response was modulated by sex, as induction was lower in females when compared with males. If sexual biases are considered, increased EROD activity may serve as an indicator of level of TCDD exposure and a sublethal predictor of effects of exposure.

  7. Bioaccumulation of organochlorine contaminants and ethoxyresorufin-O-deethylase activity in southern California round stingrays (Urobatis halleri) exposed to planar aromatic compounds.

    PubMed

    Lyons, Kady; Lavado, Ramon; Schlenk, Daniel; Lowe, Christopher G

    2014-06-01

    While contaminant concentrations have been reported for elasmobranchs around the world, no studies have examined bioaccumulation patterns across male and female age classes. The round stingray (Urobatis halleri) is a local benthic species that forages near areas of high organochlorine contamination and represents a good elasmobranch model. Polychlorinated biphenyls (PCBs), DDT, and chlordanes were measured in juvenile and adult male and female stingrays from areas in southern California, USA (n = 208), and a nearby offshore island, Santa Catalina (n = 34). Both mainland juvenile male and female stingrays showed a significant dilution effect. After maturity, summed contaminant concentrations significantly increased with size for adult males (median 11.1 µg/g lipid wt) and females (5.2 µg/g lipid wt). However, the rate of bioaccumulation was substantially greater in male stingrays than in females, likely a result of the females' ability to offload contaminants to offspring during pregnancy. In addition, males and females showed significant differences in their contaminant profiles, suggesting differential habitat use. Male and female stingrays collected from Santa Catalina Island had significantly lower concentrations (0.51 µg/g and 0.66 µg/g lipid wt, respectively), approximately 5 times less than those of mainland animals. Potential toxicity effects mediated through activation of the aryl hydrocarbon receptor were explored through ethoxyresorufin-O-deethylase (EROD) activity assays. Mainland male stingrays exhibited significantly greater EROD activities than Catalina males (481 pmol/min/mg protein and 55 pmol/min/mg protein, respectively); however, activity levels in female stingrays from both locations were comparable (297 pmol/min/mg protein and 234 pmol/min/mg protein, respectively) and lower than those in mainland males. The results suggest that PCBs and/or other structurally related contaminants may be inducing a biological response

  8. Exposure of northern leopard frogs in the Green Bay ecosystem to polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans is measured by direct chemistry but not hepatic ethoxyresorufin-O-deethylase activity

    SciTech Connect

    Huang, Y.W.; Karasov, W.H.; Patnode, K.A.; Jefcoate, C.R.

    1999-10-01

    The authors measured concentrations of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) in northern leopard frogs collected from the Green Bay ecosystem and explored the catalytic activity of hepatic cytochrome P450-associated monooxygenase (P450 enzyme) as a biomarker for exposure to aryl hydrocarbon receptor (AhR) agonists. The two hypotheses tested were PCH concentrations in northern leopard frogs would be positively correlated with sediment polychlorinated hydrocarbon (PCH) levels in wetland habitats along a contamination gradient and hepatic ethoxyresorufin-O-deethylase (EROD) activity of northern leopard frogs, which is presumably mediated by aryl hydrocarbon receptor (AhR), would be positively correlated with PCH concentrations in frog carcasses from different collection sites. In 1994 and 1995, frogs from seven sites along the lower Fox River and Green Bay, USA, were assayed for hepatic EROD activities and whole carcass concentrations of PCBs, PCDDs, and PCDFs. Tissue total PCB concentrations ranging from 3 to 154 ng/g were significantly correlated with sediment PCB levels. Only one PCDD and two PCDFs at concentrations of 6 to 8 pg/g were found in the frogs collected with frog body weight and was similar among sites except for Peter's Marsh. No significant correlation was found between EROD activity and carcass PCB concentration. This result was consistent with the fact that the frogs collected from the Green Bay ecosystem had relatively low PCB concentrations compared with what was required for induction in the laboratory.

  9. Temporal changes of ethoxyresorufin-o-deethylase (EROD) activities and lysosome accumulation in intestine of fish on chronic exposure to dietary benzo[a]pyrene: linking erod induction to cytological effects.

    PubMed

    Yuen, Bonny B H; Au, Doris W T

    2006-10-01

    Temporal changes of intestinal and hepatic ethoxyresorufin-O-deethylase (EROD) activities and quantitative changes of secondary and tertiary (e.g., 2 degrees/3 degrees) lysosomes in enterocytes were compared for the juvenile grouper (Epinephelus coioides) on chronic exposure to foodborne benzo[a]pyrene (BaP) at two environmentally realistic levels (0.25 and 12.5 microg/g fish/d) over a four-week exposure and four-week depuration period. Intestinal EROD induction was rapid (within 3 d) and sustained in the BaP-exposed fish, while a fast recovery (within one week) was observed on withdrawal of BaP intake. A dose-response relationship was demonstrated between intestinal EROD activities and the levels of foodborne BaP. Conversely, hepatic EROD induction was weak and subsided rapidly in the exposed fish, signifying that hepatic EROD activity is not a good indicator of oral intake of BaP. Significant increase of 2 degrees/3 degrees lysosomes, as measured by Vv(lysosome, mucosa), was detected in young enterocytes of fish in the high-dosing group (12.5 microg/g fish/d) at exposure day 3 and persisted until recovery week 2. Importantly, intestinal EROD activity was significantly correlated to 2 degrees/3 degrees lysosome accumulation in enterocytes (r = 0.571, p < 0.001). These results further corroborate our earlier findings that induction of EROD activities in fish do not merely indicate exposure to BaP but also are correlated to harmful biological effects. We recommend the use of these two biochemical and cytological changes in intestines as specific biomarkers to indicate current and recent exposure of fish to BaP via oral intake.

  10. Chemoprotective activity of boldine: modulation of drug-metabolizing enzymes.

    PubMed

    Kubínová, R; Machala, M; Minksová, K; Neca, J; Suchý, V

    2001-03-01

    Possible chemoprotective effects of the naturally occurring alkaloid boldine, a major alkaloid of boldo (Peumus boldus Mol.) leaves and bark, including in vitro modulations of drug-metabolizing enzymes in mouse hepatoma Hepa-1 cell line and mouse hepatic microsomes, were investigated. Boldine manifested inhibition activity on hepatic microsomal CYP1A-dependent 7-ethoxyresorufin O-deethylase and CYP3A-dependent testosterone 6 beta-hydroxylase activities and stimulated glutathione S-transferase activity in Hepa-1 cells. In addition to the known antioxidant activity, boldine could decrease the metabolic activation of other xenobiotics including chemical mutagens. PMID:11265593

  11. Thyroid hormone-induced changes in the hepatic monooxygenase system, heme oxygenase activity and epoxide hydrolase activity in adult male, female and immature rats.

    PubMed

    Leakey, J E; Mukhtar, H; Fouts, J R; Bend, J R

    1982-07-01

    In 8-day-old rat pups, pretreatment with a single injection of L-triiodothyronine or L-thyroxine decreased hepatic cytochrome P-450 content, aminopyrine N-demethylase activity and epoxide hydrolase activity but increased hepatic microsomal cytochrome c reductase, 7-ethoxyresorufin O-deethylase and heme oxygenase activities without significantly altering UDP-glucuronosyltransferase activity (towards o-aminophenol) or the microsomal yield. In adult rats of either sex such single injections of L-triiodothyronine failed to significantly alter these enzyme activities. However, multiple injections evoked changes similar to those observed in the pups, in all these enzyme activities, except that 7-ethoxyresorufin O-deethylase activity was slightly decreased rather than increased. These findings demonstrate that: (1) The hepatic monooxygenase system in the rat pup is more responsive to thyroid hormones than that in adult. (2) Thyroid hormones can decrease rat liver cytochrome P-450 content and its dependent monooxygenase activity independently of sexual maturity. (3) Thyroid hormones also decrease hepatic epoxide hydrolase activity in both pups and adults. Thus, hyperthyroidism could render the rat pup more susceptible to hepatotoxicity from electrophilic epoxides which utilize microsomal epoxide hydrolase as the major detoxication pathway.

  12. Hepatic ethoxyresorufin-O-deethylase induction in the common kingfisher from an electronic waste recycling site.

    PubMed

    Wu, Jiang-Ping; Mo, Ling; Zhi, Hui; Peng, Ying; Tao, Lin; Ren, Zi-He; Luo, Xiao-Jun; Mai, Bi-Xian

    2016-06-01

    The health effects of exposure to electronic waste (e-waste)-derived pollutants are an important issue. The authors explored the association between the hepatic levels of e-waste-derived halogenated contaminants (including polychlorinated biphenyls [PCBs], polybrominated diphenyl ethers [PBDEs], and polybrominated biphenyls [PBBs]) and hepatic ethoxyresorufin-O-deethylase (EROD) activity of the common kingfisher (Alcedo atthis) from an e-waste site and 2 reference sites in South China. The summed concentrations of PCBs, PBDEs, and PBBs ranged from 620 ng/g to 15 000 ng/g, 25 ng/g to 900 ng/g, and 14 ng/g to 49 ng/g wet weight, respectively, in the kingfishers from the e-waste site, and these values were significantly greater (2-3 orders of magnitude) than those obtained at the 2 reference sites. Correspondingly, significant hepatic EROD induction was observed in the kingfishers from the e-waste site compared with the reference sites. The EROD activity was significantly correlated to the levels of most of the PCB and PBDE congeners examined as well as PBB 153, suggesting that EROD induction may be evoked by these e-waste-derived pollutants. Environ Toxicol Chem 2016;35:1594-1599. © 2015 SETAC. PMID:26509239

  13. Hepatic ethoxyresorufin-O-deethylase induction in the common kingfisher from an electronic waste recycling site.

    PubMed

    Wu, Jiang-Ping; Mo, Ling; Zhi, Hui; Peng, Ying; Tao, Lin; Ren, Zi-He; Luo, Xiao-Jun; Mai, Bi-Xian

    2016-06-01

    The health effects of exposure to electronic waste (e-waste)-derived pollutants are an important issue. The authors explored the association between the hepatic levels of e-waste-derived halogenated contaminants (including polychlorinated biphenyls [PCBs], polybrominated diphenyl ethers [PBDEs], and polybrominated biphenyls [PBBs]) and hepatic ethoxyresorufin-O-deethylase (EROD) activity of the common kingfisher (Alcedo atthis) from an e-waste site and 2 reference sites in South China. The summed concentrations of PCBs, PBDEs, and PBBs ranged from 620 ng/g to 15 000 ng/g, 25 ng/g to 900 ng/g, and 14 ng/g to 49 ng/g wet weight, respectively, in the kingfishers from the e-waste site, and these values were significantly greater (2-3 orders of magnitude) than those obtained at the 2 reference sites. Correspondingly, significant hepatic EROD induction was observed in the kingfishers from the e-waste site compared with the reference sites. The EROD activity was significantly correlated to the levels of most of the PCB and PBDE congeners examined as well as PBB 153, suggesting that EROD induction may be evoked by these e-waste-derived pollutants. Environ Toxicol Chem 2016;35:1594-1599. © 2015 SETAC.

  14. Mixed-function oxidase activity in seabirds and its relationship to oil pollution.

    PubMed

    Peakall, D B; Jeffrey, D A; Boersma, D

    1987-01-01

    1. The hepatic activity of epoxide hydrolase, aldrin epoxidase, aminopyrine N-demethylase, 7-ethoxyresorufin O-deethylase, benzo(a)pyrene 3-hydroxylase and UDP glucuronyl transferase was determined in adult herring gulls (Larus argentatus) at various stages of the breeding season. 2. MFO activity was measured for adult Leach's storm-petrels (Oceanodroma leucorhoa), guillemot (Uria aalge) and Atlantic puffins (Fratercula arctica). For most assays the values were highest for the puffin. 3. MFO activity in both nestling and adult Atlantic puffins was determined. The degree of induction caused by a single internal dose of Prudhoe Bay crude oil in adult puffins and that caused by multiple internal doses in nestling puffins was measured. PMID:2890477

  15. Ethoxyresorufin-O-deethylase induction potency of polychlorinated diphenyl ethers in H4IIE rat hepatoma cells

    SciTech Connect

    Koistinen, J.; Sanderson, J.T.; Giesy, J.P.; Nevalainen, T.; Paasivirta, J.

    1996-11-01

    Polychlorinated diphenyl ethers (PCDEs) are structurally similar to polychlorinated biphenyls (PCBs), and some PCDE congeners have been reported to cause toxic responses similar to those caused by some of the non-ortho-substituted PCBs, which are mediated by the aryl hydrocarbon receptor (AhR). Twenty-nine PCDEs were tested for their potency as AhR agonists relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) by measuring their ability to induce the cytochrome P-450 1A1-associated enzyme activity, ethoxyresorufin-O-deethylase (EROD), in the H4IIE rat hepatoma cell bioassay. All PCDE congeners tested were found to be inactive as EROD inducers except for PCDE 156, which was a weak EROD inducer with a 2,3,7,8-TCDD equivalency factor of about 1.2 {times} 10{sup {minus}5}. During this study the authors determined that small amounts of polychlorinated dibenzofurans (PCDFs) that occurred as impurities in the PCDE preparations were the cause of the apparent EROD induction initially measured in their experiments. Once the PCDF impurities were removed by purification on florisil, little or no activity could be attributed to the PCDEs.

  16. Improving the in vitro ethoxyresorufin-O-deethylase (EROD) assay with RTL-W1 by metabolic normalization and use of β-naphthoflavone as the reference substance.

    PubMed

    Heinrich, Patrick; Diehl, Ulrike; Förster, Franziska; Braunbeck, Thomas

    2014-08-01

    The ethoxyresorufin-O-deethylase (EROD) assay is a widely applied method for the evaluation of the dioxin-like activity of single substances and environmental samples. As for most enzyme assays, the specific activity is normally related to total protein contents, the determination of which has clear limitations in high-throughput assays. EROD induction potentials are usually expressed as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents, a substance highly toxic to humans. In order to compensate for these shortcomings, two modifications of the EROD protocol are proposed: (1) EROD activity is normalized to the metabolic activity of the cells as determined by a modified thiazolyl blue tetrazolium (MTT) assay and expressed as metabolic cell equivalents (MCE) based on MTT data rather than to protein contents. Via MCE data, cytotoxicity information can always be reported in parallel to EROD data; with the protocol presented here, MTT and EROD data are collected simultaneously. (2) Among several reference substances tested (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), β-naphthoflavone and benzo[a]pyrene), β-naphthoflavone proved to be the most suitable reference for the routine in vitro EROD assay, although TCDD has generally been preferred for purely scientific reasons.

  17. Microscale In Vitro Assays for the Investigation of Neutral Red Retention and Ethoxyresorufin-O-Deethylase of Biofuels and Fossil Fuels

    PubMed Central

    Bluhm, Kerstin; Brendt, Julia; Mayer, Philipp; Anders, Nico; Schäffer, Andreas; Seiler, Thomas-Benjamin; Hollert, Henner

    2016-01-01

    Only few information on the potential toxic effectiveness of biofuels are available. Due to increasing worldwide demand for energy and fuels during the past decades, biofuels are considered as a promising alternative for fossil fuels in the transport sector. Hence, more information on their hazard potentials are required to understand the toxicological impact of biofuels on the environment. In the German Cluster of Excellence “Tailor-made Fuels from Biomass” design processes for economical, sustainable and environmentally friendly biofuels are investigated. In an unique and interdisciplinary approach, ecotoxicological methods are applied to gain information on potential adverse environmental effects of biofuels at an early phase of their development. In the present study, three potential biofuels, ethyl levulinate, 2-methyltetrahydrofuran and 2-methylfuran were tested. Furthermore, we investigated a fossil gasoline fuel, a fossil diesel fuel and an established biodiesel. Two in vitro bioassays, one for assessing cytotoxicity and one for aryl hydrocarbon receptor agonism, so called dioxin-like activity, as measured by Ethoxyresorufin-O-Deethylase, were applied using the permanent fish liver cell line RTL-W1 (Oncorhynchus mykiss). The special properties of these fuel samples required modifications of the test design. Points that had to be addressed were high substance volatility, material compatibility and low solubility. For testing of gasoline, diesel and biodiesel, water accommodated fractions and a passive dosing approach were tested to address the high hydrophobicity and low solubility of these complex mixtures. Further work has to focus on an improvement of the chemical analyses of the fuel samples to allow a better comparison of any effects of fossil fuels and biofuels. PMID:27684069

  18. Joint effects of crude oil and heavy metals on the gill filament EROD activity of marbled rockfish Sebastiscus marmoratus.

    PubMed

    Zheng, Ronghui; Chen, Huanbin; Bo, Jun; Xie, Qing; Hong, Fukun; Zhang, Yusheng

    2016-10-01

    The aim of this study was to characterize dose- and time-dependent responses of gill 7-ethoxyresorufin O-deethylase (EROD) activity from Juvenile marbled rockfish (Sebastiscus marmoratus) exposed to the water-accommodated fraction (WAF) of crude oil and heavy metal Cd(Ⅱ) or Pb(Ⅱ) alone or in mixture. Compared to the control group, gill filament EROD activity in S. marmoratus was significantly induced after exposure to the WAF from 80 to 320μg/L for 5 days in dose response experiment and after exposure to 40μg/L WAF for 6-10 days in time course experiment, respectively. In the other hand, gill filament EROD activity were not significantly affected compared to the control group or related WAF groups no matter in the dose response experiment or in the time course experiment of Cd(Ⅱ), Pb(Ⅱ) or its mixture with WAF. The results suggest the use of gill filament EROD activity as a biomarker of exposure to waterborne AhR agonists in marine ecosystems while simultaneously being exposed to environmental concentrations of Cd(Ⅱ) or Pb(Ⅱ). PMID:27290642

  19. Effects of benzo(a)pyrene exposure on the antioxidant enzyme activity of scallop Chlamys farreri

    NASA Astrophysics Data System (ADS)

    Pan, Luqing; Ren, Jiayun; Zheng, Debin

    2009-02-01

    Scallop Chlamys farreri was exposed to different concentrations of benzo(a)pyrene (BaP) (0.5 μg/L, 1.0 μg/L, 10.0 μg/L and 50.0 μg/L) for 30 days in seawater. The 7-ethoxyresorufin O-deethylase (EROD) activity was significantly induced, and increased with the increasing BaP concentration. The glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), Glutathione peroxidase (GPx) activities increased in short time at low concentration of BaP, and was significantly depressed at high concentrations. Scallop gill was more sensitive to BaP than the digestive gland, and the digestive gland was the main tissue to deal with oxyradicals. The contents of malondialdehyde (MDA) increased with the exposure time and there was a positive correlation (concentration-effect) between the MDA content and the concentration of BaP. The biomarkers determined in this experiment had important roles in detoxification, and showed great potential as biomarkers for oxidative stress. Controlled laboratory experiments designed to simulate field exposure scenarios are particularly useful in ascertaining biomarkers suitable for use with complex contaminant mixtures in the marine environment.

  20. EROD activity and antioxidant defenses of sea bass (Dicentrarchus labrax) after an in vivo chronic hydrocarbon pollution followed by a post-exposure period.

    PubMed

    Danion, Morgane; Le Floch, Stéphane; Lamour, François; Quentel, Claire

    2014-12-01

    Chronic concentrations of polycyclic aromatic hydrocarbons (PAHs) have been commonly detected in international estuaries ecosystems. Reliable indicators still need to be found in order to properly assess the impact of PAHs in fish. After an in vivo chronic exposure to hydrocarbons, the enzymatic activity of 7-ethoxyresorufin O-deethylase (EROD) and the antioxidant defense system were assessed in sea bass, Dicentrarchus labrax. A total of 45 fish were exposed to the water-soluble fraction of Arabian crude oil, similar to a complex pollution by hydrocarbons chronically observed in situ, while 45 other control fish sustained the same experimental conditions in clean seawater. Fish samples were made after a 21-day exposure period and after a 15-day recovery period in clean fresh water. Throughout the experiment, liver EROD activity was significantly higher in contaminated fish than in control fish. In addition, nonenzymatic (total glutathione) and enzymatic (GPx, SOD, and CAT) antioxidant defense parameters measured in liver were not significantly different in fish. Furthermore, in gills, glutathione content had significantly increased while SOD activity had significantly decreased in contaminated fish compared to controls. On the other hand, CAT and GPx activities were not affected. Chronic exposure to PAHs disturbing the first step (SOD) and inhibiting the second step (GPx and CAT) could induce oxidative stress in tissues by the formation of oxygen radicals. After the postexposure period, there was no significant difference between control and contaminated fish in any of the antioxidant defense parameters measured in gills, attesting to the reversibility of the effects.

  1. Contaminated soil phytoremediation by Cyperus laxus Lam. cytochrome p450 EROD-activity induced by hydrocarbons in roots.

    PubMed

    López-Martínez, S; Gallegos-Martínez, M E; Pérez-Flores, L J; Gutiérrez-Rojas, M

    2008-01-01

    Laboratory and greenhouse experiments with Cyperus laxus Lam were conducted to determine the rate and extent of phytoremediation and the effect of hydrocarbons on the cytochrome P450 EROD (7-ethoxyresorufin-O-deethylase) enzymatic activity in roots. Plants were cultivated on hydrocarbon-contaminated soil (HCS) and spiked perlite. Phytoremediation was evaluated using 6.5 kg HCS (173 +/- 15 mg total petroleum hydrocarbons [TPH] g(-1) of dry soil) pots at different moisture contents; the average removal rate was 3.46-0.25 mg TPH g(-1) dry soil month(-1) and 48% was removed when moisture was kept at 60%. The aromatic hydrocarbon fraction was the mostly removed, 60%; aliphatic, 51%; and polar 24% after 24-month experiments. In unplanted pots, TPH concentration did not exhibit significant differences with respect to the initial concentration. We confirmed that the presence of hydrocarbons induced ERODactivity up to 6.5-fold. Moreover, short-term experiments (up to 13 d) with spiked perlite demonstrated that two EROD activities in roots contributed to the total detected; 60% was found in the cytosolic and 40% in the microsomal fraction. To our knowledge, this is the first work that tries to build links between the hydrocarbon-inducible character of ERODactivity in roots and the phytoremediation ability of C. laxus in highly contaminated soils. PMID:19260214

  2. Evaluation of the Ecotoxicity of Sediments from Yangtze River Estuary and Contribution of Priority PAHs to Ah Receptor-Mediated Activities

    PubMed Central

    Liu, Li; Chen, Ling; Shao, Ying; Zhang, Lili; Floehr, Tilman; Xiao, Hongxia; Yan, Yan; Eichbaum, Kathrin; Hollert, Henner; Wu, Lingling

    2014-01-01

    In this study, in vitro bioassays were performed to assess the ecotoxicological potential of sediments from Yangtze River estuary. The cytotoxicity and aryl hydrocarbon receptor (AhR)-mediated toxicity of sediment extracts with rainbow trout (Oncorhynchus mykiss) liver cells were determined by neutral red retention and 7-ethoxyresorufin-O-deethylase assays. The cytotoxicity and AhR-mediated activity of sediments from the Yangtze River estuary ranged from low level to moderate level compared with the ecotoxicity of sediments from other river systems. However, Yangtze River releases approximately 14 times greater water discharge compared with Rhine, a major river in Europe. Thus, the absolute pollution mass transfer of Yangtze River may be detrimental to the environmental quality of estuary and East China Sea. Effect-directed analysis was applied to identify substances causing high dioxin-like activities. To identify unknown substances contributing to dioxin-like potencies of whole extracts, we fractionated crude extracts by open column chromatography. Non-polar paraffinic components (F1), weakly and moderately polar components (F2), and highly polar substances (F3) were separated from each crude extract of sediments. F2 showed the highest dioxin-like activities. Based on the results of mass balance calculation of chemical toxic equivalent concentrations (TEQs), our conclusion is that priority polycyclic aromatic hydrocarbons indicated a low portion of bio-TEQs ranging from 1% to 10% of crude extracts. Further studies should be conducted to identify unknown pollutants. PMID:25111307

  3. Evaluation of the ecotoxicity of sediments from Yangtze river estuary and contribution of priority PAHs to ah receptor--mediated activities.

    PubMed

    Liu, Li; Chen, Ling; Shao, Ying; Zhang, Lili; Floehr, Tilman; Xiao, Hongxia; Yan, Yan; Eichbaum, Kathrin; Hollert, Henner; Wu, Lingling

    2014-01-01

    In this study, in vitro bioassays were performed to assess the ecotoxicological potential of sediments from Yangtze River estuary. The cytotoxicity and aryl hydrocarbon receptor (AhR)-mediated toxicity of sediment extracts with rainbow trout (Oncorhynchus mykiss) liver cells were determined by neutral red retention and 7-ethoxyresorufin-O-deethylase assays. The cytotoxicity and AhR-mediated activity of sediments from the Yangtze River estuary ranged from low level to moderate level compared with the ecotoxicity of sediments from other river systems. However, Yangtze River releases approximately 14 times greater water discharge compared with Rhine, a major river in Europe. Thus, the absolute pollution mass transfer of Yangtze River may be detrimental to the environmental quality of estuary and East China Sea. Effect-directed analysis was applied to identify substances causing high dioxin-like activities. To identify unknown substances contributing to dioxin-like potencies of whole extracts, we fractionated crude extracts by open column chromatography. Non-polar paraffinic components (F1), weakly and moderately polar components (F2), and highly polar substances (F3) were separated from each crude extract of sediments. F2 showed the highest dioxin-like activities. Based on the results of mass balance calculation of chemical toxic equivalent concentrations (TEQs), our conclusion is that priority polycyclic aromatic hydrocarbons indicated a low portion of bio-TEQs ranging from 1% to 10% of crude extracts. Further studies should be conducted to identify unknown pollutants.

  4. Effect of β-naphthoflavone on hepatic cytochrome P4501A activity in the scribbled rabbitfish (Siganus spinus) from tropical Indo-Pacific coral reefs.

    PubMed

    Emborski, Carmen; Reyes, Andres; Biggs, Jason S

    2012-11-01

    Several classes of carcinogenic environmental organic pollutants, including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and dioxins, negatively affect aquatic ecosystems worldwide. Pollutant detection is often difficult and expensive, especially when dealing with complex mixtures and matrices. Biological markers are informative tools to identify living sources that may harbor toxic compounds and areas unsuitable for recreation. Currently, no species have established biomarkers for organopollutant monitoring in Indo-Pacific coral reefs. This study evaluated the time- and dose-dependent induction of the cytochrome P4501A (CYP1A) system in the scribbled rabbitfish, Siganus spinus (Siganidae), as a biomarker for organic pollutant exposures in these environments. Results indicate that S. spinus hepatic CYP1A enzymatic activity and protein level respond dose-, and time-dependently following a single intraperitoneal injection of the classic aryl hydrocarbon receptor agonist, β-naphthoflavone. S. spinus hepatic CYP1A protein and enzymatic activity rose as function of dose during the first two days and slowly returned to levels close to normal after 16 days, as measured using the 7-ethoxyresorufin-O-deethylase and the non-competitive enzyme-linked immunosorbent assays, respectively. These findings support use of the inducible CYP1A system of S. spinus as a biomarker for reef fish exposure to coastal marine pollution. Baseline CYP1A expression levels among Guam's wild S. spinus populations were also measured and compared.

  5. Effect of β-napthoflavone on hepatic cytochrome P4501A activity in the scribbled rabbitfish (Siganus spinus) from tropical Indo-Pacific coral reefs

    PubMed Central

    Kautz, Carmen; Reyes, Andres; Biggs, Jason S.

    2013-01-01

    Several classes of carcinogenic environmental organic pollutants, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and dioxins, negatively affect aquatic ecosystems worldwide. Pollutant detection is often difficult and expensive, especially when dealing with complex mixtures and matrices. Biological markers are informative tools to identify living sources that may harbor toxic compounds and areas unsuitable for recreation. Currently, no species have established biomarkers for organopollutant monitoring in Indo-Pacific coral reefs. This study evaluated the time- and dose-dependent induction of the cytochrome P4501A (CYP1A) system in the scribbled rabbitfish, Siganus spinus (Siganidae), as a biomarker for organic pollutant exposures in these environments. Results indicate that S. spinus hepatic CYP1A enzymatic activity and protein level respond dose-, and time-dependently following a single intraperitoneal (IP) injection of the classic aryl hydrocarbon receptor (AHR) agonist, β-napthoflavone (BNF). S. spinus hepatic CYP1A protein and enzymatic activity rose as function of dose during the first two days and slowly returned to levels close to normal after 16 days, as measured using the 7-ethoxyresorufin-O-deethylase (EROD) and the non-competitive enzyme-linked immunosorbent (ELISA) assays, respectively. These findings support use of the inducible CYP1A system of S. spinus as a biomarker for reef fish exposure to coastal marine pollution. Baseline CYP1A expression levels among Guam’s wild S. spinus populations were also measured and compared. PMID:22760666

  6. Effect of β-naphthoflavone on hepatic cytochrome P4501A activity in the scribbled rabbitfish (Siganus spinus) from tropical Indo-Pacific coral reefs.

    PubMed

    Emborski, Carmen; Reyes, Andres; Biggs, Jason S

    2012-11-01

    Several classes of carcinogenic environmental organic pollutants, including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and dioxins, negatively affect aquatic ecosystems worldwide. Pollutant detection is often difficult and expensive, especially when dealing with complex mixtures and matrices. Biological markers are informative tools to identify living sources that may harbor toxic compounds and areas unsuitable for recreation. Currently, no species have established biomarkers for organopollutant monitoring in Indo-Pacific coral reefs. This study evaluated the time- and dose-dependent induction of the cytochrome P4501A (CYP1A) system in the scribbled rabbitfish, Siganus spinus (Siganidae), as a biomarker for organic pollutant exposures in these environments. Results indicate that S. spinus hepatic CYP1A enzymatic activity and protein level respond dose-, and time-dependently following a single intraperitoneal injection of the classic aryl hydrocarbon receptor agonist, β-naphthoflavone. S. spinus hepatic CYP1A protein and enzymatic activity rose as function of dose during the first two days and slowly returned to levels close to normal after 16 days, as measured using the 7-ethoxyresorufin-O-deethylase and the non-competitive enzyme-linked immunosorbent assays, respectively. These findings support use of the inducible CYP1A system of S. spinus as a biomarker for reef fish exposure to coastal marine pollution. Baseline CYP1A expression levels among Guam's wild S. spinus populations were also measured and compared. PMID:22760666

  7. Ethoxyresorufin O-deethylase induction by TCDD, PeCDF and TCDF in ring-necked pheasant and Japanese quail hepatocytes: Time-dependent effects on concentration-response curves.

    PubMed

    Hervé, Jessica C; Crump, Doug; Giesy, John P; Zwiernik, Matthew J; Bursian, Steven J; Kennedy, Sean W

    2010-06-01

    Ethoxyresorufin O-deethylase (EROD) activity was measured in primary cultures of ring-necked pheasant (Phasianuscolchicus) and Japanese quail (Coturnix japonica) embryonic hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) for 12, 24, 36 and 48 h. In ring-necked pheasant hepatocytes there was a significant time-dependent increase in the EROD-inducing potency of TCDD, PeCDF and TCDF (i.e. decrease of the EC50). In Japanese quail hepatocytes there was no time-dependent change in the EROD-inducing potency of TCDD, PeCDF and TCDF. There was no time-dependent change in the relative potency of PeCDF and TCDF (i.e. compared to the potency of TCDD) in ring-necked pheasant hepatocytes and of PeCDF in Japanese quail hepatocytes. The results indicate that the relative potencies of these compounds at 24h are representative of their relative potencies between 12 and 48 h. However, in Japanese quail hepatocytes, the relative potency of TCDF decreased in a time-dependent manner (up to 3.6-fold difference). These results suggest that the effect of time on the EROD-inducing potency of TCDD, PeCDF and TCDF in ring-necked pheasant and Japanese quail hepatocytes is compound- and species-specific, but experimental conditions could also be involved in the differences observed.

  8. Sediment TCDD-EQs and EROD and MROD activities in Ranid frogs from agricultural and nonagricultural sites in Michigan (USA).

    PubMed

    Murphy, M B; Hecker, M; Coady, K K; Tompsett, A R; Jones, P D; Newsted, J L; Wong, H L; du Preez, L H; Solomon, K R; Carr, J A; Smith, E E; Kendall, R J; Van der Kraak, G; Giesy, J P

    2006-10-01

    In vitro studies have demonstrated atrazine-mediated induction of 7-ethoxyresorufin O-deethylase (EROD) activity. EROD is an enzyme active in the metabolism of many compounds, including many xenobiotics. These studies have suggested that atrazine may affect reproductive function by altering steroid metabolism. The goal of this study was to determine whether relationships could be detected between measured atrazine concentrations in surface waters and the liver-somatic index (LSI) and EROD and 7-methoxyresorufin O-deethylase (MROD) activities in the livers of ranid frogs. In addition, sediment dioxin toxic equivalents (TCDD-EQs) were determined using the H4IIE-luc cell bioassay. Adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana), and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south central Michigan in the summer of 2003. Atrazine concentrations at nonagricultural sites ranged from less than the limit of quantification (0.17 microg atrazine/L) to 0.23 microg atrazine/L and did not exceed 1.2 microg atrazine/L at agricultural sites. Sediment TCDD-EQs were measurable only at one agricultural site. Of the measured parameters, only LSI values in adult male frogs differed significantly between agricultural and nonagricultural sites, with greater values observed at agricultural sites. In green frogs, EROD and MROD activities were measurable in both adult and juvenile frogs and were similar among sites. Median EROD activities ranged from 13 to 21 pmol/min/mg protein in adult male green frogs and from 5 to 13 pmol/min/mg protein in adult female green frogs. Juvenile frogs had greater EROD and MROD activities than adult frogs. Bullfrogs and leopard frogs had greater activities than did green frogs. Atrazine concentrations were significantly and negatively correlated with MROD activity in adult male green frogs (Spearman R = -0.800). LSI and

  9. Evaluation of planar halogenated and polycyclic aromatic hydrocarbons in estuarine sediments using ethoxyresorufin-O-deethylase induction of H4IIE cells

    USGS Publications Warehouse

    Gale, R.W.; Long, E.R.; Schwartz, T.R.; Tillitt, D.E.

    2000-01-01

    Polycyclic aromatic hydrocarbons (PAHs) and planar halogenated hydrocarbons (PHHs), including polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) were determined in fractionated sediment extracts from the Hudson-Raritan estuary and Newark Bay, New Jersey, USA, as part of a comprehensive risk assessment. Contributions of PCDDs/PCDFs, PCBs, and PAHs to the total toxic equivalents (TEQs) were measured using an H4IIE bioassay and calculated from instrumentally determined concentrations using international toxic equivalency factors. The H4IIE TEQs of whole and fractionated extracts were compared to calculated TEQs to investigate the applicability of the bioassay approach for evaluating 7-ethoxyresorufin-O-deethylease induction by PHHs and PAHs present together in complex mixtures. Although 2,3,7,8-tetrachlorodibenzo-p-dioxin contributed from 41 to 79% of the calculated TEQs from PCDDs/PCDFs and planar PCBs in all sediments sampled, the PAH-containing fractions accounted for >80% of the total TEQs determined either instrumentally or by bioassay. Calculated TEQs from PAHs, based on reported toxic equivalency factors for only seven PAHs, were severalfold greater than the bioassay-derived TEQs of PAH-only fractions of the sediment extracts. Significant correlations were observed between bioassay and instrumentally determined toxic equivalents in the more purified fractions but not in fractions only purified by size-exclusion or argentate chromatographies alone.

  10. Evaluation of planar halogenated and polycyclic aromatic hydrocarbons in estuarine sediments using ethoxyresorufin-O-deethylase induction of H4IIE cells

    SciTech Connect

    Gale, R.W.; Long, E.R.; Schwartz, T.R.; Tillitt, D.E.

    2000-05-01

    Polycyclic aromatic hydrocarbons (PAHs) and planar halogenated hydrocarbons (PHHs), including polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) were determined in fractionated sediment extracts from the Hudson-Raritan estuary and Newark Bay, New Jersey, USA, as part of a comprehensive risk assessment. Contributions of PCDDs/PCDFs, PCBs, and PAHs to the total toxic equivalents (TEQs) were measured using an H4IIE bioassay that calculated from instrumentally determined concentrations using international toxic equivalency factors. The H4IIE TEQs of whole and fractionated extracts were compared to calculated TEQs to investigate the applicability of the bioassay approach for evaluating 7-ethoxyresorufin-O-deethylease induction by PHHs and PAHs present together in complex mixtures. Although 2,3,7,8-tetrachlorodibenzo-p-dioxin contributed from 41 to 79% of the calculated TEQs from PCDDs/PCDFs and planar PCBs in all sediments sampled, the PAH-containing fractions accounted for >80% of the total TEQs determined either instrumentally or by bioassay. Calculated TEQs from PAHs, based on reported toxic equivalency factors for only seven PAHs, were severalfold greater than the bioassay-derived TEQs of PAH-only fractions of the sediment extracts. Significant correlations were observed between bioassay and instrumentally determined toxic equivalents in the more purified fractions but not in fractions only purified by size-exclusion or argentate chromatographies alone.

  11. Detection of toxic effects of Cd2+ on different fish species via liver cytochrome P450-dependent monooxygenase activities and FTIR spectroscopy.

    PubMed

    Henczová, Mária; Deér, Aranka Kiss; Komlósi, Viktória; Mink, János

    2006-06-01

    The in vivo and in vitro effects of Cd2+ and the CYP1A inductor beta-naphthoflavone(beta-NF) on the hepatic cytochrome P450 (Cyt 450) monooxygenases were studied in silver carp (Hypophthalmichtys molitrix V.), wels (Silurus glanis L.), and carp (Cyprinus carpio). In vivo treatment of carp with a high dose of Cd2+ (10 mg kg(-1), for 3 days) caused a strong inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and a lower inhibition of 7-ethoxycoumarin-O-deethylase (ECOD) activity. The low-dose cadmium treatment (2 mg kg(-1) Cd2+, for 6+3 days) resulted in 4-fold increase in EROD and a 3-fold increase in ECOD activity. The combined treatment with Cd2+ and beta-NF in both cases led to a loss of EROD inducibility. The silver carp and wels were treated with 10 mg L(-1) Cd2+ for 72 h in water. The Cyt P450 content in the wels liver microsomes was increased significantly after treatment for 48 h, whereas there was only a slight, not significant increase in Cyt P450 content in the silver carp microsomes. While the Cd2+ treatment resulted in inhibition of the CYP1A isoenzymes (EROD and ECOD), the APND (aminopyrene-N-demethylase, CYP2B or CYP3A isoenzyme) activity was increased 3- to 4-fold in both fish species. In vitro experiments of the effect of Cd2+ led to a concentration-dependent inhibition in all three investigated fish species. The ECOD isoenzyme of silver carp was the most sensitive to Cd2+. The lowest concentration of Cd2+ resulted in 50% inhibition. The APND isoenzyme was similarly sensitive to Cd2+ in all three investigated fish species. The most sensitive species was the wels, and the least sensitive were the carp isoenzyme. FTIR spectroscopy confirmed that cadmium caused damage to the protein structure. These results support the enzyme activity measurements measured in vivo and in vitro.

  12. Effect of copper chloride in vitro and in vivo on the hepatic EROD activity in the fish Dicentrarchus labrax

    SciTech Connect

    Stien, X.; Risso, C.; Gnassia-Barelli, M.; Romeo, M.; LaFaurie, M.

    1997-02-01

    The effect of copper chloride was studied on the hepatic microsomal 7-ethoxyresorufin-O-deethylase (EROD) activity of the fish Dicentrarchus labrax intraperitoneally injected with benzo[a]pyrene (BaP). In vitro experiments showed that copper significantly decreased EROD activity, and IC50 was estimated at 50 {micro}g Cu/L. The apparent Michaelis constant (K{sub m}) of cytochrome P4501A was constant, whereas maximum velocity (V{sub max}) decreased as a function of copper added to the incubation medium. (K{sub m}) of nicotinamide adenine dinucleotide phosphate [NADPH]-cytochrome P450 reductase increased as a function of copper concentration, whereas V{sub max} remained constant. Absorption spectra showed that the amount of cytochrome P420s increased as a function of copper concentrations added to the medium at the expense of cytochrome P450s. The injection of copper and BaP to fish decreased EROD activity compared with the injection of BaP alone. An increase of immunoquantified CYP1A content measured by Western blotting was noted in microsomes of fish injected with BaP compared with controls. In the case of fish treated with copper and BaP, the band was less intense and accompanied by another band of lower molecular weight. The destruction of the native P450s spectrophotometrically measured in the presence of copper implied that the catalytic activity would be diminished. This was confirmed by decreased EROD activity after either in vitro additions or in vivo treatment with copper. Moreover, immunodetection experiments suggested that the decrease of the catalytic activity resulted more from cytochrome P450s loss than from direct inhibition of EROD activity by copper.

  13. Induction of cytochrome P450 1A1 and monooxygenase activity in Tilapia by sediment extract

    SciTech Connect

    Ueng, Y.F.; Ueng, T.H.; Liu, T.Y.

    1995-01-01

    Cytochrome P450 (P450)-dependent monooxygenases of fishes are inducible by a variety of environmental pollutants including polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Induction of fish monoxygenases may serve as a biological monitor for PAH- and PCB-types of environmental chemicals. Many studies have demonstrated environmental induction of fish monooxygenases using various experimental approaches. However, relatively few studies have been conducted using fish treated with contaminated river sediment extracts. Damsui River is the largest river in the north of Taiwan. The lower section of the river in the Taipei Metropolitan area is heavily polluted by industrial and municipal wastes. Tilapia (Oreochromis mossambicus) is one of the few species of fish that occur in the polluted river. Previous field studies showed that the levels of P450 1A1, benzo(a)pyrene hydroxylase and 7-ethoxyresorufin O-deethylase activities in tilapia collected at Fu-Ho Bridge, a polluted section of Damsui River, were higher than respective levels in fish collected from an unpolluted section. These results suggested that tilapia caught at the polluted site were exposed to substances similar in action to PAHs and PCBs, because these chemical pollutants are potent inducers of P450 1A1. PAHs and PCBs are persistent compounds that can accumulate in sediment. Tilapia are occasionally associated with the bottom and could ingest chemically contaminated sediment. In the present study, we determined the induction properties of monooxygenases using tilapia treated with extract of sediment collected from a polluted section of Damsui River. The present study demonstrates that Damsui River sediment extract has the ability to induce hepatic P450 1A1 and dependent monooxygenase activities in tilapia. 17 refs., 2 figs., 2 tabs.

  14. Simultaneous determination of cytochrome P450 1A, 2A and 3A activities in porcine liver microsomes.

    PubMed

    Johansson, Monika; Tomankova, Jana; Li, Shengjie; Zamaratskaia, Galia

    2012-09-01

    The aim of this study was to develop a robust method for the simultaneous determination of the activities of three porcine CYP450 enzymes in hepatic microsomes. A cocktail consisting of three selective CYP450 probe substrates, 7-ethoxyresorufin (CYP1A), coumarin (CYP2A) and 7-benzyloxy-4-trifluoromethylcoumarin (BFC; CYP3A), was incubated with porcine liver microsomes. The presence of 7-ethoxyresorufin appears to significantly influence the kinetics of coumarin hydroxylation and BFC O-debenzylation. These results indicate that the use of 7-ethoxyresorufin in substrate cocktails together with coumarin and BFC should be avoided.

  15. Effects of in ovo 2,3,7,8-TCDD exposure on hepatic ethoxyresorufin O-deethylase (EROD) induction and growth-related parameters in avian species

    SciTech Connect

    Janz, D.M.; Bellward, G.D.

    1994-12-31

    The effects of early in ovo TCDD exposure on CYP1A1 induction and indices of growth were determined in domestic chicken (Gallus gallus) and pigeon (Columba livia) hatchlings. TCDD (in corn oil) was injected into the air sac of eggs on embryonic day 4 (E4) (chickens, 0.1 {mu}g/kg egg; pigeons, 1.0 {mu}g/kg egg), and on E14 (pigeons, 3.0 {mu}g/kg egg). In chickens, hepatic EROD was induced 13, 15, 34, and 43-fold above control activities on E19, day of hatch (DO), day 2 after hatch (D2), and D4, respectively. Plasma thyroid hormone (T{sub 3} T{sub 4}) concentrations, which are known to peak during the perinatal period in chickens, were not affected by TCDD treatment when measured on E17, E19, D0, D2, and D4. In pigeons injected on E4, EROD was induced 15 and 6-fold on D0 and D7, respectively. There were significant decreases in yolk-free body weight, crown-rump, tibia, culmen, and wing lengths, and an elevated liver to body weight ratio (LSI) in TCDD-treated pigeons raised to D7 (p < 0.01). In pigeons injected on E14 (3{mu}g/kg), EROD was induced 14 and 10-fold on D0 and D7, respectively. Crown-rump and culmen lengths were decreased (p < 0.05) and LSI was increased (p < 0.01) on D0. There were significant decreases in all morphological parameters, and an increased LSI on D7 (p < 0.01) in TCDD-treated birds. These techniques will be used in further studies to investigate possible mechanisms of TCDD embryotoxicity in wild avian species, such as the great blue heron (Ardea herodias).

  16. Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

    SciTech Connect

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2007-12-15

    Oral administration of different doses (0.0625, 0.125 or 0.25 mg/kg corresponding to 1/1400th, 1/700th or 1/350th of LD{sub 50}) of lindane to the pregnant Wistar rats from gestation days 5 to 21 were found to produce a dose-dependent increase in the activity of cytochrome P450 (CYP)-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of CYP monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have suggested that increase in CYP activity may possibly lead to the formation of metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic CYPs was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.125 and 0.25 mg/kg) of lindane and up to 9 weeks at the highest dose (0.25 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6-week of age, have further indicated that due to the reduced activity of the CYPs during the ontogeny, lindane and its metabolites may not be effectively cleared from the brain. The data suggest that low dose prenatal exposure to the pesticide has the potential to produce overexpression of xenobiotic metabolizing CYPs in brain and liver of the offspring which may account for the behavioral changes observed in the offspring.

  17. Contribution of Priority PAHs and POPs to Ah Receptor-Mediated Activities in Sediment Samples from the River Elbe Estuary, Germany

    PubMed Central

    Otte, Jens C.; Keiter, Steffen; Faßbender, Christopher; Higley, Eric B.; Rocha, Paula Suares; Brinkmann, Markus; Wahrendorf, Dierk-Steffen; Manz, Werner; Wetzel, Markus A.; Braunbeck, Thomas; Giesy, John P.; Hecker, Markus; Hollert, Henner

    2013-01-01

    The estuary of the River Elbe between Hamburg and the North Sea (Germany) is a sink for contaminated sediment and suspended particulate matter (SPM). One major concern is the effect of human activities on the hydrodynamics, particularly the intensive dredging activities in this area that may result in remobilization of sediment-bound pollutants. The aim of this study was to identify pollutants contributing to the toxicological risk associated with re-suspension of sediments in the Elbe Estuary by use of an effect-directed analysis that combines chemical and biological analyses in with specific fractionation techniques. Sediments were collected from sites along the Elbe Estuary and a site from a small harbor basin of the Elbe Estuary that is known to be polluted. The sixteen priority EPA-PAHs were quantified in organic extracts of sediments. In addition, dioxin equivalents of sediments were investigated by use of the 7-ethoxyresorufin O-deethylase assay with RTL-W1 cells and the Ah receptor-mediated luciferase transactivation assay with H4IIE-luc cells. Quantification of the 16 priority PAHs revealed that sediments were moderately contaminated at all of the sites in the Elbe River Estuary (<0.02–0.906 µg/g dw). Sediments contained relatively small concentrations of dioxin equivalents (Bio-TEQ) with concentrations ranging from 15.5 to 322 pg/g dw, which were significantly correlated with dioxin equivalents calculated based on toxicity reference values and concentrations of PAH. The concentration of Bio-TEQ at the reference site exceeded 200,000 pg/g dw. In a potency balance the 16 PAHs explained between 47 and 118% of the Bio-TEQ in the luciferase assay, which can be explained by the constant input of PAHs bound to SPM from the upper course of the Elbe River into its estuary. Successful identification of a significant portion of dioxin-like activity to priority PAHs in complex environmental samples such as sediments has rarely been reported. PMID:24146763

  18. Chronic hydrocarbon exposure of harlequin ducks in areas affected by the Selendang Ayu oil spill at Unalaska Island, Alaska.

    PubMed

    Flint, Paul L; Schamber, Jason L; Trust, Kimberly A; Miles, A Keith; Henderson, John D; Wilson, Barry W

    2012-12-01

    We evaluated chronic exposure of harlequin ducks (Histrionicus histrionicus) to hydrocarbons associated with the 2004 M/V Selendang Ayu oil spill at Unalaska Island, Alaska. We measured levels of hepatic 7-ethoxyresorufin-O-deethylase activity (EROD) in liver biopsy samples as an indicator of hydrocarbon exposure in three oiled bays and one reference bay in 2005, 2006, and 2008. Median EROD activity in ducks from oiled bays was significantly higher than in the reference bay in seven of nine pairwise comparisons. These results indicated that harlequin ducks were exposed to lingering hydrocarbons more than three years after the spill. PMID:22933448

  19. Chronic hydrocarbon exposure of harlequin ducks in areas affected by the Selendang Ayu oil spill at Unalaska Island, Alaska

    USGS Publications Warehouse

    Flint, Paul L.; Schamber, J.L.; Trust, K.A.; Miles, A.K.; Henderson, J.D.; Wilson, B.W.

    2012-01-01

    We evaluated chronic exposure of harlequin ducks (Histrionicus histrionicus) to hydrocarbons associated with the 2004 M/V Selendang Ayu oil spill at Unalaska Island, Alaska. We measured levels of hepatic 7-ethoxyresorufin-O-deethylase activity (EROD) in liver biopsy samples as an indicator of hydrocarbon exposure in three oiled bays and one reference bay in 2005, 2006, and 2008. Median EROD activity in ducks from oiled bays was significantly higher than in the reference bay in seven of nine pairwise comparisons. These results indicated that harlequin ducks were exposed to lingering hydrocarbons more than three years after the spill.

  20. Chronic hydrocarbon exposure of harlequin ducks in areas affected by the Selendang Ayu oil spill at Unalaska Island, Alaska.

    PubMed

    Flint, Paul L; Schamber, Jason L; Trust, Kimberly A; Miles, A Keith; Henderson, John D; Wilson, Barry W

    2012-12-01

    We evaluated chronic exposure of harlequin ducks (Histrionicus histrionicus) to hydrocarbons associated with the 2004 M/V Selendang Ayu oil spill at Unalaska Island, Alaska. We measured levels of hepatic 7-ethoxyresorufin-O-deethylase activity (EROD) in liver biopsy samples as an indicator of hydrocarbon exposure in three oiled bays and one reference bay in 2005, 2006, and 2008. Median EROD activity in ducks from oiled bays was significantly higher than in the reference bay in seven of nine pairwise comparisons. These results indicated that harlequin ducks were exposed to lingering hydrocarbons more than three years after the spill.

  1. Increased exposure of vitamin A by Chrysanthemum morifolium Ramat extract in rat was not via induction of CYP1A1, CYP1A2, and CYP2B1.

    PubMed

    Wang, Ping; Pan, Xian; Chen, Guanming; Li, Jia; Liu, Li; Liu, Xiaodong; Jin, Shi; Xie, Lin; Wang, Guangji

    2012-06-01

    The aim of this study was to investigate the effect of Chrysanthemum morifolium Ramat (CM) extract on the pharmacokinetics of retinol and activities of cytochrome P450s (CYP450s) related to retinoid metabolism. Rats were treated with CM extract for 15 d. Plasma concentrations of retinol were measured following oral administration of retinol (45 mg/kg). Basal levels of retinol and retinoic acid in serum and liver were also measured. 7-Ethoxyresorufin-O-deethylase activity, phenacetin-O-deethylase activity, and 7-pentoxyresorufin-O-deethylase activities were used to assay the activities of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats, respectively. Protein expressions of the 3 CYP450s were measured by western blot. Our studies demonstrated that CM extract dose-dependently increased basal level of retinol in serum. In pharmacokinetic experiment, CM extract dose-dependently increased plasma concentrations of retinol after oral administration of retinol to rats treated with CM extract. But activities and expressions of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats were also induced by CM extract.

  2. Loss of hepatic monooxygenase activities, glutathione, and 'green pigment' formation after the administration of vinyl-cyclooctane to mice.

    PubMed

    Gervasi, P G; Citti, L; Fassina, G; Testai, E; Turchi, G

    1983-05-01

    Vinylcyclooctane, when administered to mice at 500 mg/kg, produced reduction of microsomal cytochrome P-450, heme, aminopyrine-N-demethylase and ethoxycoumarin-O-deethylase activities with respect to control values; furthermore the hepatic reduced glutathione level was depleted suggesting that glutathione is involved in the vinylcyclooctane metabolism. The reduction of cytochrome P-450 and monooxygenase activities was accompanied by the formation of abnormal 'green pigments'.

  3. Effect of prostaglandin F2 alpha on free radical generation, glutathione content and microsomal oxidase activities in rat liver microsomes induced either by ethanol or acetone.

    PubMed

    Sadovnichy, V; Müller, D; Buko, V

    1997-01-01

    We studied the effect of prostaglandin F2 alpha on parameters related to microsomal metabolism (free radical production and lipid peroxidation, glutathione content and activity of microsomal oxidases) after an induction by ethanol or acetone combined with starvation. Long-term ethanol administration led to a significant increase in lipid peroxide formation and NADPH-dependent chemiluminescence amplified by luminol and lucigenin. At the same time hydrogen peroxide production and NADPH-stimulated lipid peroxidation were enhanced although the effect did not reach the level of statistical significance. The concentration of reduced glutathione (GSH) in the liver was decreased 2-fold, whereas oxidized glutathione (GSSG) content remained unaltered. Ethanol intoxication resulted in an increase in 7-ethoxycoumarin-O-deethylase (ECOD), 7-benzyloxycoumarin-O-deethylase (BCOD) and 7-ethoxy-resorufin-O-deethylase (EROD) activities, whereas 7-pentoxyresorufin-O-deethylase (PROD) and ethylmorphin-N-demethylase (EMND) activities were unaltered. The combination of acetone treatment with starvation resulted in a significant increase in lipid and hydrogen peroxide formation, NADPH-dependent lipid peroxidation and chemiluminescence. GSH and GSSG concentration in the liver dramatically decreased 5- and 3-fold, respectively. The acetone treatment led to significant increase in EROD, ECOD, BCOD, PROD and EMND activities. The treatment of ethanol-intoxicated rats with prostaglandin F2 alpha (PGF2 alpha) exerted more pronounced prooxidant effect on liver than action of alcohol itself. At the same time, PGF2 alpha improved most of parameters changed by acetone treatment combined with starvation, decreasing lipid peroxide and radical formation and enhancing GSH and GSSG contents.

  4. Integration of multi-level biomarker responses to cadmium and benzo[k]fluoranthene in the pale chub (Zacco platypus).

    PubMed

    Kim, Woo-Keun; Lee, Sung-Kyu; Park, June-Woo; Choi, Kyungho; Cargo, Jordan; Schlenk, Daniel; Jung, Jinho

    2014-12-01

    The Cd exposure for 14 days significantly increased both the molecular (DNA single-strand breaks) and biochemical (metallothionein concentrations) biomarkers in the freshwater pale chub, Zacco platypus, whereas changes in the histological and physiological biomarker responses were negligible. The BkF exposure for 14 days led to significant increases in the mRNA expression of catalase and superoxide dismutase, 7-ethoxyresorufin-O-deethylase enzymatic activity and DNA single-strand breakage at the molecular and biochemical levels. In addition, exposure to 50μg/L of BkF induced histological alteration in the liver, with significant changes to the liver somatic index and condition factor at the physiological level. The integration of multi-level biomarker responses at the molecular, biochemical and physiological levels was highly correlated with the concentrations of Cd and BkF. PMID:25217733

  5. Environmental contaminant effects on juvenile striped bass in the San Francisco Estuary, California, USA.

    PubMed

    Spearow, Jimmy L; Kota, Rama S; Ostrach, David J

    2011-02-01

    The decline of pelagic organisms in the San Francisco Estuary (SFE) (California, USA) is attributed to several factors, including water diversions, invasive species, and exposure to environmental toxicants. The present study evaluated the effects of environmental contaminants on liver vitellogenin, metallothionein, 7-ethoxyresorufin-O-deethylase (EROD), and benzyloxyresorufin O-deethylase (BROD) activity in juvenile striped bass (Morone saxitilis) in the SFE. Analysis of juvenile striped bass liver extracts revealed site-specific elevations of vitellogenin, metallothionein, and EROD biomarkers across the estuary. Although some striped bass in the estuary showed EROD activity similar to unhandled hatchery controls, several sites in the estuary showed significantly higher EROD activity that was in the range of beta-naphthoflavone (BNF)-injected, positive controls. Overall, EROD activity averaged 283% higher in estuary fish than in hatchery controls. Chemical analyses of extracts from semipermeable membrane devices (SPMDs) deployed in the estuary for one month showed elevated polyaromatic hydrocarbon (PAH) levels. Semipermeable membrane devices extract injections-induced metallothionein and BROD in striped bass livers. These data show that environmental exposures are impacting EROD and other biomarkers in the SFE striped bass population. Previous studies in our laboratory have associated poor larval development with maternal transfer of environmental contaminants. Further studies are needed to monitor contaminant exposures by the use of biomarkers and to integrate them into a more effective pelagic species recovery plan in the SFE. PMID:21038432

  6. Environmental contaminant effects on juvenile striped bass in the San Francisco Estuary, California, USA.

    PubMed

    Spearow, Jimmy L; Kota, Rama S; Ostrach, David J

    2011-02-01

    The decline of pelagic organisms in the San Francisco Estuary (SFE) (California, USA) is attributed to several factors, including water diversions, invasive species, and exposure to environmental toxicants. The present study evaluated the effects of environmental contaminants on liver vitellogenin, metallothionein, 7-ethoxyresorufin-O-deethylase (EROD), and benzyloxyresorufin O-deethylase (BROD) activity in juvenile striped bass (Morone saxitilis) in the SFE. Analysis of juvenile striped bass liver extracts revealed site-specific elevations of vitellogenin, metallothionein, and EROD biomarkers across the estuary. Although some striped bass in the estuary showed EROD activity similar to unhandled hatchery controls, several sites in the estuary showed significantly higher EROD activity that was in the range of beta-naphthoflavone (BNF)-injected, positive controls. Overall, EROD activity averaged 283% higher in estuary fish than in hatchery controls. Chemical analyses of extracts from semipermeable membrane devices (SPMDs) deployed in the estuary for one month showed elevated polyaromatic hydrocarbon (PAH) levels. Semipermeable membrane devices extract injections-induced metallothionein and BROD in striped bass livers. These data show that environmental exposures are impacting EROD and other biomarkers in the SFE striped bass population. Previous studies in our laboratory have associated poor larval development with maternal transfer of environmental contaminants. Further studies are needed to monitor contaminant exposures by the use of biomarkers and to integrate them into a more effective pelagic species recovery plan in the SFE.

  7. The ameliorating effects of vitamin E on hepatic antioxidant system and xenobiotic-metabolizing enzymes in fenvalerate-exposed iodine-deficient rats.

    PubMed

    Kocer-Gumusel, Belma; Erkekoglu, Pinar; Caglayan, Aydan; Hincal, Filiz

    2016-01-01

    This study investigated the effects of vitamin E (VE) on hepatic antioxidant system and drug-metabolizing enzymes in fenvalerate (FEN)-exposed iodine-deficient (ID) Wistar rats. ID was produced by perchlorate containing drinking water. VE was introduced by a loading dose of 100 mg/kg/d, i.g. for the first three days in the last week of feeding period; then with a single maintenance dose of 40 mg/kg on the 4th day. During last week, FEN groups (F) received 100 mg/kg/d, i.p. FEN. VE alone did not significantly affect thyroid hormones and antioxidant parameters; however, significantly increased total cytochrome P450 (38%) and cytochrome b5 levels (36%). In all ID groups, plasma thyroid-stimulating hormone (TSH) levels increased markedly, but remained at control level in vitamin E plus FEN receiving iodine-deficient group (IDVF) group. Glutathione peroxidase activity showed marked increases in F (19%) and FEN-exposed iodine-deficient group (IDF, 48%) groups. FEN treatment significantly increased total cytochrome P450 (28%) and thiobarbituric acid reactive substance levels (36%), as well as 7-ethoxyresorufin O-deethylase (120%), 7-penthoxyresorufin O-deethylase (139%) and glutathione S-transferase (15%) activities and decreased total glutathione concentrations (28%) versus control. Overall results suggest that vitamin E has ameliorating effects on the measured parameters in ID and/or FEN exposure.

  8. Evaluation of cytochrome P450 activity in field populations of Cydia pomonella (Lepidoptera: Tortricidae) resistant to azinphosmethyl, acetamiprid, and thiacloprid.

    PubMed

    Cichón, L B; Soleño, J; Anguiano, O L; Garrido, S A S; Montagna, C M

    2013-04-01

    The Río Negro and Neuquén Valley is the most important apple and pear growing region in Argentina. Cydia pomonella L. (Lepidoptera: Tortricidae), the main fruit-tree pest is being controlled by azinphosmethyl (AzMe), acetamiprid (Acet), and thiacloprid (Thia) among other insecticides. The objective of this study was to evaluate the response of neonate larvae of codling moth to these three insecticides and on the role of cytochrome P450 monooxygenase in their toxicity. All field populations presented significantly lower mortality to a discriminating concentration (DC) of Acet and AzMe. In addition, 13 of the 14 populations showed significantly lower mortality to DC of Thia. Most of the field populations (71%) showed significantly higher 7-ethoxycoumarine O-deethylase activity compared with the laboratory-susceptible strain. While positive significant correlation (gamma = 0.59) was found between Thia and AzMe mortalities at the DC level, no significant correlations were detected between Acet and Thia (gamma = 0.35) or Acet and AzMe (gamma = 0.12). However, Acet and Thia mortalities were significantly correlated to the percentage of individuals exhibiting 7-ethoxy-coumarine O-deethylase activity activities higher than the mean upper 95% confidence limit of the susceptible strain (gamma = -0.52 and gamma = -0.63, respectively).

  9. In vitro interaction of emerging contaminants with the cytochrome p450 system of Mediterranean deep-sea fish.

    PubMed

    Ribalta, Carla; Solé, Montserrat

    2014-10-21

    The interactions of emerging contaminants with the xenobiotic and endogenous metabolizing system of deep-sea fish were compared. The drugs diclofenac, fluoxetine, and gemfibrozil belong to different pharmaceutical classes with diverse mechanistic actions, and the personal care products triclosan, galaxolide, and nonylphenol are representative of antibacterial agents, nitro-musks, and surfactants, respectively. The fish compared are representative of the middle and lower slope of deep-sea habitats. The species were adults of Trachyrynchus scabrus, Mora moro, Cataetix laticeps, and Alepocehalus rostratus. The hepatic metabolic system studied were the activities associated with several cytochrome P450 isoforms (CYPs): 7-ethoxyresorufin-O-deethylase (EROD), benzyloxy-4-[trifluoromethyl]-coumarin-O-debenzyloxylase (BFCOD), and 7-ethoxycoumarin-O-deethylase (ECOD). Results showed differences in baseline activities and sensitivity to chemicals which were species, chemical, and pathway dependent. T. scabrous was the most sensitive species to chemical interactions with the xenobiotic and endogenous metabolizing (EROD and BFCOD) systems, especially in the case of diclofenac interference with BFCOD activity (IC50 = 15.7 ± 2.2 μM). Moreover, T. scabrous and A. rostratus possessed high basal ECOD activity, and this was greatly affected by in vitro exposure to diclofenac in T. scabrous also (IC50 = 6.86 ± 1.4 μM). These results highlight the sensitivity of marine fish to emerging contaminants and propose T. scabrous (middle slope) and A. rostratus (lower slope) as sentinels and the inclusion of ECOD activity as a sensitive biomarker to these exposures. PMID:25225740

  10. Dioxin-ähnliche Wirkungen durch Grundwasser am Industriestandort Zeitz

    NASA Astrophysics Data System (ADS)

    Schirmer, Kristin; Bopp, Stephanie; Russold, Sandra; Popp, Peter

    Kurzfassung Im Rahmen der Etablierung des Standortes Zeitz (Sachsen-Anhalt) als Referenztestfeld zur Implementierung des Natural-Attenuation-Ansatzes, haben wir Grundwasser auf seine Fähigkeit untersucht, eine Dioxin-ähnliche Wirkung hervorzurufen. Die Dioxin-ähnliche Wirkung ist die Arylhydrocarbon Rezeptor-vermittelte Induktion des Proteinkomplexes Cytochrom CYP1A, welches als 7-Ethoxyresorufin-O-Deethylase (EROD) Enzymaktivität in einer Fischleberzelllinie gemessen wurde. Von 32 Probennahmestellen wiesen sieben eine signifikante EROD-Induktion auf, welche zu einem geringen Teil auf Polyzyklische Aromatische Kohlenwasserstoffe zurückzuführen war. Ein weiterer Teil der EROD-Induktion konnte den Substanzen Benzofuran, Indan und Inden zugesprochen werden, welche hier erstmalig als EROD-Induktoren identifiziert wurden. Alle Probennahmestellen mit signifikanter EROD-Induktion lagen im Anstrom bzw. westlich des früheren Standortes der Benzolanlage in Zeitz, was einen signifikanten Einfluss von Benzol vor allem auf den Transport und das Lösungsverhalten EROD-induzierender Grundwasserkontaminanten vermuten lässt. Insgesamt zeigen diese Untersuchungen, wie eine Kombination von chemischer und biologischer Analytik zu einer deutlich verbesserten Aussagekraft führt und somit zu einer nachhaltigen Überwachung der Qualität von Grundwasser beitragen kann. As part of setting up the test field Zeitz (Saxony-Anhalt, Germany) as a reference site for the implementation of Natural Attenuation as a remediation option, we have investigated groundwater for its ability to cause a dioxin-like response. The dioxin-like response is the aryl hydrocarbon receptor-mediated induction of the protein complex cytochrome CYP1A, which was measured as 7-Ethoxyresorufin-O-deethylase (EROD) enzyme activity in a fish liver cell line. Out of 32 sampling locations, seven showed significant EROD induction, which could be explained, to a minor extent, by the presence of polycyclic aromatic

  11. Effects of acetone, acetonitrile, ethanol, methanol and DMSO on cytochrome P450 in rainbow trout (Oncorhynchus mykiss) hepatic microsomes.

    PubMed

    Sakalli, Sidika; Burkina, Viktoriia; Zlabek, Vladimir; Zamaratskaia, Galia

    2015-01-01

    In vitro impacts of five organic solvents on cytochrome P450 (CYP450) enzyme activity were investigated using hepatic microsomes of rainbow trout. The rates of several CYP450-mediated reactions were investigated at solvent concentrations ranging from 0.01% to 3%. The solvents greatly affected all tested reactions. In at least 0.8% ethanol, 2% methanol or acetone, 1% acetonitrile or 3% dimethyl sulfoxide (DMSO), 7-ethoxyresorufin-O-deethylase (EROD) activity decreased and at 3% acetonitrile or ethanol, it was undetected. At 3%, all tested solvents except methanol reduced 7-benzyloxy-4-trifluoromethylcoumarin-O-debenzylase (BFCOD) activity, but at low concentrations of ethanol (2% and lower) or DMSO (1% and lower), it was induced. This was not seen with the inclusion of a pre-incubation step. p-Nitrophenolhydroxylase (PNPH) activity was not affected at concentrations below 1% DMSO, and at 2% acetonitrile it was reduced, as it was above 1% methanol or 0.5% ethanol. Acetone did not affect PNPH activity with or without a pre-incubation step. In general, the degree of inhibition was similar with and without the pre-incubation step. We conclude that the concentration of organic solvent for solubilizing the substrate and inhibitor in in vitro microsomal studies should be minimized.

  12. Biochemical responses in armored catfish (Pterygoplichthys anisitsi) after short-term exposure to diesel oil, pure biodiesel and biodiesel blends.

    PubMed

    Nogueira, Lílian; da Silva, Danilo Grünig Humberto; Oliveira, Thiago Yukio Kikuchi; da Rosa, Joel Maurício Correa; Felício, Andréia Arantes; de Almeida, Eduardo Alves

    2013-09-01

    Biodiesel fuel is gradually replacing petroleum-based diesel oil use. Despite the biodiesel being considered friendlier to the environment, little is known about its effects in aquatic organisms. In this work we evaluated whether biodiesel exposure can affect oxidative stress parameters and biotransformation enzymes in armored catfish (Pterygoplichthys anisitsi, Loricariidae), a South American endemic species. Thus, fish were exposed for 2 and 7d to 0.01mLL(-1) and 0.1mLL(-1) of pure diesel, pure biodiesel (B100) and blends of diesel with 5% (B5) and 20% (B20) biodiesel. Lipid peroxidation (malondialdehyde) levels and the activities of the enzymes glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase were measured in liver and gills. Also, DNA damage (8-oxo-7, 8-dihydro-2'-deoxyguanosine) levels in gills and 7-ethoxyresorufin-O-deethylase activity in liver were assessed. Pure diesel, B5 and B20 blends changed most of the enzymes tested and in some cases, B5 and B20 induced a higher enzyme activity than pure diesel. Antioxidant system activation in P. anisitsi was effective to counteract reactive oxygen species effects, since DNA damage and lipid peroxidation levels were maintained at basal levels after all treatments. However, fish gills exposed to B20 and B100 presented increased lipid peroxidation. Despite biodiesel being more biodegradable fuel that emits less greenhouse gases, the increased lipid peroxidation showed that biofuel and its blends also represent hazards to aquatic biota.

  13. Toxic effects upon exposure to polycyclic aromatic hydrocarbon (chrysene) in scallop Chlamys farreri during the reproduction period.

    PubMed

    Xiu, Meng; Pan, Luqing; Jin, Qian

    2016-06-01

    This study aims to investigate potential toxic effects of chrysene (CHR) on mature scallop Chlamys farreri during the reproduction period, using indicators of antioxidant defences and oxidative stress. Scallops were exposed to 0.2, 0.8 and 3.2μg/L waterborne CHR for 21 days, at day 10 scallops were induced to spawn. At days 1, 3, 6, 10, 11, 15 and 21, aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin-O-deethylase (EROD), glutathione-s-transferase (GST), glutathione (GSH), superoxide dismutase (SOD), lipid peroxidation (LPO), protein carbonyl (PC) and DNA strand breaks in digestive glands were examined by separately analysing male and female scallops. During the pre-spawn period, Levels of enzymatic activities and oxidative stress were all induced by the exposure to CHR for females and males. GST activity presented a good time- and dose-dependent relationship only in males, and GSH content showed a dose-dependent manner in both sexes. During the post-spawn period, different trends were observed, while PC contents maintained growth in time- and dose-dependent manner. Overall, males were more sensitive than females to CHR exposure in enzyme activities, and correspondingly, females suffered from more serious oxidative damages. Both GSH and PC contents seemed to be potential biomarkers for PAH exposure. These results will offer the information on toxicity of CHR in this species, and ensure the influence of gender and reproductive status on PAH detoxification metabolism.

  14. Determination of the CYP1A-inducing potential of single substances, mixtures and extracts of samples in the micro-EROD assay with H4IIE cells.

    PubMed

    Schiwy, Andreas; Brinkmann, Markus; Thiem, Ines; Guder, Gabriele; Winkens, Kerstin; Eichbaum, Kathrin; Nüßer, Leonie; Thalmann, Beat; Buchinger, Sebastian; Reifferscheid, Georg; Seiler, Thomas-Benjamin; Thoms, Brigitte; Hollert, Henner

    2015-11-01

    This protocol describes a quantitative and robust 96-well-plate-reader-based assay for the measurement of ethoxyresorufin-O-deethylase (EROD) activity using the rat hepatoma cell line H4IIE. The assay can be used to determine the cytochrome P450 subfamily 1A (CYP1A)-inducing potential of single substances, as well as of mixtures and extracts of samples. It is based on the aryl hydrocarbon receptor (AhR)-mediated induction of cytochrome P450 enzymes (subfamily 1A) in cells after exposure to dioxins and dioxin-like compounds. One enzymatic reaction catalyzed by CYP1A is the deethylation of the exogenous substrate 7-ethoxyresorufin to the fluorescent product resorufin, which is measured as EROD activity in the assay. The CYP1A-inducing potential of a sample can be reliably quantified by comparing the EROD activity with the concentration-response curve of the standard substance 2,3,7,8-tetrachlorodibenzo-p-dioxin, which can be detected at concentrations down to the picogram per liter range. A researcher familiar with the procedure can process up to 160 samples with four wells each within 3 d. The series described uses four plates with three concentrations per sample, which can be easily scaled to accommodate different sample sizes. PMID:26448361

  15. Effect of chronic exposure to ozone and nitric acid on cytochrome P450 monooxygenase system of rat lung and liver

    SciTech Connect

    Sindhu, R.K.; Mautz, W.J.; Ichiro Fujita, Nai-San Wang; Yutaka, Kikkawa

    1996-03-08

    Male F344/N rats were exposed to 0.15ppm ozone (O{sub 3}) and 50{mu}g/m{sup 3} nitric acid (HNO{sub 3}) vapor alone and in combination for 4h/day 3days/week for a total of 40 weeks. Exposure to HNO{sub 3} vapor alone caused a significant increase of 7-ethoxyresorufin O-deethylase (EROD) activity in the hepatic microsomes (p{le}0.05). Monoclonal cytochrome P450 aA1/1A2 antibody-precipitable EROD activity in the hepatic microsomes was increased by 59% (p{le}0.01) and 40T (p{le}0.05), respectively, in the HNO{sub 3} vapor and {sub 3}+HNO{sub 3} vapor groups. In the pulmonary microsomes, benzphetamine N-demethylase (BPND) activity was increased by 72% (p{le}0.01), 85% (p{le}0.01) and decreased by 15% (p{le}0.01), respectively, by exposure to O{sub 3}, O{sub 3}+HNO{sub 3} and HNO{sub 3} vapor, but was unaffected in the hepatic microsomes.

  16. Biochemical responses in the gills of Meretrix meretrix after exposure to treated municipal effluent.

    PubMed

    Wan, Ru; Meng, Fanping; Fu, Wenchao; Wang, Qun; Su, Enping

    2015-01-01

    The biochemical effects in marine bivalves exposed to increasing concentrations of treated municipal effluent (TME), as discharged into receiving marine waters, are investigated. The effluent was collected from a municipal sewage treatment plant (STP) in Qingdao (China). Meretrix meretrix were exposed to effluent volume ratio (EVR, ratio of effluent volume accounted for tailwater seawater mixture) 0%, 1%, 5%, 10%, and 20% (v/v) TME for 15 days and the following biochemical responses in gills were measured: (1) the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH) content, and lipid peroxidation levels of malondialdehyde (MDA), as oxidative stress biomarkers; (2) the activity of 7-ethoxyresorufin O-deethylase (EROD) and gluthathione S-transferase (GST), as phase I and phase II conjugation enzymes, respectively; (3) acetylcholinesterase (AChE), as a biomarker of neurotoxicity, and (4) metallothioneins (MTs), as proteins strongly induced by heavy metals. Most of the biochemical indices present high and significant variation frequency (above 50%). There is enhancement in the antioxidant enzymes, EROD, GST, AChE, and MTs, as well as consumption of GSH. The current experimental results suggest that effluent with concentrations less than 20% (v/v) do not cause lipid peroxidation damage. This implies that the activated defense is sufficient to protect the bivalves' gill tissues from cytotoxicity produced by the effluent. Furthermore, GSH, GPx, MTs, and GR are suitable, and sufficiently sensitive, biomarkers to indicate the pollution levels in marine environments receiving such effluent. PMID:25450918

  17. Nitrite-induced enhancement of toxicity of phenanthrene in fish and its implications for coastal waters

    NASA Astrophysics Data System (ADS)

    Shailaja, M. S.; Rodrigues, A.

    2003-04-01

    Coastal areas are prone to varying degrees of anthropogenic chemical contamination. In many coastal environments experiencing reducing conditions in the water column, nitrite is produced as a result of denitrification. With a view to determining the effect of a natural stress such as the presence of nitrite in water on the xenobiotic metabolism in fish, the euryhaline cichlid Oreochromis mossambicus was exposed for up to 9 days to environmentally relevant concentrations of water-borne nitrite and phenanthrene, a polycyclic aromatic hydrocarbon. Analyses of different biomarkers in the treated fish indicated significant increase in the metabolism of phenanthrene as a result of exposure to nitrite. For example, the activity of the biotransformation enzyme measured as 7-ethoxyresorufin- O-deethylase activity was, in the presence of 1 μM nitrite, nearly twice that produced by phenanthrene alone. Similarly, biliary fixed fluorescence values reflecting phenanthrene and its metabolites were rendered 1.7 times higher when exposed simultaneously to nitrite. Contact with nitrite and phenanthrene together also led to severe hepatic damage with possible cell death as inferred from the large enhancement in sorbitol dehydrogenase activity in the serum and reduced liver somatic index.

  18. Use of SPMDs and rainbow trout to examine CYP1A1 induction in creosote contaminated mesocosms

    SciTech Connect

    Whyte, J.J.; Karrow, N.; Magdic, S.; Dixon, D.G.; Bols, N.C.; Solomon, K.

    1995-12-31

    Lipid-containing semipermeable membrane devices (SPMDs) and rainbow trout (Oncorhynchus mykiss) were exposed to creosote-dosed mesocosms for a 28 day period. Creosote concentration and exposure period were varied and examined for effects on hepatic and cardiac 7-ethoxyresorufin-O-deethylase (EROD) activity in trout. SPMD uptake rates and selectivity for specific polycyclic aromatic hydrocarbons (PAHs) were also studied. Concentrations of PAHs in SPMDs were compared to PAH concentrations determined in tissues of exposed rainbow trout in order to examine effects of metabolism on PAH burden in living systems. In addition, subfractions of SPMD dialysates and rainbow trout tissue extracts were exposed to the RTL-W1 rainbow trout liver cell line and the H4IIE rat hepatoma cell line. These bioassays were used to measure 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent concentrations (TECs) of the liver residues as indicated by their relative abilities to induce cytochrome P4501A1 (CYP1A1), measured as EROD activity. This estimates the accumulation by fish of compounds that act through the Ah receptor and are potentially toxic. Hepatic and cardiac EROD activity in the trout were significantly elevated in ponds dosed with creosote as compared to the control pond (ANOVA, p < 0.05) and rose with increasing creosote concentration.

  19. The detoxification process, bioaccumulation and damage effect in juvenile white shrimp Litopenaeus vannamei exposed to chrysene.

    PubMed

    Ren, Xianyun; Pan, Luqing; Wang, Lin

    2015-04-01

    This study aimed to evaluate the effect of chrysene (CHR) on detoxification enzymes, bioaccumulation and effect of CHR on biomolecule damage in different organs of the juvenile white shrimp Litopenaeus vannamei. In this study, juvenile white shrimp L. vannamei were exposed to CHR for 21 days at four different concentrations as 0, 0.3, 2.1 and 14.7 μg/L. Results showed that CHR bioaccumulation increased rapidly at first then reached a plateau. The activities of aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin O-deethylase (EROD), epoxide hydrolase (EH), glutathione-S-transferase (GST), sulfotransferase (SULT) and uridinediphosphate glucuronyltransferase (UGT) were induced and then became stable gradually. Moreover, 2.1 and 14.7 μg/L CHR treatments increased activity of superoxide dismutase (SOD) in gills and hepatopancreas, while total antioxidant capacity (T-AOC) and GSH/GSSG were suppressed after CHR exposure. Additionally, lipid peroxidation (LPO) levels, protein carbonyl (PC) contents and DNA damage were induced throughout the exposure period, and different trends were detected with time of exposure. Overall, these novel findings of CHR bioaccumulation and resulted toxicity demonstrate that CHR could affect the physical status of L. vannamei. This study will form a solid basis for a realistic extrapolation scientific data for aquaculture water monitoring and food security.

  20. Effects of chronic dietary exposure to a low-dose of Malathion, Aroclor-1254 and 3-methylcholanthrene on three biomarkers in male mice.

    PubMed

    Hackenberger, B K; Jarić, Davorka; Hackenberger, Dubravka; Stepić, Sandra

    2010-12-01

    The aim of this research was to examine the applicability of some chronic toxicological tests in the determination of exposure to xenobiotics present in concentrations below No Observed Adverse Effect Level (NOAEL) and below the detection limit of analytical instruments. In the present experiment tested chemicals (Malathion, Aroclor-1254 and 3-methylcholanthrene (3-MC)) were mixed with wheat grains and given to male mice as feed over a period of 12 months. 7-ethoxyresorufin-O-deethylase (EROD) activity with the 3-MC and Aroclor-1254 treatments reached the peak at 9th month of exposure (26.7 and 42.4 pmol⁻¹ mg(prot)-⁻¹, respectively), while malathion did not have significant influence. Glutathione (GSH) level depletion was highest after three months of exposure. Unexpectedly, acetylcholinesterase (AChE) activity increased after treatment with malathion, an organophosphorous insecticide. In conclusion, low-level concentrations chronically administered exert certain effects on the levels of selected enzymes, e.g. biomarkers.

  1. BDE-99, but not BDE-47, is a transient aryl hydrocarbon receptor agonist in zebrafish liver cells.

    PubMed

    Yang, Jie; Zhu, Jinyong; Chan, King Ming

    2016-08-15

    Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting chemicals that affect the environment and the health of humans and wildlife. In this study, the zebrafish liver (ZFL) cell line was used in vitro to investigate two major PBDE contaminants: 2, 2', 4, 4', 5-pentabromodiphenyl ether (BDE-99) and 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47). BDE-99 was found to significantly induce cytochrome P450 (CYP1A), uridine diphosphate glucuronosyl transferase 1 family a, b (ugt1ab), 7-ethoxyresorufin-O-deethylase activity and an aryl hydrocarbon receptor (Ahr) dependent xenobiotic response element luciferase reporter system, confirming the Ahr-mediated activation of CYP1A by BDE-99. The time-course effect indicated that the role of BDE-99 in Ahr-mediated signaling is likely to be transient and highly dependent on the ability of BDE-99 to induce CYP1A and ugt1ab, and presumably its metabolism. BDE-99 also exhibited a significant dose-response effect on a developed zebrafish pregnane X receptor luciferase reporter gene system. However, the other abundant contaminant under study, BDE-47, did not exhibit the above effects. Together, these results indicated that the molecular mechanism of PBDEs induced in ZFL cells is a chemically specific process that differs between members of the PBDE family. CYP1A induction derived by BDE-99 warrants further risk assessment as the humans, wildlife and environment are exposed to a complex mixture including dioxin-like compounds and carcinogenic compounds. PMID:27343407

  2. Molecular responses as indicators of marine pollution: DNA damage and enzyme induction in Limanda limanda and Asterias rubens

    SciTech Connect

    Everaarts, J.M.; Sleiderink, H.M.; Besten, P.J. den

    1994-12-01

    During a survey from 26 August through 13 September 1991, specimens of the flatfish, Limanda limanda (dab), and the asteroid echinoderm, Asterias rubens (seastar), were collected at sampling locations along transacts radiating into the North Sea from the coastal zone of The Netherlands. In homogenates of liver tissue from male dab and the digestive gland (pyloric caeca) of female seastar, DNA damage (strand breaks) and induction of the cytochrome P450-dependent monooxygenase system (MO) were determined. Areas could be described with significantly increased percentages of strand breaks (lower integrity) both in dab and seastar. However, enhanced DNA strand breaks did not correspond with contamination gradients, expressed as concentrations of polychlorinated biphenyls (PCBs) or polyaromatic hydrocarbons. MO enzyme induction in the hepatic 13,000g fraction of male dab, measured as 7-ethoxyresorufin-O-deethylase activity, was significantly enhanced in response to low ambient temperatures. Some evidence was found for the facilitation of benzo[a]pyrene hydroxylase activity expressing the enzyme induction in the microsomal fraction of pyloric caeca of seastars, at increasing PCB concentrations. DNA integrity and enzyme induction elucidate the physiologic status and might be indicative for ambient impairment within restricted areas, and not necessarily related to the presence of anthropogenic or xeno-biotic substances. 27 refs., 5 figs., 1 tab.

  3. BDE-99, but not BDE-47, is a transient aryl hydrocarbon receptor agonist in zebrafish liver cells.

    PubMed

    Yang, Jie; Zhu, Jinyong; Chan, King Ming

    2016-08-15

    Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting chemicals that affect the environment and the health of humans and wildlife. In this study, the zebrafish liver (ZFL) cell line was used in vitro to investigate two major PBDE contaminants: 2, 2', 4, 4', 5-pentabromodiphenyl ether (BDE-99) and 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47). BDE-99 was found to significantly induce cytochrome P450 (CYP1A), uridine diphosphate glucuronosyl transferase 1 family a, b (ugt1ab), 7-ethoxyresorufin-O-deethylase activity and an aryl hydrocarbon receptor (Ahr) dependent xenobiotic response element luciferase reporter system, confirming the Ahr-mediated activation of CYP1A by BDE-99. The time-course effect indicated that the role of BDE-99 in Ahr-mediated signaling is likely to be transient and highly dependent on the ability of BDE-99 to induce CYP1A and ugt1ab, and presumably its metabolism. BDE-99 also exhibited a significant dose-response effect on a developed zebrafish pregnane X receptor luciferase reporter gene system. However, the other abundant contaminant under study, BDE-47, did not exhibit the above effects. Together, these results indicated that the molecular mechanism of PBDEs induced in ZFL cells is a chemically specific process that differs between members of the PBDE family. CYP1A induction derived by BDE-99 warrants further risk assessment as the humans, wildlife and environment are exposed to a complex mixture including dioxin-like compounds and carcinogenic compounds.

  4. Hepatic P450 enzyme activity, tissue morphology and histology of mink (Mustela vison) exposed to polychlorinated dibenzofurans.

    PubMed

    Moore, Jeremy N; Newsted, John L; Hecker, Markus; Zwiernik, Matthew J; Fitzgerald, Scott D; Kay, Denise P; Zhang, Xiaowei; Higley, Eric B; Aylward, Lesa L; Beckett, Kerrie J; Budinsky, Robert A; Bursian, Steven J; Giesy, John P

    2009-08-01

    Dose- and time-dependent effects of environmentally relevant concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ) of 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of these two congeners on hepatic P450 enzyme activity and tissue morphology, including jaw histology, of adult ranch mink were determined under controlled conditions. Adult female ranch mink were fed either TCDF (0.98, 3.8, or 20 ng TEQ(TCDF)/kg bw/day) or PeCDF (0.62, 2.2, or 9.5 ng TEQ(PeCDF)/kg bw/day), or a mixture of TCDF and PeCDF (4.1 ng TEQ(TCDF)/kg bw/day and 2.8 ng TEQ(PeCDF)/kg bw/day, respectively) for 180 days. Doses used in this study were approximately eight times greater than those reported in a parallel field study. Activities of the cytochrome P450 1A enzymes, ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-deethylase (MROD) were significantly greater in livers of mink exposed to TCDF, PeCDF, and a mixture of the two congeners; however, there were no significant histological or morphological effects observed. It was determined that EROD and MROD activity can be used as sensitive biomarkers of exposure to PeCDF and TCDF in adult female mink; however, under the conditions of this study, the response of EROD/MROD induction occurred at doses that were less than those required to cause histological or morphological changes. PMID:19458992

  5. Seasonal effect on biomarkers of exposure to petroleum hydrocarbons in fish from Kuwait's marine area.

    PubMed

    Beg, M U; Al-Subiai, S N; Al-Jandal, N; Butt, S A; Beg, K R; Al-Husaini, M

    2015-11-30

    The aquatic biota of the Arabian Gulf deals with exposure to chronic oil pollution, several constituents of which cause induction of Cytochrome P450 1A that serves as a biomarker of AhR ligand exposure. In this study, fluorescent aromatic compounds (FACs) in bile and 7-ethoxyresorufin-o-deethylase (EROD) catalytic activity were determined as a measure of exposure biomarkers in two fish species, yellow fin seabream (Acanthopagrus latus) and tonguesole (Cynoglossus arel) captured from Kuwait Bay and outside the Bay area. FACs in fish bile determined by using fixed-wavelength fluorescence (FF) showed high fluorescence ratios between FF290/335 and FF380/430 indicating predominant exposure to low molecular weight, naphthalene-rich petroleum products (375±91.0 pg ml(-1)). Exposures to benzo(a)pyrene-type high-molecular weight polycyclic aromatic hydrocarbons (PAHs) originating from burnt fuel were also present in appreciable concentration in the bile. The ratio of petrogenic to pyrogenic hydrocarbon was twofold higher in winter compared to summer months in both species. Seasonal effect on EROD was significant in tonguesole in Auha site (P<0.05); whereas seabream resisted seasonal change. Tonguesole is considered to be a suitable bioindicator of oil pollution in Kuwait Bay area.

  6. CYP 450 enzyme induction by chronic oral musk xylene in adult and developing rats.

    PubMed

    Suter-Eichenberger, R; Boelsterli, U A; Conscience-Egli, M; Lichtensteiger, W; Schlumpf, M

    1999-12-20

    Developmental and adult toxicity of musk xylene was studied in Long Evans (LE) rats fed with chow containing musk xylene (MX) in food pellets in concentrations of 1 mg, 10 mg, 33 mg, 100 mg and 1000 mg MX per 1 kg chow corresponding to a daily intake of 0.07-0.08 mg MX/kg up to 70-80 mg MX/kg body weight. Adult male and female rats were MX exposed for a minimum of 10 weeks before mating. Exposure continued throughout pregnancy, birth and lactation. The effects of MX on CYP1A1/1A2 were studied in liver microsomes by EROD (7-ethoxyresorufin-o-deethylase) for CYP1A1 and by MROD (methoxyresorufin-o-demethylase) for CYP1A2 activity and by Western blotting. MX induced these enzymes dose dependently in adult and developing rats at PN (postnatal day) 1 and 14. The lowest effective maternal dose was 2-3 mg MX/kg/day. Western blot data of CYP2B and CYP3A indicated the induction of both P450 enzyme proteins in developing rats at PN 14 at the higher dose of 70-80 mg MX/kg/day. In contrast, upon high MX exposure CYP2B but not CYP3A was found to be induced in adult first generation male and female rats, indicating differential sensitivity to MX in development.

  7. Multi-biomarker responses in fishes from two typical marine aquaculture regions of South China.

    PubMed

    He, Xiuting; Nie, Xiangping; Yang, Yufeng; Liu, Xinyu; Pan, Debo; Cheng, Zhang; Liang, Ximei

    2012-11-01

    The impact of typical pollutants upon the fish-farming was assessed by use of a battery of biomarkers in two typical marine aquaculture regions in South China. Biotransformation parameters including 7-ethoxyresorufin-O-deethylase (EROD), aminopyrine N-demethylase (APND), erythromycin N-demethylase (ERND), glutathione-S-transferase (GST) and Malondialdehyde (MDA) were measured in five cultured fish species. Pollutants such as polycyclic aromatic hydrocarbon (PAHs), organochlorinated compounds (OCs), heavy metals and antibiotics (quinolones and sulfonamides) in sediments were characterized. Higher pollutant residue levels were observed in Dapeng Cove. EROD, APND and ERND activities were lower in fish from Dapeng Cove compared with fish from Hailing Island, while it is just on the contrary for GST and MDA. ERND, APND and GST showed sensitivity corresponding to different pollutants. Small fish species seemed to exhibit more sensitive to pollutants. The study further supports usefulness of multi-biomarker approach considering multiple species to define the effects of anthropogenic inputs in marine aquaculture systems.

  8. Seasonal effect on biomarkers of exposure to petroleum hydrocarbons in fish from Kuwait's marine area.

    PubMed

    Beg, M U; Al-Subiai, S N; Al-Jandal, N; Butt, S A; Beg, K R; Al-Husaini, M

    2015-11-30

    The aquatic biota of the Arabian Gulf deals with exposure to chronic oil pollution, several constituents of which cause induction of Cytochrome P450 1A that serves as a biomarker of AhR ligand exposure. In this study, fluorescent aromatic compounds (FACs) in bile and 7-ethoxyresorufin-o-deethylase (EROD) catalytic activity were determined as a measure of exposure biomarkers in two fish species, yellow fin seabream (Acanthopagrus latus) and tonguesole (Cynoglossus arel) captured from Kuwait Bay and outside the Bay area. FACs in fish bile determined by using fixed-wavelength fluorescence (FF) showed high fluorescence ratios between FF290/335 and FF380/430 indicating predominant exposure to low molecular weight, naphthalene-rich petroleum products (375±91.0 pg ml(-1)). Exposures to benzo(a)pyrene-type high-molecular weight polycyclic aromatic hydrocarbons (PAHs) originating from burnt fuel were also present in appreciable concentration in the bile. The ratio of petrogenic to pyrogenic hydrocarbon was twofold higher in winter compared to summer months in both species. Seasonal effect on EROD was significant in tonguesole in Auha site (P<0.05); whereas seabream resisted seasonal change. Tonguesole is considered to be a suitable bioindicator of oil pollution in Kuwait Bay area. PMID:26409815

  9. Chemical residues and biochemical responses in wild and cultured European sea bass (Dicentrarchus labrax L.)

    SciTech Connect

    Fernandes, Denise; Porte, Cinta . E-mail: cpvqam@cid.csic.es; Bebianno, Maria Joao

    2007-02-15

    Cultured and wild sea bass (Dicentrarchus labrax) from the Arade Estuary were sampled in summer and winter and the degree of exposure to metals and polycyclic aromatic hydrocarbons (PAHs) assessed, together with some biochemical responses against those and other pollutants. The highest levels of copper (up to 997 {mu}g g{sup -1} dry weight) and cadmium (up to 4.22 {mu}g g{sup -1} dry weight) were detected in the liver and kidney of cultured specimens, whereas the highest exposure to PAHs was observed in wild fish. Significant alterations in some biochemical markers were detected and associated to pollutant exposure. Thus, metallothionein concentrations were higher in the tissues of cultured fish and positively correlated with metal residues. The activity 7-ethoxyresorufin O-deethylase ranged from 28 pmol/min/mg protein in cultured fish to 83 pmol/min/mg protein in wild fish collected near a marina area. Cultured fish and wild fish from the marina area had depressed acetylcholinesterase in muscle tissue and a parasitic infection in the gonads. The obtained results support the usefulness of the combined use of chemical and biochemical markers to assess the impact of anthropogenic pollutants in both wild and cultured fish.

  10. Biomarkers in the freshwater bivalve Corbicula fluminea confined downstream a domestic landfill leachate discharge.

    PubMed

    de Oliveira, Luciana Fernandes; Santos, Caroline; Dos Reis Martinez, Claudia Bueno

    2016-07-01

    Landfills represent a severe environmental problem mainly due to the generation of leachates, and this study aimed to evaluate sublethal effects of a domestic landfill leachate in the freshwater bivalve Corbicula fluminea. Clams were submitted to in situ tests along a stream, at three sites, representing increasing distances from the leachate discharge (Pq1, Pq2, and Pq3), for 1, 5, and 15 days. The following biomarkers were analyzed in the gills and digestive glands: 7-ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) activities, multixenobiotic resistance mechanism (MXR), total antioxidant capacity (TAC), reactive oxygen species (ROS), and lipid peroxidation (LPO). Metallothionein (MT) content was determined in the gills and DNA damage in hemocytes. The mortality rate of animals during in situ tests was reduced as the distance from the leachate discharge source increased. On the other hand, biomarker results showed sublethal effects on C. fluminea confined at all sites of PqS. GST, TAC, ROS, and DNA damage were the most significant biomarkers for this species and should be considered for future monitoring and assessment of freshwater environments located in landfill areas. PMID:27040540

  11. Antimutagenic activity of spearmint.

    PubMed

    Yu, Tian-Wei; Xu, Meirong; Dashwood, Roderick H

    2004-01-01

    The antimutagenic activity of spearmint (Mentha spicata), a popular food flavoring agent, was studied in the Salmonella assay. Spearmint leaves were brewed in hot water for 5 min at concentrations up to 5% (w/v), and the water extracts were tested against the direct-acting mutagens 4-nitro-1,2-phenylenediamine (NPD) and 2-hydroxyamino-3-methyl-3H-imidazo[4,5-f]quinoline (N-OH-IQ) using Salmonella typhimurium strain TA98. Nontoxic concentrations of spearmint extract inhibited the mutagenic activity of N-OH-IQ in a concentration-dependent fashion, but had no effect against NPD. These experiments by design focused on the water extract consumed commonly as an herbal tea, but chloroform and methanol extracts of spearmint also possessed antimutagenic activity against N-OH-IQ. Water extract of spearmint inhibited the mutagenic activity of the parent compound, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), in the presence of rat liver S9; however, the concentration for 50% inhibition (IC50) against IQ was approximately 10-fold higher than in assays with N-OH-IQ minus S9. At concentrations similar to those used in the Salmonella assays, spearmint extract inhibited two of the major enzymes that play a role in the metabolic activation of IQ, namely, cytochromes P4501A1 and 1A2, based on ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase assays in vitro. In vivo, rats were given spearmint water extract (2%; w/v) as the sole source of drinking fluid before, during, and after 2-week treatment with IQ; colonic aberrant crypt foci were inhibited significantly at 8 weeks (P < 0.05, compared with rats given IQ alone). Collectively, these findings suggest that spearmint tea protects against IQ and possibly other heterocyclic amines through inhibition of carcinogen activation and via direct effects on the activated metabolite(s).

  12. Biomarker responses in the bivalve Chlamys farreri to the water-soluble fraction of crude oil

    NASA Astrophysics Data System (ADS)

    Jiang, Fenghua; Zhang, Li; Yang, Baijuan; Zheng, Li; Sun, Chengjun

    2015-07-01

    To investigate the effect of the water soluble fraction of crude oil (WSF) on marine bivalves, the scallop Chlamys farreri was exposed to three WSF concentrations (0.18 mg/L, 0.32 mg/L, and 0.51 mg/L, respectively) in seawater. Petroleum hydrocarbon contents in scallops and a suite of enzymes [7-Ethoxyresorufin-O-deethylase (EROD), aryl hydrocarbon hydroxylase (AHH), glutathione S-transferase (GST), and glutathione peroxidase (GPx)] in gills and digestive glands were monitored over 10 days. The results revealed that WSF affected the activity of the four enzymes in the gills and digestive glands. EROD activity in the gills was significantly induced in most individuals of the three test groups, while in the digestive gland it was significantly induced in the low-concentration group within 4 days but was inhibited in the middle- and high-concentration groups on days 1, 4, and 10. AHH activity in the gills of all treatment groups was significantly induced on day 1. In the digestive gland, AHH activity was induced in most individuals from the treatment groups. In all treatment groups, GST activity was significantly inhibited from days 2 to 10 in the gills and was induced after day 4 in the digestive gland. GPx activity in the gills was significantly inhibited throughout the exposure period in all treatment groups. There was no overall significant difference in GPx activity in the digestive gland between the control and treatment groups. Our results also revealed that petroleum hydrocarbon concentrations in the tissues increased linearly with exposure time. EROD activity in the digestive gland and GST and GPx activity in the gill tissue were negatively correlated with petroleum hydrocarbon body burden. These enzymes play important roles in detoxification and can act as potential biomarkers for monitoring petroleum hydrocarbon contaminants in the marine environment.

  13. Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats

    PubMed Central

    Hassan, Mostafa

    2016-01-01

    Erectile dysfunction (ED) is a major health problem and is mainly associated with the persistent inability of men to maintain sufficient erection for satisfactory sexual performance. Millions of men are using sildenafil, vardenafil, and/or tadalafil for ED treatment. Cytochrome P450s (CYPs) play a central role in the metabolism of a wide range of xenobiotics as well as endogenous compounds. Susceptibility of individuals to the adverse effects of different drugs is mainly dependent on the expression of CYPs proteins. Therefore, changes in activities of phase I drug-metabolising enzymes [arylhydrocarbon hydroxylase (AHH), dimethylnitrosamine N-demethylase (DMN-dI), 7-ethoxycoumarin-O-deethylase (ECOD), and ethoxyresorufin-O-deethylase ((EROD)] and the protein expression of different CYPs isozymes (CYP1A2, CYP2E1, CYP2B1/2, CYP3A4, CYP2C23, and CYP2C6) were determined after treatment of male rats with either low or high doses of sildenafil (Viagra), tadalafil (Cialis), and/or vardenafil (Levitra) for 3 weeks. The present study showed that low doses of tadalafil and vardenafil increased DMN-dI activity by 32 and 23%, respectively. On the other hand, high doses of tadalafil, vardenafil, and sildenafil decreased such activity by 50, 56, and 52%, respectively. In addition, low doses of tadalafil and vardenafil induced the protein expression of CYP2E1. On the other hand, high doses of either tadalafil or sildenafil were more potent inhibitors to CYP2E1 expression than vardenafil. Moreover, low doses of both vardenafil and sildenafil markedly increased AHH activity by 162 and 247%, respectively, whereas high doses of tadalafil, vardenafil, and sildenafil inhibited such activity by 36, 49, and 57% and inhibited the EROD activity by 39, 49, and 33%, respectively. Low and high doses of tadalafil, vardenafil, and sildenafil inhibited the activity of NADPH-cytochrome c reductase as well as its protein expression. In addition, such drugs inhibited the expression of CYP B1/2 along

  14. Bioconcentration, metabolism and effects of diphenhydramine on behavioral and biochemical markers in crucian carp (Carassius auratus).

    PubMed

    Xie, Zhengxin; Lu, Guanghua; Hou, Kangkang; Qin, Donghong; Yan, Zhenhua; Chen, Wei

    2016-02-15

    Diphenhydramine (DPH), an antihistamine used to alleviate human allergies, is widespread in aquatic environments. However, little is known about the biochemical and behavioral effects of DPH on non-target aquatic animals. In the present study, the tissue distribution, bioconcentration, metabolism, biochemical and behavioral effects were investigated in crucian carp (Carassius auratus) exposed to various concentrations of DPH (0.84, 4.23, 21.7 and 112 μg L(-1)) for 7d. DPH can accumulate in crucian carp, and high concentrations have been observed in the liver and brain with maximum bioconcentration factors of 148 and 81.6, respectively. A portion of the absorbed DPH was metabolized by the crucian carp to N-demethyl DPH and N,N-didemethyl DPH via N-demethylation. Direct fluorimetric assay was employed to assess metabolic activity, while oxidative stress and neurotransmission biomarkers were determined by Diagnostic Reagent Kits. DPH was found to increase hepatic 7-ethoxyresorufin O-deethylase activity in crucian carp with maximal induction of 119%. Concerning the oxidative stress status, DPH significantly inhibited superoxide dismutase (SOD, 37-58%) and glutathione S-transferase (GST, 43-65%) activities and led to a significant increase in malondialdehyde (MDA, 67-140%) levels and catalase (CAT, 38-143%) and glutathione peroxidase (GPx, 39-189%) activities in fish liver. Brain acetylcholinesterase activity was also induced in DPH-exposed crucian carp with maximal induction of 174%. In addition, shoaling was significantly enhanced, while swimming activity and feeding rates were markedly suppressed at DPH concentrations equal to or higher than 21.7 μg L(-1). Furthermore, significant correlations were found between oxidative stress biomarkers (SOD, CAT, GPx, GST and MDA) and behavioral parameters. Collectively, our results confirmed that DPH can accumulate and be metabolized in fish and exert a negative effect at different levels of biological organization. PMID

  15. Newspapers and newspaper ink contain agonists for the ah receptor.

    PubMed

    Bohonowych, Jessica E S; Zhao, Bin; Timme-Laragy, Alicia; Jung, Dawoon; Di Giulio, Richard T; Denison, Michael S

    2008-04-01

    Ligand-dependent activation of the aryl hydrocarbon receptor (AhR) pathway leads to a diverse array of biological and toxicological effects. The best-studied ligands for the AhR include polycyclic and halogenated aromatic hydrocarbons, the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, as new AhR ligands are identified and characterized, their structural and physiochemical diversity continues to expand. Our identification of AhR agonists in crude extracts from diverse materials raises questions as to the magnitude and extent of human exposure to AhR ligands through normal daily activities. We have found that solvent extracts of newspapers from countries around the world stimulate the AhR signaling pathway. AhR agonist activity was observed for dimethyl sulfoxide (DMSO), ethanol, and water extracts of printed newspaper, unprinted virgin paper, and black printing ink, where activation of luciferase reporter gene expression was transient, suggesting that the AhR active chemical(s) was metabolically labile. DMSO and ethanol extracts also stimulated AhR transformation and DNA binding, and also competed with [(3)H]TCDD for binding to the AhR. In addition, DMSO extracts of printed newspaper induced cytochrome P450 1A associated 7-ethoxyresorufin-O-deethylase activity in zebrafish embryos in vivo. Although the responsible bioactive chemical(s) remain to be identified, our results demonstrate that newspapers and printing ink contain relatively potent metabolically labile agonists of the AhR. Given the large amount of recycling and reprocessing of newspapers throughout the world, release of these easily extractable AhR agonists into the environment should be examined and their potential effects on aquatic organisms assessed. PMID:18203687

  16. Gasoline effects on biotransformation and antioxidant defenses of the freshwater fish Prochilodus lineatus.

    PubMed

    Simonato, Juliana D; Fernandes, Marisa Narciso; Martinez, Cláudia B R

    2011-08-01

    Biochemical biomarkers in the Neotropical freshwater fish Prochilodus lineatus were evaluated following acute exposures to the water-soluble fraction of gasoline (WSFG). Fish were exposed to the WSFG diluted to 5% in water (WSFG group) or only to water (Control group) for 6, 24 and 96 h and the gills and liver were removed for the biochemical analyses. Fish exposed to WSFG for 24 and 96 h showed significant increase in the activity of 7-ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST) both in liver and gills, pointing toward phase I and phase II biotransformation of the compounds present in the WSFG. The results also indicated the activation of antioxidant defenses in both the liver and gills after fish exposure to WSFG. The liver showed activation of catalase (CAT) and glutathione peroxidase (GPx) after 96 h exposure. An increase in hepatic content of reduced glutathione (GSH) together with decreased glutathione reductase (GR) activity was observed after 24 and 96 h of exposure to WSFG. In the gills, only catalase (CAT) activity augmented after 6 and 24 h of exposure and GSH content increased after 24 h of WSFG exposure. However, in both the organs, activation of the antioxidant defenses was not enough to prevent oxidative damage since they showed lipid peroxidation (LPO) at one of the experimental times: the liver after 6 h and the gills only after 96 h of exposure to WSFG. This may indicate better adaptation of the liver to longer exposures, starting from 24 h. As the gills are the first organ to be exposed to xenobiotics, the antioxidant defenses were triggered immediately upon exposure to WSFG and were able to prevent the occurrence of LPO during the initial times.

  17. Gender differences in detoxification metabolism of polycyclic aromatic hydrocarbon (chrysene) in scallop Chlamys farreri during the reproduction period.

    PubMed

    Xiu, Meng; Pan, Luqing; Jin, Qian; Miao, Jingjing

    2015-04-01

    This study aims to investigate the effects of chrysene (CHR) on biotransformation and detoxification responses of mature scallop Chlamys farreri during the reproduction period. Scallops were exposed to 0.2, 0.8 and 3.2 μg/L CHR for 21 days; at day 10 scallops were induced to spawn. At days 1, 3, 6, 10, 11, 15 and 21, enzymatic activities of 7-ethoxyresorufin O-deethylase (EROD) and glutathione-s-transferase (GST), related mRNA expression levels of CYP1A1, GST-pi and P-glycoprotein (P-gp) in digestive glands and CHR bioaccumulation in tissues were examined by separately analyzing male and female scallops. During the pre-spawn period, CHR concentrations of the treated groups in tissues except the hemolymph increased rapidly. Levels of enzymatic activities and related gene expressions were all induced by the exposure to CHR for females and males. GST activity and GST-pi mRNA expression showed a good time- and dose-dependent relationship only in males, and P-gp mRNA expression exhibited a dose-dependent manner in both sexes. During the post-spawn period, spawning caused significant reductions of bioaccumulation in tissues but the gill and hemolymph. Enzymatic activities and related gene expressions were for females significantly depressed at day 21 at 0.8 or 3.2 μg/L CHR. Overall, females accumulated more CHR than males, while males were more sensitive than females to CHR exposure in gene expressions and enzyme activities. P-gp mRNA expression seemed to be a potential biomarker for PAH exposure. These results will offer the information on CHR biotransformation in this species, and ensure the influence of gender and reproductive status on PAH detoxification metabolism.

  18. Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol.

    PubMed

    Yamaori, Satoshi; Okushima, Yoshimi; Yamamoto, Ikuo; Watanabe, Kazuhito

    2014-05-25

    We previously demonstrated that cannabidiol (CBD) was a potent mechanism-based inhibitor of human cytochrome P450 1A1 (CYP1A1). However, the moiety of CBD that contributes to the potent mechanism-based inhibition of human CYP1A1 remains unknown. Thus, the effects of compounds structurally related to CBD on CYP1A1 activity were examined with recombinant human CYP1A1 in order to characterize the structural requirements for potent inactivation by CBD. When preincubated in the presence of NADPH for 20min, olivetol, which corresponds to the pentylresorcinol moiety of CBD, enhanced the inhibition of the 7-ethoxyresorufin O-deethylase activity of CYP1A1. In contrast, d-limonene, which corresponds to the terpene moiety of CBD, failed to inhibit CYP1A1 activity in a metabolism-dependent manner. Pentylbenzene, which lacks two free phenolic hydroxyl groups, also did not enhance CYP1A1 inhibition. On the other hand, preincubation of the CBD-2'-monomethyl ether (CBDM) and CBD-2',6'-dimethyl ether (CBDD) enhanced the inhibition of CYP1A1 activity. Inhibition by cannabidivarin (CBDV), which possessed a propyl side chain, was strongly potentiated by its preincubation. Orcinol, which has a methyl group, augmented CYP1A1 inhibition, whereas its derivative without an alkyl side chain, resorcinol, did not exhibit any metabolism-dependent inhibition. The preincubation of CBD-hydroxyquinone did not markedly enhance CYP1A1 inhibition. We further confirmed that olivetol, CBDM, CBDD, CBDV, and orcinol, as well as CBD (kinact=0.215min(-1)), inactivated CYP1A1 activity; their kinact values were 0.154, 0.0638, 0.0643, 0.226, and 0.0353min(-1), respectively. These results suggest that the methylresorcinol structure in CBD may have structurally important roles in the inactivation of CYP1A1.

  19. MFO activity and contaminant analysis of overwintering juvenile chinook salmon in the Fraser River

    SciTech Connect

    Wilson, J.; Glickman, B.; Addison, R.; Gordon, R.; Martens, D.

    1995-12-31

    Various organic contaminants, including some PAHs, PCBs and chlorinated dibenzo-p-dioxins and furans, induce liver cytochrome P450 1A1 (CYP 1A1) and its associated enzyme activity (ethoxyresorufin-O-deethylase; EROD). In this study, analysis of carcasses for dibenzo-p-dioxins, dibenzofurans and PCBs were compared to liver MFO activity. Juvenile chinook salmon (Oncorhynchus tshawytscha) were sampled in March, 1994 at a reference site on the Nechako River free from the influence of industrial activity and at sites near Prince George, Stoner, Longbar and Soda Creek on the Fraser River, and on the Thompson River. Fish from the Nechako site had the lowest MFO activities, accompanied by the lowest whole body dioxin and furan concentrations. Fish from Longbar, Soda Creek and the Thompson River had the highest MFO activities. Fish from Prince George contained the highest dioxin concentrations, but furans and mono-ortho substituted PCBs were highest at the Soda Creek and Thompson sites. MFO activity correlated most strongly with PCB concentrations. The results of this study suggest that liver MFO activity in O. tshawytscha could be employed as one biological index of environmental quality in the Fraser River.

  20. Methoxychlor suppresses the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible CYP1A1 expression in murine Hepa-1c1c7 cells.

    PubMed

    Han, Eun Hee; Jeong, Tae Cheon; Jeong, Hye Gwang

    2007-08-01

    Methoxychlor (MXC) is a pesticide that was developed as a replacement for dichlorodiphenyltrichloroethane (DDT). The influence of MXC on CYP1A1 expression or the functions of mouse hepatoma Hepa-1clc7 remain unclear. Cultured Hepa-1c1c7 cells were treated with MXC with or without 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to assess the role of MXC on CYP1A1 expression. MXC alone did not affect CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. In contrast, TCDD-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and MXC in a concentration-dependent manner. Treatment with ICI 182.780, an estrogen-receptor antagonist, did not affect the suppressive effects of MXC on TCDD-inducible EROD activity. TCDD-inducible CYP1A1 mRNA levels were markedly suppressed upon treatment with TCDD and MXC, and this is consistent with their effects on EROD activity. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and an electrophoretic mobility shift assay revealed that MXC reduced the transformation of the aryl hydrocarbons (Ah) receptor to a form capable of specifically binding to the DRE sequence in the promoter region of the CYP1A1 gene. These results suggest that the downregulation of CYP1A1 gene expression by MXC in Hepa-1c1c7 cells might be an antagonism of the DRE binding potential of the nuclear Ah receptor but is not mediated through the estradiol receptor.

  1. Cytochrome P450, acetylcholinesterase and gonadal histology for evaluating contaminant exposure levels in fishes from a highly eutrophic brackish ecosystem: the Orbetello Lagoon, Italy.

    PubMed

    Corsi, I; Mariottini, M; Sensini, C; Lancini, L; Focardi, S

    2003-02-01

    Biochemical markers and ovarian histology were investigated in prespawning females of grass goby (Zosterisessor ophiocephalus) and grey mullet (Mugil cephalus) collected, respectively, in late spring and summer 2000 in four sites of a highly eutrophic brackish ecosystem of central Italy, the Orbetello Lagoon. Exposure to chlorinated and aromatic hydrocarbons was evaluated in fish livers by the somatic liver index (SLI) and by measuring 7-ethoxyresorufin-O-deethylase (EROD) and benzo(a)pyrene monooxygenase (BaPMO) activities. Acetylcholinesterase (AChE) activity was measured in brain and gills to evaluate exposure to organophosphates (OPs) and carbamates (CBs). The gonad somatic index (GSI) was used to confirm ovarian maturation and ovarian histology was investigated as a potential biomarker for environmental effects. Samples from the Western Basin, near a sewage treatment plant (STP) off the town of Orbetello, showed higher SLI values and higher EROD and BaPMO activities than those collected from the Ansedonia Canal (AC) in the Eastern Basin (p<0.05) and respect to those from reference sites: the Albegna River (AR) Delta for grass goby and the Nassa Canal (NC), connected with the sea, for grey mullet both located in the Western Basin as well. Low brain AChE activity was observed in both species from the reference sites (AR and NC) in association with the presence of anomalies in developing oocytes: unexpectedly small in grass goby and irregular disintegrated cytoplasm in grey mullet. The results indicate that the Western Basin is more polluted than the Eastern Basin particularly in the Orbetello where the sewage treatment plant may be a source of aromatic and chlorinated compounds while the Albegna River and the Nassa Canal may be sources of OPs and CBs. PMID:12586116

  2. Cytochrome P4501A indices as biomarkers of contaminant exposure: A field study with plaice and flounder

    SciTech Connect

    Eggens, M.; Opperhuizen, A.

    1995-12-31

    Samples of two flatfish species, flounder (Platichthys flesus) and plaice (Pleurnectus platessa), were collected during August/September 1991 and May/June 1992 in the southern North Sea. The induction of hepatic cytochrome P4501A1 (CYP1A) in both species was examined, when exposed to environmental PCBs and PAHs. CYP1A was measured by a semi-quantitative ELISA technique and by the activity of its catalyst, 7-ethoxyresorufin O-deethylase (EROD). In plaice, both hepatic CYP1 protein level and EROD activity were significantly higher at offshore sampling locations than at coastal locations, by a factor of 1.5 to 2. In flounder, which were only collected at coastal locations, the range of values of EROD activity was much greater than in plaice, but the range in CYP1A protein content was comparable in both species. multiple regression analysis of data from plaice and flounder did not show any significant correlation between CYP1A indices, water temperature and contaminant concentrations in fish tissues. CYP1A indices also appeared to be unrelated to food type, as determined by visual screening of fish intestines. It is concluded that the induction of CYP1A in plaice and flounder from the southern North Sea is not related in a simple manner to exposure to PCBs and PAHs. From the point of view-of use as a biomarker, the measurement of CYP1A protein level and EROD activity in plaice and flounder from the open North Sea cannot be applied straightforwardly for monitoring exposure to PCBs and/or PAHs.

  3. CYP1A andother biomarker responses to effluents from a textile mill in the Volta River (Ghana) using caged tilapia (Oreochromis niloticus) andsediment-exposed mudfish (Clarias anguillaris).

    PubMed

    Gadagbui, B K; Goksrøyr, A

    1996-01-01

    Abstract The ecotoxicological effects of a textile mill effluent were investigated by caging tilapia (Oreochromis niloticus) in the Volta River, Ghana, andby exposing mudfish (Clarias anguillaris) to sediment collected from the same river. Tilapia were caged for 3 weeks at three locations (0.6, 4, and8 km) downstream from the effluent outlet. Mudfish were exposed in the laboratory for 2 weeks to sediment collected from the vicinity of the effluent outlet and8 km downstream. Upstream reference locations 2 km (tilapia) and10.2 km (mudfish) were included. Liver cytochrome P4501A (CYP1A) monooxygenase activity (measured as activity of 7-ethoxyresorufin O-deethylase, EROD, andCYP1A protein level) andtwo conjugation enzymes, UDP-glucuronosyl transferase (UDP-GT) andglutathione Stransferase (GST), were analysed. A distance-related decrease in EROD activity andCYP1A protein level was observed. EROD activity was 21-fold higher in tilapia caged at the site nearest the effluent outlet and25-fold higher in mudfish exposed to sediment collected from the vicinity of the outlet, compared with the respective reference values. UDP-GT andGST levels increased significantly by 70 and27%, respectively, in tilapia while the respective levels in mudfish were 73 and28%, compared with reference values. The results clearly indicate that the textile mill effluent contains some highly potent inducers of biotransformation enzymes. This first assessment of the biological effects of organic pollutants in the Volta River demonstrates the utility of the CYP1A system as a valuable early warning biomarker of industrial effluents andalso as a biomarker to detect exposure of aquatic resources to environmental chemical contamination in tropical waters. PMID:23888992

  4. CYP1A andother biomarker responses to effluents from a textile mill in the Volta River (Ghana) using caged tilapia (Oreochromis niloticus) andsediment-exposed mudfish (Clarias anguillaris).

    PubMed

    Gadagbui, B K; Goksrøyr, A

    1996-01-01

    Abstract The ecotoxicological effects of a textile mill effluent were investigated by caging tilapia (Oreochromis niloticus) in the Volta River, Ghana, andby exposing mudfish (Clarias anguillaris) to sediment collected from the same river. Tilapia were caged for 3 weeks at three locations (0.6, 4, and8 km) downstream from the effluent outlet. Mudfish were exposed in the laboratory for 2 weeks to sediment collected from the vicinity of the effluent outlet and8 km downstream. Upstream reference locations 2 km (tilapia) and10.2 km (mudfish) were included. Liver cytochrome P4501A (CYP1A) monooxygenase activity (measured as activity of 7-ethoxyresorufin O-deethylase, EROD, andCYP1A protein level) andtwo conjugation enzymes, UDP-glucuronosyl transferase (UDP-GT) andglutathione Stransferase (GST), were analysed. A distance-related decrease in EROD activity andCYP1A protein level was observed. EROD activity was 21-fold higher in tilapia caged at the site nearest the effluent outlet and25-fold higher in mudfish exposed to sediment collected from the vicinity of the outlet, compared with the respective reference values. UDP-GT andGST levels increased significantly by 70 and27%, respectively, in tilapia while the respective levels in mudfish were 73 and28%, compared with reference values. The results clearly indicate that the textile mill effluent contains some highly potent inducers of biotransformation enzymes. This first assessment of the biological effects of organic pollutants in the Volta River demonstrates the utility of the CYP1A system as a valuable early warning biomarker of industrial effluents andalso as a biomarker to detect exposure of aquatic resources to environmental chemical contamination in tropical waters.

  5. Combined chemical and toxicological long-term monitoring for AhR agonists with SPMD-based virtual organisms in drinking water Danjiangkou Reservoir, China.

    PubMed

    Wang, Jingxian; Song, Guoqiang; Li, Aimin; Henkelmann, Bernhard; Pfister, Gerd; Tong, Anthony Z; Schramm, Karl-Werner

    2014-08-01

    SPMD-based virtual organisms (VOs) were employed for time-integrating, long-term sampling combined biological and chemical analyses for exposure assessment of hydrophobic organic pollutants (HOPs) in a drinking water reservoir, China. The SPMDs were deployed at four and five sites in the Danjiangkou (DJK) reservoir over two periods of 26 and 31 d to sequester the hydrophobic contaminants in water. The chosen bioassay response for the extracts of the SPMDs, the induction of 7-ethoxyresorufin-o-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The known aryl hydrocarbon receptor (AhR) agonists PAHs and PCBs were analyzed by HRGC/HRMS instrument. The cause-effect relationship between the observed AhR activities and chemical concentrations of detected AhR agonists was examined. The results show that the extracts from the SPMD samples could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) was not correlated with the bioassay-derived TCDD equivalent (TEQbio). The known AhR agonists could only account for 2-10% of the observed AhR responses among which the contribution of PCBs could almost be neglected. Unidentified AhR-active compounds represented a greater proportion of the TCDD equivalent (TCDD-EQ) in SPMD samples from DJK. Based on the first assessment, the VO followed by the combination of chemical and biological analyses emerges as a resource efficient water monitoring device in ecotoxicological assessment for toxicologically relevant compounds which are readily available for uptake by resident aquatic biota in drinking water resources. PMID:24548649

  6. Modulation of 17β-estradiol induced estrogenic responses in male goldfish (Carassius auratus) by benzo[a]pyrene and ketoconazole.

    PubMed

    Yan, Zhenhua; Lu, Guanghua; Ye, Qiuxia; Liu, Jianchao

    2016-05-01

    The aquatic environment is challenged with complex mixtures of chemicals that may interact biochemically with each other in non-target aquatic organisms through a combination of actions, resulting in unpredictable mixture toxicity. This study focuses on the interactive effects of chemicals, including benzo(a)pyrene (BaP) and ketoconazole (KCZ), on 17β-estradiol (E2)-induced estrogenic responses in male goldfish (Carassius auratus). The possible interactions between BaP or KCZ and E2 were investigated on the expression of cytochromeP4501A (CYP1A, biotransformation enzyme) and on its corresponding catalytic activity 7-ethoxyresorufin-O-deethylase (EROD activity), as well as on the expression of CYP19 (steroidogenic enzyme) and E2 bioaccumulation in liver. Exposure to E2 caused a significant increase in estrogenic responses corresponding with the E2 bioaccumulation. When comparing results to the E2 exposure group, co-exposure to BaP resulted in an increase in the cyp1a mRNA expression and its corresponding EROD activity and a marked decrease in the E2 bioaccumulation, but the expression of aromatase was not altered. Conversely, co-treatment with KCZ significantly suppressed the E2-modulated expression of metabolism and synthesis enzymes, which were accompanied by an increase in the E2 bioaccumulation. These data suggest that the modulation of E2-induced estrogenic responses by BaP and KCZ were correlated to the alterations of E2 bioaccumulation in goldfish, leading to a combination of changes in the capacity of biotransformation and steroidogenesis. The complex interactions between chemicals with different modes of actions highlight the need for caution in determining the safety of combined pollution in the aquatic environment. PMID:26825522

  7. Assessment of domestic landfill leachate toxicity to the Asian clam Corbicula fluminea via biomarkers.

    PubMed

    Oliveira, Luciana F; Silva, Sandra M C P; Martinez, Claudia B R

    2014-05-01

    In order to evaluate the effects of domestic landfill leachate to bivalves Corbicula fluminea, clams were exposed to different leachate concentrations (v/v): 2, 3, 6 and 10 percent, corresponding to dilutions observed along a stream that receives this effluent, or only to clean water for comparisons. After 5 and 15 days of exposure the activity of the biotransformation enzymes 7-ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST), the multixenobiotic resistance mechanism (MXR) and lipid peroxidation (LPO) in gills and digestive gland and metallothionein (MT) content in gills were evaluated. Differences in biomarkers responses were observed between gills and digestive gland, except for MXR that decreased in both tissues of clams exposed to 6 percent for 5 days. EROD activity in gills was reduced in all leachate concentrations after 5 days and only in 2 percent after 15 days exposure, while an EROD increase was observed in digestive gland after 15 days exposure to 6 percent. GST activity increased only in the gills of clams exposed to 10 percent for 5 days. LPO varied between tissues and different conditions. A significant increase in LPO was observed in the gills, after 5 days exposure to 2 and 6 percent, and in digestive gland after 5 and 15 days exposure to 2 and 3 percent. MT content in the gills increased after 15 days exposure to 2 percent. In conclusion, different leachate concentrations tested here caused biochemical changes in C. fluminea, but due to the observed variability in biomarkers responses among leachate concentrations, it was difficult to determine patterns or thresholds concentrations. PMID:24561242

  8. Survey of receiving-water environmental impacts associated with discharges from pulp mills; 4: Bioassay-derived 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent concentration in white sucker (Catostomus commersoni) in relation to biochemical indicators of impact

    SciTech Connect

    Heuvel, M.R. van den; Dixon, D.G. . Dept. of Biology); Munkittrick, K.R.; Servos, M.R. . Great Lakes Lab. for Fisheries and Aquatic Sciences); Van Der Kraak, G.J.; McMaster, M.E. . Dept. of Zoology); Portt, C.B. )

    1994-07-01

    The H411E rat hepatoma bioassay was used to measure 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent concentrations (TECs) in livers of white sucker (Catostomus commersoni) collected downstream from eight Ontario pulp mills and five reference sites. Subsamples of liver were also chemically analyzed for dioxins and furans. Bioassay-derived TECs were compared with TECs calculated from chemical residues using toxic equivalency factors (TEFs) specifically generated for the H411E cell line. This indicated that the bioassay-derived TECs could be accounted for largely by the additive effect of the dioxin and furan congeners. Seven of the eight examined mills had significantly higher TECs than the corresponding reference locations. The bioassay-derived TECs were highest at mills that used kraft pulping and chlorine bleaching. Although lower than the kraft mills, the thermomechanical (TMP) and sulfite mills also had higher TECs than the adjacent preference locations. The TECs were compared with hepatic 7-ethoxyresorufin-O-deethylase activity (EROD), as well as with concentrations of the plasma steroid hormones 17[beta]-estradiol, 11-ketotestosterone, and testosterone. Significant correlations were found between EROD activity and TECs in both male and female white sucker. The correlation for males was stronger than that for females. Some of the variability in this relationship for females could be explained by a multivariate regression that added 17[beta]-estradiol to the analysis; a strongly negative relationship between 17[beta]-estradiol and EROD activity was superimposed on the positive EROD-TEC relationship. No significant correlations were found between TECs and 11-ketotestosterone in males, 17[beta]-estradiol in females, and gonadosomatic indexes in either sex. There were significant negative correlations between TECs and testosterone in both sexes.

  9. Combined chemical and toxicological long-term monitoring for AhR agonists with SPMD-based virtual organisms in drinking water Danjiangkou Reservoir, China.

    PubMed

    Wang, Jingxian; Song, Guoqiang; Li, Aimin; Henkelmann, Bernhard; Pfister, Gerd; Tong, Anthony Z; Schramm, Karl-Werner

    2014-08-01

    SPMD-based virtual organisms (VOs) were employed for time-integrating, long-term sampling combined biological and chemical analyses for exposure assessment of hydrophobic organic pollutants (HOPs) in a drinking water reservoir, China. The SPMDs were deployed at four and five sites in the Danjiangkou (DJK) reservoir over two periods of 26 and 31 d to sequester the hydrophobic contaminants in water. The chosen bioassay response for the extracts of the SPMDs, the induction of 7-ethoxyresorufin-o-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The known aryl hydrocarbon receptor (AhR) agonists PAHs and PCBs were analyzed by HRGC/HRMS instrument. The cause-effect relationship between the observed AhR activities and chemical concentrations of detected AhR agonists was examined. The results show that the extracts from the SPMD samples could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) was not correlated with the bioassay-derived TCDD equivalent (TEQbio). The known AhR agonists could only account for 2-10% of the observed AhR responses among which the contribution of PCBs could almost be neglected. Unidentified AhR-active compounds represented a greater proportion of the TCDD equivalent (TCDD-EQ) in SPMD samples from DJK. Based on the first assessment, the VO followed by the combination of chemical and biological analyses emerges as a resource efficient water monitoring device in ecotoxicological assessment for toxicologically relevant compounds which are readily available for uptake by resident aquatic biota in drinking water resources.

  10. Hepatic cytochrome P4501A induction in dab (Limanda limanda) after oral dosing with the polychlorinated biphenyl mixture Clophen A40

    SciTech Connect

    Sleiderink, H.M.; Everaarts, J.M.; Boon, J.P.; Goksoeyr, A.

    1995-04-01

    The flatfish dab (Limanda limanda) serves as an indicator species in pollution monitoring programs in the North Sea. The present study investigated the induction response of the monooxygenase system and haematological changes in female dab after multiple administrations of a technical mixture of polychlorinated biphenyls (PCBs). Mature female dab were dosed with 1 mg of the PCB mixture Clophen A40 (Clo A40) in sunflower oil every 6 weeks, with a maximum of three doses per fish. In all PCB-administered groups, levels of cytochrome P4501A (CYPIA) protein, measured with a semi-quantitative ELISA method, and 7-ethoxyresorufin O-deethylase (EROD) activity showed a three- to ninefold induction 14 d after dosing compared with control groups, smaller but also significant increases were observed in total cytochrome P450 ({Sigma} P450) levels. Although the PCB concentrations and the corresponding toxic equivalent (TEQ) value in muscle tissue still increased after administration of the second and third dose of Clo A40, maximum responses of the EROD activity were already reached after the first dose at a TEQ value for chlorinated biphenyls (CB-TEQ) of 2 ng/g lipid. The PCB patterns of liver and muscle tissue of female dab from the central North Sea were found to be virtually identical. Hence, the use of PCB concentrations in muscle as a qualitative model for changes in the liver appears legitimate. Haemoglobin concentrations were elevated after the third dose of Clo A40, whereas haematocrit values and the mean corpuscular haemoglobin concentration (MCHC) between treated and control groups did not differ.

  11. Tumor promoters as inhibitors of apoptosis in rat hepatocytes.

    PubMed

    Schrenk, D; Schmitz, H-J; Bohnenberger, S; Wagner, B; Wörner, W

    2004-04-01

    Multistage carcinogenesis in rat liver is widely used as an experimental model for the study of the critical events in tumor promotion. After an initial treatment with a genotoxic liver carcinogen ('initiation'), subsequent application of certain non-genotoxic agents can lead to the clonal expansion of putative preneoplastic cells ('promotion'). Obviously, the expansion of these clones is correlated with an increased occurrence of benign and malignant liver tumors at later time points. Since both proliferation and apoptosis were reported to be enhanced in putative preneoplastic liver foci, inhibition of apoptosis was suggested to play a critical role in tumor promotion. In rat hepatocytes in primary culture, the liver tumor promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibited apoptosis initiated by treatment of the cultures with UV irradiation but did not affect apoptosis in non-irradiated cultures. The suppression of apoptosis with TCDD coincided with an attenuated increase of the tumor suppressor protein p53 observed upon UV irradiation. Furthermore, TCDD treatment resulted in a marked hyperphosphorylation of p53. The fact that almost identical concentration-response curves were obtained for the phosphorylation of p53 and the induction of cytochrome P450(CYP)1A-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity indicates that p53 phosphorylation after TCDD treatment is mediated by the aryl hydrocarbon receptor (AhR) signaling cascade. With tumor-promoting 'non-dioxin-like' polychlorinated biphenyls inhibition of UV-induced apoptosis was also observed. A comparative study investigating the effects of various concentrations did not reveal, however, a clear correlation between the suppression of apoptosis and the induction of CYP2B-catalyzed 7-pentoxyresorufin O-dealkylase (PROD) activity. In summary, inhibition of UV-induced apoptosis with liver tumor promoters is observed in rat hepatocytes in culture. Hyperphosphorylation of key proteins of

  12. Integrative assessment of biomarker responses in pale chub (Zacco platypus) exposed to copper and benzo[a]pyrene.

    PubMed

    Kim, Woo-Keun; Lee, Sung-Kyu; Choi, Kyungho; Jung, Jinho

    2013-06-01

    Multi-level biomarker responses (molecular/biochemical and histological/physiological levels) were studied to assess the sublethal toxicities of copper (Cu: 1.25, 5, and 20μg/L) and benzo[a]pyrene (BaP: 0.5, 5, and 50μg/L) induced in the freshwater pale chub Zacco platypus. Except for the kidney tissues when exposed to 20μg Cu/L, no significant differences were observed at the histological or physiological levels among the treatment groups. However, various molecular and biochemical responses were observed in Z. platypus, and these responses primarily depended on exposure time. Upon Cu exposure, both DNA single-strand breaks (COMET) and metallothionein (MT) concentration significantly increased after 4 days, whereas there were no significant changes after 14 days of exposure. Both 4 and 14 days of BaP exposure induced significant increases in COMET and 7-ethoxyresorufin-O-deethylase (EROD) activity, but there was no significant difference between them. Additionally, both Cu and BaP induced acetylcholinesterase (AChE) activity only after 14 days of exposure. The current findings demonstrate that the differences in the responses of MT and EROD are associated with each chemical's particular mode of action. Biomarker responses at the molecular and biochemical levels were quantized in terms of the integrated biomarker response (IBR) index to compare the toxicities of Cu and BaP. The IBR values were well correlated with the concentrations of Cu and BaP, and the correlations were enhanced at 4 days of exposure (r(2)=0.849 and 0.945, respectively) compared with 14 days (r(2)=0. 412 and 0.634, respectively). These results suggest that the IBR index may be a useful tool for the integrative quantification of the molecular and biochemical biomarker responses in a short-term exposure to Cu and BaP. PMID:23478165

  13. Effect of butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes.

    PubMed

    Price, R J; Scott, M P; Giddings, A M; Walters, D G; Stierum, R H; Meredith, C; Lake, B G

    2008-06-01

    1. The objective of this study was to investigate the effects of four food chemicals, namely butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG) and thiabendazole (TB), on cytochrome P450 (CYP) forms in cultured human hepatocytes. 2. Treatment of human hepatocytes for 72 h with 2-200 microM TB produced concentration-dependent increases in CYP1A2, CYP2B6 and CYP3A4 mRNA levels, whereas treatment with BHT increased CYP2B6 and CYP3A4 mRNA levels. CYP1A2, CYP2B6 and CYP3A4 mRNA levels were induced around 48-, 21- and 9-fold, respectively, by 200 microM TB, with CYP2B6 and CYP 3A4 mRNA levels being induced around 12- and 7-fold, respectively, by 200 microM BHT. 3. In contrast, the treatment of human hepatocytes for 72 h with PG and CC had little or no effect on CYP mRNA levels. 4. The treatment of human hepatocytes with TB also induced CYP1A-dependent 7-ethoxyresorufin O-deethylase activity, whereas BHT induced CYP3A-dependent testosterone 6beta-hydroxylase activity. 5. In summary, the results demonstrate that TB is a mixed inducer of CYP forms in human hepatocytes inducing CYP1A, CYP2B and CYP3A forms, whereas BHT is an inducer of CYP2B and CYP3A forms.

  14. Biochemical and Transcriptomic Effects of Herring Gull Egg Extracts from Variably Contaminated Colonies of the Laurentian Great Lakes in Chicken Hepatocytes.

    PubMed

    Crump, Doug; Williams, Kim L; Chiu, Suzanne; Letcher, Robert J; Periard, Luke; Kennedy, Sean W

    2015-08-18

    Determining the effects of complex mixtures of environmental contaminants poses many challenges within the field of ecotoxicology. In this study, graded concentrations of herring gull egg extracts, collected from five Great Lakes breeding colonies with variable burdens of organohalogen contaminants (OHCs), were administered to chicken embryonic hepatocytes to determine effects on 7-ethoxyresorufin-O-deethylase (EROD) activity, porphyrin accumulation, and mRNA expression. EROD activity and porphyrin accumulation permitted the ranking of colonies based on the efficacy of eliciting an aryl hydrocarbon receptor-mediated response. An avian ToxChip polymerase chain reaction (PCR) array provided more exhaustive coverage in terms of potential toxicity pathways being affected, including xenobiotic and lipid metabolism and the thyroid hormone pathway. Herring gull eggs from Channel Shelter Island (CHSH, Lake Huron) and Gull Island (GULL, Lake Michigan) had among the highest OHC burdens, and extracts elicited a biochemical and transcriptomic response greater than that of extracts from the other three, less polluted colonies. For example, EROD EC50 values and porphyrin ECthreshold values were lower for CHSH and GULL extracts than for the other colonies. Extracts from CHSH and GULL altered 15 and 13 of 27 genes on the PCR array compared to no more than eight genes for the less contaminated sites. The combination of a well-established avian in vitro assay, two well-characterized biochemical assays, and the avian ToxChip PCR array permitted the geographical discrimination of variably contaminated herring gull eggs from the Great Lakes. Such high-throughput assays show potential promise as cost-effective tools for determining toxic potencies of complex mixtures in the environment.

  15. Water exposure assessment of aryl hydrocarbon receptor agonists in Three Gorges Reservoir, China using SPMD-based virtual organisms.

    PubMed

    Wang, Jingxian; Bernhöft, Silke; Pfister, Gerd; Schramm, Karl-Werner

    2014-10-15

    SPMD-based virtual organisms (VOs) were deployed at five to eight sites in the Three Gorges Reservoir (TGR), China for five periods in 2008, 2009 and 2011. The water exposure of aryl hydrocarbon receptor (AhR) agonists was assessed by the VOs. The chosen bioassay response for the extracts of the VOs, the induction of 7-ethoxyresorufin-O-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The results show that the extracts from the VOs could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) accounted for <11% of the observed AhR responses (TEQbio). Unidentified AhR-active compounds represented a greater proportion of the TCDD equivalent in VOs from TGR. High TEQbio value in diluted extract and low TEQbio in concentrated extract of the same sample was observed suggesting potential non-additive effects in the mixture. The levels of AhR agonists in VOs from upstream TGR were in general higher than those from downstream reservoir, indicating urbanization effect on AhR agonist pollution. The temporal variation showed that levels of AhR agonists in 2009 and 2011 were higher than those in 2008, and the potential non-additive effects in the area close to the dam were also obviously higher in 2009 and 2011 than in 2008, indicating big changes in the composition of pollutants in the area after water level reached a maximum of 175 m. Although the aqueous concentration of AhR agonists of 0.8-4.8 pg TCDDL(-1) in TGR was not alarming, the tendency of accumulating high concentration of AhR agonists in VO lipid and existence of possible synergism or antagonism in the water may exhibit a potential hazard to local biota being exposed to AhR agonists.

  16. Polycyclic aromatic hydrocarbon exposure in Steller's eiders (Polysticta stelleri) and Harlequin ducks (Histronicus histronicus) in the eastern Aleutian Islands, Alaska, USA.

    PubMed

    Miles, A Keith; Flint, Paul L; Trust, Kimberley A; Ricca, Mark A; Spring, Sarah E; Arrieta, Daniel E; Hollmen, Tuula; Wilson, Barry W

    2007-12-01

    Seaducks may be affected by harmful levels of polycyclic aromatic hydrocarbons (PAHs) at seaports near the Arctic. As an indicator of exposure to PAHs, we measured hepatic enzyme 7-ethoxyresorufin-O-deethylase activity (EROD) to determine cytochrome P4501A induction in Steller's eiders (Polysticta stelleri) and Harlequin ducks (Histronicus histronicus) from Unalaska, Popof, and Unga Islands (AK, USA) in 2002 and 2003. We measured PAHs and organic contaminants in seaduck prey samples and polychlorinated biphenyl congeners in seaduck blood plasma to determine any relationship to EROD. Using Akaike's information criterion, species and site differences best explained EROD patterns: Activity was higher in Harlequin ducks than in Steller's eiders and higher at industrial than at nonindustrial sites. Site-specific concentrations of PAHs in blue mussels ([Mytilus trossilus] seaduck prey; PAH concentrations higher at Dutch Harbor, Unalaska, than at other sites) also was important in defining EROD patterns. Organochlorine compounds rarely were detected in prey samples. No relationship was found between polychlorinated biphenyl congeners in avian blood and EROD, which further supported inferences derived from Akaike's information criterion. Congeners were highest in seaducks from a nonindustrial or reference site, contrary to PAH patterns. To assist in interpreting the field study, 15 captive Steller's eiders were dosed with a PAH known to induce cytochrome P4501A. Dosed, captive Steller's eiders had definitive induction, but results indicated that wild Steller's eiders were exposed to PAHs or other inducing compounds at levels greater than those used in laboratory studies. Concentrations of PAHs in blue mussels at or near Dutch Harbor (approximately 1,180-5,980 ng/g) approached those found at highly contaminated sites (approximately 4,100-7,500 ng/g).

  17. Impact of chemical exposure on the fish Pomatoschistus microps Krøyer (1838) in estuaries of the Portuguese Northwest coast.

    PubMed

    Monteiro, M; Quintaneiro, C; Nogueira, A J A; Morgado, F; Soares, A M V M; Guilhermino, L

    2007-01-01

    Juveniles of the estuarine fish Pomatoschistus microps were collected from autumn 2001 to summer 2002 in five stations along the Portuguese Northwest coast with different types and/or levels of environmental contamination: two reference sites with low levels of contamination (R1 and R2) and three differently impacted areas with higher levels of contamination. UI is located in an estuary under the influence of urban and industrial effluents, AA in a channel that receives intensive agriculture run-off and IE in a highly impacted industrial area. The activity of the enzymes acetylcholinesterase (AChE), lactate dehydrogenase (LDH), 7-ethoxyresorufin O-deethylase (EROD) and glutathione S-transferases (GST) were used as environmental biomarkers on P. microps. A significant seasonality effect on all the enzymatic activities was found, lower levels being registered in winter and spring on AChE, in autumn on LDH, and in winter on GST and EROD. The battery of biomarkers used was capable of discriminating sites with different types and/or levels of contamination, R1 and UI being the highest discriminated (91.7% and 66.7%, respectively). At R1 significantly lower levels of AChE and LDH were found, and EROD was significantly inducted at UI. Furthermore, IE presented higher levels of GST, and R2 and AA an inhibition of AChE in winter and spring. The results indicated that the battery of biomarkers used in this study seems to be a useful tool to distinguish between different types of environmental contamination in estuarine systems, and that P. microps is a suitable species to be used as bioindicator.

  18. Polycyclic aromatic hydrocarbon exposure in Steller's eiders (Polysticta stelleri) and harlequin ducks (Histronicus histronicus) in the Eastern Aleutian Islands, Alaska, USA

    USGS Publications Warehouse

    Miles, A.K.; Flint, P.L.; Trust, K.A.; Ricca, M.A.; Spring, S.E.; Arrieta, D.E.; Hollmen, T.; Wilson, B.W.

    2007-01-01

    Seaducks may be affected by harmful levels of polycyclic aromatic hydrocarbons (PAHs) at seaports near the Arctic. As an indicator of exposure to PAHs, we measured hepatic enzyme 7-ethoxyresorufin-O-deethylase activity (EROD) to determine cytochrome P4501A induction in Steller's eiders (Polysticta stelleri) and Harlequin ducks (Histronicus histronicus) from Unalaska, Popof, and Unga Islands (AK, USA) in 2002 and 2003. We measured PAHs and organic contaminants in seaduck prey samples and polychlorinated biphenyl congeners in seaduck blood plasma to determine any relationship to EROD. Using Akaike's information criterion, species and site differences best explained EROD patterns: Activity was higher in Harlequin ducks than in Steller's eiders and higher at industrial than at nonindustrial sites. Site-specific concentrations of PAHs in blue mussels ([Mytilus trossilus] seaduck prey; PAH concentrations higher at Dutch Harbor, Unalaska, than at other sites) also was important in defining EROD patterns. Organochlorine compounds rarely were detected in prey samples. No relationship was found between polychlorinated biphenyl congeners in avian blood and EROD, which further supported inferences derived from Akaike's information criterion. Congeners were highest in seaducks from a nonindustrial or reference site, contrary to PAH patterns. To assist in interpreting the field study, 15 captive Steller's eiders were dosed with a PAH known to induce cytochrome P4501A. Dosed, captive Steller's eiders had definitive induction, but results indicated that wild Steller's eiders were exposed to PAHs or other inducing compounds at levels greater than those used in laboratory studies. Concentrations of PAHs in blue mussels at or near Dutch Harbor (∼1,180–5,980 ng/g) approached those found at highly contaminated sites (∼4,100–7,500 ng/g).

  19. Water exposure assessment of aryl hydrocarbon receptor agonists in Three Gorges Reservoir, China using SPMD-based virtual organisms.

    PubMed

    Wang, Jingxian; Bernhöft, Silke; Pfister, Gerd; Schramm, Karl-Werner

    2014-10-15

    SPMD-based virtual organisms (VOs) were deployed at five to eight sites in the Three Gorges Reservoir (TGR), China for five periods in 2008, 2009 and 2011. The water exposure of aryl hydrocarbon receptor (AhR) agonists was assessed by the VOs. The chosen bioassay response for the extracts of the VOs, the induction of 7-ethoxyresorufin-O-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The results show that the extracts from the VOs could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) accounted for <11% of the observed AhR responses (TEQbio). Unidentified AhR-active compounds represented a greater proportion of the TCDD equivalent in VOs from TGR. High TEQbio value in diluted extract and low TEQbio in concentrated extract of the same sample was observed suggesting potential non-additive effects in the mixture. The levels of AhR agonists in VOs from upstream TGR were in general higher than those from downstream reservoir, indicating urbanization effect on AhR agonist pollution. The temporal variation showed that levels of AhR agonists in 2009 and 2011 were higher than those in 2008, and the potential non-additive effects in the area close to the dam were also obviously higher in 2009 and 2011 than in 2008, indicating big changes in the composition of pollutants in the area after water level reached a maximum of 175 m. Although the aqueous concentration of AhR agonists of 0.8-4.8 pg TCDDL(-1) in TGR was not alarming, the tendency of accumulating high concentration of AhR agonists in VO lipid and existence of possible synergism or antagonism in the water may exhibit a potential hazard to local biota being exposed to AhR agonists. PMID:25058931

  20. Microsomal enzyme activities in beluga whales from the Mackenzie River Delta, Northwest Territories, Canada

    SciTech Connect

    Lockhart, L.; Metner, D.; Muir, D.; Delorme, P.; Dahlke, L.

    1995-12-31

    On two occasions the authors have obtained samples of liver from freshly killed beluga whales harvested by Inuit hunters. The first samples were obtained from whales trapped in the Husky Lakes; with the onset of winter, ice restricted these whales to small breathing holes where they were taken by hunters. They were found to be starving, with body weights about 200 kg less than those expected for whales of their length. Liver mixed-function oxygenase activities, ethoxyresorufin-O-deethylase and aryl hydrocarbon hydroxylase, correlated closely with blubber residues of polychlorinated biphenyls. A second group of whales was taken in the summer hunt in Kugmallit Bay and showed no sign of starvation. The enzyme activities in these whales had weaker statistical relationships to PCB residues. These observations suggested that mobilization of blubber by the starving whales may have released PCBs to act pharmacologically. The authors could not test this hypothesis directly on whales, but an experiment was carried out on laboratory fish to try to examine it. Arctic char were given low dosages of PCB congener 126 and then maintained on diets of full normal ration, half-ration and quarter-ration over a period of 48 weeks, with sub-sampling at intervals. Fish receiving less than maintenance rations responded with decreases in body fat and increases in EROD activities. These laboratory results suggest that correlations between enzymatic activities and PCBs in the starving whales may indeed have been the result of the loss of blubber and concomitant release of PCBs.

  1. Changes of biomarkers with oral exposure to benzo(a)pyrene, phenanthrene and pyrene in rats

    PubMed Central

    Kang, Hwan Goo; Cho, Myung Haing; Cho, Joon Hyoung

    2007-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants present in air and food. Among PAHs, benzo(a)pyrene(BaP), phenanthrene (PH) and pyrene (PY) are considered to be important for their toxicity or abundance. To investigate the changes of biomarkers after PAH exposure, rats were treated with BaP (150 µg/kg) alone or with PH (4,300 µg/kg) and PY (2,700 µg/kg) (BPP group) by oral gavage once per day for 30 days. 7-ethoxyresorufin-O-deethylase activity in liver microsomal fraction was increased in only BaP groups. The highest concentration (34.5 ng/g) of BaP, was found in muscle of rats treated with BaP alone at 20 days of treatment; it was 23.6 ng/g in BPP treated rats at 30 days of treatment. The highest PH concentration was 47.1 ng/g in muscle and 118.8 ng/g in fat, and for PY it was 29.7 ng/g in muscle and 219.9 ng/g in fat, in BPP groups. In urine, 114-161 ng/ml 3-OH-PH was found, while PH was 41-69 ng/ml during treatment. 201-263 ng/ml 1-OH-PY was found, while PH was 9-17 ng/ml in urine. The level of PY, PH and their metabolites in urine was rapidly decreased after withdrawal of treatment. This study suggest that 1-OH-PY in urine is a sensitive biomarker for PAHs; it was the most highly detected marker among the three PAHs and their metabolites evaluated during the exposure period and for 14 days after withdrawal. PMID:17993750

  2. A comparative approach to 7, 12-dimethylbenz[a]anthracene effects: Metabolism and mutagenesis in mice and fish

    SciTech Connect

    Gallagher, K.; Cline, J.; Burkhart, J.G.; Gundersen, J.L.

    1997-10-01

    A comparative approach was used to examine the effects of exposure to the potent carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) in two divergent sentinel species, mouse and fish, containing a common transgenic reporter, the bacteriophage {O}X174am3. Effects of DMBA were examined using both in vitro and in vivo studies through the analysis of metabolites, cytochrome P450 was examined 72 hours after DMBA dosing using an assay for 7-ethoxyresorufin-o-deethylase (EROD) activity. Fish showed an increasing trend of EROD induction with increasing dose, with the EROD level at the highest dose being significantly greater than corn oil controls and the lowest DMBA dose. DMBA had less of an effect on mouse P450 levels. Metabolites of DMBA in the bile at 12 hours were quantified in both species using HPLC/PDA detection. Bile extracts were enzyme digested to differentiate glucuronide, sulfate and glutathione conjugates. Primary metabolites in mice were 2-hydroxy-7,12-dimethylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene. The same metabolites were detected in the fish with the addition of 7,12-bis-hydrodxymethylbenz[a]anthracene. In vitro assays using uninduced and 3-methylcholanthrene-induced mouse microsomes showed no increase over background mutant frequencies of 1-3x10{sup -6} when 0X DNA was incubated with DMBA. In vivo induced mutation was also examined in mice and fish liver. The 1.9 and 19 mg/kg doses of DMBA resulted in a 10-fold increase in mutation frequency over controls in fish. There was a similar increase in mutation frequency at the 19 mg/kg dose in mice. Analysis of the 1.9 mb/kg dosed mice and the replicate variance among treated and control animals is underway.

  3. Stable nitrogen isotopes of nestling tree swallows indicate exposure to different types of oil sands reclamation.

    PubMed

    Farwell, A J; Harms, N J; Smits, J E G; Dixon, D G

    2014-01-01

    Tree swallows (Tachycineta bicolor) inhabiting reclaimed wetlands on the oil sands in northern Alberta are potentially exposed to elevated levels of oil sands constituents such as polycyclic aromatic compounds (PAC) through diet. While increased detoxification enzyme activity as measured using 7-ethoxyresorufin O-deethylase in nestlings is a generally accepted indicator of exposure to oil sands constituents, there is no apparent method to detect dietary exposure specific to oil sands processed material (OSPM). In this study, stable C and N isotopes were analyzed from muscle and feathers of nestling tree swallows (15 d old) to distinguish dietary exposure of birds near reference and OSPM wetlands. High δ¹⁵N and low δ¹³C values in the nestling tissues differentiated those from the OSPM wetlands and reference sites. Lower δ¹⁵N values of nestlings compared to the δ¹⁵N values of larval chironomids from an earlier study suggested that the majority of the diet of the nestlings was derived from non-OSPM sources, despite residence near and on the OSPM wetlands. Our finding of limited utilization of OSPM resources by tree swallows indicates either low abundance or diversity of dietary items emerging from OSPM wetlands, or sensory avoidance of prey from those wetlands. Minimal consumption of OSPM-derived dietary sources may be attributed to published findings of limited adverse effects on tree swallow reproduction, or growth and development for these same nestlings. This study demonstrated that stable isotope analysis, particularly for N isotopes, may serve as a useful tool to trace dietary exposure to OSPM constituents as part of avian ecotoxicology assessments of reclaimed wetlands on the oil sands. PMID:24627996

  4. Stable nitrogen isotopes of nestling tree swallows indicate exposure to different types of oil sands reclamation.

    PubMed

    Farwell, A J; Harms, N J; Smits, J E G; Dixon, D G

    2014-01-01

    Tree swallows (Tachycineta bicolor) inhabiting reclaimed wetlands on the oil sands in northern Alberta are potentially exposed to elevated levels of oil sands constituents such as polycyclic aromatic compounds (PAC) through diet. While increased detoxification enzyme activity as measured using 7-ethoxyresorufin O-deethylase in nestlings is a generally accepted indicator of exposure to oil sands constituents, there is no apparent method to detect dietary exposure specific to oil sands processed material (OSPM). In this study, stable C and N isotopes were analyzed from muscle and feathers of nestling tree swallows (15 d old) to distinguish dietary exposure of birds near reference and OSPM wetlands. High δ¹⁵N and low δ¹³C values in the nestling tissues differentiated those from the OSPM wetlands and reference sites. Lower δ¹⁵N values of nestlings compared to the δ¹⁵N values of larval chironomids from an earlier study suggested that the majority of the diet of the nestlings was derived from non-OSPM sources, despite residence near and on the OSPM wetlands. Our finding of limited utilization of OSPM resources by tree swallows indicates either low abundance or diversity of dietary items emerging from OSPM wetlands, or sensory avoidance of prey from those wetlands. Minimal consumption of OSPM-derived dietary sources may be attributed to published findings of limited adverse effects on tree swallow reproduction, or growth and development for these same nestlings. This study demonstrated that stable isotope analysis, particularly for N isotopes, may serve as a useful tool to trace dietary exposure to OSPM constituents as part of avian ecotoxicology assessments of reclaimed wetlands on the oil sands.

  5. Variation of Basal EROD Activities in Ten Passerine Bird Species – Relationships with Diet and Migration Status

    PubMed Central

    Rainio, Miia J.; Kanerva, Mirella; Wahlberg, Niklas; Nikinmaa, Mikko; Eeva, Tapio

    2012-01-01

    Inter-specific differences in animal defence mechanisms against toxic substances are currently poorly understood. The ethoxyresorufin-O-deethylase (EROD) enzyme plays an important role in defence against toxic chemicals in a wide variety of animals, and it is an important biomarker for environmental contamination. We compared basal hepatic EROD activity levels among ten passerine species to see if there is inter-specific variation in enzyme activity, especially in relation to their diet and migration status. Migratory insectivores showed higher EROD activity compared to granivores. We hypothesize that the variable invertebrate diet of migratory insectivores contains a wider range of natural toxins than the narrower diet of granivores. This may have affected the evolution of mixed function oxidases (MFO) system and enzyme activities. We further tested whether metabolic rates or relative liver size were associated with the variation in detoxification capacity. We found no association between EROD activity and relative (per mass unit) basal metabolic rate (BMR). Instead, EROD activity and relative liver mass (% of body mass) correlated positively, suggesting that a proportionally large liver also functions efficiently. Our results suggest that granivores and non-migratory birds may be more vulnerable to environmental contaminants than insectivores and migratory birds. The diet and migration status, however, are phylogenetically strongly connected to each other, and their roles cannot be fully separated in our analysis with only ten passerine species. PMID:22479477

  6. Development of in vivo biotransformation enzyme assays for ecotoxicity screening: In vivo measurement of phases I and II enzyme activities in freshwater planarians.

    PubMed

    Li, Mei-Hui

    2016-08-01

    The development of a high-throughput tool is required for screening of environmental pollutants and assessing their impacts on aquatic animals. Freshwater planarians can be used in rapid and sensitive toxicity bioassays. Planarians are known for their remarkable regeneration ability but much less known for their metabolic and xenobiotic biotransformation abilities. In this study, the activities of different phase I and II enzymes were determined in vivo by directly measuring fluorescent enzyme substrate disappearance or fluorescent enzyme metabolite production in planarian culture media. For phase I enzyme activity, O-deethylation activities with alkoxyresorufin could not be detected in planarian culture media. By contrast, O-deethylation activities with alkoxycoumarin were detected in planarian culture media. Increases in 7-ethoxycoumarin O-deethylase (ECOD) activities was only observed in planarians exposed to 1μM, but not 10μM, β-naphthoflavone for 24h. ECOD activity was inhibited in planarians exposed to 10 and 100μM rifampicin or carbamazepine for 24h. For phase II enzyme activity, DT-diaphorase, arylsulfatases, uridine 5'-diphospho (UDP)-glucuronosyltransferase or catechol-O-methyltransferase activity was determined in culture media containing planarians. The results of this study indicate that freshwater planarians are a promising model organism to monitor exposure to environmental pollutants or assess their impacts through the in vivo measurement of phase I and II enzyme activities.

  7. Development of in vivo biotransformation enzyme assays for ecotoxicity screening: In vivo measurement of phases I and II enzyme activities in freshwater planarians.

    PubMed

    Li, Mei-Hui

    2016-08-01

    The development of a high-throughput tool is required for screening of environmental pollutants and assessing their impacts on aquatic animals. Freshwater planarians can be used in rapid and sensitive toxicity bioassays. Planarians are known for their remarkable regeneration ability but much less known for their metabolic and xenobiotic biotransformation abilities. In this study, the activities of different phase I and II enzymes were determined in vivo by directly measuring fluorescent enzyme substrate disappearance or fluorescent enzyme metabolite production in planarian culture media. For phase I enzyme activity, O-deethylation activities with alkoxyresorufin could not be detected in planarian culture media. By contrast, O-deethylation activities with alkoxycoumarin were detected in planarian culture media. Increases in 7-ethoxycoumarin O-deethylase (ECOD) activities was only observed in planarians exposed to 1μM, but not 10μM, β-naphthoflavone for 24h. ECOD activity was inhibited in planarians exposed to 10 and 100μM rifampicin or carbamazepine for 24h. For phase II enzyme activity, DT-diaphorase, arylsulfatases, uridine 5'-diphospho (UDP)-glucuronosyltransferase or catechol-O-methyltransferase activity was determined in culture media containing planarians. The results of this study indicate that freshwater planarians are a promising model organism to monitor exposure to environmental pollutants or assess their impacts through the in vivo measurement of phase I and II enzyme activities. PMID:27062342

  8. Inhibitory activity of cigarette-smoke condensate on the mutagenicity of heterocyclic amines.

    PubMed

    Lee, C K; Munoz, J A; Fulp, C; Chang, K M; Rogers, J C; Borgerding, M F; Doolittle, D J

    1994-07-01

    Cigarette-smoke condensate (CSC) is a complex mixture containing over 3800 identified chemicals including nicotine, water, mutagens, antimutagens, cytotoxins and inert chemicals. Although CSC is mutagenic in the Ames test, its effect on the activity of other mutagens has not been characterized. Using the Ames Salmonella bacterial mutagenesis assay, we found CSC exerts a significant inhibitory effect on mutagens requiring bioactivation. Those studied included heterocyclic amines (Glu-P-1, Glu-P-2, IQ, MeIQ, Trp-P-1 and Trp-P-2), benzo[a]pyrene (B[a]P) and aflatoxin B1. However, CSC had no effect on the activity of direct-acting mutagens (2-nitrofluorene, sodium azide, 4-nitro-1,2-phenylenediamine, 4-nitroquinoline N-oxide and methyl methanesulfonate). With indirect-acting mutagens, the reduced number of revertants observed in the presence of CSC was not attributable to cytotoxicity. CSC exhibited a potent inhibitory effect on the cytochrome P-450 dependent monooxygenases, ethoxyresorufin O-deethylase and B[a]P hydroxylase. This suggests inhibition of the cytochrome P-450 isozymes as one possible mechanism for the antimutagenicity of CSC. Fractionation studies of CSC revealed that the neutral, weakly acidic (phenolic) and basic fractions are all effective as antimutagens against Glu-P-1, a representative heterocyclic amine. This indicates that several classes of chemicals contribute to the inhibitory effect of CSC on the mutagenicity of the heterocyclic amines. PMID:7517501

  9. Crude cacao Theobroma cacao extract reduces mutagenicity induced by benzo[a]pyrene through inhibition of CYP1A activity in vitro.

    PubMed

    Ohno, Marumi; Sakamoto, Kentaro Q; Ishizuka, Mayumi; Fujita, Shoichi

    2009-08-01

    Polyphenols have been shown to have potent antioxidant activity, and therefore, food containing polyphenols is expected to contribute to the prevention of cancer. However, food contains not only polyphenols but also various other constituents. We used the Ames test to investigate the effects of crude extracts of whole cacao products, which are known to be rich in polyphenols, on the mutagenicity of benzo[a]pyrene (B[a]P) in Salmonella typhimurium strain TA 98 and tert-butyl hydroperoxide (t-BuOOH) in S. typhimurium strain TA 102. B[a]P induces mutagenicity by metabolic activation and t-BuOOH induces it by generation of free radicals. While white chocolate did not modulate the numbers of revertant colonies produced by B[a]P treatment, milk chocolate and cacao powder extracts did. On the other hand, surprisingly, none of the cacao products tested affected the number of revertant colonies when t-BuOOH was used as the mutagen. At maximum concentration (13.25 mg cacao powder/ml), the crude cacao powder extract reduced ethoxyresorufin O-deethylase activity to 17.4% of the control, suggesting that whole cacao products inhibit cytochrome P450 (CYP) 1A activity. In conclusion, inhibition of CYP1A activity by cacao products may prevent DNA damage by reducing metabolic activation of carcinogens.

  10. Polycyclic aromatic hydrocarbon-induced CYP1B1 activity is suppressed by perillyl alcohol in MCF-7 cells

    SciTech Connect

    Chan, Nelson L.S.; Wang Huan; Wang Yun; Leung, H.Y.; Leung, Lai K. . E-mail: laikleung@yahoo.com

    2006-06-01

    Perillyl alcohol (POH) is a dietary monoterpene with potential applications in chemoprevention and chemotherapy. Although clinical trials are under way, POH's physiological and pharmacological properties are still unclear. In the present study, the effect of POH on polycyclic aromatic hydrocarbon (PAH)-induced genotoxicity, and the related expression were examined in MCF-7 cells. Exposure to environmental toxicant increases the risk of cancer. Many of these compounds are pro-carcinogens and are biotransformed into their ultimate genotoxic structures by xenobiotic metabolizing enzymes. CYP1A1 and 1B1 are enzymes that catalyze the biotransformation of dimethylbenz[a]anthracene (DMBA). Our data revealed that 0.5 {mu}M of POH was effective in blocking DMBA-DNA binding. Ethoxyresorufin-O-deethylase (EROD) assay indicated that the administration of POH inhibited the DMBA-induced enzyme activity in MCF-7 cells. Enzyme kinetic analysis revealed that POH inhibited CYP1B1 but not CYP1A1 activity. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay also demonstrated that the monoterpene reduced CYP1B1 mRNA abundance induced by DMBA. The present study illustrated that POH might inhibit and downregulate CYP1B1, which could protect against PAH-induced carcinogenesis.

  11. Biological effects and bioaccumulation of pharmaceutically active compounds in crucian carp caged near the outfall of a sewage treatment plant.

    PubMed

    Liu, Jianchao; Lu, Guanghua; Zhang, Zhenghua; Bao, Yijun; Liu, Fuli; Wu, Donghai; Wang, Yonghua

    2015-01-01

    Pharmaceutically active compounds (PhACs) have been universally detected in rivers, lakes and coastal waters that are affected by effluents from sewage treatment plants (STPs). In this study, the biological effects and bioaccumulation of PhACs were assessed in crucian carp (Carassius auratus) caged in an effluent-receiving river for 21 days. Compared with control fish in the laboratory and at a reference site, a significant reduction in hepatosomatic index (HSI) and increase in the biotransformation enzymes ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities were observed in the fish that was caged downstream from the STP outfall. In general, the total concentrations of PhACs detected in fish tissues were in the order as follows: liver > brain > gill > muscle > bile. The bioaccumulation factors (BAFs) for PhACs were between 195 and 2782 in the major storage tissue liver. The corresponding results for both risk quotient (RQ) and enhanced integrated biomarker response (EIBR) based on laboratory and field studies, respectively, indicated that environmental risk for adverse effects to aquatic organisms were clearly higher at the downstream of the STP outfall than at the upstream. PMID:25406643

  12. Monooxygenase activity of black-crowned night-heron (BCNH) nestlings in Virginia, the Great Lakes and San Francisco Bay

    USGS Publications Warehouse

    Rattner, B.A.; Melancon, M.J.; Custer, T.W.; Hothem, R.L.; King, K.A.; LeCaptain, L.J.; Spann, J.W.

    1990-01-01

    To evaluate cytochrome P-450 related parameters as biomarkers of pollutant exposure, rates of arylhydrocarbon hydroxylase (AHH), ethoxyresorufin-O-deethylase (EROD), benzyloxyROD (BROD), pentoxyROD (PROD) and ethoxycoumarinOD (ECOD) were studied in 10-day-old BCNHs (Nycticorax nycticorax). Nestlings were collected from Chincoteague National Wildlife Refuge, VA ('controls') and from polluted sites including. Cat Island, Green Bay, WI, and Bair and West Marin Islands, San Francisco Bay, CA. Livers were frozen (-70.C) for monooxygenase assays and SDS-PAGE. Microsomal AHH and BROD activities were greater (P2 standard deviations from the control mean (induced up to 3-fold). EROD, PROD and ECOD did not differ among sites. Absence of an EROD response with AHH and BROD induction in BCNHs is different than responses in other species. The association of pollutant burdens with P-450 parameters is being studied. These biomarkers may serve as a rapid screen of exposure in a national contaminant biomonitoring program and other assessment activities.

  13. Relationship between polychlorinated biphenyl 126 treatment and cytochrome P4501A activity in chickens, as measured by in vivo caffeine and ex vivo ethoxyresorufin metabolism

    SciTech Connect

    Feyk, L.A.; Giesy, J.P.; Lambert, G.H.

    1999-09-01

    Cytochrome P4501A (CYPIA) activity is often used as a biomarker of exposure of wildlife to polyhalogenated diaromatic hydrocarbons (PHDHs) and is usually measured ex vivo in liver tissue. A caffeine breath test with radiolabeled substrate ({sup 14}C-CBT) has been developed to measure in vivo avian CYPIA activity. Research goals were to develop stable isotope methods ({sup 13}C-CBT), determine dose-response relationships between caffeine N-demethylation (CNDM) and PHDH exposure, and assess the relative utility of the CBT and ex vivo ethoxyresorufin-O-deethylase (EROD) assay. The {sup 13}C-CBT methods were developed with 20 chickens (Gallus domesticus). Chickens received three intraperitoneal injections of 0, 1, 5, or 50 {micro}g 3,3{prime},4,4{prime},5-pentachlorobiphenyl (PCB 126)/kg body weight, and CNDM was quantified by measurement of {sup 13}CO{sub 2}/{sup 12}CO{sub 2} in expired breath. The {sup 13}C-CBT was not as sensitive or specific as the EROD assay as an indicator of PHDH exposure and effect in birds. Constitutive CNDM of great interindividual variability was observed, and the magnitude of induction was greater for EROD activity than for CNDM (approximately 1,000- and 2-fold, respectively). Variability associated with baseline {sup 13}CO{sub 2}/{sup 12}CO{sub 2} ratios in expired breath reduced the sensitivity of the {sup 13}C-CBT method.

  14. Benzo(a)pyrene Metabolism and EROD and GST Biotransformation Activity in the Liver of Red- and White-Blooded Antarctic Fish.

    PubMed

    Strobel, Anneli; Burkhardt-Holm, Patricia; Schmid, Peter; Segner, Helmut

    2015-07-01

    Climate change and anthropogenic pollution are of increasing concern in remote areas such as Antarctica. The evolutionary adaptation of Antarctic notothenioid fish to the cold and stable Southern Ocean led to a low plasticity of their physiological functions, what may limit their capacity to deal with altered temperature regimes and pollution in the Antarctic environment. Using a biochemical approach, we aimed to assess the hepatic biotransformation capacities of Antarctic fish species by determining (i) the activities of ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST), and (ii) the metabolic clearance of benzo(a)pyrene by hepatic S9 supernatants. In addition, we determined the thermal sensitivity of the xenobiotic biotransformation enzymes. We investigated the xenobiotic metabolism of the red-blooded Gobionotothen gibberifrons and Notothenia rossii, the hemoglobin-less Chaenocephalus aceratus and Champsocephalus gunnari, and the rainbow trout Oncorhynchus mykiss as a reference. Our results revealed similar metabolic enzyme activities and metabolic clearance rates between red- and white-blooded Antarctic fish, but significantly lower rates in comparison to rainbow trout. Therefore, bioaccumulation factors for metabolizable lipophilic contaminants may be higher in Antarctic than in temperate fish. Likewise, the thermal adaptive capacities and flexibilities of the EROD and GST activities in Antarctic fish were significantly lower than in rainbow trout. As a consequence, increasing water temperatures in the Southern Ocean will additionally compromise the already low detoxification capacities of Antarctic fish. PMID:25965896

  15. Benzo(a)pyrene Metabolism and EROD and GST Biotransformation Activity in the Liver of Red- and White-Blooded Antarctic Fish.

    PubMed

    Strobel, Anneli; Burkhardt-Holm, Patricia; Schmid, Peter; Segner, Helmut

    2015-07-01

    Climate change and anthropogenic pollution are of increasing concern in remote areas such as Antarctica. The evolutionary adaptation of Antarctic notothenioid fish to the cold and stable Southern Ocean led to a low plasticity of their physiological functions, what may limit their capacity to deal with altered temperature regimes and pollution in the Antarctic environment. Using a biochemical approach, we aimed to assess the hepatic biotransformation capacities of Antarctic fish species by determining (i) the activities of ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST), and (ii) the metabolic clearance of benzo(a)pyrene by hepatic S9 supernatants. In addition, we determined the thermal sensitivity of the xenobiotic biotransformation enzymes. We investigated the xenobiotic metabolism of the red-blooded Gobionotothen gibberifrons and Notothenia rossii, the hemoglobin-less Chaenocephalus aceratus and Champsocephalus gunnari, and the rainbow trout Oncorhynchus mykiss as a reference. Our results revealed similar metabolic enzyme activities and metabolic clearance rates between red- and white-blooded Antarctic fish, but significantly lower rates in comparison to rainbow trout. Therefore, bioaccumulation factors for metabolizable lipophilic contaminants may be higher in Antarctic than in temperate fish. Likewise, the thermal adaptive capacities and flexibilities of the EROD and GST activities in Antarctic fish were significantly lower than in rainbow trout. As a consequence, increasing water temperatures in the Southern Ocean will additionally compromise the already low detoxification capacities of Antarctic fish.

  16. Xenobiotic metabolizing enzyme activities in cells used for testing skin sensitization in vitro.

    PubMed

    Fabian, E; Vogel, D; Blatz, V; Ramirez, T; Kolle, S; Eltze, T; van Ravenzwaay, B; Oesch, F; Landsiedel, R

    2013-09-01

    For ethical and regulatory reasons, in vitro tests for scoring potential toxicities of cosmetics are essential. A test strategy for investigating potential skin sensitization using two human keratinocytic and two human dendritic cell lines has been developed (Mehling et al. Arch Toxicol 86:1273–1295, 2012). Since prohaptens may be metabolically activated in the skin, information on xenobiotic metabolizing enzyme (XME) activities in these cell lines is of high interest. In this study, XME activity assays, monitoring metabolite or cofactor, showed the following: all three passages of keratinocytic (KeratinoSens® and LuSens) and dendritic (U937 und THP-1) cells displayed N-acetyltransferase 1 (NAT1) activities (about 6–60 nmol/min/mg S9-protein for acetylation of para-aminobenzoic acid). This is relevant since reactive species of many cosmetics are metabolically controlled by cutaneous NAT1. Esterase activities of about 1–4 nmol fluorescein diacetate/min/mg S9-protein were observed in all passages of investigated keratinocytic and about 1 nmol fluorescein diacetate/min/mg S9-protein in dendritic cell lines. This is also of practical relevance since many esters and amides are detoxified and others activated by cutaneous esterases. In both keratinocytic cell lines, activities of aldehyde dehydrogenase (ALDH) were observed (5–17 nmol product/min/mg cytosolic protein). ALDH is relevant for the detoxication of reactive aldehydes. Activities of several other XME were below detection, namely the investigated cytochrome P450-dependent alkylresorufin O-dealkylases 7-ethylresorufin O-deethylase, 7-benzylresorufin O-debenzylase and 7-pentylresorufin O-depentylase (while NADPH cytochrome c reductase activities were much above the limit of quantification), the flavin-containing monooxygenase, the alcohol dehydrogenase as well as the UDP glucuronosyl transferase activities.

  17. Biomarker responses in mudskipper (Periophthalmus waltoni) from the coastal areas of the Persian Gulf with oil pollution.

    PubMed

    Shirani, Mehrnoosh; Mirvaghefi, Alireza; Farahmand, Hamid; Abdollahi, Mohammad

    2012-11-01

    A suite of 5 different biomarker responses were selected and measured in 3 different phases of detoxification process in mudskipper Periophthalmus waltoni from 3 different stations including Soltani Inlet, Shif Island and Ameri Port in Bushehr coastal area of the Persian Gulf. The selected biomarkers were 7-ethoxyresorufin O-deethylase (EROD), glutathione S-transferase (GST), biliary fluorescent aromatic compounds (FACs), DNA damage using the Comet assay and micronucleus (MN). Spatial variations in biomarker responses were observed in different sites. EROD, GST, FACs, DNA damage and MN were significantly elevated in mudskippers in the most oil impacted site (Soltani inlet). Based on the assessments, bile metabolites, EROD and GST induction appear to be sensitive to polycyclic aromatic hydrocarbons (PAHs) and can be considered as complementary biomarkers; therefore P. waltoni has the potential to be used as a bioindicator in these types of ecosystems.

  18. Environmental contamination and developmental abnormalities in eggs and hatchlings of the common snapping turtle (Chelydra serpentina serpentina) from the Great Lakes-St Lawrence River basin (1989-1991).

    PubMed

    Bishop, C A; Ng, P; Pettit, K E; Kennedy, S W; Stegeman, J J; Norstrom, R J; Brooks, R J

    1998-01-01

    During 1989-1991, we assessed developmental abnormalities in embryos and hatchlings from eggs of the common snapping turtle (Chelydra serpentina serpentina). Eggs were collected and artificially incubated from eight sites in Ontario, Canada and Akwesasne/New York, USA. In eggs from the same clutches we measured 20 organochlorine pesticides, 48 polychlorinated biphenyl (PCBs) congeners including 6 non-ortho PCBs, 8 polychlorinated dibenzodioxins (PCDDs), 14 polychlorinated dibenzofurans (PCDFs) and total mercury. We found a significant increase in abnormal development with increasing polychlorinated aromatic hydrocarbon exposure in eggs, particularly PCDD and PCDF concentrations. In contrast, the risk of abnormality was not significantly higher as toxic equivalent concentrations increased in eggs. We also found significant 7-ethoxyresorufin O-deethylase and Cytochrome P4501A responses in livers of hatchling turtles from Lake Ontario relative to hatchlings from a clean, inland site whereas we did not find any evidence of porphyria in the hatchlings from either site. PMID:15093107

  19. Role of active oxygen species in the photodestruction of microsomal cytochrome P-450 and associated monooxygenases by hematoporphyrin derivative in rats

    SciTech Connect

    Das, M.; Dixit, R.; Mukhtar, H.; Bickers, D.R.

    1985-02-01

    The cytochrome P-450 in hepatic microsomes prepared from rats pretreated with hematoporphyrin derivative was shown to be rapidly destroyed in the presence of long-wave ultraviolet light. The photocatalytic destruction of the heme-protein was dependent on both the dose of ultraviolet light and of hematoporphyrin derivative administered to the animals. The destructive reaction was accompanied by increased formation of cytochrome P-420, loss of microsomal heme content, and diminished catalytic activity of cytochrome P-450-dependent monooxygenases such as aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase. The specificity of the effect on cytochrome P-450 was confirmed by the observation that other heme-containing moieties such as myoglobin and cytochrome c were not susceptible to photocatalytic destruction. The destruction of cytochrome P-450 was a photodynamic process requiring oxygen since quenchers of singlet oxygen, including 2,5-dimethylfuran, histidine, and beta-carotene, each substantially diminished the reaction. Scavengers of superoxide anion such as superoxide dismutase and of H/sub 2/O/sub 2/ such as catalase did not protect against photodestruction of cytochrome P-450, whereas inhibitors of the hydroxyl radical, including benzoate, mannitol, and ethyl alcohol, did afford protection. These results indicate that lipid-rich microsomal membranes and the heme-protein cytochrome P-450 embedded therein are potential targets of injury in cells exposed to hematoporphyrin derivative photosensitization.

  20. Dual effects of phloretin on aflatoxin B1 metabolism: activation and detoxification of aflatoxin B1.

    PubMed

    Gao, Shang Shang; Chen, Xiao Yan; Zhu, Ri Zhe; Choi, Byung-Min; Kim, Sun Jun; Kim, Bok-Ryang

    2012-01-01

    Typically, chemopreventive agents involve either induction of phase II detoxifying enzymes and/or inhibition of cytochrome P450 enzymes (CYPs) that are required for the activation of procarcinogens. In this study, we investigated the protective effects of phloretin against aflatoxin B1 (AFB1) activation to the ultimate carcinogenic intermediate, AFB(1)-8, 9-epoxide (AFBO), and its subsequent detoxification. Phloretin markedly inhibited formation of the epoxide with human liver microsomes in a dose-dependent manner. Phloretin also inhibited the activities of nifedipine oxidation and ethoxyresorufin O-deethylase (EROD) in human liver microsomes. These data show that phloretin strongly inhibits CYP1A2 and CYP3A4 activities, which are involved in the activation of AFB1. Phloretin increased glutathione S-transferase (GST) activity of alpha mouse liver 12 (AML 12) cells in a dose-dependent manner. GST activity toward AFBO in cell lysates treated with 20 μM phloretin was 23-fold that of untreated control cell lysates. The expression of GSTA3, GSTA4, GSTM1, GSTP1 and GSTT1 was induced by phloretin in a dose-dependent manner in AML 12 cells. GSTP1, GSTM1, and GSTT1 were able to significantly increase the conjugation of AFBO with glutathione. Concurrently, induction of the GST isozyme genes was partially associated with the Nrf2/ARE pathway. Taken together, the results demonstrate that phloretin has a strong chemopreventive effect against AFB1 through its inhibitory effect on CYP1A2, CYP3A4, and its inductive effect on GST activity. PMID:22253071

  1. Effect of cefixime and cefdinir, oral cephalosporins, on cytochrome P450 activities in human hepatic microsomes.

    PubMed

    Niwa, Toshiro; Shiraga, Toshifumi; Hashimoto, Tomoko; Kagayama, Akira

    2004-01-01

    The effects of two kinds of oral cephalosporins, cefixime and cefdinir, on cytochrome P450 (CYP) activities in human hepatic microsomes were investigated. Both cefixime and cefdinir at 2 mM concentration neither inhibited nor stimulated CYP1A1/2-mediated 7-ethoxyresorufin O-deethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated 7-benzyloxyresorufin O-debenzylation, CYP2C8/9-mediated tolbutamide methylhydroxylation, CYP2C19-mediated S-mephenytoin 4'-hydroxylation, CYP2D6-mediated bufuralol 1'-hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, CYP3A4-mediated nifedipine oxidation, or CYP3A4-mediated testosterone 6beta-hydroxylation. The free fractions of cefixime and cefdinir in the incubation mixture, which were measured by ultracentrifugation, were 86.1-93.8% and 94.1-97.8%, respectively. These results suggest that both cefixime and cefdinir would not cause clinically significant interactions with other drugs, which are metabolized by CYPs, via the inhibition of metabolism.

  2. E2 potentializes benzo(a)pyrene-induced hepatic cytochrome P450 enzyme activities in Nile tilapia at high concentrations.

    PubMed

    Rodrigues, Aline Cristina Ferreira; Moneró, Tatiana de Oliveira; Frighetto, Rosa Toyoko Shiraishi; de Almeida, Eduardo Alves

    2015-11-01

    In the aquatic environment, biotransformation enzymes are established biomarkers for assessing PAH exposure in fish, but little is known about the effect of 17β-estradiol (E2) on these enzymes during exposure to benzo(a)pyrene (BaP). In this study, Nile tilapia (Oreochromis niloticus) were exposed for 3, 5, and 10 days to BaP (300 μg L(-1)) and E2 (5 μg L(-1)). These substances were applied isolated or mixed. In the mixture experiment, fish were analyzed pre- and postexposure in order to better understand whether preexposure to the hormone masks the responses activated by PAH or vice versa. Phase I enzymes ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-depenthylase (PROD), and benzyloxyresorufin-O-debenzylase (BROD) activities as well as the phase II enzyme glutathione S-transferase (GST) were analyzed. Isolated E2 treatment decreased EROD activity after 3 days, but this enzyme activity returned to control values after 5 and 10 days of exposure. Isolated BaP treatment significantly induced EROD activity after 3 and 5 days, and the activity returned to control levels after ten exposure days. Combined treatment (E2 + Bap) significantly increased EROD activity, both in the pre- and postexposure. This increase was even higher than in the isolated BaP treatment, suggesting a synergism between these two compounds. When E2 and BaP were used singly, they did not change BROD and PROD activities. However, combined treatment (E2 + Bap) significantly increased PROD activity. Isolated BaP treatment increased GST activity after 10 days. However, this response was not observed in the mixture treatment, suggesting that E2 suppressed the GST induction modulated by BaP. The results put together indicated that E2 altered the biotransformation pathway regarding enzymes activated by BaP in Nile tilapia.

  3. Xenobiotic and steroid biotransformation activities in rainbow trout gill epithelial cells in culture.

    PubMed

    Leguen; Carlsson; Perdu-Durand; Prunet; Pärt; Cravedi

    2000-03-01

    The biotransformation of xenobiotics and steroids was investigated in cultured respiratory epithelial cells from rainbow trout (Oncorhynchus mykiss) gills. As a first approach, ethoxyresorufin-O-deethylase (EROD), chosen as a marker of CYP1A activity, was measured in monolayers of adherent cells. The induction of this enzyme was studied in cells exposed to beta-naphthoflavone (BNF) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in concentrations ranging from 10(-6) to 10(-12) M. After 24 h, TCDD showed a maximal induction at a concentration of 10(-9) M while BNF showed a maximal induction at a concentration of 10(-7) M. Concurrently, a variety of substrates involved in cytochrome P450-dependent metabolism as well as phase II reactions, namely ethoxycoumarin, aniline and testosterone were incubated with cultured gill cells for 2 or 8 h and with freshly isolated hepatocytes for comparison. Our results revealed a significant cytochrome P450-dependent activity in gill cells with ethoxycoumarin and aniline, but no hydroxylation was observed with testosterone as substrate. No trace of sulfate conjugate was detected. With 2.5 µM aniline as substrate, 2-hydroxyaniline accounted for 32.1% of the radioactivity after 2 h incubation whereas acetanilide amounted to 6.4%. Significant differences were found between gill cells and isolated hepatocytes in the capacity of these systems to conduct oxidative and conjugating metabolic pathways. Qualitatively, the main difference was observed for testosterone which is hydroxylated in position 6beta and 16beta and conjugated to glucuronic acid in liver cells, whereas reductive biotransformation giving rise to dihydrotestosterone and androstanediol and traces of androstenedione were observed in gill cells. Quantitatively, the biotransformation activity in gill epithelial cells, expressed as pmol/h per mg protein, was between 1.5 and 14% of the activity level observed in isolated hepatocytes, depending on the substrate.

  4. Inhibition of gizzard shade (Dorosoma cepedianum) P4501A activity by in vivo and in vitro administration of clotrimazole

    SciTech Connect

    Levine, S.; Czosnyka, H.; Oris, J.

    1995-12-31

    The ability of the 1-substituted imidazole agent clotrimazole to inhibit in vivo and in vitro hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity was investigated using gizzard shad (Dorosoma cepedianum) pre-treated with clotrimazole and then given waterborne exposures of benzo[a]pyrene (BaP). Gizzard shad pre-treated with 50 mg clotrimazole/kg and then exposed for 1 or 3 d to BaP (0.86 {micro}g/L) had significantly lower hepatic EROD activity compared to fish that were exposed to BaP alone. Following 1 and 3 d of BaP exposure, groups pre-treated with clotrimazole had 7% and 28% of the EROD activity respectively relative to groups exposed to BaP alone. In addition, there was 8x and 11x more parent BaP in whole-fish extracts from gizzard shad pre-treated with clotrimazole after 1 and 3 d of BaP exposure, respectively, compared to fish exposed to BaP alone. Clotrimazole produced a ``type 11`` binding spectral complex with BaP-treated microsomes and was an effective in vitro inhibitor of EROD activity in micromolar concentrations. The IC{sub 50} for EROD activity was 0.57 {micro}M clotrimazole. The mechanism of inhibition by clotrimazole was determined to be noncompetitive (mixed type) using kinetics experiments. Noncompetitive inhibition of monooxygenase activity is believed to arise from the interaction created via the non-bonded electrons of the nitrogen in the imidazole ring with the name moiety of cytochrome P450, resulting in inhibition of enzymatic activity. The high inhibitory potency of clotrimazole on P4501A catalyzed reactions may prove valuable for its use as a probe in determining whether chemical toxicity is manifested through a cytochrome P450-mediated pathway.

  5. Mixed estrogenic and anti-estrogenic activities of yuehchukene--a bis-indole alkaloid.

    PubMed

    Ng, P C; Ho, D D; Ng, K H; Kong, Y C; Cheng, K F; Stone, G

    1994-10-13

    Anti-estrogenic effects of yuehchukene were observed in rat uterotrophic, mice vaginal smear and MCF-7 cell growth assays. Whereas yuehchukene per se was estrogenic in these bioassay models, the co-administration of yuehchukene and an optimal dose of 3,17 beta-estradiol (estradiol) could attenuate the maximum estrogenic response due to estradiol alone. The anti-estrogenic effect of yuehchukene in rat uterine hypertrophy was corroborated by a parallel attenuation of ornithine decarboxylase activity in these tissues. Yuehchukene binds to rat, mice and MCF-7 cell estrogen receptors with a relative binding affinity of 1/150 to 1/300. This binding affinity was positively related to estrogenicity as determined by uterotrophic assay and MCF-7 cell growth. However, this estrogenic effect did not correlate with the degree of competitive receptor binding by a weaker agonist. Indole-3-carbinol and methylbutadienylindole could induce ethoxyresorufin O-deethylase and estradiol-2-hydroxylase in rat liver and MCF-7 cells. It is postulated that the 'free' indole moiety of yuehchukene could possess similar induction activity. Thus yuehchukene may have a dual pharmacological function. While the intact molecule is a weak estrogen, the 'free' indole moiety in yuehchukene may induce an enhancement of estradiol-2-hydroxylase, thus terminating the biological activity of the endogenous estrogen pool. There is obvious benefit in attenuating the estrogen level in post-menopausal breast cancer patients without going directly to the use of tamoxifen or aromatase inhibitor. Yuehchukene may serve this purpose. In this context, the pharmacological evaluation of a hydroxylated yuehchukene analogue and the anti-estrogenic effect of methylbutadienylindole acid-condensation products are now being studied in earnest.

  6. Oil shale processing as a source of aquatic pollution: monitoring of the biologic effects in caged and feral freshwater fish.

    PubMed Central

    Tuvikene, A; Huuskonen, S; Koponen, K; Ritola, O; Mauer, U; Lindström-Seppä, P

    1999-01-01

    The biologic effects of the oil shale industry on caged rainbow trout (Oncorhynchus mykiss) as well as on feral perch (Perca fluviatilis) and roach (Rutilus rutilus) were studied in the River Narva in northeast Estonia. The River Narva passes the oil shale mining and processing area and thus receives elevated amounts of polycyclic aromatic hydrocarbons (PAHs), heavy metals, and sulfates. The effects of the chemical load were monitored by measuring cytochrome P4501A (CYP1A)-dependent monooxygenase (MO) activities [7-ethoxyresorufin O-deethylase and aryl hydrocarbon hydroxylase (AHH)] as well as conjugation enzyme activities [glutathione S-transferase (GST) and UDP-glucuronosyltransferase] in the liver of fish. CYP1A induction was further studied by detecting the amount and occurrence of the CYP1A protein. Histopathology of tissues (liver, kidney, spleen, and intestine) and the percentage of micronuclei in fish erythrocytes were also determined. Selected PAHs and heavy metals (Cd, Cu, Hg, and Pb) were measured from fish muscle and liver. In spite of the significant accumulation of PAHs, there was no induction of MO activities in any studied fish species. When compared to reference samples, AHH activities were even decreased in feral fish at some of the exposed sites. Detection of CYP1A protein content and the distribution of the CYP1A enzyme by immunohistochemistry also did not show extensive CYP1A induction. Instead, GST activities were significantly increased at exposed sites. Detection of histopathology did not reveal major changes in the morphology of tissues. The micronucleus test also did not show any evidence of genotoxicity. Thus, from the parameters studied, GST activity was most affected. The lack of catalytic CYP1A induction in spite of the heavy loading of PAHs was not studied but has been attributed to the elevated content of other compounds such as heavy metals, some of which can act as inhibitors for MOs. Another possible explanation of this lack of

  7. Characterization and profiling of hepatic cytochromes P450 and phase II xenobiotic-metabolizing enzymes in beluga whales (Delphinapterus leucas) from the St. Lawrence River Estuary and the Canadian Arctic.

    PubMed

    McKinney, Melissa A; Arukwe, Augustine; De Guise, Sylvain; Martineau, Daniel; Béland, Pierre; Dallaire, André; Lair, Stéphane; Lebeuf, Michel; Letcher, Robert J

    2004-07-30

    Cytochromes P450 (CYP, phase I) and conjugating (phase II) enzymes can be induced by and influence the toxicokinetics (metabolism) and toxicity of xenobiotic contaminants in exposed organisms. Beluga whale (Delphinapterus leucas) from the endangered St. Lawrence (SL) River Estuary population exhibit deleterious health effects and various severe pathologies that have been associated with contaminant exposure. In contrast, such effects (e.g. reproductive and immunological impairment) are generally less frequent in less exposed populations in the Canadian Arctic (CA). In the present study, opportunistic sampling resulted in the collection immediately after death of liver tissue from a single female neonate SL beluga (SL6) and male and female CA beluga (n=10) from the Arviat region of western Hudson Bay, in addition to sampling of stranded carcasses of male and female SL beluga (n=5) at least 12 h postmortem. We immunologically characterized cross-reactive proteins of hepatic microsomal CYP1A, CYP2B, CYP3A, CYP2E, epoxide hydrolase (EH) and uridine diphosphoglucuronosyl transferase (UDPGT) isozymes. Cross-reactive proteins were found in all SL and CA beluga using anti-rat CYP1A1, anti-rainbow trout CYP3A, anti-human CYP2E1, anti-rabbit EH and anti-human UDPGT1A1 polyclonal antibodies (Abs), whereas faintly cross-reactive CYP2B proteins were only found in SL6 and the CA samples using an anti-rabbit CYP2B1 Ab. In corresponding catalytic activity assessments, only SL6 and all CA beluga microsomal samples exhibited CYP1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activity (51-260 pmol/mg/min), CYP3A-mediated activity (113-899 pmol/mg/min) based on the formation of 6beta-hydroxytestosterone using a testosterone hydroxylase assay, and UDPGT activity (830-4956 pmol/mg/min) based on 1-naphthylglucuronide formation. The marginal cross-reactivity with the anti-CYP2B1 Ab and lack of catalytically measurable hydroxytestosterone isomers associated with CYP2B-type activity in

  8. Effect of benzo[a]pyrene on detoxification and the activity of antioxidant enzymes of marine microalgae

    NASA Astrophysics Data System (ADS)

    Shen, Chen; Miao, Jingjing; Li, Yun; Pan, Luqing

    2016-04-01

    The objective of this study was to examine the effect of benzo[a]pyrene (BaP) on the detoxification and antioxidant systems of two microalgae, Isochrysis zhanjiangensis and Platymonas subcordiformis. In our study, these two algae were exposed to BaP for 4 days at three different concentrations including 0.5 μg L-1 (low), 3 μg L-1 (mid) and 18 μg L-1 (high). The activity of detoxification enzymes, ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) increased in P. subcordiformis in all BaP-treated groups. In I. zhanjiangensis, the activity of these two enzymes increased at the beginning of exposure, and then decreased in the groups treated with mid- and high BaP. The activity of antioxidant enzyme superoxide dismutase (SOD) increased in I. zhanjiangensis in all BaP-treated groups, and then decreased in high BaP-treated group, while no significant change was observed in P. subcordiformis. The activity of antioxidant enzyme catalase (CAT) increased in I. zhanjiangensis and P. subcordiformis in all BaPtreated groups. The content of malondialdehyde (MDA) in Isochrysis zhanjiangensis increased first, and then decreased in high BaP-treated group, while no change occurred in P. subcordiformis. These results demonstrated that BaP significantly influenced the activity of detoxifying and antioxidant enzymes in microalgae. The metabolic related enzymes (EROD, GST and CAT) may serve as sensitive biomarkers of measuring the contamination level of BaP in marine water.

  9. Induction of mixed-function oxidase activity in mouse lymphoid tissues by polycyclic aromatic hydrocarbons

    SciTech Connect

    Griffin, G.D.; Egan, B.Z.; Lee, N.E.; Burtis, C.A.

    1986-01-01

    Polycyclic aromatic hydrocarbon (PAH) exposure can cause mixed-function oxidase (MFO) enzyme induction in certain tissues of various organisms. Measurements of such induction might serve as a useful bioindicator of human exposure to PAHs, provided readily obtainable human tissues can be utilized for such measurements. The authors have investigated the MFO activity in various lymphoid tissues of the C3H mouse as a model system and have studied the effect of systemic PAH treatment on such enzyme activity. An MFO enzyme assay was used to measure the activity of 7-ethoxyresorufin deethylase, an enzyme activity that may be specific for the cytochrome P-448 subset of MFO enzymes (those enzymes that are induced in cells or tissues following PAH administration). Intraperitoneal injection of mice with 180 mg/kg (4.6 mg) benzo(a)pyrene (BaP) or 160 mg/kg (4.0 mg) 3-methylcholanthrene (MC) produced a significant induction in MFO activity in mouse spleen S9 fractions 48 h after the injection. Induction ratios (induced activity/control activity) between 4 and 5 were seen with BaP; MC produced induction ratios of 2.5-3.0. Enzyme activity was not induced in the spleen within 16 h following BaP or MC administration. Other experiments indicated that MFO activity could be induced in thymus cells 48 h after either BaP or MC treatment. Treatment with BaP or MC did produce significant enzyme induction in the liver and lung tissues from the animals both 16 and 48 h after chemical treatment.

  10. In Vitro expression of drug metabolizing enzyme activities in human adult keratinocytes under various culture conditions and their response to inducers.

    PubMed

    Hirel, B; Chesne, C; Pailheret, J P; Guillouzo, A

    1995-02-01

    In this study we analysed the expression and induction of several drug metabolizing enzymes involved in either phase I or phase II reactions, in adult human keratinocytes cultured in submerged conditions. We also evaluated the influence of confluence, subcultivation and cryopreservation on the expression of these enzymes. Besides ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) activities, which have been shown previously to be maintained in such cultures, three additional enzyme activities were measured (i.e. phenacetin deethylase, a phase I enzyme, and procainamide N-acetyltransferase and paracetamol sulfotransferase, two phase II enzymes). Post-confluent keratinocytes showed decreased activities in comparison with preconfluent cells and the different enzymes tested revealed different patterns. After confluence, some activities, such as those of procainamide N-acetyltrans-ferase, phenacetin deethylase and paracetamol sulfotransferase, showed only a slight decrease, whereas EROD and GST activities were decreased by 65 and 50%, respectively. No major differences were observed between keratinocytes in primary culture and those in second subculture. After freezing, xenobiotic metabolizing enzyme activities were only slightly reduced, if at all. Induction of EROD and GST enzymes was also analysed. Maximum EROD activity was obtained with 1 muM 3-methylcholanthrene (3-MC) and 20 muM benzanthracene (BA), in both pre-confluent and post-confluent cultures. At their optimal concentration 3-MC was a stronger inducer than BA. GST activity was slightly induced by the different compounds tested only in pre-confluent keratinocytes. In conclusion, the presence of a variety of drug metabolizing enzymes in adult human keratinocytes cultured in submerged conditions suggests that this model is suitable for investigating epidermal biotransformation of drugs and other chemicals and for determining the potential cutaneous toxicity of metabolites.

  11. The expressions of protooncogenes and CYP1A in lungs of rats exposed to sulfur dioxide and benzo(a)pyrene.

    PubMed

    Qin, Guohua; Meng, Ziqiang

    2006-06-01

    Sulfur dioxide (SO2) is a ubiquitous air pollutant, present in low concentrations in the urban air, and in higher concentrations in the working environment. Benzo(a)pyrene (B(a)P), a polycyclic aromatic hydrocarbon, is a ubiquitous environmental contaminant with diverse toxicological effects. To investigate the interactions between SO2 and B(a)P, male Wistar rats were exposed to intratracheally instilled with benzo(a)pyrene (B(a)P; 3 mg) or SO2 (20 ppm) inhalation alone or together. The mRNA of CYP1A1 and 1A2, c-fos, and c-jun and protein levels of c-fos and c-jun were analyzed in lungs using a real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay and Western blot analysis, respectively. And 7-ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities were detected. In lungs of rats exposed to SO2 alone, the gene transcription of CYP1A1 and 1A2, the EROD and MROD activities were decreased. Meanwhile, the mRNA and protein levels of c-jun and c-fos were increased significantly. Exposure to B(a)P alone induced CYP1A1, CYP1A2 mRNA levels, the protein levels of c-jun, and the EROD and MROD activities in lungs. However, exposure to B(a)P plus inhaled SO2 neither increased nor decreased CYP1A1/2 mRNA expressions, EROD, and MROD activities in lungs, versus exposure to B(a)P alone. Nevertheless, exposure to B(a)P plus inhaled SO2 increased the mRNA and protein levels of c-jun and c-fos in lungs compared with lungs exposed to SO2 alone. Accordingly, the SO2-induced decreases of CYP1A1/2 might not influence the metabolic activation of B(a)P. However, when B(a)P and SO2 were given in the combinations, one might postulate that a synergistic effect on the expressions of c-fos and c-jun between SO2 and B(a)P, which might be one of the possible mechanisms of combination effects between B(a)P and the air pollutants.

  12. The metabolite 3,4,3',4'-tetrachloroazobenzene (TCAB) exerts a higher ecotoxicity than the parent compounds 3,4-dichloroaniline (3,4-DCA) and propanil.

    PubMed

    Xiao, Hongxia; Kuckelkorn, Jochen; Nüßer, Leonie Katharina; Floehr, Tilman; Hennig, Michael Patrick; Roß-Nickoll, Martina; Schäffer, Andreas; Hollert, Henner

    2016-05-01

    3,4,3',4'-tetrachloroazobenzene (TCAB) is not commercially manufactured but formed as an unwanted by-product in the manufacturing of 3,4-dichloroaniline (3,4-DCA) or metabolized from the degradation of chloranilide herbicides, like propanil. While a considerable amount of research has been done concerning the toxicological and ecotoxicological effects of propanil and 3,4-DCA, limited information is available on TCAB. Our study examined the toxicity of TCAB in comparison to its parent compounds propanil and 3,4-DCA, using a battery of bioassays including in vitro with aryl hydrocarbon receptor (AhR) mediated activity by the 7-ethoxyresorufin-O-deethylase (EROD) assay and micro-EROD, endocrine-disrupting activity with chemically activated luciferase gene expression (CALUX) as well as in vivo with fish embryo toxicity (FET) assays with Danio rerio. Moreover, the quantitative structure activity response (QSAR) concepts were applied to simulate the binding affinity of TCAB to certain human receptors. It was shown that TCAB has a strong binding affinity to the AhR in EROD and micro-EROD induction assay, with the toxic equivalency factor (TEF) of 8.7×10(-4) and 1.2×10(-5), respectively. TCAB presented to be a weak endocrine disrupting compound with a value of estradiol equivalence factor (EEF) of 6.4×10(-9) and dihydrotestosterone equivalency factor (DEF) of 1.1×10(-10). No acute lethal effects of TCAB were discovered in FET test after 96h of exposure. Major sub-lethal effects detected were heart oedema, yolk malformation, as well as absence of blood flow and tail deformation. QSAR modelling suggested an elevated risk to environment, particularly with respect to binding to the AhR. An adverse effect potentially triggering ERβ, mineralocorticoid, glucocorticoid and progesterone receptor activities might be expected. Altogether, the results obtained suggest that TCAB exerts a higher toxicity than both propanil and 3,4-DCA. This should be considered when assessing the

  13. Polychlorinated biphenyls: correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs)

    SciTech Connect

    Leece, B.; Denomme, M.A.; Towner, R.; Li, S.M.A.; Safe, S.

    1985-01-01

    The in vivo quantitative structure-activity relationships (QSARs) for several polychlorinated biphenyls (PCBs) were determined in the immature male Wistar rat. The ED25 and ED50 values for hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction as well as for body weight loss and for thymic atrophy were determined for nine PCB congeners and 4'-bromo-2,3,4,5-tetrachlorobiphenyl. The most active compounds were the coplanar PCB congeners, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyl; for example, their ED50 values for body weight loss were 3.25 and 15.1 ..mu..mol/kg, respectively. The in vivo toxicity of the coplanar PCB, 3,3',4,4'-tetrachlorobiphenyl, was significantly lower (ED50 for body weight loss = 730 ..mu..mol/kg) than the values observed for the more highly chlorinated homologs, and this was consistent with the more rapid metabolism of the lower chlorinated congener. The dose-response biologic and toxic effects of several mono-ortho-chloro-substituted analogs of the coplanar PCBs, including 2,3,4,4',5-, 2,3,3',4,4'-, 2',3,4,4',5- and 2,3',4,4',5-penta-, 2,3,3',4,4',5- and 2,3,3',4,4',5-hexachlorobiphenyl were also determined, and members of this group of compounds were all less toxic than 3,3',4,4',5-penta and 3,3',4,4',5,5'-hexachlorobiphenyl. There was a good rank order correlation between the in vivo QSAR data and the in vitro QSAR data and the in vitro QSARs for PCBs that were developed from their relative receptor binding affinities and potencies as inducers of AHH and EROD in rat hepatoma H-4-II E cells in culture.

  14. Effect of Fe(2)O(3) on the capacity of benzo(a)pyrene to induce polycyclic aromatic hydrocarbon-metabolizing enzymes in the respiratory tract of Sprague-Dawley rats.

    PubMed

    Garçon, Guillaume; Gosset, Pierre; Zerimech, Farid; Grave-Descampiaux, Béatrice; Shirali, Pirouz

    2004-04-21

    In this work, the question that needs to be answered was whether concurrent exposure to iron oxides and polycyclic aromatic hydrocarbons (PAHs) could affect the induction of PAH-metabolizing enzymes. Male Sprague-Dawley rats were intratracheally instilled with hematite (Fe(2)O(3); 3mg), benzo(a)pyrene (B(a)P; 3mg), or B(a)P (3mg)-coated onto Fe(2)O(3) particles (3mg). Forty-eight hours later, we investigated mRNA expressions of cytochrome p4501a1 (cyp1a1), microsomal epoxide hydrolase (meh), and glutathione-S-transferase-ya and -yc (gst-ya and gst-yc, respectively), protein concentrations of CYP1A1, and 7-ethoxyresorufin O-deethylase (EROD) activities in lungs. Exposure to B(a)P alone or coated-onto Fe(2)O(3) particles induced cyp1a1 gene transcription (P < 0.01) and increased both the CYP1A1 protein levels (P < 0.01) and the EROD activities (P < 0.001). However, in this work, we focused our attention on the potential of Fe(2)O(3) in B(a)P/Fe(2)O(3) mixtures to affect the capacity of B(a)P to induce PAH-metabolizing enzymes. Exposure to B(a)P-coated onto Fe(2)O(3) particles increased meh mRNA expressions (1.15-fold, P < 0.05), CYP1A1 protein concentrations (1.85-fold, P < 0.05), and EROD activities (1.95-fold, P < 0.01), versus exposure to B(a)P alone. Hence, animal short-term exposure to B(a)P-coated onto Fe(2)O(3) particles favored dramatically the induction of PAH-bioactivating enzymes to the detriment of PAH-inactivating enzymes in lungs. Taken together, these results support the hypothesis that the Fe(2)O(3)-induced increase of the metabolic activation of B(a)P might rely on several properties of Fe(2)O(3), including its capacity to enhance the rate of CYP1A1 hemoprotein elaboration. The influence of Fe(2)O(3) in B(a)P/Fe(2)O(3) mixtures on the ability of B(a)P to induce PAH-metabolizing enzymes will also be one of the fundamental ways that Fe(2)O(3) can affect B(a)P carcinogenicity in lungs.

  15. Biomarkers of contaminant exposure in northern pike (Esox lucius) from the Yukon River Basin, Alaska

    USGS Publications Warehouse

    Hinck, J.E.; Blazer, V.S.; Denslow, N.D.; Myers, M.S.; Gross, T.S.; Tillitt, D.E.

    2007-01-01

    As part of a larger investigation, northern pike (n = 158; Esox lucius) were collected from ten sites in the Yukon River Basin (YRB), Alaska, to document biomarkers and their correlations with organochlorine pesticide (total p,p'-DDT, total chlordane, dieldrin, and toxaphene), total polychlorinated biphenyls (PCBs), and elemental contaminant (arsenic, cadmium, copper, lead, total mercury, selenium, and zinc) concentrations. A suite of biomarkers including somatic indices, hepatic 7-ethoxyresorufin O-deethylase (EROD) activity, vitellogenin concentrations, steroid hormone (17B- ustradiol and 16-kebtestosteront) concentrations, splenic macrophage aggregates (MAs), oocyte atresia, and other microscopic anomalies in various tissues were documented in YRB pike. Mean condition factor (0.50 to 0.68), hepatosomatic index (1.00% to 3.56%), and splenosomatic index (0.09% to 0.18%) were not anomalous at any site nor correlated with any contaminant concentration. Mean EROD activity (0.71 to 17.51 pmol/min/mg protein) was similar to basal activity levels previously measured in pike and was positively correlated with selenium concentrations (r = 0.88, P < 0.01). Vitellogenin concentrations in female (0.09 to 5.32 mg/mL) and male (0.01 mg/mL in male pike from multiple sites indicated exposure to estrogenic compounds. Mean steroid hormone concentrations and percent oocyte atresia were not anomalous in pike from any YRB site. Few site differences were significant for mean MA density (1.86 to 6.42 MA/mm2), size (812 to 1481 ??m2), and tissue occupied (MA-%; 0.24% to 0.75%). A linear regression between MA-% and total PCBs was significant, although PCB concentrations were generally low in YRB pike (???63 ng/g), and MA-% values in female pike (0.24% to 0.54%) were lower than in male pike (0.32% to 0.75%) at similar PCB concentrations. Greater numbers of MAs were found as zinc concentrations increased in YRB female pike, but it is unlikely that this is a causative relationship

  16. Aryl hydrocarbon receptor-mediated activity of particulate organic matter from the Paso del Norte airshed along the U.S.-Mexico border.

    PubMed Central

    Arrieta, Daniel E; Ontiveros, Cynthia C; Li, Wen-Whai; Garcia, Jose H; Denison, Michael S; McDonald, Jacob D; Burchiel, Scott W; Washburn, Barbara Shayne

    2003-01-01

    In this study, we determined the biologic activity of dichloromethane-extracted particulate matter < 10 micro m in aerodynamic diameter (PM10) obtained from filters at three sites in the Paso del Norte airshed, which includes El Paso, Texas, USA; Juarez, Chihuahua, Mexico, and Sunland Park, New Mexico, USA. The extracts were rich in polycyclic aromatic hydrocarbons (PAHs) and had significant biologic activity, measured using two in vitro assay systems: ethoxyresorufin-(O-deethylase (EROD) induction and the aryl hydrocarbon-receptor luciferase reporter system. In most cases, both EROD (5.25 pmol/min/mg protein) and luciferase activities (994 relative light units/mg) were highest in extracts from the Advance site located in an industrial neighborhood in Juarez. These values represented 58% and 55%, respectively, of induction associated with 1 micro M ss-naphthoflavone exposures. In contrast, little activity was observed at the Northeast Clinic site in El Paso, the reference site. In most cases, luciferase and EROD activity from extracts collected from the Tillman Health Center site, situated in downtown El Paso, fell between those observed at the other two sites. Overall, a statistically significant correlation existed between PM10 and EROD and luciferase activities. Chemical analysis of extracts collected from the Advance site demonstrated that concentrations of most PAHs were higher than those reported in most other metropolitan areas in the United States. Calculations made with these data suggest a cancer risk of 5-12 cases per 100,000 people. This risk estimate, as well as comparisons with the work of other investigators, raises concern regarding the potential for adverse health effects to the residents of this airshed. Further work is needed to understand the sources, exposure, and effects of PM10 and particulate organic material in the Paso del Norte airshed. PMID:12896850

  17. Effects of embryonic and adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic microsomal testosterone hydroxylase activities in great blue herons (Ardea herodias)

    SciTech Connect

    Sanderson, J.T.; Giesy, J.P.; Janz, D.M.; Bellward, G.D.

    1997-06-01

    In a continuing effort to evaluate biomarkers of exposure of great blue herons (Ardea herodias) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons, the authors examined the effect of TCDD on hepatic microsomal testosterone hydroxylase activities. Heron embryos were exposed in ovo to 2 {micro}g TCDD/kg egg (or corn oil vehicle) and sacrificed at hatch or 7 d posthatch. Adult herons were exposed intraperitoneally to 20 {micro}g TCDD/kg and sacrificed 2 weeks later. The sex of the birds was known for the adults only. Hepatic microsomes of herons of each age group were able to hydroxylate testosterone at the 2{beta}, 6{beta}, 15{alpha}, 16{alpha}, or 16{beta} positions. In 7-d-old chicks, an additional unidentified compound was formed. The age of the untreated herons had a strong influence on the activities of the five hydroxylases, with changes of up to 17-fold. The TCDD significantly induced 2{beta}-, 6{beta}, and 15{alpha}-testosterone hydroxylase activities in the adult females, 15{alpha} in the adult males, and 6{beta}-testosterone hydroxylase activity in the hatchlings. In the 7-d-old chicks, induction was no longer apparent. A significant correlation existed between hepatic microsomal ethoxyresorufin O-deethylase (EROD) and 6{beta}-testosterone hydroxylase activity in hatchlings and adult female herons. The TCDD-induced changes in testosterone hydroxylase activities occurred at doses that resulted in tissue concentrations and levels of EROD induction that were environmentally relevant, but did not result in overt toxicities.

  18. Reducing persistent organic pollutants while maintaining long chain omega-3 fatty acid in farmed Atlantic salmon using decontaminated fish oils for an entire production cycle.

    PubMed

    Berntssen, M H G; Olsvik, P A; Torstensen, B E; Julshamn, K; Midtun, T; Goksøyr, A; Johansen, J; Sigholt, T; Joerum, N; Jakobsen, J-V; Lundebye, A-K; Lock, E-J

    2010-09-01

    Oily fish are an important source of health promoting nutrients such as the very long chain marine omega-3 (VLC-n3) fatty acids and simultaneously a source of potentially hazardous contaminants. Fish oils that are used in fish feed are the main source for both contaminants and VLC-n3. Decontamination techniques have recently been developed to effectively remove persistent organic contaminants from fish oils. The aim of the present study was to assess the level of potentially hazardous contaminants and the health beneficial fatty acids in Atlantic salmon reared on novel decontaminated feeds. Atlantic salmon were fed for 18 months (an entire seawater production cycle) on diets based on decontaminated or non-treated (control) fish oils until market size (approximately 5 kg). The level of known notorious persistent organic pollutants (POPs, i.e. dioxins, dioxin-like polychlorinated biphenyls (DL-PCBs), non dioxin-like PCBs, poly brominated diphenyl ethers (PBDE), and organochlorine pesticides), as well as fatty acid composition were analysed in fish oils, the two diets, and Atlantic salmon fillet. The oil decontamination process was a two-step procedure using active carbon and short path distillation. The fillet levels of POPs in market size fish were reduced by 68-85% while the concentration of very long chain omega-3 fatty acids was reduced by 4-7%. No differences in biomarkers of dioxin-like component exposures, such as hepatic gene expression of CYP1A or AhR2B, CYP1A protein expression and 7-ethoxyresorufin O-deethylase (EROD) activity, were observed between salmon raised on normal or decontaminated feeds, thus indicating that the difference in POPs levels were of no biological significance to the fish. Atlantic salmon reared on decontaminated feeds had sum polychlorinated dibenzodioxins/furans (PCDD/Fs) and DL-PCB concentrations that were comparable with terrestrial food products such as beef, while the level of marine omega-3 fatty acids remained as high as for

  19. Reduced cytochrome P4501A activity and recovery from oxidative stress during subchronic benzo[a]pyrene and benzo[e]pyrene treatment of rainbow trout.

    PubMed

    Curtis, Lawrence R; Garzon, Claudia B; Arkoosh, Mary; Collier, Tracy; Myers, Mark S; Buzitis, Jon; Hahn, Mark E

    2011-07-01

    This study assessed the role of aryl hydrocarbon receptor (AHR) affinity, and cytochrome P4501A (CYP1A) protein and activity in polyaromatic hydrocarbon (PAH)-induced oxidative stress. In the 1-100nM concentration range benzo[a]pyrene (BaP) but not benzo[e]pyrene (BeP) competitively displaced 2nM [(3)H]2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin from rainbow trout AHR2α. Based on appearance of fluorescent aromatic compounds in bile over 3, 7, 14, 28 or 50days of feeding 3μg of BaP or BeP/g fish/day, rainbow trout liver readily excreted these polyaromatic hydrocarbons (PAHs) and their metabolites at near steady state rates. CYP1A proteins catalyzed more than 98% of ethoxyresorufin-O-deethylase (EROD) activity in rainbow trout hepatic microsomes. EROD activity of hepatic microsomes initially increased and then decreased to control activities after 50days of feeding both PAHs. Immunohistochemistry of liver confirmed CYP1A protein increased in fish fed both PAHs after 3days and remained elevated for up to 28days. Neither BaP nor BeP increased hepatic DNA adduct concentrations at any time up to 50days of feeding these PAHs. Comet assays of blood cells demonstrated marked DNA damage after 14days of feeding both PAHs that was not significant after 50days. There was a strong positive correlation between hepatic EROD activity and DNA damage in blood cells over time for both PAHs. Neither CYP1A protein nor 3-nitrotyrosine (a biomarker for oxidative stress) immunostaining in trunk kidney were significantly altered by BaP or BeP after 3, 7, 14, or 28days. There was no clear association between AHR2α affinity and BaP and BeP-induced oxidative stress.

  20. Mixed-function oxidase enzyme activity and oxidative stress in lake trout (Salvelinus namaycush) exposed to 3,3{prime},4,4{prime}5-pentachlorobiphenyl (PCB-126)

    SciTech Connect

    Palace, V.P.; Klaverkamp, J.F.; Lockhart, W.L. |; Metner, D.A.; Muir, D.C.G.; Brown, S.B.

    1996-06-01

    Juvenile lake trout were intraperitoneally injected with corn oil containing nominal concentrations of 0, 0.6, 6.3, or 25 {micro}g [{sup 14}C]-3,3{prime},4,4{prime},5-pentachlorobiphenyl (PCB-126) per gram of body weight. The PCB-126 accumulated in liver in a dose-dependent manner to a sustained concentration by 6 weeks and remained elevated for the 30-week experimental period. Mixed-function oxidase (MFO) enzyme activity was elevated in the two highest dose groups relative to the control group, but not in the low-dose group throughout the 30 weeks. Oxidative stress, measured by the thiobarbituric acid reactive substances test, was correlated with ethoxyresorufin O-deethylase and was elevated in liver of the two highest PCB dose groups but not the low-dose group. The activities of the enzymatic antioxidants superoxide dismutase, catalase, and glutathione peroxidase were unaffected by PCB-126 exposure. The nonenzymatic antioxidants superoxide dismutase, catalase, and glutathione peroxidase were unaffected by PCB-126 exposure. The nonenzymatic antioxidant tocopherol was depleted to approximately 75% of the control concentration in liver of all three PCB-dosed groups. Hepatic ascorbic acid levels were not different in any of the treatment groups. Retinol was depleted by greater than an order of magnitude in liver of the two highest dose groups but not in the los-dose group. This study demonstrates a correlation between hepatic MFO activity and oxidative stress in PCB-exposed lake trout. Tocopherol and retinol may be important mediators of oxidative stress but additional study is required to confirm the antioxidant activity of retinol.

  1. Changes in cytochrome P4501A activity during development in common tern chicks fed polychlorinated biphenyls, as measured by the caffeine breath test

    SciTech Connect

    Feyk, L.A.; Giesy, J.P.; Bosveld, A.T.C.; Van den Berg, M.

    2000-03-01

    Cytochrome P4501A (CYPIA) activity is often used as a biomarker of exposure of wildlife to polyhalogenated diaromatic hydrocarbons and is usually measured ex vivo in liver tissue. A caffeine breath test (CBT) with radiolabeled substrate ({sup 14}C-caffeine) was used to measure in vivo CYP1A activity twice during development in 14 common tern (Sterna hirundo) chicks treated with polyhalogenated diaromatic hydrocarbons. Tern hatchlings were fed fish spiked with 3,3{prime}, 4,4{prime},5-pentachlorobiphenyl (PCB 126) and 2,2{prime},4,4{prime},5,5{prime}-hexachlorobiphenyl (PCB 153) such that the diet contained an average of 23, 99, or 561 pg of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents per gram of fish for 21 d. Sixteen additional common tern chicks were similarly dosed with polyhalogenated diaromatic hydrocarbons but were not subjected to the CBT procedure. In weeks 1 and 2, caffeine N-demethylation and ethoxyresorufin-O-deethylation activity on day 21 were elevated in birds that received the greatest PCB dose. There was less constitutive and greater induction of ethoxyresorufin-O-deethylation activity than caffeine N-demethylation. The {sup 14}C-CBT was less invasive than the ethoxyresorufin-O-deethylase assay. Only one morphological parameter differed significantly between CBT subjects and no-CBT subjects fed the same level of PCBs. Bursa weight was significantly less in control CBT subjects than in control no-CBT subjects, but bursa weights did not differ among CBT and no-CBT birds from the two PCB treatment groups. No alterations of survival or growth occurred in CBT subjects compared with no-CBT subjects.

  2. Effects of 17alpha-ethynylestradiol on hormonal responses and xenobiotic biotransformation system of Atlantic salmon (Salmo salar).

    PubMed

    Mortensen, Anne S; Arukwe, Augustine

    2007-11-30

    Pharmaceuticals are ubiquitous pollutants in the aquatic environment where their potential effects on non-target species like fish has only recently become subject of systematic investigations. In the present study, experiments were undertaken to examine the effects of a synthetic pharmaceutical endocrine disruptor, ethynylestradiol (EE2), given in water at 5 or 50 ng/L and sampled at days 0 (control), 3 and 7 after exposure, on hepatic phase I and II biotransformation and hormonal pathways of juvenile salmon using quantitative (real-time) polymerase chain reaction (qPCR), Vtg ELISA and 7-ethoxyresorufin O-deethylase (EROD) catalytic activity. Our data show that EE2 produced time- and concentration-specific modulation of estrogen receptor isoforms (ERalpha, ERbeta) and androgen receptor-beta (ARbeta). EE2 produced a concentration-specific induction of vitellogenin (Vtg) and zona radiata protein (Zr-protein) at day 3 after exposure. At day 7, Vtg and Zr-protein mRNA (and plasma Vtg protein) expression were significantly decreased in the group given 5 ng EE2/L, compared to dimethyl sulfoxide (DMSO) control group. In the xenobiotic biotransformation pathway, EE2 produced a significant increase of aryl hydrocarbon receptor-alpha (AhRalpha) at day 3 in the group given 5 ng EE2/L and AhRbeta was decreased at the same concentration at day 7. While CYP3A was not significantly affected by EE2 exposure, the CYP1A1, AhR nuclear translocator (Arnt) and AhR repressor (AhRR) mRNA showed an apparent EE2 concentration and time-dependent decrease. The expression of uridine diphosphoglucuronosyl transferase (UGT) and glutathione S-transferase class pi-like (GSTpi-like) mRNA were decreased after exposure to 50ng EE2/L at both day 3 and 7 after exposure. The effect of EE2 on the CYP1A1 gene expressions paralleled effect on EROD and AhRR mRNA, suggesting a direct role of EE2 in controlling cellular detoxification machinery. Interestingly, the carrier vehicle, DMSO produced significant

  3. Dioxinlike components in incinerator fly ash: a comparison between chemical analysis data and results from a cell culture bioassay.

    PubMed Central

    Till, M; Behnisch, P; Hagenmaier, H; Bock, K W; Schrenk, D

    1997-01-01

    Potent polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxinlike polychlorinated biphenyls (PCBs) are among the most relevant toxic emissions from incinerators. Induction of cytochrome P450 1A1-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity in mammalian cell culture (EROD bioassay) is thought to be a selective and sensitive parameter used for the quantification of dioxinlike compounds. Fly ash extracts from municipal waste incinerators (MWI), a crematorium, wood combustors, and a noble metal recycling facility were analyzed in the EROD bioassay using rat hepatocytes in primary culture. Fractions containing 2,3,7,8-substituted PCDDs/PCDFs, dioxinlike PCBs, and 16 major polycyclic aromatic hydrocarbons (PAHs) were isolated from the extract and analyzed by gas chromatography-mass spectrometry (GC-MS) and by the EROD bioassay. It was found that with MWI samples the bioassay of the extract resulted in a two- to fivefold higher estimate of TCDD equivalents (TEQ) than the chemical analysis of PCDDs/PCDFs and PCBs. However, the outcome of both methods was significantly correlated, making the bioassay useful as a rough estimate for the sum of potent PCDDs/PCDFs and dioxinlike PCBs in extracts from MWI fly ash samples and in a fly ash sample from a crematorium. In noble metal recycling facility and wood combustor samples, higher amounts of PAHs were found, contributing to more pronounced differences between the results of both methods. The remaining unexplained inducing potency in fly ash samples probably results from additional dioxinlike components including certain PAHs not analyzed in this study.The hypothesis that emissions from MWI of hitherto unidentified dioxinlike compounds are higher by orders of magnitude than emissions of potent PCDDs/PCDFs and dioxinlike PCBs could not be confirmed. We found no indication for a marked synergistic interaction of dioxinlike fly ash components in the bioassay. Images Figure 1. Figure

  4. Towards science-based sediment quality standards-Effects of field-collected sediments in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Brinkmann, Markus; Eichbaum, Kathrin; Reininghaus, Mathias; Koglin, Sven; Kammann, Ulrike; Baumann, Lisa; Segner, Helmut; Zennegg, Markus; Buchinger, Sebastian; Reifferscheid, Georg; Hollert, Henner

    2015-09-01

    Sediments can act as long-term sinks for environmental pollutants. Within the past decades, dioxin-like compounds (DLCs) such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) have attracted significant attention in the scientific community. To investigate the time- and concentration-dependent uptake of DLCs and PAHs in rainbow trout (Oncorhynchus mykiss) and their associated toxicological effects, we conducted exposure experiments using suspensions of three field-collected sediments from the rivers Rhine and Elbe, which were chosen to represent different contamination levels. Five serial dilutions of contaminated sediments were tested; these originated from the Prossen and Zollelbe sampling sites (both in the river Elbe, Germany) and from Ehrenbreitstein (Rhine, Germany), with lower levels of contamination. Fish were exposed to suspensions of these dilutions under semi-static conditions for 90 days. Analysis of muscle tissue by high resolution gas chromatography and mass spectrometry and of bile liquid by high-performance liquid chromatography showed that particle-bound PCDD/Fs, PCBs and PAHs were readily bioavailable from re-suspended sediments. Uptake of these contaminants and the associated toxicological effects in fish were largely proportional to their sediment concentrations. The changes in the investigated biomarkers closely reflected the different sediment contamination levels: cytochrome P450 1A mRNA expression and 7-ethoxyresorufin-O-deethylase activity in fish livers responded immediately and with high sensitivity, while increased frequencies of micronuclei and other nuclear aberrations, as well as histopathological and gross pathological lesions, were strong indicators of the potential long-term effects of re-suspension events. Our study clearly demonstrates that sediment re-suspension can lead to accumulation of PCDD/Fs and PCBs in fish

  5. How flood events affect rainbow trout: evidence of a biomarker cascade in rainbow trout after exposure to PAH contaminated sediment suspensions.

    PubMed

    Brinkmann, Markus; Hudjetz, Sebastian; Kammann, Ulrike; Hennig, Michael; Kuckelkorn, Jochen; Chinoraks, Michelle; Cofalla, Catrina; Wiseman, Steve; Giesy, John P; Schäffer, Andreas; Hecker, Markus; Wölz, Jan; Schüttrumpf, Holger; Hollert, Henner

    2013-03-15

    Increasing frequency and intensity of flood events are major concerns in the context of climate change. In addition to the direct hydrological implications of such events, potential ecotoxicological impacts are of increasing interest. It is vital to understand mechanisms of contaminant uptake from suspended particulate matter (SPM) and related effects in aquatic biota under realistic conditions. However, little is known about these processes. Due to recent changes in climate, during summer temperatures of German rivers frequently exceed 25°C. Effects of re-suspension of sediments on biota under elevated temperature regimes are likely to differ from those under lower temperature regimes. To elucidate this differential response of aquatic vertebrates, rainbow trout were exposed to suspensions of sediment from the Rhine River that was spiked with a mixture of polycyclic aromatic hydrocarbons (PAH). The experiments were conducted under two different temperature regimes (24°C or 12°C). Physicochemical parameters, including concentration of PAHs in SPM, and biomarkers in fish (biliary PAH metabolites, 7-ethoxyresorufin O-deethylase activity, lipid peroxidation (LPO), mRNA expression of some genes and micronuclei) were measured over the course of a 12d study. Concentrations of pyrene and phenanthrene decreased over time, while no decrease was observed for chrysene and benzo[a]pyrene. The biomarker cascades, more specifically the temporal dynamics of biomarker reactions, did not only show quantitative differences (i.e. different induction intensity or rate of biomarker responses) at the two temperatures but also qualitative differences, i.e. different biomarker responses were observed. A slight significant increase of biliary metabolites in fish was observed in un-spiked sediment at 24°C. In bile of fish exposed to PAH spiked sediment concentrations of 1-hydroxypyrene and 1-hydroxyphenanthrene increased significantly during the first two days, and then decreased. At 12

  6. Primary cultured cells as sensitive in vitro model for assessment of toxicants--comparison to hepatocytes and gill epithelia.

    PubMed

    Zhou, Bingsheng; Liu, Chunsheng; Wang, Jingxian; Lam, Paul K S; Wu, Rudolf S S

    2006-11-16

    In an effort to develop cultured cell models for toxicity screening and environmental biomonitoring, we compared primary cultured gill epithelia and hepatocytes from freshwater tilapia (Oreochromis niloticus) to assess their sensitivity to AhR agonist toxicants. Epithelia were cultured on permeable supports (terephthalate membranes, "filters") and bathed on the apical with waterborne toxicants (pseudo in vivo asymmetrical culture conditions). Hepatocytes were cultured in multi-well plates and exposed to toxicants in culture medium. Cytochrome P4501A (measured as 7-Ethoxyresorufin-O-deethylase, EROD) was selected as a biomarker. For cultured gill epithelia, the integrity of the epithelia remained unchanged on exposure to model toxicants, such as 1,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene B[a]P, polychlorinated biphenyl (PCB) mixture (Aroclor 1254), and polybrominated diphenyl ether (PBDE) mixture (DE71). A good concentration-dependent response of EROD activity was clearly observed in both cultured gill epithelia and hepatocytes. The time-course response of EROD was measured as early as 3h, and was maximal after 6h of exposure to TCDD, B[a]P and Aroclor 1254. The estimated 6h EC50 for TCDD, B[a]P, and Aroclor 1254 was 1.2 x 10(-9), 5.7 x 10(-8) and 6.6 x 10(-6)M. For the cultured hepatocytes, time-course study showed that a significant induction of EROD took place at 18 h, and the maximal induction of EROD was observed at 24h after exposure. The estimated 24h EC50 for TCDD, B[a]P, and Aroclor 1254 was 1.4 x 10(-9), 8.1 x 10(-8) and 7.3 x 10(-6)M. There was no induction or inhibition of EROD in DE71 exposure to both gill epithelia and hepatocytes. The results show that cultured gill epithelia more rapidly induce EROD and are slightly more sensitive than cultured hepatocytes, and could be used as a rapid and sensitive tool for screening chemicals and monitoring environmental AhR agonist toxicants.

  7. Structural features of cytochrome P450 1A associated with the absence of EROD activity in liver of the of the loricariid catfish Pterygoplichthys sp

    PubMed Central

    Parente, T.E.M.; Rebelo, M.F.; da-Silva, M.L.; Woodin, B.R.; Goldstone, J. V.; Bisch, P.M.; Paumgartten, F.J.R.; Stegeman, J.J.

    2011-01-01

    The Amazon catfish genus Pterygoplichthys (Loricariidae, Siluriformes) is closely related to the loricariid genus Hypostomus, in which at least two species lack detectable ethoxyresorufin-O-deethylase (EROD) activity, typically catalyzed by cytochrome P450 1 (CYP1) enzymes. Pterygoplichthys sp. liver microsomes also lacked EROD, as well as activity with other substituted resorufins, but aryl hydrocarbon receptor agonists induced hepatic CYP1A mRNA and protein suggesting structural/functional differences in Pterygoplichthys CYP1s from those in other vertebrates. Comparing the sequences of CYP1As of Pterygoplichthys sp. and of two phylogenetically-related siluriform species that do catalyze EROD (Ancistrus sp., Loricariidae and Corydoras sp., Callichthyidae) showed that these three proteins share amino acids at 17 positions that are not shared by any fish in a set of 24 other species. Pterygoplichthys and Ancistrus (the loricariids) have an additional 22 amino acid substitutions in common that are not shared by Corydoras or by other fish species. Pterygoplichthys has six exclusive amino acid substitutions. Molecular docking and dynamics simulations indicate that Pterygoplichthys CYP1A has a weak affinity for ER, which binds infrequently in a productive orientation, and in a less stable conformation than in CYP1As of species that catalyze EROD. ER also binds with the carbonyl moiety proximal to the heme iron. Pterygoplichthys CYP1A has amino acids substitutions that reduce the frequency of correctly oriented ER in the AS preventing the detection of EROD activity. The results indicate that loricariid CYP1As may have a peculiar substrate selectivity that differs from CYP1As of most vertebrates. PMID:21840383

  8. Survey of receiving-water environmental impacts associated with discharges from pulp mills; 2: Gonad size, liver size, hepatic erod activity and plasma sex steroid levels in white sucker

    SciTech Connect

    Munkittrick, K.R.; Servos, M.R. . Great Lakes Lab. for Fisheries and Aquatic Sciences); Van Der Kraak, G.J.; McMaster, M.E. . Dept. of Zoology); Portt, C.B. ); Heuvel, M.R. van den . Dept. of Biology)

    1994-07-01

    Fish collected from the receiving areas of 12 Canadian pulp mills were examined, including sites receiving effluent from kraft mills using chlorine as well as sulfite mills. Field collections included sampling of receiving water for chemistry and toxicity testing, and sampling of local fish for organ weights, hepatic MFO (ethoxyresorufin-O-deethylase, EROD) activity, plasma steroid levels, and levels of liver dioxins. The main objectives of this study were to determine whether the discharge of effluent from pulp mills to sites other than Jackfish Bay was associated with physiological or biochemical disruptions in wild fish, whether there was any correlation between waste treatment and the presence of biological responses in wild fish, and whether there was any association between the use of chlorine as a bleaching agent and these responses. Although white sucker collected near bleached-kraft mills exhibited the highest EROD induction and dioxin levels, elevated enzyme activity was observed in fish from sites that did not use chlorine, and depressions in plasma sex steroid levels was not correlated with the level of EROD activity. The absence of chlorine bleaching or the presence of secondary treatment did not eliminate responses in fish, including decreased circulating levels of sex steroids, decreased gonadal size, and increase liver size. This survey has shown that (a) induction of hepatic EROD enzymes and depressions of plasma sex steroid levels during gonadal growth are found downstream of several pulp mills; (b) these changes are seen at some mills without chlorine bleaching and at mills that have secondary treatment; (c) substantial dilutions of nontoxic effluent do not appear to remove these responses; (d) the dominant factor determining the presence or absence of responses appeared to be dilution level; and (e) lab toxicity tests on invertebrates, rainbow trout, and fat-head minnows could not predict the presence of these responses in wild fish.

  9. Generation of Tg(cyp1a:gfp) Transgenic Zebrafish for Development of a Convenient and Sensitive In Vivo Assay for Aryl Hydrocarbon Receptor Activity.

    PubMed

    Xu, Hongyan; Li, Caixia; Li, Yan; Ng, Grace Hwee Boon; Liu, Chunsheng; Zhang, Xiaoyan; Gong, Zhiyuan

    2015-12-01

    Both dioxins/dioxin-like compounds and polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants and cause multiple adverse health effects on human and wildlife. Cyp1a is the most commonly used biomarker induced by these pollutants through activation of the aryl hydrocarbon receptor (AhR) pathway. Here we generated Tg(cyp1a:gfp) transgenic zebrafish for establishing a convenient in vivo assay for analysing these xenobiotic compounds. The Tg(cyp1a:gfp) larvae at 4 day post-fertilization were tested with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and GFP induction was observed mainly in the kidney, liver and gut. Similar GFP expression was also induced strongly by two dioxin-like chemicals, co-planar polychlorinated biphenyl (PCB126) and polychlorinated dibenzo-p-furan (PeCDF) and relatively weakly by two PAHs, 3-methylcholanthrene (3-MC) and benzo[a]pyrene (BAP). The lowest observed effective concentration (LOEC) of TCDD was estimated to be ∼1 pM and the EC50 (effective concentration to induce GFP in 50 % of Tg(cyp1a:gfp) larvae) was ∼10 pM. PCB126 and PeCDF had ∼10× lower potencies in GFP induction than TCDD, while the potencies for 3-MC and BAP were at least 1000× lower. The sensitivity of Tg(cyp1a:gfp) larvae to respond TCDD was also favourable compared to that of ethoxyresorufin-O-deethylase (EROD) assay in both zebrafish larvae and adult livers. As GFP-based assay in transgenic zebrafish can be easily accommodated in multi-well dishes, the Tg(cyp1a:gfp) zebrafish should provide not only a valuable biomonitoring tool for aquatic contaminants but also a potential high-throughput chemical screening platform for identification of new AhR agonists.

  10. Evolved resistance to PCB- and PAH-induced cardiac teratogenesis, and reduced CYP1A activity in Gulf killifish (Fundulus grandis) populations from the Houston Ship Channel, Texas.

    PubMed

    Oziolor, Elias M; Bigorgne, Emilie; Aguilar, Lissette; Usenko, Sascha; Matson, Cole W

    2014-05-01

    The Houston Ship Channel (HSC), connecting Houston, Texas to Galveston Bay and ultimately the Gulf of Mexico, is heavily industrialized and includes several areas that have historically been identified as containing significant levels of mercury, dioxins, furans, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). Gulf killifish, Fundulus grandis, inhabit this entire estuarine system, including the most contaminated areas. F. grandis is the sister species of the well-established estuarine model organism Fundulus heteroclitus, for which heritable resistance to both PCB and PAH toxicity has been documented in several populations. F. grandis collected from two Superfund sites on the HSC and from a reference population were used to establish breeding colonies. F1 embryos from HSC populations were approximately 1000-fold more resistant to PCB126- and 2-5-fold more resistant to coal tar-induced cardiovascular teratogenesis, relative to embryos from the reference population. Reciprocal crosses between reference and contaminated populations exhibit an intermediate level of resistance, confirming that observed protection is genetic and biparentally inherited. Ethoxyresorufin-O-deethylase (EROD) data confirm a reduction in basal and induced cytochrome P4501A (CYP1A) activity in resistant populations of F. grandis. This result is consistent with responses previously described for resistant populations of F. heteroclitus, specifically a recalcitrant aryl hydrocarbon receptor (AHR) pathway. The decreased levels of cardiovascular teratogenesis, and decrease in CYP1A inducibility in response to PCB126 and a PAH mixture, suggest that HSC F. grandis populations have adapted to chronic contaminants exposures via a mechanism similar to that previously described for F. heteroclitus. To the best of our knowledge, this is the first documentation of evolved pollution resistance in F. grandis. Additionally, the mechanistic similarities between the population

  11. Evolved resistance to PCB- and PAH-induced cardiac teratogenesis, and reduced CYP1A activity in Gulf killifish (Fundulus grandis) populations from the Houston Ship Channel, Texas.

    PubMed

    Oziolor, Elias M; Bigorgne, Emilie; Aguilar, Lissette; Usenko, Sascha; Matson, Cole W

    2014-05-01

    The Houston Ship Channel (HSC), connecting Houston, Texas to Galveston Bay and ultimately the Gulf of Mexico, is heavily industrialized and includes several areas that have historically been identified as containing significant levels of mercury, dioxins, furans, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). Gulf killifish, Fundulus grandis, inhabit this entire estuarine system, including the most contaminated areas. F. grandis is the sister species of the well-established estuarine model organism Fundulus heteroclitus, for which heritable resistance to both PCB and PAH toxicity has been documented in several populations. F. grandis collected from two Superfund sites on the HSC and from a reference population were used to establish breeding colonies. F1 embryos from HSC populations were approximately 1000-fold more resistant to PCB126- and 2-5-fold more resistant to coal tar-induced cardiovascular teratogenesis, relative to embryos from the reference population. Reciprocal crosses between reference and contaminated populations exhibit an intermediate level of resistance, confirming that observed protection is genetic and biparentally inherited. Ethoxyresorufin-O-deethylase (EROD) data confirm a reduction in basal and induced cytochrome P4501A (CYP1A) activity in resistant populations of F. grandis. This result is consistent with responses previously described for resistant populations of F. heteroclitus, specifically a recalcitrant aryl hydrocarbon receptor (AHR) pathway. The decreased levels of cardiovascular teratogenesis, and decrease in CYP1A inducibility in response to PCB126 and a PAH mixture, suggest that HSC F. grandis populations have adapted to chronic contaminants exposures via a mechanism similar to that previously described for F. heteroclitus. To the best of our knowledge, this is the first documentation of evolved pollution resistance in F. grandis. Additionally, the mechanistic similarities between the population

  12. Evaluation of α-cyano ethers as fluorescent substrates for assay of cytochrome P450 enzyme activity

    PubMed Central

    Kang, Kyung-Don; Jones, Paul D.; Huang, Huazhang; Zhang, Rong; Mostovich, Lyudmila A.; Wheelock, Craig E.; Watanabe, Takaho; Gulyaeva, Lyudmila F.; Hammock, Bruce D.

    2006-01-01

    We have previously reported the synthesis of four α-cyano-containing ethers based on 2-naphthaldehyde (2-NA) as cytochrome P450 (P450) fluorescent substrates. Activity detection was based on the formation of fluorescent 2-NA following substrate hydrolysis. A major limitation of these substrates was the need to remove NADPH, a required cofactor for P450 oxidation, before measuring 2-NA fluorescence. In this article, we report the synthesis of a new series of novel P450 substrates using 6-dimethylamino-2-naphthaldehyde (6-DMANA), which has a green fluorescent emission that is well separated from the NADPH spectrum. A major advantage of the 6-DMANA substrates is that NADPH removal is not required before fluorescence detection. We used eight α-cyano ether-based substrates to determine the O-dealkylation activity of human, mouse, and rat liver microsomes. In addition, substrate activities were compared with the commercial substrate 7-ethoxyresorufin (7-ER). The catalytic turnover rates of both the 6-DMANA- and 2-NA-based substrates were in some cases threefold faster than the catalytic turnover rate of 7-ER. The 2-NA-based substrates had greater turnover than did the 6-DMANA-based substrates. Murine and rat liver microsomes prepared from animals that had been treated with various P450 inducers were used to examine for isozyme-selective turnover of the substrates. The vastly improved optical properties and synthetic flexibility of the α-cyano ether compounds suggest that they are possibly good general P450 substrates. PMID:16083846

  13. Evaluation of alpha-cyano ethers as fluorescent substrates for assay of cytochrome P450 enzyme activity.

    PubMed

    Kang, Kyung-Don; Jones, Paul D; Huang, Huazhang; Zhang, Rong; Mostovich, Lyudmila A; Wheelock, Craig E; Watanabe, Takaho; Gulyaeva, Lyudmila F; Hammock, Bruce D

    2005-09-15

    We have previously reported the synthesis of four alpha-cyano-containing ethers based on 2-naphthaldehyde (2-NA) as cytochrome P450 (P450) fluorescent substrates. Activity detection was based on the formation of fluorescent 2-NA following substrate hydrolysis. A major limitation of these substrates was the need to remove NADPH, a required cofactor for P450 oxidation, before measuring 2-NA fluorescence. In this article, we report the synthesis of a new series of novel P450 substrates using 6-dimethylamino-2-naphthaldehyde (6-DMANA), which has a green fluorescent emission that is well separated from the NADPH spectrum. A major advantage of the 6-DMANA substrates is that NADPH removal is not required before fluorescence detection. We used eight alpha-cyano ether-based substrates to determine the O-dealkylation activity of human, mouse, and rat liver microsomes. In addition, substrate activities were compared with the commercial substrate 7-ethoxyresorufin (7-ER). The catalytic turnover rates of both the 6-DMANA- and 2-NA-based substrates were in some cases threefold faster than the catalytic turnover rate of 7-ER. The 2-NA-based substrates had greater turnover than did the 6-DMANA-based substrates. Murine and rat liver microsomes prepared from animals that had been treated with various P450 inducers were used to examine for isozyme-selective turnover of the substrates. The vastly improved optical properties and synthetic flexibility of the alpha-cyano ether compounds suggest that they are possibly good general P450 substrates.

  14. Effects of triclosan on the detoxification system in the yellow catfish (Pelteobagrus fulvidraco): expressions of CYP and GST genes and corresponding enzyme activity in phase I, II and antioxidant system.

    PubMed

    Ku, Peijia; Wu, Xiaoyan; Nie, Xiangping; Ou, Ruikang; Wang, Lan; Su, Tian; Li, Yigang

    2014-11-01

    Triclosan (TCS), a broad-spectrum antibacterial agent widely used in pharmaceuticals and personal case products (PPCPs), has been universally detected in aquatic ecosystem in recent years. Unfortunately, there is limited information about its potential impacts on responses of genes and enzymes related to fish detoxification. In the present work, we cloned CYP3A and alpha-GST of yellow catfish (Pelteobagrus fulvidraco) and tested the transcriptional expression of CYP1A, CYP3A and GST as well as the alterations of their corresponding enzymes, including ethoxyresorufin-O-deethylase (EROD), aminopyrine N-demethylase (APND), erythromycin N-demethylase (ERND), glutathione S-transferase (GST) and catalase (CAT), and also the oxidative product malondialdehyde (MDA) content in the liver of P. fulvidraco exposed to TCS. Amino acids of CYP3A and GST were deduced and phylogenetic tree was constructed respectively. High identity percent was exhibited between P. fulvidraco and other species, such as other fish, birds and mammals. Results indicated that TCS significantly elevated CYP1A and GST but decreased CYP3A expression, EROD activity and MDA content at lower concentrations of TCS at 24h. Moreover, CYP3A and GST were significantly inhibited at 72 h but induced at 168 h at lower concentrations. However, CYP3A was always induced at the highest concentration during the exposure period. Furthermore, CYP3A, GST, GST enzyme and MDA content exhibited a dose-effect relationship to some extent, but no significant responses were observed in ERND, APND and CAT except for individual treatments. Taken together, EROD was the most sensitive to TCS exposure as compared to other enzymes. Meanwhile, mRNA responses were more sensitive in yellow catfish.

  15. Competitive inhibition of carcinogen-activating CYP1A1 and CYP1B1 enzymes by a standardized complex mixture of PAH extracted from coal tar

    SciTech Connect

    Mahadevan, B.; Marston, C.P.; Luch, A.; Dashwood, W.M.; Brooks, E.; Pereira, C.; Doehmer, J.; Baird, W.M.

    2007-03-15

    A complex mixture of polycyclic aromatic hydrocarbons (PAH) extracted from coal tar, the Standard Reference Material (SRM) 1597, was recently shown to decrease the levels of DNA binding of the 2 strong carcinogens benzo(a)pyrene (BP) and dibenzo(a,l)pyrene (DBP) in the human mammary carcinoma-derived cell line MCF-7. The present study was designed to further elucidate the biochemical mechanisms involved in this inhibition process. We examined the effects of SRM 1597 on the metabolic activation of BP and DBP toward DNA-binding derivatives in Chinese hamster cells expressing either human cytochrome P450 (CYP) 1A1 or CYP1B1. The data obtained from biochemical experiments revealed that SRM 1597 competitively inhibited the activity of both human enzymes as analyzed by 7-ethoxyresorufin O-deethylation assays. While the Michaelis-Menten constant (K-M) was {lt} 0.4 {mu}M in the absence of SRM 1597, this value increased up to 1.12 (CYP1A1) or 4.45 {mu}M (CYP1B1) in the presence of 0.1 {mu} g/ml SRM 1597. Hence the inhibitory effects of the complex mixture on human CYP1B1 were much stronger when compared to human CYP1A1 Taken together, the decreases in PAH-DNA adduct formation on co-treatment with SRM 1597 revealed inhibitory effects on the CYP enzymes that convert carcinogenic PAH into DNA-binding metabolites. The implications for the tumorigenicity of complex environmental PAR mixtures are discussed.

  16. Evaluation of mutagenic and antimutagenic activities of alpha-bisabolol in the Salmonella/microsome assay.

    PubMed

    Gomes-Carneiro, M R; Dias, Daniela M M; De-Oliveira, A C A X; Paumgartten, Francisco J R

    2005-08-01

    alpha-Bisabolol (BISA) is a sesquiterpene alcohol found in the oils of chamomile (Matricaria chamomilla) and other plants. BISA has been widely used in dermatological and cosmetic formulations. This study was undertaken to investigate the mutagenicity and antimutagenicity of BISA in the Salmonella/microsome assay. Mutagenicity of BISA was evaluated with TA100, TA98, TA97a and TA1535 Salmonella typhimurium strains, without and with addition of S9 mixture. No increase in the number of his+ revertant colonies over the negative (solvent) control values was observed with any of the four tester strains. In the antimutagenicity assays, BISA was tested up to the highest nontoxic dose (i.e. 50 and 150 microg/plate, with and without S9 mix, respectively) against direct-acting (sodium azide, SA; 4-nitroquinoline-N-oxide, 4-NQNO; 2-nitrofluorene, 2-NF; and nitro-o-phenylenediamine, NPD) as well as indirect-acting (cyclophosphamide, CP; benzo[a]pyrene, B[a]P; aflatoxin B1, AFB1; 2-aminoanthracene, 2-AA; and 2-aminofluorene, 2-AF) mutagens. BISA did not alter mutagenic activity of SA and of NPD, and showed only a weak inhibitory effect on the mutagenicity induced by 4-NQNO and 2-NF. The mutagenic effects of AFB1, CP, B[a]P, 2-AA and 2-AF, on the other hand, were all markedly and dose-dependently reduced by BISA. It was also found that BISA inhibited pentoxyresorufin-o-depentylase (PROD, IC50 2.76 microM) and ethoxyresorufin-o-deethylase (EROD, 33.67 microM), which are markers for cytochromes CYP2B1 and 1A1 in rat liver microsomes. Since CYP2B1 converts AFB1 and CP into mutagenic metabolites, and CYP1A1 activates B[a]P, 2-AA and 2-AF, results suggest that BISA-induced antimutagenicity could be mediated by an inhibitory effect on the metabolic activation of these promutagens. PMID:15936245

  17. 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

  18. Relative potency of polychlorinated dibenzo-p-dioxins and dibenzofurans for inducing mixed-function oxygenase activity in rainbow trout

    SciTech Connect

    Parrott, J.L.; Dixon, D.G.; Hodson, P.V.; Servos, M.R.; Huestis, S.L.

    1995-06-01

    Toxic equivalent factors (TEFs) were generated for various polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) to compare the relative potencies as inducers of liver mixed-function oxygenase (MFO) activity in rainbow trout (Oncorhynchus mykiss). Trout, dosed orally with one of five PCDD congeners, either [{sup 3}H]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PnCDD), 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (1,2,3,6,7,8-HxCDD), [{sup 14}C]-1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (1,2,3,4,7,8-HxCDD), or [{sup 14}C]-1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) or one of four PCDF congeners, either 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1,2,3,7,8-PnCDF), 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PnCDF), or 1,2,3,4,7,8--hexachlorodibenzofuran (HxCDF), showed increases in liver ethoxyresorufin O-deethylase (EROD) activity up to 250-fold. Liver concentrations of congeners were better predictors of EROD activity than oral dose. TEFs, ratios of the potency of each congener to that of TCDD, were calculated comparing ``threshold`` PCDD concentrations that induced EROD significantly above control levels. In cases of nonparallel dose-response curves between congeners, these comparisons are more relevant to environmental situations as PCDDs are compared at concentrations closer to those in the environment, instead of at higher pharmaceutical levels. Threshold-based TEFs were: PnCDD, 1.8; 1,2,3,6,7,8-HxCDD and 1,2,3,4,7,8-HxCDD, 0.4; HpCDD, 0.05; 2,3,4,7,8-PnCDF, 2; TCDF, 0.5; 1,2,3,7,8-PnCDF and HxCDF, 0.4. The ranking of potencies of the PCDFs was the same in fish as in mammalian tests, with the exception of PnCDD and 2,3,4,7,8-PnCDF, which were more potent to fish than was TCDD.

  19. Reduced cytochrome P4501A activity and recovery from oxidative stress during subchronic benzo[a]pyrene and benzo[e]pyrene treatment of rainbow trout

    SciTech Connect

    Curtis, Lawrence R.; Garzon, Claudia B.; Arkoosh, Mary; Collier, Tracy; Myers, Mark S.; Buzitis, Jon; Hahn, Mark E.

    2011-07-01

    This study assessed the role of aryl hydrocarbon receptor (AHR) affinity, and cytochrome P4501A (CYP1A) protein and activity in polyaromatic hydrocarbon (PAH)-induced oxidative stress. In the 1-100 nM concentration range benzo[a]pyrene (BaP) but not benzo[e]pyrene (BeP) competitively displaced 2 nM [{sup 3}H]2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin from rainbow trout AHR2{alpha}. Based on appearance of fluorescent aromatic compounds in bile over 3, 7, 14, 28 or 50 days of feeding 3 {mu}g of BaP or BeP/g fish/day, rainbow trout liver readily excreted these polyaromatic hydrocarbons (PAHs) and their metabolites at near steady state rates. CYP1A proteins catalyzed more than 98% of ethoxyresorufin-O-deethylase (EROD) activity in rainbow trout hepatic microsomes. EROD activity of hepatic microsomes initially increased and then decreased to control activities after 50 days of feeding both PAHs. Immunohistochemistry of liver confirmed CYP1A protein increased in fish fed both PAHs after 3 days and remained elevated for up to 28 days. Neither BaP nor BeP increased hepatic DNA adduct concentrations at any time up to 50 days of feeding these PAHs. Comet assays of blood cells demonstrated marked DNA damage after 14 days of feeding both PAHs that was not significant after 50 days. There was a strong positive correlation between hepatic EROD activity and DNA damage in blood cells over time for both PAHs. Neither CYP1A protein nor 3-nitrotyrosine (a biomarker for oxidative stress) immunostaining in trunk kidney were significantly altered by BaP or BeP after 3, 7, 14, or 28 days. There was no clear association between AHR2{alpha} affinity and BaP and BeP-induced oxidative stress. - Highlights: > No direct association between aryl hydrocarbon receptor affinity and polyaromatic hydrocarbon induced oxidative stress. > There was a strong correlation between cytochrome P4501A activity and oxidative stress as measured with the comet assay. > There was no correlation between cytochrome P

  20. Active biomonitoring in freshwater environments: early warning signals from biomarkers in assessing biological effects of diffuse sources of pollutants

    NASA Astrophysics Data System (ADS)

    Wepener, V.; van Vuren, J. H. J.; Chatiza, F. P.; Mbizi, Z.; Slabbert, L.; Masola, B.

    Effluents are a main source of direct and continuous input of pollutants in aquatic ecosystems. Relating observed effects to specific pollutants or even classes of pollutants remains a very difficult task due to the usually unknown, complex and often highly variable composition of effluents. It is recognized that toxicants interfere with organism integrity at the biochemical level and give rise to effects at the individual level and is manifested in reduced ecologically relevant characteristics such as growth, reproduction and survival, and ultimately at the ecosystem level. By integrating multiple endpoints at different ecologically relevant levels of organization within one test organism, it should be possible to gain understanding in how different levels of organization within this organism respond to toxic exposure and how responses at these different levels are interrelated. This paper presents results from a field study in the Rietvlei Wetland system, Gauteng, South Africa using the freshwater mollusk ( Melanoides tuberculata) and freshwater fish ( Oreochromis mossambicus) as bioindicator organisms. Active biomonitoring (ABM) exposures were conducted where organisms were exposed for 28 days in an effluent dominated river during high flow conditions in April 2003. The river receives effluent from a wastewater treatment plant and an industrial complex, so that up to 75% of the total flow of the river is effluent-based. Effects of field exposure were determined using cellular biomarkers e.g. DNA damage, HSP 70, metallothionein, acetylcholine esterase, lactate dehydrogenase and ethoxyresorufin-o-deethylase activity. The results clearly indicate that although the traditional mortality-based whole effluent toxicity testing did not indicate any toxicity, the in situ exposed organisms were stressed. A multivariate statistical approach was particularly useful for integrating the biomarker responses and highlighting sites at which more detailed analysis of chemical

  1. Polybrominated diphenyl ethers and polychlorinated dibenzo-p-dioxins and dibenzofurans in surface dust at an E-waste processing site in Southeast China.

    PubMed

    Leung, Anna O W; Zheng, Jinshu; Yu, Chik Kin; Liu, Wing Keung; Wong, Chris K C; Cai, Zongwei; Wong, Ming H

    2011-07-01

    Surface dust collected from printed circuit board recycling workshop floors, roads, a schoolyard, and an outdoor food market in Guiyu, China, a village intensely involved in e-waste processing, were investigated for levels of polybrominated diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). PBDE concentrations in dust from workshop-floors (14,800 ± 5130 ng/g) and on adjacent roads to the workshops (24,900 ± 31,600 ng/g) were highest among the study sites whereas PCDD/F concentrations were highest at the schoolyard (1316 pg/g) and in a workshop (1264 pg/g). Analyses of <2 mm and <53 μm dust particle sizes did not show any significant differences in PBDE concentrations. The cytotoxicity was investigated using two bioassays: 7-ethoxyresorufin O-deethylase (EROD-TEQ) and MTT. EROD-TEQ values ranged from 260 to 432 pg/g, with the highest in dust collected from a street lined with workshops. Using the MTT assay, cytoxicity of dust from the plastic chips drying district in Guiyu was higher than dust from the other sites investigated. This study showed that the primitive recycling of e-waste introduced toxic pollutants into the environment which are potentially harmful to the health of e-waste workers and local residents, especially children, and warrants an urgent investigation into POPs related health impacts.

  2. Contribution of hepatic cytochrome CYP1A and metallothionein mRNA abundance to biomonitoring-A case study with European flounder (Platichthys flesus) from the Gulf of Gdańsk.

    PubMed

    Kopecka-Pilarczyk, Justyna; Schirmer, Kristin

    2016-10-01

    The aim of the research was to explore the contribution of hepatic cytochrome CYP1A and metallothionein (MT) mRNA expression to biological effect monitoring. The study was conducted in the European flounder (Platichthys flesus) from the Gulf of Gdańsk. mRNA abundance was measured using reverse transcriptase polymerase chain reaction (RT-PCR) in liver RNA of fish sampled from three coastal stations and from one offshore station in the inner Gulf. The contribution of the mRNA-based biomarkers to the assessment of the environment was determined in conjunction with a selection of commonly applied biochemical markers: 7-ethoxyresorufin-O-deethylase (EROD), glutathione-S-transferase (GST), catalase (CAT), metallothioneins (MT), fluorescent aromatic compounds (FACs), all measured in the same individual fish. The mRNA biomarkers contributed to the separation between the sampling sites, but no correlations between CYP1A mRNA and EROD nor between MT mRNA and MT proteins were found, which should be attributed to the different levels these biomarkers correspond to and to the differences in factors that may affect them. One case of strong correlation between CYP1A mRNA and FACs was encountered. The overall results of this study suggest that biomarkers measured at the mRNA abundance level constitute a valuable addition to biomonitoring studies by providing additional information and contributing to the differentiation of results. PMID:27276230

  3. Chemical and bioanalytical characterization of dioxins in indoor dust in Hong Kong.

    PubMed

    Kang, Yuan; Cheung, Kwai Chung; Cai, Zong Wei; Wong, Ming H

    2011-05-01

    In the present work, air-conditioner filter dust samples collected from commercial office, secondary school, shopping mall, electronic factory and manufacturing plant in Hong Kong were collected for 7-ethoxyresorufin O-deethylase (EROD) assay using a hepatoma cell line (H4IIE) and chemical analysis of dioxins including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and PCBs with dioxin-like structure. The result of EROD assay showed that bioassay derived TEQ of 2,3,7,8-TCDD (TEQ(bio)) of dust samples varied from 320 to 730 pg/g. Chemical analyses revealed that chemical derived TEQ of 2,3,7,8-TCDD (TEQ(cal)) of dust samples ranged from 134 to 531 pg/g. In addition, the TEQ(cal) of samples were significantly correlated with TEQ(bio) of samples (R=0.83, P<0.01). The average daily doses (ADDs) of dioxins via indoor dust with the estimated ADDs of dioxins via air and food were compared. The results showed that indoor dust is an important medium of exposure to dioxins. PMID:21300406

  4. Passive sampler for combined chemical and toxicological long-term monitoring of groundwater: the ceramic toximeter.

    PubMed

    Bopp, Stephanie K; McLachlan, Michael S; Schirmer, Kristin

    2007-10-01

    We present the development of a passive sampling device that combines chemical with biological assessment of water following time-integrating, long-term sampling. The new device, which was designated the Ceramic Toximeter, brings together the simplicity of the Ceramic Dosimeter as a ceramic membrane-based, solid-sorbent sampler and the uniqueness of a recently developed solid-phase, solvent-free bioassay. In this bioassay, Biosilon, i.e., polystyrene polymer beads, is used to present sorbed contaminants to vertebrate cells that adhere to the contaminant-loaded Biosilon and respond. Focusing on Biosilon as sorbent, its ability to accumulate 16 polycyclic aromatic hydrocarbons (PAHs) was explored. When tested up to 42 days in the laboratory or 1 year in groundwater at a contaminated gasworks site, Biosilon-filled Ceramic Toximeters yielded back-calculated time-weighted average aqueous PAH concentrations that agreed well with concentrations obtained by frequent snapshot sampling. The chosen bioassay response, the induction of 7-ethoxyresorufin-O-deethylase, was as predicted in the laboratory setting but could only partly be explained by the analyzed PAHs in the field. Based on this first assessment, the Ceramic Toximeter emerges as a resource efficient water monitoring device with a variety of potential future applications. PMID:17969708

  5. Polybrominated diphenyl ethers and polychlorinated dibenzo-p-dioxins and dibenzofurans in surface dust at an E-waste processing site in Southeast China.

    PubMed

    Leung, Anna O W; Zheng, Jinshu; Yu, Chik Kin; Liu, Wing Keung; Wong, Chris K C; Cai, Zongwei; Wong, Ming H

    2011-07-01

    Surface dust collected from printed circuit board recycling workshop floors, roads, a schoolyard, and an outdoor food market in Guiyu, China, a village intensely involved in e-waste processing, were investigated for levels of polybrominated diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). PBDE concentrations in dust from workshop-floors (14,800 ± 5130 ng/g) and on adjacent roads to the workshops (24,900 ± 31,600 ng/g) were highest among the study sites whereas PCDD/F concentrations were highest at the schoolyard (1316 pg/g) and in a workshop (1264 pg/g). Analyses of <2 mm and <53 μm dust particle sizes did not show any significant differences in PBDE concentrations. The cytotoxicity was investigated using two bioassays: 7-ethoxyresorufin O-deethylase (EROD-TEQ) and MTT. EROD-TEQ values ranged from 260 to 432 pg/g, with the highest in dust collected from a street lined with workshops. Using the MTT assay, cytoxicity of dust from the plastic chips drying district in Guiyu was higher than dust from the other sites investigated. This study showed that the primitive recycling of e-waste introduced toxic pollutants into the environment which are potentially harmful to the health of e-waste workers and local residents, especially children, and warrants an urgent investigation into POPs related health impacts. PMID:21639085

  6. Biological fate and effects of propranolol in an experimental aquatic food chain.

    PubMed

    Ding, Jiannan; Lu, Guanghua; Li, Sheng; Nie, Yang; Liu, Jianchao

    2015-11-01

    The aim of this study was to evaluate the trophic transfer of the β-blocker propranolol (PRP) in an experimental aquatic food chain involving the green algae Scenedesmus obliquus, the water flea Daphnia magna and the crucian carp Carassius auratus, as well as the metabolism and effects of PRP in the liver of crucian carp. After a 48 h PRP aqueous exposure for algae, with a subsequent 48 h dietary exposure for daphnia and an 8d dietary exposure for crucian carp, PRP was observed in each trophic level, despite significant bioaccumulation did not occur in daphnia and crucian carp. A portion of the absorbed PRP was metabolized by the crucian carp to N-desisopropylated propranolol, propranolol glucuronic acid, monohydroxylated propranolol, hydroxypropranolol glucuronide and dihydroxypropranolol glucuronide, which were similar to those in mammals. In addition, multiple biomarkers in the liver of crucian carp (7-ethoxyresorufin O-deethylase, EROD; 7-benzyloxyresorufin O-dealkylation, BROD; superoxide dismutase, SOD and malondialdehyde, MDA) were measured. BROD and MDA were not significantly affected by PRP, while EROD and SOD did change significantly during the 8d dietary exposure. This work indicated that the trophic transfer of PRP, resulting in biochemical perturbations of fish biological systems, should be a concern for the assessment of the environmental risks to aquatic food chains.

  7. Sensitivity of embryos of chicken, domestic duck, and common eider duck to polychlorinated and non-halogenated aromatic hydrocarbons

    SciTech Connect

    Brunstroem, B.

    1995-12-31

    Embryos of chicken (Gallus domesticus), domestic duck (Anas platyrhynchos), and common eider duck (Somateria mollissima) were exposed in ovo to PCBs and to polycyclic aromatic hydrocarbons. Two coplanar PCBs, 3,3{prime},4,4{prime}-tetrachlorobiphenyl (PCB {number_sign}77) and 3,3{prime},4,4{prime},5-pentachlorobiphenyl (PCB {number_sign}126), were considerably more lethal and potent as inducers of 7-ethoxyresorufin O-deethylase (EROD) in chicken embryos (Gallus domesticus) than in embryos of the other two species. In chicken embryos, these compounds caused edema and eye and beak deformities. An artificial mixture of 18 PAHs which all have been detected in environmental samples, was slightly more toxic to embryos of the domestic duck and the common eider duck than to chicken embryos. The most potent compound in the mixture was benzo(k)fluoranthene. When chicken embryo livers were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vitro, EROD was induced by very low concentrations and the EC{sub 50} value obtained was 5 {times} 10{sup {minus}12} M. Livers from embryos of eider ducks and domestic ducks were 2--4 orders of magnitude less responsive to TCDD than chicken embryo livers in terms of EROD induction in vitro.

  8. Biological activity and physicochemical parameters of marine halogenated natural products 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole and 2,4,6-tribromoanisole.

    PubMed

    Vetter, W; Hahn, M E; Tomy, G; Ruppe, S; Vatter, S; Chahbane, N; Lenoir, D; Schramm, K-W; Scherer, G

    2005-01-01

    Physicochemical parameters (vapor pressure, water solubility, Henry's law constant) and biological activities of two halogenated natural products frequently detected in marine samples and food were determined. Synthetic 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole (Q1) and 2,4,6-tribromoanisole (TBA) were available in pure form. The physicochemical parameters were in the range of anthropogenic chlorinated compounds of concern. The aqueous solubilities at 25 degrees C (S(w,25)) of Q1 and TBA were 4.6 microg/L and 12,200 microg/L, respectively, whereas subcooled liquid vapor pressures were 0.00168 Pa (Q1) and 0.06562 Pa (TBA) as measured by the gas chromatographic-retention time technique. Q1 was negative by established test systems for the determination of ethoxyresorufin-O-deethylase (EROD) induction and by sulforhodamine B assay. EROD induction potency was at least 10(-7) times lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). At a relatively high concentration (20 microM), Q1 inhibited specific binding of 2 nM [(3)H]TCDD to the in vitro-expressed human aryl hydrocarbon receptor (AHR) by 18%; lower concentrations showed no effect. Molecular modeling showed that Q1 is nonplanar, consistent with its relatively modest affinity as an AHR ligand. When tested for cell-growth inhibitory/cytocidal activity in human tumor cells, Q1 was only marginally, if at all, active with an IC(50) value >50 microM compared with five to ten times lower IC(50) values for potent cytotoxins tested in the test system used. Furthermore, standard pesticide tests on insecticidal, herbicidal, and fungicidal activity did not provide any significant activity at highest concentrations. For TBA, the results in all tests were comparable with Q1. The SRB assay was also applied to the halogenated natural product 4,6-dibromo-2-(2',4'-dibromo)phenoxyanisole, but no toxic response was found. Although it was apparent that Q1 and TBA had been proven to have relatively low biological

  9. Risks of waterborne copper exposure to a cultivated freshwater Neotropical catfish (Rhamdia quelen).

    PubMed

    Mela, M; Guiloski, I C; Doria, H B; Rabitto, I S; da Silva, C A; Maraschi, A C; Prodocimo, V; Freire, C A; Randi, M A F; Ribeiro, C A Oliveira; de Assis, H C Silva

    2013-02-01

    As it is the case in all animal food production systems, it is often necessary to treat farmed fish for diseases and parasites. Quite frequently, fish farmers still rely on the aggressive use of copper to control bacterial infections and infestations by ecto-parasites, and to manage the spread of diseases. The susceptibility of the neotropical fish Rhamdia quelen to copper was here evaluated at different waterborne copper concentrations (2, 7 or 11 μg Cu L(-1)) for 96 h, through a multi biomarkers approach. Liver histopathological findings revealed leukocyte infiltration, hepatocyte vacuolization and areas of necrosis, causing raised levels of lesions upon exposure to 7 and 11 μg Cu L(-1). Decreased occurrence of free melano-macrophages and increased densities of melano-macrophage centers were noted upon exposure to 11 μg Cu L(-1). Gills showed damages on their secondary lamellae already at 2 μg Cu L(-1); hypertrophy and loss of the microridges of pavement cells at 7 and 11 μg L(-1), and increased in chloride cell (CC) apical surface area (4.9-fold) and in CC density (1.5-fold) at 11 μg Cu L(-1). In the liver, catalase (CAT), glutathione peroxidase activities (GPx) and glutathione concentration (GSH) remained unchanged, compared to the control group. However, there was inhibition of 7-ethoxyresorufin-O-deethylase (EROD) at all copper concentrations tested. Glutathione reductase activity (GR) was reduced and levels of lipid peroxidation (LPO) were increased at 11 μg Cu L(-1). Glutathione S-transferase activity (GST) at 7 μg Cu L(-1) and superoxide dismutase activity (SOD) at both 7 and 11 μg Cu L(-1) were reduced. However, copper exposure did not alter brain and muscle acetylcholinesterase (AChE) activity. Osmoregulatory function was also disturbed, in agreement with the above-mentioned changes noted in the gills, as detected by plasma osmolality reduction in the group exposed to 11 μg Cu L(-1), and plasma chloride reduction at 2 μg Cu L(-1). These

  10. Davis Pond Freshwater Prediversion Biomonitoring Study: Freshwater Fisheries and Eagles

    USGS Publications Warehouse

    Jenkins, Jill A.; Bourgeois, E. Beth; Jeske, Clint W.

    2008-01-01

    pesticides and other contaminants. Biomarker data on individual fish, generated at the USGS National Wetlands Research Center (Lafayette, La.), included percent white blood cells in whole blood, spleen weight to body weight ratio, liver weight to body weight ratio, condition factor, splenic macrophage aggregates, and liver microsomal 7-ethoxyresorufin-o-deethylase (EROD) activity. Fish age was estimated by comparing total lengths with values from the same species in the Southeast United States as determined from the literature. Contaminant analyses were coordinated by the U.S. Fish and Wildlife Service (USFWS) Analytical Control Facility (Laurel, Md.), where residues of organochlorine (OC) pesticides, total polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), aliphatic hydrocarbons (AHs), and trace elements were determined. The organic contaminant data were generated at the Mississippi State University Chemical Lab (Mississippi State, Miss.), and the inorganic contaminant data were generated by the Texas A&M University Geochemical and Environmental Research Group (College Station, Tex.). Statistical tests were performed to assess relationships among contaminants, fish age, fish species, and collection sites.

  11. Discovery and Biological Characterization of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole as an Aryl Hydrocarbon Receptor Activator Generated by Photoactivation of Tryptophan by Sunlight

    PubMed Central

    Diani-Moore, Silvia; Ma, Yuliang; Labitzke, Erin; Tao, Hui; Warren, J. David; Anderson, Jared; Chen, Qiuying; Gross, Steven S.; Rifkind, Arleen B.

    2011-01-01

    Activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is required for AHR dependent transcriptional activation and TCDD toxicity. We previously reported that aqueous tryptophan exposed to sunlight through window glass (aTRP) contains multiple photoproducts, including the well characterized 6-formylindolo[3,2-b]carbazole (FICZ), capable of activating the AHR and inducing CYP1A and CYP1A-mediated enzyme activities. We report here the isolation from aTRP and chemical characterization and synthesis of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole (IPI), a compound previously identified as a natural product of marine ascidia and now shown to be a TRP photoproduct with AHR-inducing properties. IPI, FICZ and TCDD produced equieffective induction of CYP1A-mediated 7-ethoxyresorufin deethylase (EROD) activity in chick embryo primary hepatocytes and mammalian Hepa1c1c7 cells. EROD induction by IPI was markedly curtailed in AHR-defective c35 cells, supporting the AHR dependence of the IPI response. Although IPI had a higher EC50 for EROD induction than FICZ, the much larger amount of IPI than FICZ in aTRP makes IPI a prominent contributor to EROD induction in aTRP. IPI was detected in TRP-containing culture medium under ambient laboratory conditions but not in TRP-free medium, consistent with its production from TRP. Cotreatment of hepatocytes with submaximal EROD-inducing doses of IPI and FICZ or TCDD produced additive increases in EROD without synergistic or inhibitory interactions. IPI and FICZ were readily metabolized by cultured hepatocytes. In addition to increasing CYP1A4 mRNA and EROD, IPI and FICZ decreased hepatocyte phosphoenolpyruvate carboxykinase mRNA expression and glucose output, biological effects associated with TCDD metabolic dysregulation. The findings underscore a role for sunlight in generating AHR-activating bioactive molecules. PMID:21722628

  12. Monoclonal antibody-directed phenotyping of cytochrome P-450-dependent aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase in mammalian tissues

    SciTech Connect

    Fujino, T.; West, D.; Park, S.S.; Gelboin, H.V.

    1984-07-25

    The distribution of cytochromes P-450 that catalyze aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase were studied with monoclonal antibody (MAb) 1-7-1 which completely inhibits these activities of a purified 3-methylcholanthrene-induced rat liver cytochrome P-450. The degree of inhibition by MAb 1-7-1 quantitatively assesses the contribution of different cytochromes P-450 in the liver, lung, and kidney microsomes from untreated, 3-methylcholanthrene- and phenobarbital (PB)-treated rats, mice, guinea pigs, and hamsters. Enzyme sensitivity to MAb 1-7-1 inhibition defines two types of cytochrome P-450 contributing to aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase. The MAb 1-7-1 sensitive cytochrome P-450 is a major contributor to aryl hydrocarbonhydroxylase in rat liver, lung, and kidney of 3-methylcholanthrene-treated rats, C57BL/6 mice, guinea pigs, and hamsters. 7-Ethoxycoumarin 0-deethylase is also a function of both the MAb 1-7-1-sensitive and insensitive classes of cytochromeP-450. The ratio of the classes contributing to aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase differs in the various tissues and species and after inducer treatment. All of the 7-ethoxycoumarin O-deethylase activity in guinea pigs and hamsters is a function of cytochromes P-450 different than the MAb 1-7-1-sensitive cytochrome P-450 responsible for aryl hydrocarbon hydroxylase activity. Thus, the MAb 1-7-1 antigenically defines the type of cytochromes P-450 contributing to each reaction.

  13. Activities.

    ERIC Educational Resources Information Center

    Kincaid, Charlene; And Others

    1993-01-01

    Presents an activity in which students collect and organize data from a real-world simulation of the scientific concept of half life. Students collect data using a marble sifter, analyze the data using a graphing calculator, and determine an appropriate mathematical model. Includes reproducible worksheets. (MDH)

  14. Activities.

    ERIC Educational Resources Information Center

    Mathematics Teacher, 1982

    1982-01-01

    The material presented is designed to help students explore geometric patterns involving Fibonnaci numbers and the golden ratio, and to aid in review of basic geometry skills. Worksheet masters intended for duplication are provided. Suggestions are made of possible classroom extensions to the initial activities. (MP)

  15. Some polybrominated diphenyl ether (PBDE) flame retardants with wide environmental distribution inhibit TCDD-induced EROD activity in primary cultured carp (Cyprinus carpio) hepatocytes.

    PubMed

    Kuiper, R V; Bergman, A; Vos, J G; van den Berg, M

    2004-06-10

    Ethoxyresorufin-O-deethylase (EROD) activity, a catalytic function of the cytochrome P450 1A (CYP1A) microsomal oxygenase subfamily, is a popular biomarker for exposure to xenobiotics, polyhalogenated aromatic hydrocarbons (PHAHs) in particular. It has found wide use in aquatic pollution assessment both in vivo and in vitro. In such studies, subjects are often exposed to complex mixtures where various constituents can interfere with EROD-activity, possibly resulting in inadequate estimation of toxic hazard or biological response. The present study investigates the effects of polybrominated diphenyl ethers (PBDEs), a relatively new and increasingly detected group of environmental contaminants, on the validity of EROD activity as exposure marker in carp (Cyprinus carpio) hepatocytes. Freshly isolated hepatocytes of a genetically uniform strain of male carp were co-exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at concentrations of 0, 1, 3, 10, 30, and 100 pM, and one of the highly purified PBDE/PCB congeners (at concentrations of 0, 0.25, and 2.5 microM) or cleaned-up and untreated DE-71 samples (0, 0.1, and 1 microM). PBDEs were selected from the 209 possible congeners based on their relative abundance in environmental samples: BDE-47, BDE-99, BDE-100, and BDE-153. A tentative metabolite of BDE-47, 6OH-BDE-47, was also included. In addition, a commercial pentabrominated dipenylether mixture (DE-71) was tested for interference with EROD activity both with and without clean-up by carbon fractionating which removed possible planar contaminants. Polychlorinated biphenyl (PCB)-153, a reported inhibitor of EROD activity in flounder, was included for comparison. Cells were cultured for a total period of 8 days; exposure started at day 3 after cell isolation. After 5 days of exposure, cell pellets were frozen before EROD activity was determined. Upon exposure to TCDD, the cells responded with increased EROD activity as expected. Significant reduction of TCDD

  16. Biological and chemical determination of dioxin-like compounds in sediments by means of a sediment triad approach in the catchment area of the river Neckar.

    PubMed

    Hollert, Ner; Dürr, Matthias; Olsman, Helena; Halldin, Krister; van Bavel, E; Brack, Werner; Tysklind, Mats; Engwall, Magnus; Braunbeck, Thomas

    2002-10-01

    To evaluate the sediment quality of selected sites in the catchment area of the River Neckar, an integrative assessment approach was used to assess the ecological hazard potential of dioxin-like sediment compounds. The approach is based on 7-ethoxyresorufin-O-deethylase (EROD) induction in embryonic chicken liver culture and comprehensive chemical analyses of polycyclic aromatic hydrocarbons (priority PAHs according to the US Environmental Protection Agency). The majority of the sediment extracts exhibited high potencies as EROD-inducers. In one sediment sample, which was influenced by a sewage treatment plant, a very high concentration of 930 ng bioassay 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (bio-TEQs )/g organic carbon could be determined. However, in none of the samples, more than 6% of the EROD-inducing potency could be explained by the PAHs analyzed chemically. Thus, non-analyzed compounds with EROD-inducing potency were present in the extracts. A fractionation of sediment samples according to pH allowed to localize the major part of EROD-inducing compounds in the neutral fractions. However, a significant portion of the EROD induction could also be explained by the acidic fractions. Following the concept of the Sediment Quality Triad according to Chapman, in situ alterations of macrozoobenthos were examined. A comparison of the results predicted by the EROD assay and chemical analyses with alterations in situ, as measured by means of the saprobic index and the ecotoxicological index according to Carmargo, revealed a high ecological relevance of the results of bioassays and chemical analyses for major sites. PMID:12463678

  17. A new approach of Integrated Health Responses (IHR(s)) modeling for ecological risk/health assessments of an urban stream.

    PubMed

    Kim, Ja-Hyun; Yeom, Dong-Hyuk; An, Kwang-Guk

    2014-08-01

    The objective of this study was to evaluate the ecological health of an urban stream using Integrated Health Responses (IHRs). Water chemistry analysis, habitat health, and ecotoxicity tests were conducted in the stream along with analyses of molecular/biochemical, physiological biomarkers, and population-level responses in indicator species. Chemical stresses, measured as nutrient levels, ionic content and organic matter concentrations were significantly greater (p<0.01) at the downstream than the reference site (RF). The habitat health was largely impacted in the downstream reaches and had a negative relation with the land-use pattern of % urban area. Comet assay, 7-ethoxyresorufin-O-deethylase (EROD), acetylcholinesterase (AChE), and vitellogenin (VTG) were evaluated for low-level biomarker responses on DNA/physiological conditions of target species. The multi-metric fish model (Mm-F) was used to test the community-level response in relation to chemical and physical habitat stresses. The impaired responses of separate biomarker and bioindicator at the downstream sites occurred at all organizations from molecular/biochemical level to community level. Using all biomarkers/bioindicators, the star-plot model of IHRs was developed and then the integrative health/risk assessments were conducted in the urban stream. The reduced values of IHRs occurred in the downstream sites and the impacts were attributed to effluents from wastewater treatment plants (WTPs) and industrial complex. Ecological health impairments, thus, were evident in the urban reach, and reflected the long-term community responses as well as short-term responses of molecular biomarkers. The degradation of the urban stream was mainly due to a combined effect of chemical pollution and physical habitat modifications.

  18. Correlation between CYP1A1 transcript, protein level, enzyme activity and DNA adduct formation in normal human mammary epithelial cell strains exposed to benzo[a]pyrene

    PubMed Central

    Divi, Rao L.; Einem Lindeman, Tracey L.; Shockley, Marie E.; Keshava, Channa; Weston, Ainsley; Poirier, Miriam C.

    2014-01-01

    The polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BP) is thought to bind covalently to DNA, through metabolism by cytochrome P450 1A1 (CYP1A1) and CYP1B1, and other enzymes, to form r7, t8, t9-trihydroxy-c-10-(N 2-deoxyguanosyl)-7,8,9,10-tetrahydro-benzo[a]-pyrene (BPdG). Evaluation of RNA expression data, to understand the contribution of different metabolic enzymes to BPdG formation, is typically presented as fold-change observed upon BP exposure, leaving the actual number of RNA transcripts unknown. Here, we have quantified RNA copies/ng cDNA (RNA cpn) for CYP1A1 and CYP1B1, as well as NAD(P)H:quinone oxidoreductase 1 (NQO1), which may reduce formation of BPdG adducts, using primary normal human mammary epithelial cell (NHMEC) strains, and the MCF-7 breast cancer cell line. In unexposed NHMECs, basal RNA cpn values were 58–836 for CYP1A1, 336–5587 for CYP1B1 and 5943–40112 for NQO1. In cells exposed to 4.0 µM BP for 12h, RNA cpn values were 251–13234 for CYP1A1, 4133–57078 for CYP1B1 and 4456–55887 for NQO1. There were 3.5 (mean, range 0.2–15.8) BPdG adducts/108 nucleotides in the NHMECs (n = 16), and 790 in the MCF-7s. In the NHMECs, BP-induced CYP1A1 RNA cpn was highly associated with BPdG (P = 0.002), but CYP1B1 and NQO1 were not. Western blots of four NHMEC strains, chosen for different levels of BPdG adducts, showed a linear correlation between BPdG and CYP1A1, but not CYP1B1 or NQO1. Ethoxyresorufin-O-deethylase (EROD) activity, which measures CYP1A1 and CYP1B1 together, correlated with BPdG, but NQO1 activity did not. Despite more numerous levels of CYP1B1 and NQO1 RNA cpn in unexposed and BP-exposed NHMECs and MCF-7cells, BPdG formation was only correlated with induction of CYP1A1 RNA cpn. The higher level of BPdG in MCF-7 cells, compared to NHMECs, may have been due to a much increased induction of CYP1A1 and EROD. Overall, BPdG correlation was observed with CYP1A1 protein and CYP1A1/1B1 enzyme activity, but not with CYP1B1 or NQO

  19. Induction of cytochrome P4501A1 by aryl hydrocarbon receptor agonists in porcine aorta endothelial cells in culture and cytochrome P4501A1 activity in intact cells.

    PubMed

    Stegeman, J J; Hahn, M E; Weisbrod, R; Woodin, B R; Joy, J S; Najibi, S; Cohen, R A

    1995-02-01

    Endothelium is a single-cell layer lining blood vessels and constituting capillaries and could be a primary site of chemical effects in the cardiovasculature and systemically. Cytochrome P4501A1 (CYP1A1) is strongly inducible in vertebrate endothelium in vivo by aryl hydrocarbon receptor (AhR) agonists [Mol. Pharmacol. 36:723-729 (1989); Mol. Pharmacol. 41:1039-1046 (1992)]. We investigated CYP1A expression and activity in porcine aorta endothelial cells (PAEC) exposed in culture to the AhR agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4'-tetrachlorobiphenyl (TCB), benzo[a]pyrene (BP), or beta-naphthoflavone (BNF). Immunoblotting with monoclonal anti-CYP1A1 and polyclonal anti-CYP1A1 and anti-CYP1A2 antibodies showed that CYP1A1 was induced in cultures exposed to TCDD, TCB, BP, or BNF but was not detectable in untreated or dimethylsulfoxide-exposed cultures. CYP1A1 was strongly induced at intermediate concentrations (0.1 microM or 1.0 microM) of TCB, BP, or BNF, but induction was suppressed by higher concentrations, a response not due to general toxicity; cell viability (trypan blue exclusion) was > 97% with BNF or TCB at up to 10 microM. CYP1A1 induction by TCDD was maximal at 0.3-1.0 nM. ED50 values for induction of CYP1A1 by TCDD, TCB, and BP were 0.016 nM, 3-10 nM, and 180 nM, respectively. Immunohistochemical analysis confirmed CYP1A1 induction in PAEC but also showed that only some cells in the cultures were induced. Subcellular fractionation, marker enzyme analysis, and immunoblot analysis showed that PAEC had a typical complement of microsomal electron-transport components. NADPH-cytochrome P450 reductase showed comparable rates (approximately 40 nmol/min/mg) in induced and control cultures. Cultures maximally induced by 0.1 microM TCB had microsomal CYP1A1 [ethoxyresorufin-O-deethylase (EROD)] activity averaging 25 pmol/min/mg. Addition of purified rat reductase to PAEC microsomes increased the EROD rates 3-fold. EROD rates measured in intact

  20. Ecotoxicological risks associated with land treatment of petrochemical wastes. II. Effects on hepatic phase I and phase II detoxification enzymes in cotton rats.

    PubMed

    Carlson, Ruth; Wilson, James; Lochmiller, Robert; Janz, David; Schroder, Jackie; Basta, Nicholas

    2003-02-28

    The purpose of this study was to evaluate possible exposure and resultant hepatic effects of petrochemical waste on cotton rats (Sigmodon hispidus) living on landfarmed sites. Male and female cotton rats were collected in summer, fall, and winter from four landfarm sites and four ecologically similar reference sites. Hepatic methoxyresorufin O-deethylase (MROD) activity was significantly induced in male and female rats collected from landfarms compared to rats collected from reference sites. In contrast, changes in ethoxyresorufin O-deethylase (EROD) activity were inconsistent due to season, sex, and treatment variation. A significant decrease in EROD and MROD activity was found in cotton rats held for 48 h prior to sacrifice compared to rats euthanized on the day of capture. These results indicate that when using hepatic EROD and MROD activities as biochemical markers of exposure to aryl hydrocarbon receptor agonists, animals should be euthanized as quickly as possible after capture. The cotton rats collected from one landfarm unit exhibited a pattern of consistent elevation of EROD, MROD, and pent-oxyresorufin O-deethylase (PROD) activity. This unit also had a pattern of elevated CYP1A2 protein expression determined by Western blotting. There were no consistent alterations from contaminant exposure on hepatic glutathione S-transferase (GST) activity, glutathione levels, or CYP1A1 protein. Hepatic EROD and MROD activities varied considerably between seasons and sex of rats. In conclusion, consistent induction of hepatic EROD and MROD activities in cotton rats was found in three out of four sampled landfarm sites compared to the rats collected from the reference sites, indicating exposure to contaminants-likely polyaromatic hydrocarbons.

  1. Nonrespiratory metabolic function and morphology of lung following exposure to polybrominated biphenyls in rats

    SciTech Connect

    McCormack, K.M.; Roth, R.A.; Wallace, K.B.; Ross, L.M.; Hook, J.B.

    1982-01-01

    Exposure to polybrominated biphenyls (PBBs) resulted in increased activity of microsomal arylhydrocarbon hydroxylase and ethoxyresorufin-O-deethylase in rat lung. Clearance of 5-hydroxytryptamine (5-HT) and angiotensin I by perfused lungs was decreased by PBBs. However, PBBs had no effect on the activity of epoxide hydrolase, monoamine oxidase, or angiotensin-converting enzyme in lung. The only hisotpathlogic change detected in lungs from PBB-treated rats was an increase in alveolar type II cell lamellar bodies. Selective accumulation of certain PBB congeners by lung was not observed in this investigation.

  2. Qualitative and quantitative changes in cytochrome P-450-dependent xenobiotic metabolism in pulmonary microsomes and isolated Clara cell populations derived from ozone-exposed rats

    SciTech Connect

    Rietjens, I.M.C.M.; Dormans, J.A.M.A.; Rombout, P.J.A.; van Bree, L.

    1988-01-01

    The effect of a prolonged ozone exposure (1.6 mg ozone/m/sup 3/; 7 d; 24 h/d) on pulmonary cytochrome P-450-dependent xenobiotic metabolism was studied both in whole rat lung as well as in isolated bronchiolar Clara cell preparations. Ozone exposure was demonstrated to result in significant quantitative but also qualitative changes. All components of the pulmonary microsomal electron transport system appeared to be significantly increased in the lungs of exposed animals both per lung and per gram lung, although increases were no longer observed when expressed per milligram microsomal lung protein. Remarkably, it was demonstrated that the increases in the components of the pulmonary cytochrome P-450 system were not accompanied by a concomitant increase in all cytochrome P-450-dependent substrate conversions. In whole-lung microsomes ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities were unchanged or even significantly reduced when expressed per lung, per gram lung, per milligram microsomal protein, or per picomole cytochrome P-450. In contrast to these observations, pentoxyresorufin O-dealkylation appeared to be significantly increased upon ozone exposure when expressed per lung, per gram lung, and even per picomole cytochrome P-450.

  3. Reciprocal inhibiting interactive mechanism between the estrogen receptor and aryl hydrocarbon receptor signaling pathways in goldfish (Carassius auratus) exposed to 17β-estradiol and benzo[a]pyrene.

    PubMed

    Yan, Zhenhua; Lu, Guanghua; He, Junjie

    2012-06-01

    In the aquatic environment, both the estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) responses are established biomarkers for assessing exposure to pollutants. These receptor responses can also be affected by the presence of other classes of pollutants and may result in misinterpretation of existing pollution. In this study, we investigated the interaction between ER-vitellogenin (VTG) and AhR-cytochrome P450 1A (CYP1A) signaling pathways in goldfish (Carassius auratus) after 10 days exposure to pollutants. 17β-Estradiol (E(2)) and benzo[a]pyrene (BaP) were selected as the ER and AhR agonists, respectively. The messenger RNA (mRNA) expression of ER-VTG and AhR-CYP1A in liver was determined using quantitative real-time polymerase chain reaction (QRT-PCR). VTG, endogenous E(2) and 7-ethoxyresorufin-O-deethylase (EROD) were also studied. Exposure to E(2) and BaP alone significantly induced the gene expression of ERα-VTG and AhR2-CYP1A, respectively. Moreover, the obvious expression of related proteins was also observed. However, these inductions were significantly reduced after combined exposure to E(2) and lower concentrations of BaP (20 and 50 μg/L), indicative of a reciprocal inhibiting ER-AhR interaction. However, high concentrations (100 μg/L) of BaP did not affect the E(2)-induced gene expression. Changes in VTG protein were in accordance with the expression of VTG mRNA, and more VTG protein was observed in liver than in serum. The induced endogenous E(2) levels were suppressed by the presence of BaP. While the gene expression of CYP1A showed a concentration-dependent increase, EROD induction exhibited a bell-shaped concentration-response curve. Taken together, these results demonstrate a reciprocal inhibiting mode of ER-AhR interactions and may lead to a possible underestimation of actual exposure.

  4. Two cytochrome P-450 isoforms catalysing O-de-ethylation of ethoxycoumarin and ethoxyresorufin in higher plants.

    PubMed Central

    Werck-Reichhart, D; Gabriac, B; Teutsch, H; Durst, F

    1990-01-01

    The O-dealkylating activities of 7-ethoxycoumarin O-de-ethylase (ECOD) and 7-ethoxyresorufin O-de-ethylase (EROD) have been fluorimetrically detected in microsomes prepared from manganese-induced Jerusalem artichoke tubers. Cytochrome P-450 dependence of the reactions was demonstrated by light-reversed CO inhibition, NADPH-dependence, NADH-NADPH synergism and by use of specific inhibitors: antibodies to NADPH-cytochrome P-450 reductase, mechanism-based inactivators and tetcyclasis. Apparent Km values of 161 microM for 7-ethoxycoumarin and 0.4 microM for 7-ethoxyresorufin were determined. O-De-ethylase activity was also detected in microsomes prepared from several other plant species, including wheat, maize, tulip, avocado and Vicia. ECOD and EROD were low or undetectable in uninduced plant tissues, and both activities were stimulated by wounding or by chemical inducers. Two distinct cytochrome P-450 isoforms are involved in ECOD and EROD activities since (1) they showed different distributions among plant species; (2) they showed contrasting inhibition and induction patterns; and (3) ECOD but not EROD activity was supported by cumene hydroperoxide. PMID:2241905

  5. NTP technical report on the toxicology and carcinogenesis studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (CAS No. 1746-01-6) in female Harlan Sprague-Dawley rats (Gavage Studies).

    PubMed

    2006-04-01

    year 2 of the study, and those of 22 ng/kg rats were less than those of the vehicle controls the last 10 weeks of the study. THYROID HORMONE CONCENTRATIONS: Alterations in serum thyroid hormone levels were evaluated at the 14-, 31- and 53-week interim evaluations. At 14 weeks, there were significant decreases in serum total and free thyroxine (T4) levels and increases in serum total triiodothyronine (T3) and thyroid stimulating hormone (TSH). At 31 weeks, there were significant decreases in serum total and free T4 levels and increases in serum total T3 but no significant effect on TSH. At 53 weeks, there were significant decreases in serum total T4 levels and increases in serum total T3. There were no significant effects on total T4 or TSH levels. HEPATIC CELL PROLIFERATION DATA: To evaluate hepatocyte replication, analysis of labeling of replicating hepatocytes with 5-bromo-2'-deoxyuridine was conducted at the 14-, 31-, and 53-week interim evaluations. The hepatocellular labeling index was significantly higher in the 22 ng/kg group compared to vehicle controls at 14 weeks. At the 31-week interim evaluation, the labeling indices in hepatocytes were significantly higher in all dosed groups than in the vehicle controls. At 53 weeks, labeling indices were significantly higher in the 46 and 100 ng/kg groups than in the vehicle controls. CYTOCHROME P450 ENZYME ACTIVITIES: To evaluate the expression of known dioxin-responsive genes, CYP1A1-associated 7-ethoxyresorufin-O-deethylase (EROD) activity and CYP1A2-associated acetanilide-4-hydroxylase (A4H) activity were evaluated at 14, 31, and 53 weeks. In addition, pentoxyresorufin-O-deethylase (PROD) activity was analyzed. Hepatic EROD, PROD, and A4H activities were significantly higher in all dosed groups relative to vehicle controls at the 14-, 31-, and 53-week interim evaluations. Pulmonary EROD was also significantly higher in all dosed groups compared to vehicle controls at 14, 31, and 53 weeks. DETERMINATIONS OF TCDD

  6. NTP toxicology and carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) (CAS No. 57465-28-8) in female Harlan Sprague-Dawley rats (Gavage Studies).

    PubMed

    2006-01-01

    ENZYME ACTIVITIES: To evaluate the expression of known dioxin-responsive genes, CYP1A1 associated 7-ethoxyresorufin-O-deethylase (EROD) activity and CYP1A2-associated acetanilide 4-hydroxylase (A-4-H) activity were evaluated at the 14-, 31-, and 53-week interim evaluations. In addition, CYP2B associated pentoxyresorufin-O-deethylase (PROD) activity was also analysed. Hepatic PROD (CYP2B1) and hepatic and pulmonary EROD (CYP1A1) activity were significantly greater in all dosed groups than in vehicle controls at weeks 14, 31, and 53. Hepatic A-4-H (CYP1A2) activity was significantly greater in the 30, 100, 175, 300, 550, and 1,000 ng/kg groups compared to vehicle controls at weeks 14, 31, and 53. DETERMINATIONS of PCB 126 CONCENTRATIONS IN TISSUES: The tissue disposition of PCB 126 was analyzed in the liver, lung, fat, and blood of all rats in vehicle controls and all dosed groups at the 14-, 31-, and 53-week interim evaluations and in 10 rats per group including vehicle controls at the end of the 2-year study (104 weeks). Detectable concentrations of PCB 126 were observed in the liver, fat, lung, and blood. Measurable concentrations of PCB 126 were present in the liver and fat at weeks 31, 53, and 104. Hepatic and fat concentrations increased with increasing doses of PCB 126. Measurable concentrations of PCB 126 were present in vehicle control lung tissue at 53 and 104 weeks. No PCB 126 was observed in the blood from the vehicle control rats. Lung and blood concentrations tended to increase with increasing doses of PCB 126, with a few exceptions. In the stop-exposure group, PCB 126 concentrations in liver and fat were lower than the levels observed in the 30 ng/kg group. In the stop-exposure group, lung tissue PCB 126 concentrations were equivalent to the levels observed in the 30 ng/kg group. In blood from the stop-exposure group, PCB 126 concentrations were equivalent to the levels observed in the 100 ng/kg group. PATHOLOGY AND STATISTICAL ANALYSES: Absolute and

  7. Toxicology and carcinogenesis studies of a binary mixture of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) (Cas No. 57465-28-8) and 2,3',4,4',5-pentachlorobiphenyl (PCB 118) (Cas No. 31508-00-6) in female Harlan Sprague-Dawley rats (gavage studies).

    PubMed

    2006-11-01

    TEQ/kg at 53 weeks. Cytochrome P450 Enzyme Activities: CYP1A1-associated 7-ethoxyresorufin-O-deethylase (EROD) and CYP1A2-associated acetanilide-4-hydroxylase (A4H) activities were evaluated at the 14-, 31-, and 53-week interim evaluations to evaluate the expression of known dioxin-responsive genes. In addition, CYP2B-associated pentoxyresorufin-O-deethylase (PROD) activity was also analyzed. Hepatic and pulmonary EROD (CYP1A1) activity, hepatic A4H (CYP1A2) activity, and hepatic PROD (CYP2B1) activity were significantly greater in all dosed groups compared to the vehicle controls at weeks 14, 31, and 53. Determinations of PCB 126 and PCB 118 Concentrations in Tissues: The tissue disposition of PCB 126 and PCB 118 was analyzed in the liver, lung, fat, and blood of up to 10 rats in each group at the 14-, 31-, and 53-week interim evaluations, except for the 360 ng TEQ/kg group at 53 weeks. The tissue disposition of PCB 126 and PCB 118 was also analyzed in 10 rats per group at the end of the 2-year study in the vehicle control, 7, 22, and 72 ng TEQ/kg core study groups and the 360 ng TEQ/kg stop-exposure group. Detectable concentrations of PCB 126 and PCB 118 were observed in the liver, fat, lung, and blood. The highest levels of PCB 126 were seen in the liver whereas the highest levels of PCB 118 were seen in the fat. In general, tissue concentrations increased with increasing doses of the mixture and increasing duration of exposure. Hepatic levels of PCB 126 and PCB 118 in the 72 ng TEQ/kg group at the end of the 2-year study were 284 ng/g and 3,769 ng/g, respectively. On a TCDD equivalents basis this corresponds to 28 ng TEQ/g and 0.4 ng TEQ/g for PCB 126 and PCB 118, respectively. Cessation of administration of the mixture in the stop-exposure group led to declines in the tissue concentrations of both PCB 126 and PCB 118 to levels comparable to those observed in the 7 ng TEQ/kg group at the end of the 2-year study. Pathology and Statistical Analyses: At 14, 31, and

  8. Nomega-hydroxy-L-arginine homologues and hydroxylamine as nitric oxide-dependent vasorelaxant agents.

    PubMed

    Beranova, Petra; Chalupsky, Karel; Kleschyov, Andrei L; Schott, Christa; Boucher, Jean-Luc; Mansuy, Daniel; Munzel, Thomas; Muller, Bernard; Stoclet, Jean-Claude

    2005-06-15

    Endothelium-independent relaxant activities of N(omega)-hydroxy-L-arginine (L-NOHA) homologues and hydroxylamine, a possible intermediate in nitric oxide (NO) formation, were examined in rat aortic rings. Addition of one -CH(2)- group to the -(CH(2))(x)- chain between the alpha-amino acid and the hydroxyguanidine group (x=4) almost abolished-while deletion of one or two -CH(2)- (x=1 or 2) enhanced-the relaxant activity of L-NOHA homologues. N(omega)-hydroxy-nor-L-arginine- (x=2) and hydroxylamine-induced relaxations were blunted by a NO scavenger and by inhibitors of the guanylyl cyclase pathway, but not by NO synthase or cytochrome P(450) inhibitors (except 7-ethoxyresorufin). However, aortic NO formation was detected (using electron paramagnetic resonance) in the presence of concentrations of these compounds higher than those producing relaxation. These findings support the view that endothelium-independent vasorelaxations induced by both L-NOHA homologues with a required chain length xactivation of guanylyl cyclase, through a 7-ethoxyresorufin-inhibited mechanism.

  9. Identification of a novel series of N-phenyl-5-[(2-phenylbenzimidazol-1-yl)methyl]-1,3,4-oxadiazol-2-amines as potent antioxidants and radical scavengers.

    PubMed

    Ayhan-Kilcigil, Gulgun; Kuş, Canan; Çoban, Tülay; Özdamar, Elcin D; Can-Eke, Benay

    2014-04-01

    In this study, some novel 5-[[2-(phenyl/p-chlorophenyl)-benzimidazol-1-yl]-methyl]-N-substituted phenyl-1,3,4-oxadiazol-2-amine derivatives (28-45) with an oxadiazole ring were synthesized. The antioxidant properties and radical scavenging activities of the compounds were investigated employing various in vitro systems: hepatic microsomal NADPH-dependent inhibition of lipid peroxidation levels, scavenging of DPPH free radicals, and inhibition of microsomal ethoxyresorufin O-deethylase activity (EROD). Compounds 34 and 41 were found to be good scavengers of DPPH radicals (76% and 84%) when compared to BHT (90%). Almost all of the compounds examined were found to possess a good inhibitor effect on the microsomal EROD activity. Moreover, 32 and 41 were more active analogs (97% and 98%) on the microsomal EROD activity than caffeine (85%).

  10. EROD induction in microsomes and primary hepatocyte cultures prepared from individual double-crested cormorant embryo livers

    SciTech Connect

    Davis, J.A.; Fry, D.M.; Wilson, B.W.

    1994-12-31

    Double-crested cormorants (Phalacrocorax auritus) are being studied as a high trophic level indicator species for toxic contamination in San Francisco Bay and other locations on the California coast. In 1993, median ethoxyresorufin-o-deethylase (EROD) activities in embryo liver microsomes sampled from San Francisco Bay colonies were 4.2-fold and 2.3-fold higher than two coastal locations. In 1994 cormorant embryo livers from these same locations were again analyzed for liver microsomal EROD activity. In addition, basal and maximal EROD activity were measured in primary hepatocyte cultures from portions of the same livers used for microsomal EROD analysis to determine whether factors other than contaminant burdens in the egg contribute to the observed differences in activity. Differences in basal activity and induction capacity among the populations are discussed in the context of the hypothesis that polluted habitats select for increased metabolic capacity in affected populations.

  11. Toxicology and carcinogenesis studies of 3,3',4,4'-tetrachloroazobenzene (TCAB) (CAS No. 14047-09-7) in Harlan Sprague-Dawley rats and B6C3F1 mice (gavage studies).

    PubMed

    2010-11-01

    dosed groups of females were significantly less than those of the vehicle controls. The hematology results indicate that TCAB induced a microcytic normochromic responsive anemia in male Sprague-Dawley rats. Serum concentrations of total thyroxine (T4) and free T4 were significantly decreased in a dose-related manner in all dosed groups in both sexes compared to their respective vehicle controls; total triiodothyronine (T3) and thyroid stimulating hormone (TSH) concentrations were generally unaffected. There were no statistically significant differences in the BrdU labeling indices in the liver of males or females exposed to TCAB compared to their respective vehicle controls. Significant induction of hepatic 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-deethylase activities was observed in all dosed groups of males and females. Significant induction of hepatic acetanilide-4-hydroxylase activity was observed in males exposed to 3 mg/kg or greater and all treated groups of females. EROD activities in the lung generally increased with increasing dose and were significantly greater in all treated groups of males and females compared to their respective vehicle controls. The highest concentrations of TCAB were observed in fat tissue with lower concentrations in the liver and lung. TCAB concentrations were significantly increased in a dose-dependent manner in all tissues from dosed groups relative to vehicle controls. At the end of the 3-month study, absolute and relative liver weights were significantly greater than those of the vehicle controls in all dosed groups of males and in females administered 10 mg/kg or greater. Absolute and relative lung weights were significantly greater in 100 mg/kg males and 3 mg/kg or greater females. Absolute and relative right kidney and spleen weights were generally significantly greater for all dosed groups of males. Absolute thymus weights of 10 mg/kg or greater males and absolute and relative thymus weights of 1 mg/kg or

  12. Toxicology and carcinogenesis studies of 3,3',4,4'-tetrachloroazobenzene (TCAB) (CAS No. 14047-09-7) in Harlan Sprague-Dawley rats and B6C3F1 mice (gavage studies).

    PubMed

    2010-11-01

    dosed groups of females were significantly less than those of the vehicle controls. The hematology results indicate that TCAB induced a microcytic normochromic responsive anemia in male Sprague-Dawley rats. Serum concentrations of total thyroxine (T4) and free T4 were significantly decreased in a dose-related manner in all dosed groups in both sexes compared to their respective vehicle controls; total triiodothyronine (T3) and thyroid stimulating hormone (TSH) concentrations were generally unaffected. There were no statistically significant differences in the BrdU labeling indices in the liver of males or females exposed to TCAB compared to their respective vehicle controls. Significant induction of hepatic 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-deethylase activities was observed in all dosed groups of males and females. Significant induction of hepatic acetanilide-4-hydroxylase activity was observed in males exposed to 3 mg/kg or greater and all treated groups of females. EROD activities in the lung generally increased with increasing dose and were significantly greater in all treated groups of males and females compared to their respective vehicle controls. The highest concentrations of TCAB were observed in fat tissue with lower concentrations in the liver and lung. TCAB concentrations were significantly increased in a dose-dependent manner in all tissues from dosed groups relative to vehicle controls. At the end of the 3-month study, absolute and relative liver weights were significantly greater than those of the vehicle controls in all dosed groups of males and in females administered 10 mg/kg or greater. Absolute and relative lung weights were significantly greater in 100 mg/kg males and 3 mg/kg or greater females. Absolute and relative right kidney and spleen weights were generally significantly greater for all dosed groups of males. Absolute thymus weights of 10 mg/kg or greater males and absolute and relative thymus weights of 1 mg/kg or

  13. Reduction of dioxin-like toxicity in effluents by additional wastewater treatment and related effects in fish.

    PubMed

    Maier, Diana; Benisek, Martin; Blaha, Ludek; Dondero, Francesco; Giesy, John P; Köhler, Heinz-R; Richter, Doreen; Scheurer, Marco; Triebskorn, Rita

    2016-10-01

    Efficiency of advanced wastewater treatment technologies to reduce micropollutants which mediate dioxin-like toxicity was investigated. Technologies compared included ozonation, powdered activated carbon and granular activated carbon. In addition to chemical analyses in samples of effluents, surface waters, sediments, and fish, (1) dioxin-like potentials were measured in paired samples of effluents, surface waters, and sediments by use of an in vitro biotest (reporter gene assay) and (2) dioxin-like effects were investigated in exposed fish by use of in vivo activity of the mixed-function, monooxygenase enzyme, ethoxyresorufin O-deethylase (EROD) in liver. All advanced technologies studied, based on degradation or adsorption, significantly reduced dioxin-like potentials in samples and resulted in lesser EROD activity in livers of fish. Results of in vitro and in vivo biological responses were not clearly related to quantification of targeted analytes by use of instrumental analyses. PMID:27262214

  14. Assessment of contamination of the Svitava and Svratka rivers in the Czech Republic using selected biochemical markers.

    PubMed

    Blahová, Jana; Havelková, Marcela; Kruzíková, Kamila; Hilscherová, Klára; Halouzka, Roman; Modrá, Helena; Grabic, Roman; Halírová, Jarmila; Jurcíková, Jana; Ocelka, Tomás; Harustiaková, Danka; Svobodová, Zdenka

    2010-03-01

    The aim of the present study is to assess aquatic ecosystem contamination using selected biochemical markers: cytochrome P450, ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), tripeptide glutathione, vitellogenin, and 11-ketotestosterone in chub (Leuciscus cephalus L.). Seven locations on the Svitava and Svratka rivers (in the Brno conurbation, Czech Republic) were assessed. The results were compared with the levels of the most important inductors of these biomarkers: organic pollutants hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), DDT and its metabolites, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons in bottom sediment, fish muscle, and semipermeable membrane devices (SPMDs) and metals in sediment. The highest levels of pollutants were observed at sites situated downstream from Brno, especially at Modrice and Rajhradice. Significant positive correlations (p < 0.05) were found between EROD activity and HCH concentration in SPMDs, and also between GST and EROD activity with HCB concentration in muscle, after adjusting for age.

  15. Impact of dispersed fuel oil on cardiac mitochondrial function in polar cod Boreogadus saida.

    PubMed

    Dussauze, Matthieu; Camus, Lionel; Le Floch, Stéphane; Pichavant-Rafini, Karine; Geraudie, Perrine; Coquillé, Nathalie; Amérand, Aline; Lemaire, Philippe; Theron, Michael

    2014-12-01

    In this study, impact of dispersed oil on cardiac mitochondrial function was assessed in a key species of Arctic marine ecosystem, the polar cod Boreogadus saida. Mature polar cod were exposed during 48 h to dispersed oil (mechanically and chemically) and dispersants alone. The increase observed in ethoxyresorufin-O-deethylase activity and polycyclic aromatic hydrocarbon metabolites in bile indicated no difference in contamination level between fish exposed to chemical or mechanical dispersion of oil. Oil induced alterations of O2 consumption of permeabilised cardiac fibres showing inhibitions of complexes I and IV of the respiratory chain. Oil did not induce any modification of mitochondrial proton leak. Dispersants did not induce alteration of mitochondrial activity and did not increase oil toxicity. These data suggest that oil exposure may limit the fitness of polar cod and consequently could lead to major disruption in the energy flow of polar ecosystem.

  16. Active-R filter

    DOEpatents

    Soderstrand, Michael A.

    1976-01-01

    An operational amplifier-type active filter in which the only capacitor in the circuit is the compensating capacitance of the operational amplifiers, the various feedback and coupling elements being essentially solely resistive.

  17. Use of octopus as a bioindicator species: Baseline studies

    SciTech Connect

    Holdway, D.A.; Butty, J.S.; Brennan, S.E.; Ahokas, J.T.

    1995-12-31

    The Australian octopus Octopus pallidus, is abundant, territorial, has a large digestive gland. This study was undertaken to assess octopii as a potential bioindicator species by establishing the efficacy of capturing octopi using traplines, and determining the impact of various modifying factors on the activities of digestive gland mixed-function oxidase (MFO) enzymes including ethoxyresorufin O-deethylase (EROD), ethoxycoumarin O-deethylase (ECOD) and total P-450. Trap success rates in Port Phillip Bay were 15--28% for the ``potentially contaminated`` site and 85% for the reference site. Cytochrome P-450 showed significant seasonal differences, with no site or sex differences. Mean ({+-} SE) Autumn P-450 values of 74.8 ({+-}5.5) pmol/mg protein were higher than Winter values of 51.2 ({+-}7.6), which were higher than Spring values of 21.8 ({+-}4.0) pmol/mg protein. Summer P-450 values of 61.4 ({+-} 9.8) pmol/mg protein were only different from Spring values. Mean ({+-} SE) Spring ECOD activity of 3.3 ({+-} 0.7) pmol/min/mg protein was lower than Summer, Autumn and Winter ECOD values of 8.9 ({+-} 1.6) 6.5 ({+-} 1.2) and 8.6 ({+-} 2.3) pmol/min/mg protein respectively. Females had roughly half the ECOD activities of males (3.8 {+-} 0.8 compared to 7.4 {+-} 0.9 pmol/min/mg protein). All octopi digestive gland EROD activities were low (roughly 0.2 pmol/min/mg protein) with no sex, site nor seasonal differences. Potential for using octopus as a bioindicator appears promising but sensitivity to chemical exposure has yet to be determined.

  18. Identification of cytochrome P4501A inducers in complex mixtures of polycyclic aromatic hydrocarbons

    SciTech Connect

    Villeneuve, D.L.; DeVita, W.M.; Crunkilton, R.L.

    1998-12-31

    An in vitro ethoxyresorufin O-deethylase (EROD) assay was used to study the ability of individual polycyclic aromatic hydrocarbons (PAHs) and mixtures of PAHs to induce Ah receptor (AhR) mediated cytochrome P4501A activity in PLHC-1 fish hepatoma cells. The purpose was to identify the most potent inducers from a set of thirteen separate PAHs and describe interactions occurring in complex mixtures of these PAHs. Where possible, potency was expressed in terms of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TCDD-EQ) by normalizing the PAH results to a TCDD standard curve. The most potent inducers were benzo(k)fluoranthene > benzo(a)pyrene {approx} benzo(b)fluoranthene > chrysene {approx} benzo(a)anthracene. At equal concentrations, these PAHs yielded potencies of 1670, 940, 655, 255, and 185 pg TCDD-EQ/g, respectively. Analysis of various mixtures of the thirteen PAHs suggested that complex interactions may be occurring.

  19. Antioxidant responses in clam Venerupis philippinarum exposed to environmental pollutant hexabromocyclododecane.

    PubMed

    Zhang, Hui; Pan, Luqing; Tao, Yanxia

    2014-01-01

    The objective of this study was to assess the potential toxic effects of hexabromocyclododecane (HBCD) on tissues of clam Venerupis philippinarum using parameters of antioxidant defenses and oxidative stress. Antioxidant biomarkers including ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), and glutathione (GSH), as well as DNA damage and lipid peroxidation (LPO) in gills and digestive glands of V. philippinarum, were analyzed after a 1-, 3-, 6-, 10-, and 15-day exposure to seawater containing HBCD at environmentally related concentrations, respectively. The results showed that the activity of most antioxidant enzymes increased, and different trends were detected with exposure time extending. The oxidative stress could be obviously caused in the gills and digestive glands under the experimental conditions. This could provide useful information for toxic risk assessment of environmental pollutant HBCD.

  20. Glycine N-methyltransferase is a mediator of cytochrome P4501A1 gene expression.

    PubMed

    Raha, A; Joyce, T; Gusky, S; Bresnick, E

    1995-10-01

    Cytochrome P4501A1, the isozyme most closely approximating aryl hydrocarbon hydroxylase activity under conditions of induction, is thought to be regulated by several trans-acting factors, including the 4S polycyclic aromatic hydrocarbon-binding protein; this protein has recently been identified as glycine N-methyltransferase (Raha et al. (1994) J. Biol. Chem. 269, 5750-5756). Previous studies had shown that partially purified liver preparations containing the 4S binding protein interacted with 5'-flanking regions of the cytochrome P4501A1 gene. Consequently, the ability of the 4S binding protein to serve as a mediator in the regulation of the cytochrome P4501A1 gene was investigated further. Introduction of an antisense 24-mer oligonucleotide to glycine N-methyltransferase cDNA into rat hepatoma H4IIE cells by lipofectin resulted in a 60% reduction in the benzo(a)pyrene-mediated induction of ethoxyresorufin-O-deethylase activity and protein over the sense and scrambled antisense oligonucleotide controls. In addition, the antisense oligonucleotide caused a marked reduction in the steady-state level of cytochrome P4501A1 mRNA; no such effect was observed with the sense oligonucleotide. Introduction of GNMT polyclonal antibodies into H4IIE cells by a streptolysin-O permeabilization technique markedly reduced both benzo(a)pyrene-binding and benzo(a)-pyrene-induced ethoxyresorufin-O-deethylase activities, but had no effect on 2,3,7,8-tetrachlorodibenzo-p-dioxin induction. Collectively, these findings suggest that, in addition to the Ah (dioxin) receptor, glycine N-methyltransferase appears to be both a polycyclic aromatic hydrocarbon-binding protein and a mediator of the induction of the cytochrome P4501A1 gene by polycyclic hydrocarbons such as benzo(a)pyrene. PMID:7574713

  1. Sequencing and characterization of mixed function monooxygenase genes CYP1A1 and CYP1A2 of Mink (Mustela vison) to facilitate study of dioxin-like compounds

    SciTech Connect

    Zhang Xiaowei; Moore, Jeremy N.; Newsted, John L.; Hecker, Markus Zwiernik, Matthew J.; Jones, Paul D.; Bursian, Steven J.

    2009-02-01

    As part of an ongoing effort to understand aryl hydrocarbon receptor (AhR) mediated toxicity in mink, cDNAs encoding for CYP1A1 and the CYP1A2 mixed function monooxygenases were cloned and characterized. In addition, the effects of selected dibenzofurans on the expression of these genes and the presence of their respective proteins (P4501A) were investigated, and then correlated with the catalytic activities of these proteins as measured by ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-deethylase (MROD) activities. The predicted protein sequences for CYP1A1 and CYP1A2 comprise 517 and 512 amino acid residues, respectively. The phylogenetic analysis of the mink CYP1As with protein sequences of other mammals revealed high sequence homology with sea otter, seals and the dog, with amino acid identities ranging from 89 to 95% for CYP1A1 and 81 to 93% for CYP1A2. Since exposure to both 2,3,7,8-Tetrachlorodibenzofuran (TCDF) and 2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) resulted in dose-dependent increases of CYP1A1 mRNA, CYP1A2 mRNA and CYP1A protein levels an underlying AhR-mediated mechanism is suggested. The up-regulation of CYP1A mRNA in liver was more consistent to the sum adipose TEQ concentration than to the liver TEQ concentration in minks treated with TCDF or PeCDF. The result suggested that the hepatic-sequestered fraction of PeCDF was biologically inactive to the induction of CYP1A1 and CYP1A2.

  2. Seasonal patterns of polycyclic aromatic hydrocarbons in digestive gland and arm of octopus (Octopus vulgaris) from the Northwest Atlantic.

    PubMed

    Semedo, Miguel; Oliveira, Marta; Gomes, Filipa; Reis-Henriques, Maria Armanda; Delerue-Matos, Cristina; Morais, Simone; Ferreira, Marta

    2014-05-15

    Among organic pollutants existing in coastal areas, polycyclic aromatic hydrocarbons (PAHs) are of great concern due to their ubiquity and carcinogenic potential. The aim of this study was to evaluate the seasonal patterns of PAHs in the digestive gland and arm of the common octopus (Octopus vulgaris) from the Northwest Atlantic Portuguese coast. In the different seasons, 18 PAHs were determined and the detoxification capacity of the species was evaluated. Ethoxyresorufin O-deethylase (EROD) and ethoxycoumarin O-deethylase (ECOD) activities were measured to assess phase I biotransformation capacity. Individual PAH ratios were used for major source (pyrolytic/petrogenic) analysis. Risks for human consumption were determined by the total toxicity equivalence approach. Generally, low levels of PAHs were detected in the digestive gland and in the arm of octopus, with a predominance of low molecular over high molecular weight compounds. PAHs exhibited seasonality in the concentrations detected and in their main emission sources. In the digestive gland, the highest total PAH levels were observed in autumn possibly related to fat availability in the ecosystem and food intake. The lack of PAH elimination observed in the digestive gland after captivity could be possibly associated to a low biotransformation capacity, consistent with the negligible/undetected levels of EROD and ECOD activity in the different seasons. The emission sources of PAHs found in the digestive gland varied from a petrogenic profile observed in winter to a pyrolytic pattern in spring. In the arm, the highest PAH contents were observed in June; nevertheless, levels were always below the regulatory limits established for food consumption. The carcinogenic potential calculated for all the sampling periods in the arm were markedly lower than the ones found in various aquatic species from different marine environments. The results presented in this study give relevant baseline data for environmental

  3. Seasonal patterns of polycyclic aromatic hydrocarbons in digestive gland and arm of octopus (Octopus vulgaris) from the Northwest Atlantic.

    PubMed

    Semedo, Miguel; Oliveira, Marta; Gomes, Filipa; Reis-Henriques, Maria Armanda; Delerue-Matos, Cristina; Morais, Simone; Ferreira, Marta

    2014-05-15

    Among organic pollutants existing in coastal areas, polycyclic aromatic hydrocarbons (PAHs) are of great concern due to their ubiquity and carcinogenic potential. The aim of this study was to evaluate the seasonal patterns of PAHs in the digestive gland and arm of the common octopus (Octopus vulgaris) from the Northwest Atlantic Portuguese coast. In the different seasons, 18 PAHs were determined and the detoxification capacity of the species was evaluated. Ethoxyresorufin O-deethylase (EROD) and ethoxycoumarin O-deethylase (ECOD) activities were measured to assess phase I biotransformation capacity. Individual PAH ratios were used for major source (pyrolytic/petrogenic) analysis. Risks for human consumption were determined by the total toxicity equivalence approach. Generally, low levels of PAHs were detected in the digestive gland and in the arm of octopus, with a predominance of low molecular over high molecular weight compounds. PAHs exhibited seasonality in the concentrations detected and in their main emission sources. In the digestive gland, the highest total PAH levels were observed in autumn possibly related to fat availability in the ecosystem and food intake. The lack of PAH elimination observed in the digestive gland after captivity could be possibly associated to a low biotransformation capacity, consistent with the negligible/undetected levels of EROD and ECOD activity in the different seasons. The emission sources of PAHs found in the digestive gland varied from a petrogenic profile observed in winter to a pyrolytic pattern in spring. In the arm, the highest PAH contents were observed in June; nevertheless, levels were always below the regulatory limits established for food consumption. The carcinogenic potential calculated for all the sampling periods in the arm were markedly lower than the ones found in various aquatic species from different marine environments. The results presented in this study give relevant baseline data for environmental

  4. Induction of hepatic cytochrome P450 isozymes, benzo(a)pyrene metabolism and DNA binding following exposure to polycyclic aromatic hydrocarbon residues generated during repeated fish fried oil in rats

    SciTech Connect

    Pandey, Manoj K.; Yadav, Sanjay; Parmar, Devendra; Das, Mukul . E-mail: mditrc@rediffmail.com

    2006-06-01

    In the present study the effect of repeated fish fried oil (RFFO) and its extract (RFFE) on hepatic cytochrome P450 (CYP) isozymes, benzo(a)pyrene (BP) metabolism and DNA adduct formation was undertaken. HPLC analysis of RFFO showed the presence of several polycyclic aromatic hydrocarbons. CYP in microsomes from control and RFFO-treated animals showed a peak at 450 nm; however, a shift of 2 nm in the SORET region along with significant induction was observed in microsomes prepared from 3-methylcholanthrene (MC)- and RFFE-treated animals. Activities of hepatic ethoxyresorufin-O-deethylase, methoxyresorufin-O-deethylase, aryl hydrocarbon hydroxylase and erythromycin-N-demethylase were found to be significantly (P < 0.05) induced following exposure of RFFE, whereas none of these enzymes were altered in RFFO-treated group. Immunoblot analysis revealed that RFFE and MC were potent inducers of CYP1A1, 1A1/2 and 3A1 isozymes, where as RFFO showed no change in these protein levels. RT-PCR analysis showed induction of cDNA of CYP1A1 and CYP3A1 by RFFE treatment. Hepatic microsomes prepared from RFFE exposed animals enhanced BP metabolism with a concomitant increase in the relative proportion of BP 7,8-diol. Hepatic microsomes prepared from animals pretreated with RFFE and MC significantly enhanced the binding of [{sup 3}H]-BP to calf thymus DNA. The overall results suggest that exposure to RFFE may induce hepatic CYP isozymes thereby producing enhanced reactive metabolites with a potential to bind with DNA that may result in cancer.

  5. Selective enhancement of xenobiotic metabolizing systems of rat lungs by prolonged exposure to ozone

    SciTech Connect

    Takahashi, Y.; Miura, T.

    1987-04-01

    Male Wistar rats were exposed to 0.2 and 0.4 ppm O/sub 3/ for 4, 8, and 12 weeks and to 0.1 and 0.2 ppm O/sub 3/ for 4 weeks to examine the effects of prolonged exposure to O/sub 3/ on the xenobiotic metabolizing systems in the lung. Exposures to 0.2 and 0.4 ppm O/sub 3/ caused a significant increase in the NADPH-cytochrome P-450 reductase activity and cytochrome P-450 content in a dose-dependent manner during 4-12 weeks, whereas NADH-cytochrome b5 reductase was not altered. After 12 weeks of exposure to 0.4 ppm O/sub 3/, NADPH-cytochrome P-450 reductase and cytochrome P-450 reached a maximum showing 138 and 221% those of the control levels, respectively. At 0.1 ppm O/sub 3/, the cytochrome P-450 content still increased significantly to 152% that of the control on the fourth week. In parallel to the increment of cytochrome P-450 benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase increased significantly during 4-12 weeks of exposures to 0.2 and 0.4 ppm O/sub 3/. After a 4-week exposure to 0.1 and 0.2 ppm O/sub 3/, benzphetamine N-demethylase increased to the largest degree among the enzymes metabolizing four kinds of xenobiotics examined. 7-Ethoxycoumarin O-deethylase also increased significantly but of smaller magnitude, whereas coumarin hydroxylase was not affected. These results show that prolonged exposures to 0.1-0.4 ppm O/sub 3/ persistently enhance pulmonary cytochrome P-450 systems. It is also suggested that some isozyme(s) of pulmonary cytochrome P-450, especially that catalyzing benzphetamine N-demethylation, are preferentially increased by exposure to low levels of O/sub 3/.

  6. Active turbulence in active nematics

    NASA Astrophysics Data System (ADS)

    Thampi, S. P.; Yeomans, J. M.

    2016-07-01

    Dense, active systems show active turbulence, a state characterised by flow fields that are chaotic, with continually changing velocity jets and swirls. Here we review our current understanding of active turbulence. The development is primarily based on the theory and simulations of active liquid crystals, but with accompanying summaries of related literature.

  7. Activity Scale.

    ERIC Educational Resources Information Center

    Kerpelman, Larry C.; Weiner, Michael J.

    This twenty-four item scale assesses students' actual and desired political-social activism in terms of physical participation, communication activities, and information-gathering activities. About ten minutes are required to complete the instrument. The scale is divided into two subscales. The first twelve items (ACT-A) question respondents on…

  8. Proteasome Activators

    PubMed Central

    Stadtmueller, Beth M.; Hill, Christopher P.

    2011-01-01

    Summary Proteasomes degrade a multitude of protein substrates in the cytosol and nucleus, and thereby are essential for many aspects of cellular function. Because the proteolytic sites are sequestered in a closed barrel-shaped structure, activators are required to facilitate substrate access. Structural and biochemical studies of two activator families, 11S and Blm10, have provided insights to proteasome activation mechanisms, although the biological functions of these factors remain obscure. Recent advances have improved our understanding of the third activator family, including the 19S activator, which targets polyubiquitylated proteins for degradation. PMID:21211719

  9. Active ratchets

    NASA Astrophysics Data System (ADS)

    Angelani, L.; Costanzo, A.; Di Leonardo, R.

    2011-12-01

    We analyze self-propelling organisms, or active particles, in a periodic asymmetric potential. Unlike standard ratchet effect for Brownian particles requiring external forcing, in the case of active particles asymmetric potential alone produces a net drift speed (active ratchet effect). By using theoretical models and numerical simulations we demonstrate the emergence of the rectification process in the presence of an asymmetric piecewise periodic potential. The broken spatial symmetry (external potential) and time symmetry (active particles) are sufficient ingredients to sustain unidirectional transport. Our findings open the way to new mechanisms to move in directional manner motile organisms by using external periodic static fields.

  10. Astronomy Activities.

    ERIC Educational Resources Information Center

    Greenstone, Sid

    This document consists of activities and references for teaching astronomy. The activities (which include objectives, list of materials needed, and procedures) focus on: observing the Big Dipper and locating the North Star; examining the Big Dipper's stars; making and using an astrolabe; examining retograde motion of Mars; measuring the Sun's…

  11. Faculty Activism

    ERIC Educational Resources Information Center

    Academe, 2005

    2005-01-01

    Blending scholarship and activism, whether domestic or international, takes some real work. Two scholar-activists reflect on why and how activism can be more than academic labor in this feature of the "Academe" journal. This feature includes the following brief reflections on political work, both local and global that demonstrates how on campus…

  12. Catalyst activator

    DOEpatents

    McAdon, Mark H.; Nickias, Peter N.; Marks, Tobin J.; Schwartz, David J.

    2001-01-01

    A catalyst activator particularly adapted for use in the activation of metal complexes of metals of Group 3-10 for polymerization of ethylenically unsaturated polymerizable monomers, especially olefins, comprising two Group 13 metal or metalloid atoms and a ligand structure including at least one bridging group connecting ligands on the two Group 13 metal or metalloid atoms.

  13. Outdoor Activities.

    ERIC Educational Resources Information Center

    Minneapolis Independent School District 275, Minn.

    Twenty-four activities suitable for outdoor use by elementary school children are outlined. Activities designed to make children aware of their environment include soil painting, burr collecting, insect and pond water collecting, studies of insect galls and field mice, succession studies, and a model of natural selection using dyed toothpicks. A…

  14. Activation analysis

    SciTech Connect

    Alfassi, Z.B. . Dept. of Nuclear Engineering)

    1990-01-01

    This volume contains 16 chapters on the application of activation analysis in the fields of life sciences, biological materials, coal and its effluents, environmental samples, archaeology, material science, and forensics. Each chapter is processed separately for the data base.

  15. Integrin activation

    PubMed Central

    Ginsberg, Mark H.

    2014-01-01

    Integrin-mediated cell adhesion is important for development, immune responses, hemostasis and wound healing. Integrins also function as signal transducing receptors that can control intracellular pathways that regulate cell survival, proliferation, and cell fate. Conversely, cells can modulate the affinity of integrins for their ligands a process operationally defined as integrin activation. Analysis of activation of integrins has now provided a detailed molecular understanding of this unique form of “inside-out” signal transduction and revealed new paradigms of how transmembrane domains (TMD) can transmit long range allosteric changes in transmembrane proteins. Here, we will review how talin and mediates integrin activation and how the integrin TMD can transmit these inside out signals. [BMB Reports 2014; 47(12): 655-659] PMID:25388208

  16. Active Cytokinins

    PubMed Central

    Mornet, René; Theiler, Jane B.; Leonard, Nelson J.; Schmitz, Ruth Y.; Moore, F. Hardy; Skoog, Folke

    1979-01-01

    Four series of azidopurines have been synthesized and tested for cytokinin activity in the tobacco callus bioassay: 2- and 8-azido-N6-benzyladenines, -N6-(Δ2-isopentenyl)adenines, and -zeatins, and N6-(2- and 4-azidobenzyl)adenines. The compounds having 2-azido substitution on the adenine ring are as active as the corresponding parent compounds, while those with 8-azido substitution are about 10 or more times as active. The 8-azidozeatin, which is the most active cytokinin observed, exhibited higher than minimal detectable activity at 1.2 × 10−5 micromolar, the lowest concentration tested. The shape of the growth curve indicates that even a concentration as low as 5 × 10−6 micromolar would probably be effective. By comparison, the lowest active concentration ever reported for zeatin has been 5 × 10−5 micromolar, representing a sensitivity rarely attained. All of the azido compounds have been submitted to photolysis in aqueous ethanol, and the photoproducts have been detected and identified by low and high resolution mass spectrometry. They are rationalized as products of abstraction and insertion reactions of the intermediate nitrenes. The potential of the major released products as cytokinins was also assessed by bioassay. 2-Azido-N6-(Δ2-isopentenyl)adenine competed with [14C]kinetin for the cytokinin-binding protein isolated from wheat germ. When the azido compound was photolysed in the presence of this protein, its attachment effectively blocked the binding of [14C]kinetin. PMID:16661017

  17. Active microwaves

    NASA Technical Reports Server (NTRS)

    Evans, D.; Vidal-Madjar, D.

    1994-01-01

    Research on the use of active microwaves in remote sensing, presented during plenary and poster sessions, is summarized. The main highlights are: calibration techniques are well understood; innovative modeling approaches have been developed which increase active microwave applications (segmentation prior to model inversion, use of ERS-1 scatterometer, simulations); polarization angle and frequency diversity improves characterization of ice sheets, vegetation, and determination of soil moisture (X band sensor study); SAR (Synthetic Aperture Radar) interferometry potential is emerging; use of multiple sensors/extended spectral signatures is important (increase emphasis).

  18. Activity report

    SciTech Connect

    Yu, S W

    2008-08-11

    This report is aimed to show the author's activities to support the LDRD. The title is 'Investigation of the Double-C Behavior in the Pu-Ga Time-Temperature-Transformation Diagram' The sections are: (1) Sample Holder Test; (2) Calculation of x-ray diffraction patterns; (3) Literature search and preparing publications; (4) Tasks Required for APS Experiments; and (5) Communications.

  19. Classroom Activities.

    ERIC Educational Resources Information Center

    Stuart, Frances R.

    This pamphlet suggests activities that may be used in the elementary school classroom. Chapter I lists various short plays that children can easily perform which encourage their imagination. Chapter II details a few quiet classroom games such as "I Saw,""Corral the Wild Horse,""Who Has Gone from the Room," and "Six-Man-Football Checkers." A number…

  20. Learning Activities.

    ERIC Educational Resources Information Center

    Tipton, Tom, Ed.

    1983-01-01

    Presents a flow chart for naming inorganic compounds. Although it is not necessary for students to memorize rules, preliminary skills needed before using the chart are outlined. Also presents an activity in which the mass of an imaginary atom is determined using lead shot, Petri dishes, and a platform balance. (JN)

  1. Leaf Activities.

    ERIC Educational Resources Information Center

    Mingie, Walter

    Leaf activities can provide a means of using basic concepts of outdoor education to learn in elementary level subject areas. Equipment needed includes leaves, a clipboard with paper, and a pencil. A bag of leaves may be brought into the classroom if weather conditions or time do not permit going outdoors. Each student should pick a leaf, examine…

  2. Get Active

    MedlinePlus

    ... Lifting small weights – you can even use bottled water or cans of food as weights Watch these videos for muscle strengthening exercises to do at home or at the gym. If you do muscle-strengthening activities with weights, check out the do’s and don’ ...

  3. Activated Sludge.

    ERIC Educational Resources Information Center

    Saunders, F. Michael

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers: (1) activated sludge process; (2) process control; (3) oxygen uptake and transfer; (4) phosphorus removal; (5) nitrification; (6) industrial wastewater; and (7) aerobic digestion. A list of 136 references is also presented. (HM)

  4. Glucokinase activators.

    PubMed

    Filipski, Kevin J; Futatsugi, Kentaro; Pfefferkorn, Jeffrey A; Stevens, Benjamin D

    2012-07-01

    In this review we highlight recently disclosed progress in the field of small-molecule activators of the human glucokinase enzyme. Several of the reported chemotypes possess structural features that diverge from known leads; some of these modifications appear to be specifically designed to modulate tissue selectivity or discrete parameters of enzyme function (e.g., S0.5 v Vmax). This review will inform the reader of the extent of continued effort being directed toward discovery of a first-in-class drug for Type II diabetes mellitus that functions through this target. Patents were selected from those published in December 2009 up to November 2011; foreign filings were translated where possible to understand the claims and biological techniques utilized to characterize the reported glucokinase activators. Overall, there appears to be a recent trend leading to reduced patent filings for small-molecule glucokinase activators. There are many possible explanations for this trend; however, it is likely that the field has reached maturity and that the downturn of new disclosures represents the transition of many of these programs to the clinic.

  5. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time.

  6. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time. PMID:26803804

  7. Effects of multiple exposures of small doses of Pembina Cardium crude oil and diesel in rats.

    PubMed

    Khan, A A; Coppock, R W; Schuler, M M

    2001-04-01

    In lands used for agricultural purposes, petroleum- or diesel-contaminated wastes and accidental spills of crude oil at some drilling sites pose exposure risks for occupational public, livestock, and wildlife. This study has assessed the effects of an Alberta crude oil, Pembina Cardium crude oil (PCCO), and a commercial diesel fuel #2 (CDF-2) in Sprague-Dawley rats after repeated exposures at small dose levels. Rats were given by gavage on day 1, 3, 5, and 8 specified dosages of either the control vehicle, methylcellulose (MC) (1.25 ml/kg), or PCCO (0.25-1.25 ml/kg), or CDF-2 (1.25 ml/kg). Exposure of rats to these dose levels of the test substances caused no overt symptoms of intoxication. A small but statistically significant increase in liver somatic index was observed in rats exposed to 1.25 ml/kg doses of PCCO and CDF-2; however, kidney somatic index was not significantly affected by these treatments. Blood analyses for hematological and clinical indicators of systemic impairments did not show any significant changes (p > 0.05) between the control and PCCO- or CDF-2-exposed rats. Biochemical assessment of liver and kidney tissues showed that compared to the control group, the PCCO- and CDF-2-exposed groups had a marked and significant increase (p < 0.05) in the hepatic activity of ethoxyresorufin-O-deethylase (EROD, a cytochrome P-450 [CYP] 1A1/A2-linked enzyme). In PCCO-exposed rats, the induction of EROD was dose-dependent. Exposure of rats with PCCO and CDF-2 also caused dose-related increases from the unexposed (control) or MC dosed rats in (1) hepatic activities of aryl hydrocarbon hydroxylase (AHH, a CYP 1A1-linked enzyme), ethoxycoumarin-O-deethylase (ECOD, a CYP 2B/1A-linked enzyme), glutathione transferase (GT), and NADPH-catalyzed microsomal lipid peroxidation; and (ii) ECOD activity in kidneys. The induction of hepatic CYP-linked enzymatic activities by PCCO and CDF-2 could be due to de novo synthesis of selected isoforms, as evidenced by the

  8. Oxidative and conjugative metabolism of xenobiotics by livers of cattle, sheep, swine and rats.

    PubMed

    Smith, G S; Watkins, J B; Thompson, T N; Rozman, K; Klaassen, C D

    1984-02-01

    Homogenate preparations from fresh livers of cattle, sheep, swine and rats were assayed for microsomal cytochrome P-450 content, for mixed-function oxidase activities and for a wide array of conjugative activities using numerous xenobiotic substrates. Results show that hepatic enzymatic capabilities toward xenobiotics do not parallel phylogenetic classifications, thus strengthening the view that most of the comparative data available at present is more descriptive than predictive of relationships among species. Livestock species differed widely from rats in having lower activities of benzo(alpha)pyrene hydroxylase, glutathione S-transferase and acetyltransferase toward isoniazid and sulfamethazine and UDP-glucuronosyl-transferase toward bilirubin. Acetyltransferase activities toward beta-naphthylamine and 2-aminofluorene were not detected in livers of livestock species studied. Cattle livers were remarkably high in activities of styrene oxide hydrolase, ethoxyresorufin O-deethylase, 2-naphthol sulfotransferase and p-aminobenzoic acid acetyltransferase; but notably low in activity of glutathione-S-transferase toward sulfobromophthalein and 1,2-dichloro-4-nitrobenzene. Swine livers had low activity of glutathione-S-transferase toward four of six substrates and low acetyltransferase activity toward four of five substrates. Sheep livers generally were higher than cattle livers in sulfo- and UDP-glucuronsyltransferase activities and lower in acetyl- and glutathionyl-S-transferase. Findings emphasize the risk of error in extra-polations among species and in extrapolations among substrates.

  9. Active tectonics

    SciTech Connect

    Not Available

    1986-01-01

    This study is part of a series of Studies in Geophysics that have been undertaken for the Geophysics Research Forum by the Geophysics Study Committee. One purpose of each study is to provide assessments from the scientific community to aid policymakers in decisions on societal problems that involve geophysics. An important part of such assessments is an evaluation of the adequacy of current geophysical knowledge and the appropriateness of current research programs as a source of information required for those decisions. The study addresses our current scientific understanding of active tectonics --- particularly the patterns and rates of ongoing tectonic processes. Many of these processes cannot be described reasonably using the limited instrumental or historical records; however, most can be described adequately for practical purposes using the geologic record of the past 500,000 years. A program of fundamental research focusing especially on Quaternary tectonic geology and geomorphology, paleoseismology, neotectonics, and geodesy is recommended to better understand ongoing, active tectonic processes. This volume contains 16 papers. Individual papers are indexed separately on the Energy Database.

  10. Mutual in vivo interactions between benzo[a]pyrene and tributyltin in brook trout (Salvelinus fontinalis)

    SciTech Connect

    Padros, J.; Pelletier, E.; Reader, S.; Denizeau, F.

    2000-04-01

    Tributyltin (TBT), an organometal used as an antifouling biocide, has been reported to inhibit cytochrome P450 (P450) 1A isozyme. Benzo[a]pyrene (BaP), a widespread carcinogenic polycyclic aromatic hydrocarbon, is both metabolized and bioactivated to carcinogenic BaP diol-epoxide (BPDE) metabolites primarily by hepatic P450 1A. Hence, TBT may inhibit the metabolism and bioactivation of BaP. This study was therefore designed to examine the potential in vivo interactions between BaP and TBT in a model fish. Male brook trout (Salelinus fontinalis) were given a single intraperitoneal injection of either BaP, TBT, or both in combination. After 48 h, blood, bile, and liver samples were collected and analyzed for a suite of biomarkers associated with P450 activity, BaP metabolism and bioactivation, and TBT metabolism. The results showed that TBT significantly inhibited (a) the induction of hepatic P450 1A-mediated ethoxyresorufin O-deethylase (EROD) and P450-mediated 3-cyano-7-ethoxycoumarin-O-deethylase (CN-ECOD) activities by BaP, (b) the formation of biliary BaP metabolites, and (c) the formation of (+)-anti-BPDE-plasma albumin adducts as measured by high-performance liquid chromatography-fluorescence. Notably, TBT alone did not inhibit EROD activity but induced CN-ECOD activity. Gas chromatography-mass spectrometry analysis indicated that the combined BaP + TBT dose resulted in higher levels of dibutyltin metabolites in the bite (p < 0.05). The present study supports the hypothesis that a single, high dose of TBT can antagonize the metabolism and bioactivation of BaP at least by inhibiting the induction of P4501A. On the other hand, BaP unexpectedly potentiated the metabolism of TBT, suggesting that hepatic isoforms other than P3501A may be responsible for TBT metabolism. Finally, this study supports the utility of a biomarker approach to screen potential xenobiotic interactions in aquatic organisms and to obtain mechanistic insights.

  11. Differential effects of two lots of aroclor 1254: congener-specific analysis and neurochemical end points.

    PubMed Central

    Kodavanti, P R; Kannan, N; Yamashita, N; Derr-Yellin, E C; Ward, T R; Burgin, D E; Tilson, H A; Birnbaum, L S

    2001-01-01

    the effects on ethoxyresorufin-O-deethylase (EROD) or methoxyresorufin-O-deethylase (MROD) activities. It is possible that the differential effects seen in neuronal cells could be caused by differences in the composition of ortho-congeners in these two mixtures, because PCBs with ortho-lateral substitutions can exhibit different activities on the selected neurochemical end points. Because of these differential effects with different lot numbers, the composition of Aroclor mixtures used in investigations should be disclosed. PMID:11713001

  12. Effects of methapyrilene on rat hepatic xenobiotic metabolizing enzymes and liver morphology.

    PubMed

    Graichen, M E; Neptun, D A; Dent, J G; Popp, J A; Leonard, T B

    1985-02-01

    Short-term treatment of rats with hepatocarcinogens elicits a consistent pattern of phenotypic changes in hepatic drug metabolizing enzymes, the most striking of which is a marked increase in microsomal epoxide hydrolase (EH) activity. The antihistaminic drug methapyrilene induces a high incidence of hepatocellular carcinoma in F-344 rats. The studies reported here were designed to assess the effects of methapyrilene on hepatic EH activity, cytochrome P-450-dependent mixed-function oxidase activities, liver morphology, and liver-derived serum enzymes. Male F-344 rats were treated with three daily oral doses of methapyrilene-HCl, up to 300 mg/kg/day, and were sacrificed 48 hr after the last dose. Hepatic microsomal EH and cytosolic DT-diaphorase activities were increased in a dose-related fashion, to 420 and 230% of control, respectively. Cytochrome P-450 content and benzphetamine-N-demethylase and ethoxycoumarin-O-deethylase activities were concomitantly decreased to 35-50% of control. Serum gamma-glutamyl transpeptidase and alanine aminotransferase activities were elevated 22- to 27-fold, and serum bile acids to 36-fold by treatment with methapyrilene. Periportal lesions, characterized by inflammation, nuclear and nucleolar enlargement, bile duct hyperplasia, and hepatocellular necrosis, were observed following methapyrilene administration. The severity of the periportal lesion correlated with elevations in the serum chemistry parameters. The increases noted in microsomal EH activity supports the suggestion that this enzyme may be a useful biochemical marker for exposure to hepatocarcinogens. PMID:2859228

  13. DAVIC activities

    NASA Astrophysics Data System (ADS)

    Fujiwara, Hiroshi

    1995-12-01

    DAVIC (Digital Audio Visual Council) is the defacto standardization organization established in Mar. 1994, based on international consensus for digital audio visual services. After completion of MPEG2 standardization, the broadcasting industry, the communication industry, the computer industry, and consumer electronics industry have started development of concrete services and products. Especially the interactive digital audio visual services, such as Video On Demand (VOD) or Near Video On Demand (NVOD), have become hot topics all over the world. Such interactive digital audio visual services are combined technologies of multi-media coding, digital transmission and computer networking. Therefore more than 150 organizations from all industry sectors have participated in DAVIC and are contributing from their own industrial contexts. DAVIC's basic policy is to use the available technologies specified by the other standards bodies as much as possible. So DAVIC's standardization activities have close relationship with ISO IEC/JTC1/SC29, ITU-T SG 9, ATM-Forum, IETF, IMA, DVB, etc. DAVIC is trying to specify Applications, Reference Models, Security, Usage Information Control, and the interfaces and protocols among the Content Provider, the Server, the core network, the access network, and the Set Top Unit. DAVIC's first goal is to specify DAVIC1.0 based on CFP1 (Call for Proposal) and CFP2 by Dec. 1995, and the next direction is under preparation for further progress based on CFP3 and CFP4.

  14. Induction of CYP1A in marine fish species from the Gulf of Mexico

    SciTech Connect

    Willett, K.L.; McDonald, S.; Narasimhan, T.R.; Connor, K.; Safe, S.; Kennicutt, M.C.

    1994-12-31

    Ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) activities in over twenty species of fish, invertebrates, and fauna were used as biomarkers of exposure to polynuclear aromatic hydrocarbons (PAHs) in the Gulf of Mexico. The highest AHH and EROD activities in fish were detected in pinfish, tile, flounder, and hardhead catfish. In contrast, minimal to non-detectable induction was observed in invertebrates. Analysis of induction results showed that with the exception of a few species, there was a linear correlation between the induction of EROD vs AHH activity suggesting that ethoxyresorufin and benzo[a]pyrene serve as comparable substrates for CYP1A. In contrast, AHH activity was not induced in either hardhead catfish or lizard fish; whereas, the levels of EROD activity varied from 4.0 to 155 pmol/min/mg. These results indicate that there is some species-dependent variability in the catalytic activity of CYP1A protein in marine fish species, and that more reliable indicators of exposure to PAHs such as CYP1A mRNA levels should also be utilized in environmental monitoring studies. The results of Northern analysis of CYP1A mRNA levels in fish will be presented.

  15. Oxidative stress in Nile tilapia (Oreochromis niloticus) and armored catfish (Pterygoplichthys anisitsi) exposed to diesel oil.

    PubMed

    Nogueira, Lílian; Rodrigues, Aline Cristina Ferreira; Trídico, Camila Pereira; Fossa, Carlos Eduardo; de Almeida, Eduardo Alves

    2011-09-01

    Considering that diesel oil is one of the most common aquatic contaminants, we compare the oxidative stress between two species of fish with different habitats (Pterygoplichthys anisitsi, benthic and Oreochromis niloticus, nektonic) exposed to diesel oil. Malondialdehyde concentrations (MDA) and the activities of ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase were all analyzed in the fishes' livers and gills after 2 and 7 days of exposure to different concentrations of diesel (0.1 and 0.5 mL/L). In the tilapia, MDA levels and the activities of EROD and GST activity in the liver, as well as MDA levels and the activities of GST and SOD in the gill had statistically significant differences between the treatments and between the times of exposure. For the catfish, the same occurred in the case of MDA, EROD, and SOD in the liver and in CAT and SOD in the gills. There were significant differences in the enzyme activity and lipid peroxidation between the species. Although the activity of most enzymes seemed to be more expressive and responsive to diesel in O. niloticus, diesel oil also caused significant effects on oxidative stress parameters in P. anisitsi, even though this species is benthic and thus has less access to insoluble fractions of diesel oil. Therefore, both species can be used as sentinel organisms in environmental biomonitoring of diesel contamination.

  16. Active knee joint flexibility and sports activity.

    PubMed

    Hahn, T; Foldspang, A; Vestergaard, E; Ingemann-Hansen, T

    1999-04-01

    The aim of the study was to estimate active knee flexion and active knee extension in athletes and to investigate the potential association of each to different types of sports activity. Active knee extension and active knee flexion was measured in 339 athletes. Active knee extension was significantly higher in women than in men and significantly positively associated with weekly hours of swimming and weekly hours of competitive gymnastics. Active knee flexion was significantly positively associated with participation in basketball, and significantly negatively associated with age and weekly hours of soccer, European team handball and swimming. The results point to sport-specific adaptation of active knee flexion and active knee extension.

  17. IASS Activity

    NASA Astrophysics Data System (ADS)

    Hojaev, Alisher S.; Ibragimova, Elvira M.

    2015-08-01

    It’s well known, astronomy in Uzbekistan has ancient roots and traditions (e.g., Mirzo Ulugh Beg, Abū al-Rayhān al-Bīrūnī, Abū ‘Abdallāh al-Khwārizmī) and astronomical heritage carefully preserved. Nowadays uzbek astronomers play a key role in scientific research but also in OAD and Decadal Plan activity in the Central Asia region. International Aerospace School (IASS) is an amazing and wonderful event held annually about 30 years. IASS is unique project in the region, and at the beginning we spent the Summer and Winter Schools. At present in the summer camp we gather about 50 teenage and undergraduate students over the country and abroad (France, Malaysia, Turkey, Azerbaijan, Pakistan, Russia, etc.). They are selected on the basis of tests of astronomy and space issues. During two weeks of IASS camp the invited scientists, cosmonauts and astronauts as well as other specialists give lectures and engage in practical exercises with IASS students in astronomy, including daily observations of the Sun and night sky observations with meniscus telescope, space research and exploration, aerospace modelling, preparation and presentation of original projects. This is important that IASS gives not theoretical grounds only but also practically train the students and the hands-on training is the major aims of IASS. Lectures and practice in the field of astronomy carried out with the direct involvement and generous assistance of Uranoscope Association (Paris, France). The current 26-th IASS is planned to held in July 2015.

  18. Activation Energy

    NASA Technical Reports Server (NTRS)

    Gadeken, Owen

    2002-01-01

    Teaming is so common in today's project management environment that most of us assume it comes naturally. We further assume that when presented with meaningful and challenging work, project teams will naturally engage in productive activity to complete their tasks. This assumption is expressed in the simple (but false) equation: Team + Work = Teamwork. Although this equation appears simple and straightforward, it is far from true for most project organizations whose reality is a complex web of institutional norms based on individual achievement and rewards. This is illustrated by the very first successful team experience from my early Air Force career. As a young lieutenant, I was sent to Squadron Officer School, which was the first in the series of Air Force professional military education courses I was required to complete during my career. We were immediately formed into teams of twelve officers. Much of the course featured competition between these teams. As the most junior member of my team, I quickly observed the tremendous pressure to show individual leadership capability. At one point early in the course, almost everyone in our group was vying to become the team leader. This conflict was so intense that it caused us to fail miserably in our first outdoor team building exercise. We spent so much time fighting over leadership that we were unable to complete any of the events on the outdoor obstacle course. This complete lack of success was so disheartening to me that I gave our team little hope for future success. What followed was a very intense period of bickering, conflict, and even shouting matches as our dysfunctional team tried to cope with our early failures and find some way to succeed. British physician and researcher Wilfred Bion (Experiences in Groups, 1961) discovered that there are powerful psychological forces inherent in all groups that divert from accomplishing their primary tasks. To overcome these restraining forces and use the potential

  19. The effect of propylene glycol on the P450-dependent metabolism of acetaminophen and other chemicals in subcellular fractions of mouse liver

    SciTech Connect

    Snawder, J.E.; Benson, R.W.; Leakey, J.E.A.; Roberts, D.W. )

    1993-01-01

    Propylene glycol (PG) decreases the hepatotoxicity of acetominophen (APAP). To elucidate the mechanism for this response, the authors measured the effect of PG on the in vitro metabolism of APAP by subcellular liver fractions from 6-10 week-old male B6C3F1 mice. The fractions were assayed for their ability to bioactivate APAP to N-acetyl-p-benzoquinone imine, which was trapped as APAP-glutathione conjugates or APAP-protein adducts, and for dimethyl-nitrosamine-N-demethylase (DMN), 4-nitrophenol hydroxylase (4-NPOH), and phenacetin-O-deethylase (PAD) activities. Activity in the crude mitochondrial-rich (10,000 [times] g pellet) fraction was low and PG had no effect. PG inhibited DMN and 4-NPOH, indicators of IIE1-dependent activity, and the formation of APAP-glutathione conjugates and APAP-protein adducts in both heavy (15,000 [times] g pellet) and light (100,000 [times] g pellet) microsomes. PAD, a measure of IA2-dependent activity, was not inhibited. These data demonstrate that PG selectively inhibits IIE1 activity, including the bioactivation of APAP, and implicates this as the mechanism for PG-mediated protection of APAP hepatotoxicity in mice. 27 refs., 1 fig., 1 tab.

  20. Carrier effects of dosing the h4iie cells with 3,3′,4,4tt´etrachlorobiphenyl (PCB77) in dimethyl sulfoxide or isooctane

    USGS Publications Warehouse

    Yu, Kyung O.; Fisher, Jeff W.; Burton, G. Allen; Tillitt, Donald E.

    1997-01-01

    A rat hepatoma cell line, H4IIE serves as a bioassay tool to assess the potential toxicity of dioxin-like chemicals, including polychlorinated biphenyls (PCB) in environmental samples. PCB exposure to these cells induces cytochrome (CYP) P4501A1 activity in a dose-dependent fashion, thus allowing assessment of mixtures. The objective of this study was to determine the effect of different carriers, dimethyl sulfoxide (DMSO) and isooctane on the concentrations of PCBs in the H411E cells and induction of CYPIA1 activity as measured by ethoxyresorufm O-deethylase (EROD) activity. H4IIE cells were dosed with three micrograms of UL-14C-PCB77/ plate dissolved in DMSO or isooctane, and were harvested at sequential time periods for 4 days. PCB77 concentration and EROD activity were measured in the cells. EROD activity was greater when using DMSO as compared to isooctane, while there was no difference in the distribution of PCB77-derived radioactivities within the cell culture system based upon the carrier solvent used to deliver PCB77.

  1. Are deep-sea organisms dwelling within a submarine canyon more at risk from anthropogenic contamination than those from the adjacent open slope? A case study of Blanes canyon (NW Mediterranean)

    NASA Astrophysics Data System (ADS)

    Koenig, Samuel; Fernández, Pilar; Company, Joan B.; Huertas, David; Solé, Montserrat

    2013-11-01

    Due to their geomorphological structure and proximity to the coastline, submarine canyons may act as natural conduit routes for anthropogenic contaminants that are transported from surface waters to the deep-sea. Organisms dwelling in these canyon environments might thus be at risk of experiencing adverse health effects due to higher pollution exposure. To address this question, chemical and biochemical analyses were conducted on two of the most abundant deep-sea fish species in the study area, namely Alepocephalus rostratus and Lepidion lepidion, and the most abundant deep-sea commercial decapod crustacean Aristeus antennatus sampled inside Blanes canyon (BC) and on the adjacent open slope (OS). Persistent organic pollutants (POPs) levels, including polychlorinated biphenyl (PCB), dichlorodiphenyltrichloroethane (DDT) and derivatives, hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB) were determined in muscle tissue of selected samples from 900 m and 1500 m depth. Potential effects resulting from contaminant exposure were determined using hepatic biomarkers such as ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-deethylase (PROD), catalase (CAT), carboxylesterase (CbE), glutathione-S-transferase (GST), total glutathione peroxidase (GPX), glutathione reductase (GR) and superoxide-dismutase (SOD) enzyme activities and lipid peroxidation levels (LP). L. lepidion and A. antennatus tissues exhibited higher POP levels inside BC compared to the OS at 900 m depth. These findings were consistent with biomarker data (i.e. enzymatic response to presence of contaminant agents). Elevated xenobiotic-metabolizing (EROD and PROD) and antioxidant enzymes (CAT and GPX) indicated higher contaminant exposure in both species caught within BC. No difference in POP accumulation between sites was observed in L. lepidion at 1500 m depth, nor in biomarker data, suggesting that the pollution gradient was less pronounced at greater depths. This trend was further corroborated

  2. Cytochrome P4501A biomarker indication of oil exposure in harlequin ducks up to 20 years after the Exxon Valdez oil spill.

    PubMed

    Esler, Daniel; Trust, Kimberly A; Ballachey, Brenda E; Iverson, Samuel A; Lewis, Tyler L; Rizzolo, Daniel J; Mulcahy, Daniel M; Miles, A Keith; Woodin, Bruce R; Stegeman, John J; Henderson, John D; Wilson, Barry W

    2010-05-01

    Hydrocarbon-inducible cytochrome P4501A (CYP1A) expression was measured, as ethoxyresorufin-O-deethylase (EROD) activity, in livers of wintering harlequin ducks (Histrionicus histrionicus) captured in areas of Prince William Sound, Alaska, USA, oiled by the 1989 Exxon Valdez spill and in birds from nearby unoiled areas, during 2005 to 2009 (up to 20 years following the spill). The present work repeated studies conducted in 1998 that demonstrated that in harlequin ducks using areas that received Exxon Valdez oil, EROD activity was elevated nearly a decade after the spill. The present findings strongly supported the conclusion that average levels of hepatic EROD activity were higher in ducks from oiled areas than those from unoiled areas during 2005 to 2009. This result was consistent across four sampling periods; furthermore, results generated from two independent laboratories using paired liver samples from one of the sampling periods were similar. The EROD activity did not vary in relation to age, sex, or body mass of individuals, nor did it vary strongly by season in birds collected early and late in the winter of 2006 to 2007, indicating that these factors did not confound inferences about observed differences between oiled and unoiled areas. We interpret these results to indicate that harlequin ducks continued to be exposed to residual Exxon Valdez oil up to 20 years after the original spill. This adds to a growing body of literature suggesting that oil spills have the potential to affect wildlife for much longer time frames than previously assumed.

  3. Assessment of seasonal and sex-related variability of biomarkers in carp (Cyprinus carpio L.) from Karakaya Dam Lake, Turkey.

    PubMed

    Güngördü, Abbas; Ozmen, Murat

    2011-05-01

    This study examines seasonal changes in the activities of selected biomarkers in carp (Cyprinus carpio L.) from Karakaya Dam Lake and evaluates the influence of gender and environmental factors on those activities. Physicochemical characteristics of water were evaluated in the lakewater. Fish were sampled on seasonal basis, and liver ethoxyresorufin-O-deethylase (EROD), glutathione-S-transferase, glutathione reductase, plasma lactate dehydrogenase, aspartate and alanine aminotransferase, and brain acetylcholinesterase (AChE) activities were assayed. Plasma vitellogenin level and hepatosomatic index and condition factors were also determined. Strong seasonal variations were observed but there were no gender differences among selected markers. The highest vitellogenin level of male fish was detected as 606ng/mL which represents the estrogenicity of water in the lake in September 2005. In addition, the seasonal changes of some biomarkers such as EROD and AChE showed that the lake may be at risk of pollution by some xenobiotics arising from agricultural and/or industrial activities.

  4. Effects of dredging in Göteborg harbor, Sweden, assessed by biomarkers in eelpout (Zoarces viviparus).

    PubMed

    Sturve, Joachim; Berglund, Asa; Balk, Lennart; Broeg, Katja; Böhmert, Björn; Massey, Simon; Savva, Demetris; Parkkonen, Jari; Stephensen, Eiríkur; Koehler, Angela; Förlin, Lars

    2005-08-01

    We used a battery of biomarkers in fish to study the effects of the extensive dredging in Göteborg harbor situated at the river Göta alv estuary, Sweden. Eelpout (Zoarces viviparus) were sampled along a gradient into Göteborg harbor, both before and during the dredging. Biomarker responses in the eelpout before the dredging already indicated that fish in Göteborg harbor are chronically affected by pollutants under normal conditions compared to those in a reference area. However, the results during the dredging activities clearly show that fish were even more affected by remobilized pollutants. Elevated ethoxyresorufin-O-deethylase activities and cytochrome P4501A levels indicated exposure to polycyclic aromatic hydrocarbons. Elevated metallothionein gene expression indicated an increase in metal exposure. An increase in general cell toxicity, measured as a decrease in lysosomal membrane stability, as well as effects on the immune system also could be observed in eelpout sampled during the dredging. The results also suggest that dredging activities in the Göta alv estuary can affect larger parts of the Swedish western coast than originally anticipated. The present study demonstrates that the application of a set of biomarkers is a useful approach in monitoring the impact of anthropogenic activities on aquatic environments.

  5. Identification of biomarkers responsive to chronic exposure to pharmaceuticals in target tissues of Carcinus maenas.

    PubMed

    Aguirre-Martínez, G V; Del Valls, T A; Martín-Díaz, M L

    2013-01-01

    A 28-day bioassay was performed with Carcinus maenas to evaluate chronic effects caused by exposure to caffeine and ibuprofen (0.1-50 μg L(-1)) in sea water. Lysosomal membrane stability (LMS) was evaluated in hemolymph applying the neutral red retention assay (NRRA); several biomarkers including ethoxyresorufin O-deethylase (EROD), dibenzylfluorescein dealkylase (DBF), glutathione S-transferase (GST), glutathione peroxidase (GPX), lipid peroxidation (LPO) and DNA damage were studied in gill, hepatopancreas, muscle and gonad tissues. In crabs exposed to environmental concentrations of the drugs, retention time was reduced by 50%. EROD and DBFOD activities were induced by caffeine in muscle and hepatopancreas tissues (p < 0.05); GST activity was activated by ibuprofen in gill, hepatopancreas and muscle at the highest concentrations tested (p < 0.05). All tissues showed GPX activity and LPO induction (p < 0.05). Crabs exposed to caffeine and ibuprofen showed evidence of DNA damage mainly in hepatopancreas tissues (p < 0.05). Environmental concentrations of pharmaceuticals induce LMS and the biochemical responses studied in this crab. This methodology is a suitable technique for assessing pharmaceutical toxicity in the marine environment. PMID:23562135

  6. Enoxacin is an inducer of CYP1A2 in rat liver.

    PubMed

    Schulz, T G; Stahlmann, R; Edwards, R J; Debri, K; Davies, D S; Neubert, D

    1995-10-26

    The induction of cytochrome P450 by enoxacin, ciprofloxacin, and ofloxacin was investigated in female Wistar rats. Animals were treated orally with daily doses ranging from 10 to 400 mg enoxacin per kg body wt, 400 mg ciprofloxacin, or 400 mg ofloxacin per kg body wt for up to 7 days. Activities of methoxyresorufin O-demethylase (MROD) and ethoxyresorufin O-deethylase (EROD) were determined fluorimetrically in hepatic microsomes. MROD activity was increased 2.6-fold after treatment with 100 mg enoxacin per kg body wt for 7 days. Lower doses of enoxacin did not induce MROD activity significantly. Antipeptide antibodies directed specifically against different rat cytochrome P450 enzymes demonstrated that CYP1A2, but not CYP1A1, was induced in rats treated with enoxacin. After ciprofloxacin or ofloxacin treatment, no induction of MROD or EROD activity was observed. Neither ciprofloxacin nor ofloxacin caused any change in CYP1A1 or CYP1A2 apoprotein levels. Further investigations with antipeptide antibodies showed that there was no induction of CYP2B1, CYP2B2, CYP2E1, CYP3A1, CYP3A2, CYP4A1, or CYP4A2 following treatment with enoxacin, ciprofloxacin, or ofloxacin. It is concluded that enoxacin, but not ciprofloxacin or ofloxacin, is an inducer of CYP1A2 in rat liver.

  7. Inhibitory effects of H2-receptor antagonists on cytochrome P450 in male ICR mice.

    PubMed

    Kim, D H; Kim, E J; Han, S S; Roh, J K; Jeong, T C; Park, J H

    1995-08-01

    1. The present study was undertaken to examine the effects of H2-receptor antagonists including newly developed mifentidine derivatives, IY-80843 and IY-80845, on cytochrome P450(P450) in vitro and in vivo. 2. Initially, 3-methylcholanthrene-, phenobarbital-, ethanol- and dexamethasone-induced liver microsomes were prepared from male ICR mice to study in vitro effects of above chemicals on ethoxyresorufin O-deethylase(EROD), pentoxyresorufin O-dealkylase(PROD), p-nitrophenol hydroxylase and erythromycin N-demethylase(ERDM) activities, respectively. It was found that histamine, cimetidine and famotidine were not inhibitory to four enzyme activities. Meanwhile, mifentidine slightly inhibited EROD and PROD activities and its derivatives IY-80843 and IY-80845 strongly inhibited PROD, EROD and ERDM activities. 3. Prolongation of hexobarbital-induced sleeping time was determined in male ICR mice to confirm in vitro inhibitory effects of mifentidine and its derivatives in vivo. It was observed that cimetidine, mifentidine, IY-80843 and IY-80845 caused dose-dependent increases in the sleeping time, indicating the inhibition of P450 responsible for hexobarbital metabolism. 4. It was concluded that mifentidine and its derivatives are P450 inhibitors and that our newly synthesized IY-80843 is most inhibitory. 5. The present results indicate that mifentidine and its derivatives not only antagonise the H2-receptor but also inhibit P450 enzymes. PMID:7576828

  8. Cytochrome P4501A biomarker indication of oil exposure in harlequin ducks up to 20 years after the Exxon Valdez oil spill.

    PubMed

    Esler, Daniel; Trust, Kimberly A; Ballachey, Brenda E; Iverson, Samuel A; Lewis, Tyler L; Rizzolo, Daniel J; Mulcahy, Daniel M; Miles, A Keith; Woodin, Bruce R; Stegeman, John J; Henderson, John D; Wilson, Barry W

    2010-05-01

    Hydrocarbon-inducible cytochrome P4501A (CYP1A) expression was measured, as ethoxyresorufin-O-deethylase (EROD) activity, in livers of wintering harlequin ducks (Histrionicus histrionicus) captured in areas of Prince William Sound, Alaska, USA, oiled by the 1989 Exxon Valdez spill and in birds from nearby unoiled areas, during 2005 to 2009 (up to 20 years following the spill). The present work repeated studies conducted in 1998 that demonstrated that in harlequin ducks using areas that received Exxon Valdez oil, EROD activity was elevated nearly a decade after the spill. The present findings strongly supported the conclusion that average levels of hepatic EROD activity were higher in ducks from oiled areas than those from unoiled areas during 2005 to 2009. This result was consistent across four sampling periods; furthermore, results generated from two independent laboratories using paired liver samples from one of the sampling periods were similar. The EROD activity did not vary in relation to age, sex, or body mass of individuals, nor did it vary strongly by season in birds collected early and late in the winter of 2006 to 2007, indicating that these factors did not confound inferences about observed differences between oiled and unoiled areas. We interpret these results to indicate that harlequin ducks continued to be exposed to residual Exxon Valdez oil up to 20 years after the original spill. This adds to a growing body of literature suggesting that oil spills have the potential to affect wildlife for much longer time frames than previously assumed. PMID:20821550

  9. Biomarkers of PAH exposure in an intertidal fish species from Prince William Sound, Alaska: 2004-2005.

    PubMed

    Huggett, Robert J; Neff, Jerry M; Stegeman, John J; Woodin, Bruce; Parker, Keith R; Brown, John S

    2006-10-15

    Polycyclic aromatic hydrocarbon (PAH) exposure biomarkers were measured in high cockscomb prickleback (Anoplarchus purpurescens) fish collected from both previously oiled and unoiled shore in Prince William Sound (PWS), Alaska, to test the hypothesis that fish living in the nearshore environment of the sound were no longer being exposed to PAH from the Exxon Valdez oil spill. Pricklebacks spend their entire lives in the intertidal zone of rocky shores with short-term movements during feeding and breeding restricted to an area of about 15 meters in diameter. Fish were assayed for the PAH exposure biomarkers, bile fluorescent aromatic compounds (FAC), and liver ethoxyresorufin O-deethylase (EROD) activity (a measure of cytochrome P450 1A (CYP1A) monooxygenase activity). Bile FAC concentrations and EROD activities were low and not significantly different in fish from previously oiled and unoiled sites. The similar low EROD activity and bile FAC concentrations in fish from oiled and unoiled shores, supports the hypothesis that these low-level biomarker responses were not caused by exposure of the fish to residues of the spilled oil. PMID:17120588

  10. Comparisons of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on chemically impacted and nonimpacted subpopulations of Fundulus heteroclitus. 2: Metabolic considerations

    SciTech Connect

    Prince, R.; Cooper, K.R.

    1995-04-01

    A previous paper reported resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in a subpopulation of Fundulus heteroclitus inhabiting the chemically impacted estuary of Newark Bay, New Jersey, as compared to a chemically nonimpacted subpopulation of F. heteroclitus in Tuckerton, New Jersey. This paper reports the results of toxicokinetic and metabolic investigations. The rate of [{sup 3}H]TCDD elimination following a single dermal treatment of [{sup 3}H]TCDD were similar between the Newark and Tuckerton F. heteroclitus subpopulations, as were the capabilities to metabolize TCDD. The Newark F. heteroclitus subpopulation consistently exhibited elevated hepatic P4501A catalytic activity (two- to fivefold), as measured by ethoxyresorufin O-deethylase (EROD), compared to the Tuckerton subpopulation. EROD activity in Newark F. heteroclitus could not be induced by dermally administered [{sup 3}H]TCDD, ranging from 0.020 to 8.0 ng/g [{sup 3}H]TCDD. The Tuckerton fish exhibited a linear increase in EROD activity at 96 h following dermal administration of [{sup 3}H]TCDD, ranging from 0.80 to 8.0 ng/g [{sup 3}H]TCDD. The maximum mean induction in the Tuckerton fish was 30-fold greater than the Tuckerton vehicle control mean. These data indicate that the Newark fish were resistant to both the toxicity of TCDD and the ability of TCDD to induce P4501A activity, which may imply an alteration in the Ah receptor complex of Newark F. heteroclitus.

  11. Physical Activity (Exercise)

    MedlinePlus

    ... fitness. Your fitness routine should include aerobic and strength-training activities, and may also include stretching activities. Aerobic ... Examples include walking, jogging, bicycling, swimming, and tennis. Strength-training activities These activities increase the strength and endurance ...

  12. Structures of pulp-mill-related inducers of mixed function oxygenase (MFO) in rainbow trout

    SciTech Connect

    Parrott, J.L.; Hodson, P.V.; Bennie, D.T.; Efler, S.M.; Burnison, B.K.

    1994-12-31

    There are many known inducers of MFO activity in fish, such as polychlorinated dioxins, furans, biphenyls and polyaromatic hydrocarbons (PAHs). Since a specific chemical structure is required for Ah receptor binding to initiate induction, chemical structure is a critical factor controlling potency. Elevated hepatic MFO activity is common in fish downstream of pulp mill effluent discharges. The identity of the MFO-inducer(s) in pulp mill effluents is, as yet, unknown, although initial theories linked dioxins and furans in effluents with induction. The author have extracted effluent from several Canadian pulp mills, and have identified many non-chlorinated compounds with structures similar to known MFO inducers. PAHs such as substituted naphthalenes, chrysene and phenanthrene have been detected in effluent or defoamers used in pulp mils, but none induced ethoxyresorufin-O-deethylase (EROD) activity of rainbow trout (Oncorhynchus mykiss) after 4 d exposures at levels up to 1,000 {micro}g/L. Some multi-ringed compounds found in effluent or sediments from pulp mills induced EROD, while others, such as nonyl phenols, phthalates and benzothioazole showed no induction. These results are expanding the range of known inducers and will aid the development of models relating potency to chemical structure.

  13. Effects of beta-naphthoflavone on hepatic biotransformation and glutathione biosynthesis in largemouth bass (Micropterus salmoides).

    PubMed

    Hughes, Erin M; Gallagher, Evan P

    2004-01-01

    We are investigating the effects of in vivo exposure of prototypical enzyme inducing agents on hepatic biotransformation enzyme expression in largemouth bass (Micropterus salmoides), a predatory game fish found throughout the United States and Canada. The current study targeted those genes involved in biotransformation and oxidative stress that may be regulated by Ah-receptor-dependent pathways. Exposure of bass to beta-naphthoflavone (beta-NF, 66 mg/kg, i.p.) elicited a 7-9-fold increase in hepatic microsomal cytochrome P4501A-dependent ethoxyresorufin O-deethylase (EROD) activities, but did not affect cytosolic GST catalytic activities toward 1-chloro-2,4-dinitrobenzene (CDNB) or 5-androstene-3,17-dione (ADI). Glutathione S-transferase A (GST-A) mRNA expression exhibited a transient, but non-significant increase following exposure to beta-NF, and generally tracked the minimal changes observed in GST-CDNB activities. Expression of the mRNA encoding glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme in glutathione (GSH) biosynthesis, was increased 1.7-fold by beta-NF. Changes in GCLC mRNA expression were paralleled by increases in intracellular GSH. In summary, largemouth bass hepatic CYP1A-dependent and GSH biosynthetic pathways, and to a lesser extent GST, are responsive to exposure to beta-NF.

  14. Comparing the response of biochemical indicators (biomarkers) and biological indices to diagnose the ecological impact of an oil spillage in a Mediterranean river (NE Catalunya, Spain).

    PubMed

    Damásio, Joana B; Barata, Carlos; Munné, Antoni; Ginebreda, Antoni; Guasch, Helena; Sabater, Sergi; Caixach, Josep; Porte, Cinta

    2007-01-01

    Three biomarkers of hydrocarbon exposure, liver 7-ethoxyresourfin-O-deethylase activity (EROD), fluorescent hydrocarbon compounds (FACs) in bilis, and the liver antioxidant enzyme catalase (CAT) were examined in the autochthonous fish species Barbus meridionalis collected in the river Fluvià (NE Catalunya, Spain) after an oil spillage. Four different locations were sampled, including the impacted site, upstream and downstream sites and a reference site. Biomarker responses were compared with diatom and macroinvertebrate community assemblage metrics (Specific Pollution Sensitivity index - IPS, and Iberian Biological Monitoring Working Party - IBMWP, respectively). Chemical analyses denoted that polycyclic aromatic hydrocarbon levels in sediment were much higher at the impacted site than in downstream reaches. Four fold increase of EROD activity together with increased levels of biliary FACs in barbs collected at the spilled site indicated exposure of inhabiting fish to the oil. Additionally, CAT activity was significantly depressed (four fold) when compared to other stations, thus suggesting that fish collected from the impacted sites could be more susceptible to suffer oxidative stress. Biological indices (particularly that of the diatom community IPS) showed slight significant effects between control and impacted sites, indicating that more tolerant taxa were favoured because of the oil spillage. These results support the need to include biochemical responses measured in local species in monitoring programmes aimed to diagnose specific pollution effects in stressed river ecosystems. PMID:16959291

  15. Wild fish from the Bay of Quinte Area of Concern contain elevated tissue concentrations of PCBs and exhibit evidence of endocrine-related health effects.

    PubMed

    Simmons, D B D; McMaster, M E; Reiner, E J; Hewitt, L M; Parrott, J L; Park, B J; Brown, S B; Sherry, J P

    2014-05-01

    The Bay of Quinte (BOQ) is an Area of Concern listed under the Great Lakes Water Quality Agreement. The presence of dioxins and dioxin-like PCBs in fish in the BOQ AOC has led to restrictions on fish consumption by humans, which is a beneficial use impairment. Adult yellow perch (Perca flavescens) and brown bullhead (Ameiurus nebulosus) were sampled from Trenton, Belleville, and Deseronto (reference site) in the BOQ. A suite of hormone assays and various measures of exposure and/or sublethal health effects were used to assess the health status of fish of both species and sex. Condition factor, hepatosomatic index, ethoxyresorufin-O-deethylase activity, circulating steroid and thyroid hormones, thyroid activation, oocyte size distribution, spermatogenic cell stages, and plasma vitellogenin were among the endpoints that were significantly (p < 0.05) affected by location. Many of those effects corresponded with significantly (p < 0.05) greater tissue concentrations of polychlorinated biphenyls (PCBs) at Belleville and Trenton. Hepatic extracts from brown bullhead sampled from Trenton had significantly (p < 0.05) greater binding activity to the androgen receptor and sex steroid binding protein. Taken together, these data and preliminary data from a concomitant study suggest that PCBs are likely being hydroxylated in vivo, resulting in enhanced bioactivity at endocrine receptors and measurable health responses. The present study supports the growing body of evidence that PCBs and their metabolites can affect fish thyroid and steroid hormone systems. PMID:24576942

  16. Reproductive and biochemical biomarkers in largemouth bass sampled downstream of a pulp and paper mill in Florida

    USGS Publications Warehouse

    Sepulveda, M.S.; Gallagher, E.P.; Wieser, C.M.; Gross, T.S.

    2004-01-01

    The objective of this study was to evaluate the effects of bleached/unbleached kraft mill effluents (B/UKME) on the reproductive parameters of free-ranging Florida largemouth bass (Micropterus salmoides floridanus). The reproductive parameters measured included gonadosomatic index (GSI), histological evaluation of gonads, and plasma concentrations of vitellogenin (VTG), 17??-estradiol, and 11-ketotestosterone (11-KT). Hepatic ethoxyresorufin-O-deethylase (EROD) activity was measured as a marker of exposure to cytochrome P450-inducing agents in these effluents. Endpoints were compared among adult bass sampled from tributary and mainstream effluent-contaminated and reference sites. Females sampled from the site closest to the mill outfall had a significant five-fold increase in EROD activity compared to bass sampled from reference streams. Although sex hormones were significantly reduced in bass from exposed sites, there were no differences in VTG and GSI across sites. The absence of organism-level responses was probably not related to a lack of sensitivity, as previous studies in our laboratory have shown that bass exposed to these effluents exhibit changes in GSI and in other measures associated with reproductive success. In females, inverse relationships were observed between VTG and GSI and EROD activity. These relationship, however, were not consistent within all of the sites studied. Collectively, our findings indicate that hepatic EROD induction is an effective marker of B/UKME exposure in largemouth bass and that it might be associated with antiestrogenic effects in this species. ?? 2003 Elsevier Inc. All rights reserved.

  17. A toxic equivalency factor scale for polychlorinated biphenyls (PCBs) in chicken hepatocytes

    SciTech Connect

    Tysklind, M.; Bosveld, A.T.C.; Sinnige, T.; Berg, M. van den

    1995-12-31

    The relative potencies of 20 polychlorinated biphenyls (PCBs) were studied in a chicken embryo hepatocyte system. The 20 congeners were selected according to a full 2{sup 4}-factorial design based on the principal properties of all 154 tetra- through heptachlorinated PCBs. The principal properties were obtained using principal component analysis (PCA) on a multitude of different physico-chemical properties of the PCBs. Toxic equivalency factors (TEFs) were determined for seven out of the twenty PCB congeners, viz. PCB{number_sign}41, PCB{number_sign}60, PCB{number_sign}78, PCB{number_sign}126, PCB{number_sign}169, PCB{number_sign}190, and PCB{number_sign}193, which elicit measurable catalytic ethoxyresorufin-O-deethylase (EROD) activity in the chicken hepatocytes. A multivariate quantitative structure-activity relationship (QSAR) was developed by using partial least-squares to latent variables (PLS) in order to model the relationship between the set of physico-chemical descriptors of the PCBs and their TEF-values. The model showed good correlations between observed and predicted TEF-values for this training set of congeners. From the QSAR, TEF-values were predicted for a large number PCB congeners not yet tested regarding EROD activity in chicken hepatocytes. The predicted TEF-values were validated by TEF-values reported in the literature.

  18. The anticarcinogen 3,3'-diindolylmethane is an inhibitor of cytochrome P-450.

    PubMed

    Stresser, D M; Bjeldanes, L F; Bailey, G S; Williams, D E

    1995-08-01

    Dietary indole-3-carbinol inhibits carcinogenesis in rodents and trout. Several mechanisms of inhibition may exist. We reported previously that 3,3'-diindolylmethane, an in vivo derivative of indole-3-carbinol, is a potent noncompetitive inhibitor of trout cytochrome P450 (CYP) 1A-dependent ethoxyresorufin O-deethylase with Ki values in the low micromolar range. We now report a similar potent inhibition by 3,3'-diindolylmethane of rat and human CYP1A1, human CYP1A2, and rat CYP2B1 using various CYP-specific or preferential activity assays. 3,3'-Diindolylmethane also inhibited in vitro CYP-mediated metabolism of the ubiquitous food contaminant and potent hepatocarcinogen, aflatoxin B1. There was no inhibition of cytochrome c reductase. In addition, we found 3,3'-diindolylmethane to be a substrate for rat hepatic microsomal monooxygenase(s) and tentatively identified a monohydroxylated metabolite. These observations indicate that 3,3'-diindolylmethane can inhibit the catalytic activities of a range of CYP isoforms from lower and higher vertebrates in vitro. This broadly based inhibition of CYP-mediated activation of procarcinogens may be an indole-3-carbinol anticarcinogenic mechanism applicable to all species, including humans.

  19. Stock-specific variation of trophic position, diet and environmental stress markers in Atlantic salmon Salmo salar during feeding migrations in the Baltic Sea.

    PubMed

    Vuori, K; Kiljunen, M; Kanerva, M; Koljonen, M-L; Nikinmaa, M

    2012-11-01

    This study investigated stock-specific variation in selected ecophysiological variables during the feeding migrations of Atlantic salmon Salmo salar in the Baltic Sea. Oxidative stress biomarkers and EROD (ethoxyresorufin-O-deethylase, Cyp1A enzyme) activity were used as indicators of possible environmental stress and stable isotopes as determinants of diet and trophic position. Latvian S. salar stocks Daugava and Gauja had distinct stable-isotope signatures compared to the other stocks, indicating differences in migration patterns, residency or arrival times, or dietary specialization among stocks. Salmo salar originating from Daugava and Gauja also had lower catalase enzyme activity than the other stocks. Post-smolts originating from rivers of the Gulf of Finland had elevated EROD activities compared to fish of the same age from Bothnian Bay rivers, which could indicate exposure to organochlorine pollutants. No other stock-specific differences in oxidative stress biomarkers were found. The study demonstrates how genetic, oxidative stress biomarker, EROD and stable-isotope data may be combined to study trophic position, prey prevalence and environmental stress of mixed S. salar stocks foraging in the sea.

  20. Assessment of some innate immune responses in dab (Limanda limanda L.) from the North Sea as part of an integrated biological effects monitoring

    NASA Astrophysics Data System (ADS)

    Skouras, Andreas; Lang, Thomas; Vobach, Michael; Danischewski, Dirk; Wosniok, Werner; Scharsack, Jörn Peter; Steinhagen, Dieter

    2003-10-01

    The marine flatfish dab (Limanda limanda), which lives in direct contact with contaminated sediments, is frequently used as a sentinel species in international monitoring programmes on the biological effects of contaminants. In this study, immune responses were recorded as indicators of sublethal chronic effects of contaminants, in addition to measurement of the induction of mono-oxygenase ethoxyresorufin O-deethylase (EROD) in liver cells, the inhibition of acetylcholin esterase (AChE) in muscle and a quantification of grossly visible diseases and parasites. In total, 336 dab were analysed from five sampling areas in the North Sea, including the German Bight, the Dogger Bank, the Firth of Forth, and two locations close to oil and gas platforms (Ekofisk and Danfield). When considering plasma lysozyme levels, pinocytosis and respiratory burst activity of head kidney leucocytes, a clear gradient could be observed with decreased levels in individuals collected from the Firth of Forth and locations near the oil or gas platforms compared with dab from the Dogger Bank or the German Bight. Individuals with induced EROD activity displayed reduced lysozyme and respiratory burst activities. Lysozyme levels were also reduced in dab with lymphocystis or with nematodes. The data obtained indicate that the assessment of innate immune parameters in a monitoring programme provides supplementary information about immunomodulatory effects associated with the exposure of fish to contaminants. In particular, concentrations of plasma lysozyme, which can be analysed in an easy and inexpensive assay, are considered to be an appropriate parameter for use in a battery of other bioindicators.

  1. The sublethal effects of petroleum refinery effluents: Mixed function oxygenase (MFO) induction in rainbow trout

    SciTech Connect

    Sherry, J.; Scott, B.; Parrott, J.; Hodson, P.; Rao, S.

    1995-12-31

    Canada uses a single biological parameter which is based on the ability of rainbow trout (Oncorhynchus mykiss) to survive a 24 hour exposure to assess and regulate the toxicity of refinery effluents. The acute toxicity of Canadian refinery effluents is generally well controlled. Long term exposures to sublethal toxicants, which are not covered by the current regulations, could have adverse ecological effects. Since PAHs, such as benzo(a)pyrene, can occur in refinery effluents, the authors tested the hypothesis that refinery effluents can induce mixed-function oxygenase measured as ethoxyresorufin-O-deethylase activity (EROD) activity in fish. Two end of pipe effluent samples were collected from each of four Ontario refineries. All effluents induced EROD activity in young trout in a dose dependent manner. The EROD parameter has potential as a bioindicator of exposure to refinery effluents. The samples were also tested for toxicity to fathead minnow (Pimephales promelas) larvae and to a fish cell line (Ictalurus nebulosus). Fathead minnow growth was significantly reduced by six out of eight samples, and larval survival was affected by one sample. The in vitro data were less consistent: weak toxicity was detected in some samples but the dose response relationship was poor. Direct acting mutagens were detected in two effluents using the Ames Fluctuation assay.

  2. Atrazine promotes biochemical changes and DNA damage in a Neotropical fish species.

    PubMed

    Santos, Thais G; Martinez, Cláudia B R

    2012-11-01

    The effects of Atrazine, an herbicide used worldwide and considered as a potential contaminant in aquatic environments, were assessed on the Neotropical fish Prochilodus lineatus acutely (24 and 48 h) exposed to 2 or 10 μg L(-1) of atrazine by using a set of biochemical and genetic biomarkers. The following parameters were measured in the liver: activity of the biotransformation enzymes ethoxyresorufin-O-deethylase (EROD) and glutathione S transferase (GST), antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), content of reduced glutathione (GSH), generation of reactive oxygen species (ROS) and occurrence of lipid peroxidation (LPO); in brain and muscle the activity of acetylcholinesterase (AChE) and DNA damage (comet assay) on erythrocytes, gills and liver cells. A general decreasing trend on the biotransformation and antioxidant enzymes was observed in the liver of P. lineatus exposed to atrazine; except for GR, all the other antioxidant enzymes (SOD, CAT and GPx) and biotransformation enzymes (EROD and GST) showed inhibited activity. Changes in muscle or brain AChE were not detected. DNA damage was observed in the different cell types of fish exposed to the herbicide, and it was probably not from oxidative origin, since no increase in ROS generation and LPO was detected in the liver. These results show that atrazine behaves as enzyme inhibitor, impairing hepatic metabolism, and produces genotoxic damage to different cell types of P. lineatus.

  3. Mammalian and teleost cell line bioassay and chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent concentrations in lake trout (Salvelinus namaycush) from Lake Superior and Lake Ontario, North America

    SciTech Connect

    Whyte, J.J.; Heuvel, M.R. van den; Clemons, J.H.; Dixon, D.G.; Bols, N.C.; Huestis, S.Y.; Servos, M.R.

    1998-11-01

    For livers of lake trout from three Great Lakes sites, the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent concentrations (TEQs) were determined in four ways. Bioassay-derived (BD) TEQs were measured with rat (H4IIE) and rainbow trout (RTL-W1) cell lines, and chemistry-derived (CD) TEQs were calculated with TCDD equivalency factors (TEFs) derived with H4IIE and RTL-W1. Generally, BD-TEQs and CD-TEQs for individual samples did not differ significantly for either H4IIE or RTL-W1, indicating that all of the AhR-active compounds in a sample were accounted for by the congener analysis and that these compounds acted in an additive fashion in both mammalian and piscine systems. However, contributions of individual chemicals to overall CD-TEQs differed with H4IIE and RTL-W1 TEFs, and for some individual samples. TEQs did depend on the method used. Hepatic TEQs and ethoxyresorufin-O-deethylase (EROD) levels differed significantly between sites. For TEQs, the order was Glenora > Jackfish Bay > Black Bay; for EROD activity, the order was Jackfish Bay > Glenora = Black Bay. No correlation was found between hepatic TEQs and EROD activity, which suggests that the two measurements are evaluating different but related consequences of contaminant exposure.

  4. Contaminant accumulation and multi-biomarker responses in field collected zebra mussels (Dreissena polymorpha) and crayfish (Procambarus clarkii), to evaluate toxicological effects of industrial hazardous dumps in the Ebro river (NE Spain).

    PubMed

    Faria, Melissa; Huertas, David; Soto, David X; Grimalt, Joan O; Catalan, Jordi; Riva, Mari Carmen; Barata, Carlos

    2010-01-01

    Large amounts of industrial waste containing high concentrations of mercury, cadmium and organochlorine residues were dumped in a reservoir adjacent to a chlorine-alkali plant in the village of Flix(Catalonia, Spain), situated at the shore of the lower Ebro river. Effects of these contaminants to aquatic river invertebrates were assessed by integrating analyses of metals and organochlorine residues in field collected zebra mussels and crayfish with a wide range of biomarkers. Biological responses included levels of metallothioneins, activities of ethoxyresorufin-O-deethylase, oxidative stress biomarkers (glutathione content, enzymatic activities of superoxide dismutase, catalase, glutathione s-transferase, glutathione peroxidise and glutathione reductase), levels of lipid peroxidation and of DNA strand breaks. The results obtained evidenced similar response patterns in mussels and crayfish with increasing toxic stress levels from upper parts of the river towards the meander located immediately downstream from the most polluted site, close to the waste dumps. The aforementioned stress levels could be related with concentrations of mercury, cadmium, hexachlorobenzene, polychlorobiphenyls and dichlorodiphenyltrichloroethanes from 4- to 195-fold greater than local background levels. The response of biomarkers to these pollutant concentrations differences was reflected in high activities and levels of antioxidant enzymes, metallothioneins, lipid peroxidation and DNA strand breaks and decreased levels of glutathione.

  5. Some effects of the fungicide propiconazole on cytochrome P450 and glutathione S-transferase in brown trout (Salmo trutta).

    PubMed

    Egaas, E; Sandvik, M; Fjeld, E; Källqvist, T; Goksøyr, A; Svensen, A

    1999-03-01

    The fungicide propiconazole (1-(2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl) -1H-1,2,4-triazole) induced the hepatic cytochrome P4501A (CYP1A) activity towards ethoxyresorufin-O-deethylase (EROD), the content of CYP1A protein as quantified by enzyme-linked immunosorbent assay (ELISA) and the glutathione S-transferase (GST) activity towards the three commonly used substrates CDNB(1-chloro-2,4-dinitrobenzene), cumene hydroperoxide (CU) and ethachrynic acid (EA) in brown trout (Salmo trutta) depending on dose and body weight. An exponential dose response relationship existed between propiconazole exposure and CYP1A activity. A 2. order polynomial regression of the propiconazole concentration (square root transformed) on the data for CDNB, EU and CU revealed a bell-shaped pattern of the GST induction. Reverse-phase HPLC of the GSH-affinity chromatography purified GST isozymes in trout exposed to respectively 8.3, 23, 93, 313 and 606 microg l(-1) propiconazole in the water indicated that the propiconazole treatment may lead to changes in the composition of the subunits compared to the controls. Thus, propiconazole exposure through the water changed the properties of the brown trout hepatic CYP1A and GST, and these changes may be used as a bioindicator on the molecular level of exposure and effect of propiconazole in controlled experiments. The use in monitoring of propiconazole exposure under natural field conditions is possible, however needs further investigation.

  6. Preliminary risk assessment of the wet landscape option for reclamation of oil sands mine tailings: bioassays with mature fine tailings pore water.

    PubMed

    Madill, R E; Orzechowski, M T; Chen, G; Brownlee, B G; Bunce, N J

    2001-06-01

    Chemical and biological assays have been carried out on the "pore water" that results from the settling of the tailings that accompany bitumen recovery from the Athabasca oil sands. Examination of the nonacidic extracts of pore water by gas chromatography-mass spectroscopy allowed the identification of numerous two- to three-ring polycyclic aromatic compounds (PACs), to a total concentration of 2.6 micrograms/L of pore water. The PACs were biodegraded by microflora naturally present in the pore water. Acute toxicity was associated principally with the acidic fraction (naphthenic acids) of pore water extracts according to the Microtox assay; other work has shown that acute toxicity dissipates fairly rapidly. Both individual PACs and concentrated pore water extracts showed minimal levels of binding to the rat Ah receptor and induced minimal ethoxyresorufin-O-deethylase activity in primary rat hepatocytes, showing an insignificant risk of inducing monooxygenase activity. Taken together with previous work showing negligible mutagenic activity of these extracts, we conclude that it should be possible to develop tailing slurries into biologically productive artificial lakes.

  7. White sucker (Catostomus commersoni) growth and sexual maturation in pulp mill-contaminated and reference rivers

    SciTech Connect

    Gagnon, M.M.; Bussieres, D.; Dodson, J.J. ); Hodson, P.V. )

    1995-02-01

    Induction of hepatic ethoxyresorufin-O-deethylase (EROD) activity and accumulation of chlorophenolic compounds typical of bleached-kraft mill effluent (BKME) in fish sampled downstream of a pulp mill on the St. Maurice River, Quebec, Canada, provided evidence of chemical exposure to BKME. In comparison, fish sampled over the same distances and in similar habitats in a noncontaminated reference river, the Gatineau River, demonstrated low EROD activity and contamination levels. Accelerated growth of white suckers occurred between 2 and 10 years of age in both rivers at downstream stations relative to upstream stations, suggesting the existence of gradients of nutrient enrichment independent of BKME contamination. The impact of BKME exposure was expressed as reduced investment in reproduction, as revealed by greater length at maturity, reduced gonad size, and more variable fecundity. These effects were not obvious in simple upstream-downstream comparisons, but became evident when fish from the uncontaminated Gatineau River showed increased gonadal development and reduced age and size at maturity in response to enhanced growth rates.

  8. Biomonitoring of Environmental Status and Trends (BEST) Program: selected methods for monitoring chemical contaminants and their effects in aquatic ecosystems

    USGS Publications Warehouse

    Schmitt, Christopher J.; Dethloff, Gail M.

    2000-01-01

    This document describes the suite of biological methods of the U.S. Geological Survey- Biomonitoring of Environmental Status and Trends program for monitoring chemical contaminants and their effects on fish. The methods, which were selected by panels of experts, are being field-tested in rivers of the Mississippi River, Columbia River, and Rio Grande basins. General health biomarkers include a health assessment index based on gross observation; histopathological examination of selected organs and tissues; condition factor; and the heptosomatic and splenosomatic indices. Immune system indicators are plasma lysozyme activity and measures of splenic macrophage aggregates. Reproductive biomarkers include plasma concentrations of sex steroid hormones (17b-estradiol and 11-ketotestosterone) and vitellogenin, gonadal histopathology (including reproductive stage and, in females, gonadal atresia), and the gonadosomatic index. Indicators of exposure to polycyclic aromatic and polyhalogenated hydrocarbons are the H4IIE rat hepatoma cell bioassay (performed on solvent extracts of composite fish samples) and hepatic ethoxyresorufin-O-deethylase activity. Stable nitrogen isotope ratios are used to assess the trophic position of the fish and their exposure to sewage and other animal wastes. For each indicator we describe endpoint(s) and methods, and discuss the indicator?s value and limitations for contaminant monitoring and assessment.

  9. Effect of exposure of rabbit hepatocytes to sulfur-containing anthelmintics (oxfendazole and fenbendazole) on cytochrome P4501A1 expression.

    PubMed

    Gleizes-Escala, C; Lesca, P; Larrieu, G; Dupuy, J; Pineau, T; Galtier, P

    1996-04-01

    The expression of cytochrome P4501A1 and 1A2 was investigated in rabbit hepatocytes maintained in primary cultures for 96 hr in the absence or presence of 100 mum of the benzimidazole anthelmintics oxfendazole or fenbendazole. Total cytochrome P-450, ethoxyresorufin O-deethylase and acetanilide hydroxylase activities were significantly increased in cell cultures receiving benzimidazoles. These increases were more marked after exposure of cultured hepatocytes to oxfendazole (OFZ) than to fenbendazole (FBZ). Western and Northern blot analysis of microsomes and RNA prepared from these cultures revealed increased levels of both protein and specific mRNA for P4501A1. The inhibition of these inductions in the presence of actinomycin D suggests a transcriptional way of activation of this gene. The ability of OFZ to bind to the Ah receptor has been examined. Data obtained from competition experiments with dioxin demonstrated that OFZ and other compounds in the benzimidazole series are not ligand of the Ah receptor. From saturation experiments and Scatchard plot analysis, rabbit hepatocyte Ah receptor (K(d) = 10.6 nm) seems to belong, as does the human Ah receptor, to a low-affinity category. Different induction rates obtained with several benzimidazole drugs suggest that the sulfur atom within the molecule is critical for CYP1A1 induction. The widely used benzimidazole anthelmintics OFZ and FBZ may exert an inducing effect through an original pathway that does not require a specific binding step to the Ah receptor.

  10. PAH metabolites, GST and EROD in European eel (Anguilla anguilla) as possible indicators for eel habitat quality in German rivers.

    PubMed

    Kammann, Ulrike; Brinkmann, Markus; Freese, Marko; Pohlmann, Jan-Dag; Stoffels, Sandra; Hollert, Henner; Hanel, Reinhold

    2014-02-01

    The stock of the European eel (Anguilla anguilla L.) continues to decline and has reached a new minimum in 2011. Poor health status of the spawners due to organic contaminants is one of the possible causes for this dramatic situation. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants, which are rapidly metabolized in vertebrates. EROD (ethoxyresorufin-O-deethylase) and GST (glutathione-S-transferase) are two enzymes involved in PAH detoxification in fish. In this study, PAH metabolites as well as EROD and GST activity in a large, comprising dataset of more than 260 migratory and pre-migratory eels from five large German river basin districts were used to describe PAH exposure and its metabolism as possible indicators for the habitat quality for eels. Eel from the river Elbe appear to be moderately contaminated with PAH. Highest mean values of PAH metabolites were analysed in fish from the river Rhine. However, the results suggest that contaminants such as PAH are metabolized in the fish and may have contributed to EROD activity in eels caught from the Elbe estuary to 600 km upstream. Since the eel's onset of cessation of feeding is closely linked to maturation and migration, we propose bile pigments as new indicators contributing to identify the proportion of migratory eel, which is crucial information for eel management plans. We showed that PAH metabolites normalized to bile pigments as well as EROD could be used to describe the habitat quality and might be suitable parameters in search for suitable stocking habitats.

  11. Biomarkers of exposure of brown bullheads (Ameiurus nebulosus) to contaminants in the lower Great Lakes, North America

    SciTech Connect

    Arcand-Hoy, L.D.; Metcalfe, C.D.

    1999-04-01

    Brown bullheads (Ameiurus nebulosus) from three contaminated sites (Detroit River, Hamilton Harbour, and Black River) and two relatively clean reference sites (Old Woman Creek and Bay of Quinte) in the lower Great Lakes were monitored for several biomarkers of exposure to PAHs. Bullheads from the contaminated sites had elevated hepatosomatic indices, increased ethoxyresorufin-O-deethylase (EROD) activity, decreased hepatic retinoid stores, and a greater incidence of hepatic neoplasms. Fluorescent aromatic compounds (FACs) in the bile were also elevated in bullheads from the Black River and Hamilton Harbour in comparison to fish from reference sites. A correlation was found between reduction of hepatic retinoid stores and induction of hepatic EROD activity in bullheads. Principal component analysis of biomarker data demonstrated that biomarker patterns in Detroit River bullheads were different from those of Black River and Hamilton Harbour bullheads. Biomarkers in fish are useful monitoring tools for detecting contamination of the aquatic environment, but interpretation of results is limited by within- and between-site variability in the responses, some of which may be explained by mobility of the fish. In contaminated areas, bile fluorescent aromatic compounds appear to be the best indicator of recent exposure to polynuclear aromatic hydrocarbons, whereas responses to other biochemical biomarkers appear to be over a longer time period.

  12. Functional expression of Carassius auratus cytochrome P4501A in a novel Shewanella oneidensis expression system and application for the degradation of benzo[a]pyrene.

    PubMed

    Chang, Ziwei; Lu, Ming; Shon, Kwang-Jae; Park, Jang-Su

    2014-06-10

    Cytochrome P4501A (CYP1A) in fish has attracted an increasing interest because of its important roles in the metabolic activation of certain xenobiotics such as aromatic hydrocarbons. CYPs are reported to be expressed in yeast, insect cells and Escherichia coli, but are critical for high-level expression. Besides, this study found that the purification of recombinant goldfish CYP1A would result in a loss of enzyme activity. Because large quantities of functional CYP1A are required, it is necessary to find a suitable host with high-level expression. In the present study, a novel expression system using Shewanella oneidensis was established successfully for the production of goldfish CYP1A. A signal peptide in the expression vector leads to the high-level expression in the periplasmic space of Shewanella. The recombinant CYP1A in Shewanella reached up to 1μmol per liter of culture, and showed the typical P450 hemoprotein spectra. An ethoxyresorufin O-deethylase assay revealed the amount of functional proteins in Shewanella to be almost ten times more than those in other expression systems. Furthermore, the CYP1A-mediated degradation of benzo[a]pyrene was also observed by (1)H NMR spectroscopy. These results indicate the possible application of periplasmic fractions to obtain sufficient quantities of functional CYP1A for further studies.

  13. Effects of an oil spill in a harbor assessed using biomarkers of exposure in eelpout.

    PubMed

    Sturve, Joachim; Balk, Lennart; Liewenborg, Birgitta; Adolfsson-Erici, Margaretha; Förlin, Lars; Carney Almroth, Bethanie

    2014-12-01

    Oil spills occur commonly, and chemical compounds originating from oil spills are widespread in the aquatic environment. In order to monitor effects of a bunker oil spill on the aquatic environment, biomarker responses were measured in eelpout (Zoarces viviparus) sampled along a gradient in Göteborg harbor where the oil spill occurred and at a reference site, 2 weeks after the oil spill. Eelpout were also exposed to the bunker oil in a laboratory study to validate field data. The results show that eelpout from the Göteborg harbor are influenced by contaminants, especially polycyclic aromatic hydrocarbons (PAHs), also during "normal" conditions. The bunker oil spill strongly enhanced the biomarker responses. Results show elevated ethoxyresorufin-O-deethylase (EROD) activities in all exposed sites, but, closest to the oil spill, the EROD activity was partly inhibited, possibly by PAHs. Elevated DNA adduct levels were also observed after the bunker oil spill. Chemical analyses of bile revealed high concentrations of PAH metabolites in the eelpout exposed to the oil, and the same PAH metabolite profile was evident both in eelpout sampled in the harbor and in the eelpout exposed to the bunker oil in the laboratory study.

  14. Contamination and correlation with toxicity of sediment samples from the Skagerrak and Kattegat

    NASA Astrophysics Data System (ADS)

    Magnusson, K.; Ekelund, R.; Dave, G.; Granmo, Å.; Förlin, L.; Wennberg, L.; Samuelsson, M.-O.; Berggren, M.; Brorström-Lundén, E.

    1996-02-01

    The pollution state in the Skagerrak and Kattegat was investigated by determination of pollutant concentrations and toxicity of sediment samples from 11 stations in the area. A comparison was made with the sediment from a reference site near the Faroe Islands. Polycyclic aromatic hydrocarbons (PAH) and organochlorines were determined in whole sediment and heavy metals and ammonia were analysed in filtered pore water. Toxicity was bioassayed in whole sediment with Nitocra spinipes and Daphnia magna, in pore water with Mytilus edulis larvae and in solvent extracts from sediment with tests measuring etoxyresorufin-O-deethylase (EROD) activity in Oncorhyncus mykiss and rate of denitrification. Sites close to Göteborg and in an area from the Oslo fjord to the Norwegian Trench were most polluted. Sediment from the Faroe Islands was least polluted and also least toxic. Multivariate statistical analysis indicates that the different tests were sensitive to different kinds of pollutants. Effects on mussel larvae correlated strongest with the occurrence of ammonia, manganese, cadmium and PAHs, Nitocra with α-hexachlorocyclohexane (HCH) and p,p'-DDD, Daphnia with arsenic and γ-HCH, fish EROD activity with benzo[ghi]perylene and unknown compounds associated with organic carbon, and denitrification with chlordanes, dieldrin and a few PAHs. The results indicate that sampling sites close to Göteborg are so polluted that harmful effects on the ecosystem probably occur.

  15. The role of biomarkers to assess oil-contaminated sediment quality using toxicity tests with clams and crabs.

    PubMed

    Morales-Caselles, Carmen; Martín-Díaz, María Laura; Riba, Inmaculada; Sarasquete, Carmen; Delvalls, Tomás Angel

    2008-06-01

    A 28-d bioassay was conducted with two invertebrate species with different feeding habits, the clam Ruditapes philippinarum and the shore crab Carcinus maenas. The purpose of the present study was to assess the quality of sediments affected by oil spills in different areas of the Spanish coast. The organisms were exposed to environmental samples of oil-contaminated sediments during four weeks and, after the experiment, a suite of biomarkers of exposure was measured: The phase one detoxification system was assessed by ethoxyresorufin-O-deethylase (EROD) activity; glutathione-S-transferase (GST) is a phase-two detoxification enzyme but also is implicated in oxidative stress events; glutathione peroxidase (GPX), glutathione reductase (GR), and the ferric reducing ability of plasma (FRAP) assay were analyzed to determine the antioxidant activity of the tissues. The biomarker results were correlated with the chemical compounds bound to sediments (polycyclic aromatic hydrocarbons [PAHs], polychlorinated biphenyls [PCBs], Zn, Cd, Pb, Cu, Ni, Co, V) and a principal component analysis was carried out with the purpose of linking all the variables and to detect those contaminated sediments potentially harmful to the biota. Results showed induction of biomarkers in both invertebrate species and significant differences (p < 0.05; p < 0.01) were established among sediments affected by different spills. The use of the selected biomarkers together with the sediment chemical analysis assesses the bioavailability of contaminants and has proven to be a suitable tool to monitor the environmental quality of sediments affected by oil spills. PMID:18198936

  16. Comparative study of 17 β-estradiol on endocrine disruption and biotransformation in fingerlings and juveniles of Japanese sea bass Lateolabrax japonicus.

    PubMed

    Thilagam, Harikrishnan; Gopalakrishnan, Singaram; Bo, Jun; Wang, Ke-Jian

    2014-08-30

    Estrogenic contaminants in the aquatic environment are associated with endocrine disruption and feminization in fish. The effects of endocrine disrupting chemicals (EDCs) on fish have been well documented. However, very few studies have focused on 17 β-estradiol (E2) and its effects on endocrine system and biotransformation in a single prolonged exposure. This study investigated changes in the levels of serotonin (5-hydroxytryptamine) and acetyl choline esterase (AchE) in brain, cortisol in plasma and Ethoxyresorufin-O-deethylase (EROD) activity in gill of two different size groups (fingerlings and juveniles) of Japanese sea bass (Lateolabrax japonicus) upon exposure to two sub-lethal concentrations (200 and 2000 ng L(-1)) of E2 for 30 d. The results indicate that cortisol level and EROD activity significantly increased in both groups, whereas serotonin level increased in juveniles and decreased in fingerlings due to E2 exposure. The correlation analysis revealed that E2 significantly affected the endocrine and biotransformation systems in both age groups. PMID:24882444

  17. Muscular and hepatic pollution biomarkers in the fishes Phycis blennoides and Micromesistius poutassou and the crustacean Aristeus antennatus in the Blanes Submarine Canyon (NW Mediterranean).

    PubMed

    Solé, Montserrat; Hambach, Bastian; Cortijo, Verónica; Huertas, David; Fernández, Pilar; Company, Joan B

    2009-07-01

    Submarine canyons are regarded as a sink for pollutants. In order to determine if this theory applied to deep-sea species from an important fishing ground (the Blanes submarine canyon) located in the NW Mediterranean, we sampled the commercial fish Phycis blennoides and Micromesistius poutassou and the crustacean Aristeus antennatus. Specimens were sampled inside and outside (in the open continental slope) the submarine canyon; both are regarded as potentially affected by exposure to different anthropogenic chemicals. Several pollution biomarkers in muscle (activity of cholinesterases) and liver/hepatopancreas (catalase, glutathione S-transferases, carboxylesterases, ethoxyresorufin O-deethylase in fish or mixed function oxygenase (MFO)-related reductases in crustacean, and lipid peroxidation levels) were measured. Chemical analysis of the persistent organic pollutants, namely polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs) was also performed on the fish and crustacean muscle. Biomarker activities and levels were discussed in relation to pollutant exposure, habitat, and parameters including sex, size, and species. Biochemical responses and chemical analysis of PCBs evidenced interspecies differences as well as sex and size-related ones, mainly in A. antennatus. An indication of higher exposure to pollutants inside the canyon was observed, which was more clearly reflected in the fish than in the crustacean. However, further research is required to confirm this observation. PMID:18941829

  18. Effects of 3,3',4,4',5-pentachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin injected into the yolks of double-crested cormorant (Phalacrocorax auritus) eggs prior to incubation

    USGS Publications Warehouse

    Powell, D.C.; Aulerich, R.J.; Meadows, J.C.; Tillitt, D.E.; Kelly, M.E.; Stromborg, K.L.; Melancon, M.J.; Fitzgerald, S.D.; Bursian, S.J.

    1998-01-01

    Double-crested cormorant (Phalacrocorax auritus) eggs were injected with either 3,3',4,4',5-pentachlorobiphenyl (polychlorinated biphenyl [PCB] 126; 70-698 ?g/kg egg) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 1.3-11.7 ?g/kg egg) prior to incubation. These compounds were injected into the yolks of cormorant eggs collected from incomplete clutches at isolated colonies on Lake Winnipegosis, Manitoba, Canada. Eggs were incubated for approximately 26 to 28 d. After hatching the brain, bursa, heart, liver, and spleen were dissected and weighed. Torsos were preserved in formalin for examination of the gonads. Median lethal doses (LD50s) calculated from mortality data at hatching were 177 and 4.0 ?g/kg egg for PCB 126 and TCDD, respectively. No significant differences were found in the incidence of developmental abnormalities in any of the treatment groups. Bursa weights were significantly less in the greatest (11.7 ?g/kg egg) TCDD group compared to the vehicle control group. Spleen weights were significantly less in the 349 ?g PCB 126/kg egg and the 5.4 and 11.7 ?g TCDD/kg egg groups when compared to the vehicle control group. No histological alterations of the gonads were found. Hepatic ethoxyresorufin-O-deethylase activity in all PCB 126 and TCDD dose groups was significantly greater compared to the control activity. The toxic equivalency factor for PCB 126 was 0.02

  19. Effects of Baicalin on Oral Pharmacokinetics of Caffeine in Rats

    PubMed Central

    Noh, Keumhan; Nepal, Mahesh Raj; Jeong, Ki Sun; Kim, Sun-A; Um, Yeon Ji; Seo, Chae Shin; Kang, Mi Jeong; Park, Pil-Hoon; Kang, Wonku; Jeong, Hye Gwang; Jeong, Tae Cheon

    2015-01-01

    Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated IC50 values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats. PMID:25767690

  20. Biochemical and toxicopathic biomarkers assessed in smallmouth bass recovered from a polychlorinated biphenyl-contaminated river.

    PubMed

    Anderson, M J; Cacela, D; Beltman, D; Teh, S J; Okihiro, M S; Hinton, D E; Denslow, N; Zelikoff, J T

    2003-01-01

    Smallmouth bass (Micropterus dolomieu) were collected to quantify the nature and prevalence of biomarker responses, including biochemical indices, toxicopathic lesions and general health indices, among fish collected from polychlorinated biphenyl (PCB)-contaminated and nearby uncontaminated reaches of the Kalamazoo River, Michigan, USA. Blood and tissue samples (gill, liver, spleen, head kidney, trunk kidney, thyroid and gonads) were collected and preserved at necropsy for biochemical and histological analyses. The body condition factor and liver somatic index were significantly lower in fish collected from the downstream, contaminated site. Plasma vitellogenin was not detected in male fish collected from either site. Liver ethoxyresorufin-O-deethylase activity and liver and spleen superoxide dismutase activity were significantly depressed in fish collected from the downstream site. Significant toxicopathic lesions such as glycogen depletion, enhanced macrophage aggregates, hepatic foci of cellular alteration (i.e. preneoplastic lesions) and neoplasia were also detected in the liver of fish collected from the downstream site. This study indicates that many of the biochemical and histopathological biomarker responses were associated with liver and body tissue PCB concentrations. Taken together, the biomarkers of exposure and effect strongly suggest that fish within the downstream site are adversely affected by PCBs and other chemical stressors. PMID:14602522

  1. Semipermeable membrane devices link site-specific contaminants to effects: Part 1 - Induction of CYP1A in rainbow trout from contaminants in Prince William Sound, Alaska.

    PubMed

    Springman, Kathrine R; Short, Jeffrey W; Lindeberg, Mandy R; Maselko, Jacek M; Khan, Colin; Hodson, Peter V; Rice, Stanley D

    2008-12-01

    Extracts from semi-permeable membrane devices (SPMDs) deployed on beaches in Prince William Sound (PWS), Alaska, were used to evaluate if complex contaminant mixtures from different sources can be distinguished by the resulting cytochrome P450 1A (CYP1A) activity in exposed test animals. Deployment sites included canneries, salmon hatcheries, and beaches where lingering oil remains from discharges during the 1964 earthquake or the 1989 Exxon Valdez oil spill. Other sites were selected at random to evaluate region-wide contaminant inputs or were located in salmon streams to evaluate contaminants carried and released by migrating salmon carcasses following reproduction. Following standard deployments of approximately 28 d, an aliquot of the accumulated contaminants was intraperitoneally injected without cleanup into juvenile rainbow trout (Oncorhynchus mykiss). After 2 d and 7 d, the activity of CYP1A was measured by the ethoxyresorufin-o-deethylase (EROD) assay. Exposure to extracts from the oiled sites and one hatchery site with numerous creosote pilings elicited strong EROD responses, whereas fish exposed to salmon stream extracts elicited weak but significant responses during late summer compared to late spring. Responses from the other sites were not significant, indicating contaminants from these sources are unlikely to cause CYP1A induction in resident biota. Rather than simply assessing extant contaminants, this method evaluates the potency of the different sites for bringing about aryl hydrocarbon receptor responses in resident biota. PMID:18845333

  2. Interaction of isosafrole, beta-naphthoflavone and other CYP1A inducers in liver of rainbow trout (Oncorhynchus mykiss) and eelpout (Zoarces viviparus).

    PubMed

    Ronisz, D; Förlin, L

    1998-11-01

    The CYP1A enzyme in liver of rainbow trout (Oncorhynchus mykiss) and eelpout (Zoarces viviparus) was induced by intraperitoneal injections of isosafrole (ISF), beta-naphthoflavone (BNF), retene, 3,3',4,4'-tetrachlorobiphenyl (TCB), Clophen A50 and combinations of these compounds. The livers were sampled 5 days after injection and the microsomal fraction was used to measure the activity of CYP1A (as ethoxyresorufin-O-deethylase (EROD)) and the level of the enzyme (measured semiquantitatively as absorbance using enzyme-linked immunosorbant assay (ELISA)). Induction of CYP1A above the additive effect was observed when ISF was given together with BNF or retene. It was suggested that ISF may stabilize the enzyme or its mRNA or that ISF metabolites inhibit CYP1A processing of BNF and retene, thus increasing the effective doses of these compounds in fish liver. The results indicate a need for further studies of interactions between different CYP1A inducers in fish and a comparison of CYP1A response between different fish species. These results may have implications for the use of CYP1A induction in fish as a biomarker in aquatic systems, since a high EROD activity could be due not only to the presence of one potent inducer, but to synergistic effects of two or more inducers at low concentrations. PMID:9972470

  3. Effects of water accommodated fractions of crude oils and diesel on a suite of biomarkers in Atlantic cod (Gadus morhua).

    PubMed

    Holth, T F; Eidsvoll, D P; Farmen, E; Sanders, M B; Martínez-Gómez, C; Budzinski, H; Burgeot, T; Guilhermino, L; Hylland, K

    2014-09-01

    The aim of this study was to characterize concentration- and time-dependent responses in juvenile Atlantic cod (Gadus morhua) following exposure for one and three weeks to the water-soluble fraction (WAF) of three weathered oils: Arabian Light crude oil (ALC), North Sea crude oil (NSC) and ship-diesel. The sum of polycyclic aromatic hydrocarbons (PAH) in water was highest after one week of exposure and within environmentally relevant concentrations. PAH metabolites in bile confirmed exposure to and uptake of PAHs. Hepatic cytochrome P450 1A (CYP1A) gene expression (mRNA quantification) increased dramatically following exposure to all three oil types (fold-change up to 165) and there was a time lag between gene and protein expression. Hepatic CYP1A protein concentration and ethoxyresorufin-O-deethylase (EROD) activity were more variable among individuals and treatments than gene expression. EROD activity in liver and gills increased in fish exposed to WAF from the two crude oils, but not in fish exposed to WAF from diesel. Exposure to diesel appeared to induce oxidative stress to a greater extent than exposure to crude oils. Other biomarkers (glutathione S-transferases, acetylcholine esterase, vitellogenin) did not appear to respond to the exposure and hence did not discriminate among oils. Biomarker responses in cod after exposure to weathered crude oils and diesel suggested that the CYP1A system and oxidative stress markers have the highest potential for discriminating among different oil types and to monitor the environmental consequences of spills.

  4. Comparative study of 17 β-estradiol on endocrine disruption and biotransformation in fingerlings and juveniles of Japanese sea bass Lateolabrax japonicus.

    PubMed

    Thilagam, Harikrishnan; Gopalakrishnan, Singaram; Bo, Jun; Wang, Ke-Jian

    2014-08-30

    Estrogenic contaminants in the aquatic environment are associated with endocrine disruption and feminization in fish. The effects of endocrine disrupting chemicals (EDCs) on fish have been well documented. However, very few studies have focused on 17 β-estradiol (E2) and its effects on endocrine system and biotransformation in a single prolonged exposure. This study investigated changes in the levels of serotonin (5-hydroxytryptamine) and acetyl choline esterase (AchE) in brain, cortisol in plasma and Ethoxyresorufin-O-deethylase (EROD) activity in gill of two different size groups (fingerlings and juveniles) of Japanese sea bass (Lateolabrax japonicus) upon exposure to two sub-lethal concentrations (200 and 2000 ng L(-1)) of E2 for 30 d. The results indicate that cortisol level and EROD activity significantly increased in both groups, whereas serotonin level increased in juveniles and decreased in fingerlings due to E2 exposure. The correlation analysis revealed that E2 significantly affected the endocrine and biotransformation systems in both age groups.

  5. Variability in antioxidant/detoxification enzymes of Sinonovacula constricta exposed to benzo[a]pyrene and phenanthrene.

    PubMed

    Li, Lei; Jiang, Mei; Shen, Xinqiang

    2016-08-15

    The purpose of this study was to investigate the toxic effects induced by benzo[a]pyrene and phenanthrene. For this purpose, a study was performed on the clam exposed to 0.0, 0.5, 4.5μgL(-1) B(a)P and PHE for 15days using parameters of antioxidant defenses and oxidative stress. Antioxidant biomarkers including ethoxyresorufin-O-deethylase, glutathione S-transferase, superoxide dismutase, and glutathione and rylhydrocarbon hydroxylasein gills of Sinonovacula constricta, were analyzed after a 1-, 3-, 9- and 15-day exposure to seawater containing B(a)P and PHE. Integrated biomarker response was calculated by combining multiple biomarkers into a single value. The results showed that the activity of all antioxidant biomarkers was induced throughout the exposure period, and different patterns of variations were detected with exposure time. In addition, the study showed that the two concentrations used caused the activation of different general detoxification mechanisms, and the same concentration at different two PAH compounds induced different toxicity responses. PMID:27216044

  6. Biomarker sensitivity for polynuclear and halogenated aromatic hydrocarbon contamination in fish species from Galveston Bay

    SciTech Connect

    Willett, K.; McDonald, S.; Steinberg, M.; Beatty, K.; Safe, S.

    1995-12-31

    The Galveston Bay estuary exhibits a contamination gradient for polynuclear aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons, which is useful for comparing biomarker response sensitivity in fish taken from different bay locations. Two fish species, hardhead catfish (Arius felis) and Atlantic croaker (Micropogon undulatus), were collected from four stations where sediment total PAHs ranged from 68 to > 1,000 ng/g. Hardhead catfish showed no consistent CYP1A mediated responses (hepatic ethoxyresorufin-O-deethylase activity (EROD), CYP1A mRNA levels, or CYP1A immunoreactive protein) in the field collected fish or in fish dosed with up to 15 mg/kg benzo(a)pyrene (BaP). Significant differences were seen in field collected hardhead catfish in biliary concentrations of naphthalene, phenanthrene, and BaP metabolites. Conversely, in croakers taken from the same four Galveston Bay locations, there were significant elevations IN EROD and glutathione-S-transferase activities, CYP1A immunoreactive protein, and biliary PAH metabolites at the contaminated stations. These studies suggest that croaker is a good monitoring species especially with respect to induction of CYP1A mediated responses by PAHs. Biliary PAH metabolites and PAH-DNA adducts were sensitive to PAH contamination in both species.

  7. Biomarker sensitivity for polynuclear aromatic hydrocarbon contamination in two marine fish species collected in Galveston Bay, Texas

    SciTech Connect

    Willett, K.L.; Steinberg, M.A.; Safe, S.H.; McDonald, S.J.; Beatty, K.B.; Kennicutt, M.C.

    1997-07-01

    The Galveston Bay estuary exhibited a contamination gradient for polynuclear aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons, and the comparative sensitivity of various biomarkers in fish from different bay locations were determined. Two fish species, hardhead catfish (Arius felis) and Atlantic croaker (Micropogon undulatus), were collected from four stations where sediment total PAHs ranged from 68 > 1,000 ng/g. The induction of cytochrome P4501A-(CYP1A)-dependent hepatic ethoxyresorufin-O-deethylase (EROD) activity, CYPIA mRNA levels, or CYPIA immunoreactive protein in hardhead catfish was highly variable in the field-collected fish and in fish dosed with up to 15 mg/kg benzo[a]pyrene (BaP). In contrast, significant differences were seen in biliary concentrations of naphthalene, phenanthrene, and BaP metabolites in hardhead catfish from polluted versus less polluted areas. In croakers taken from the same four Galveston Bay locations, EROD and glutathione S-transferase activities, immunoreactive CYP1A protein, biliary PAH metabolites, and PAH-DNA adducts were higher at the contaminated stations compared with less polluted locations. These studies suggest that the croaker is a good species for monitoring contaminants that induce CYP1A-mediated responses. Biliary PAH metabolites and PAH-DNA adducts were also sensitive indicators of exposure to PAH contamination in both species of fish.

  8. Use of a Novel Double-Crested Cormorant ToxChip PCR Array and the EROD Assay to Determine Effects of Environmental Contaminants in Primary Hepatocytes.

    PubMed

    Crump, Doug; Farhat, Amani; Chiu, Suzanne; Williams, Kim L; Jones, Stephanie P; Langlois, Valerie S

    2016-03-15

    In vitro screening tools and 'omics methods are increasingly being incorporated into toxicity studies to determine mechanistic effects of chemicals and mixtures. To date, the majority of these studies have been conducted with well-characterized laboratory animal models. In the present study, well-established methods developed for chicken embryonic hepatocyte (CEH) studies were extended to a wild avian species, the double-crested cormorant (DCCO; Phalacrocorax auritus), in order to compare the effects of several environmental contaminants on cytotoxicity, ethoxyresorufin O-deethylase (EROD) activity, and mRNA expression. Five organic flame retardants and one plasticizer decreased cormorant hepatocyte viability in a similar manner to that observed in previous studies with CEH. EROD activity was induced in a concentration-dependent manner following exposure to two dioxin-like chemicals and the calculated EC50 values were concordant with domestic avian species from similar species sensitivity categories. Transcriptomic effects were determined using a novel DCCO PCR array, which was designed, constructed and validated in our laboratory based on a commercially available chicken PCR array. The DCCO array has 27 target genes covering a wide range of toxicity pathways. Gene profiles were variable among the 10 chemicals screened; however, good directional concordance was observed with regard to results previously obtained in CEH. Overall, the application of well-established methods (i.e., CEH and chicken PCR array) to the double-crested cormorant demonstrated the portability of the techniques to an indicator species of ecological relevance. PMID:26894911

  9. Muscular and hepatic pollution biomarkers in the fishes Phycis blennoides and Micromesistius poutassou and the crustacean Aristeus antennatus in the Blanes Submarine Canyon (NW Mediterranean).

    PubMed

    Solé, Montserrat; Hambach, Bastian; Cortijo, Verónica; Huertas, David; Fernández, Pilar; Company, Joan B

    2009-07-01

    Submarine canyons are regarded as a sink for pollutants. In order to determine if this theory applied to deep-sea species from an important fishing ground (the Blanes submarine canyon) located in the NW Mediterranean, we sampled the commercial fish Phycis blennoides and Micromesistius poutassou and the crustacean Aristeus antennatus. Specimens were sampled inside and outside (in the open continental slope) the submarine canyon; both are regarded as potentially affected by exposure to different anthropogenic chemicals. Several pollution biomarkers in muscle (activity of cholinesterases) and liver/hepatopancreas (catalase, glutathione S-transferases, carboxylesterases, ethoxyresorufin O-deethylase in fish or mixed function oxygenase (MFO)-related reductases in crustacean, and lipid peroxidation levels) were measured. Chemical analysis of the persistent organic pollutants, namely polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs) was also performed on the fish and crustacean muscle. Biomarker activities and levels were discussed in relation to pollutant exposure, habitat, and parameters including sex, size, and species. Biochemical responses and chemical analysis of PCBs evidenced interspecies differences as well as sex and size-related ones, mainly in A. antennatus. An indication of higher exposure to pollutants inside the canyon was observed, which was more clearly reflected in the fish than in the crustacean. However, further research is required to confirm this observation.

  10. [Adapting physical activities for an active retirement].

    PubMed

    Renaudie, François

    2016-01-01

    The benefits of doing adapted physical exercise for elderly people have been proven. For more than thirty years, the French Federation for an Active Retirement has been striving to help people age well by proposing multiple activities to remain in good health after the age of 50. Doctors, activity leaders and federal instructors are attentive to each individual's capacities. PMID:27449307

  11. Learning as Activity.

    ERIC Educational Resources Information Center

    Jonassen, David H.

    2002-01-01

    Integrates contemporary theories of learning into a theory of learning as activity. Explains ecological psychology, changes in understanding of learning, activity systems and activity theory (including the integration of consciousness and activity), and activity structure; and discusses learning as a cognitive and social process. (LRW)

  12. Physical Activity Assessment

    Cancer.gov

    Current evidence convincingly indicates that physical activity reduces the risk of colon and breast cancer. Physical activity may also reduce risk of prostate cancer. Scientists are also evaluating potential relationships between physical activity and other cancers.

  13. Facts about Physical Activity

    MedlinePlus

    ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Facts about Physical Activity ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs File Formats Help: How ...

  14. Enzyme activities in activated sludge flocs.

    PubMed

    Yu, Guang-Hui; He, Pin-Jing; Shao, Li-Ming; Lee, Duu-Jong

    2007-12-01

    This study quantified the activities of enzymes in extracellular polymeric substances (EPS) and in pellets. Seven commonly adopted extraction schemes were utilized to extract from aerobic flocs the contained EPS, which were further categorized into loosely bound (LB) and tightly bound (TB) fractions. Ultrasonication effectively extracted the EPS from sludge flocs. Enzyme assay tests showed that the protease activity was localized mainly on the pellets, alpha-amylase and alpha-glucosidase activities were largely bound with LB-EPS, and few protease, alpha-amylase, or alpha-glucosidase activities were associated with the TB-EPS fraction. There exists no correlation between the biochemical compositions of EPS and the distribution of enzyme activities in the sludge matrix. The 44-65% of alpha-amylase and 59-100% of alpha-glucosidase activities noted with the LB-EPS indicate heterogeneous hydrolysis patterns in the sludge flocs with proteins and carbohydrates.

  15. A gene to organism approach--assessing the impact of environmental pollution in eelpout (Zoarces viviparus) females and larvae.

    PubMed

    Asker, Noomi; Carney Almroth, Bethanie; Albertsson, Eva; Coltellaro, Mariateresa; Bignell, John Paul; Hanson, Niklas; Scarcelli, Vittoria; Fagerholm, Björn; Parkkonen, Jari; Wijkmark, Emma; Frenzilli, Giada; Förlin, Lars; Sturve, Joachim

    2015-07-01

    A broad biomarker approach was applied to study the effects of marine pollution along the Swedish west coast using the teleost eelpout (Zoarces viviparus) as the sentinel species. Measurements were performed on different biological levels, from the molecular to the organismal, including measurements of messenger RNA (mRNA), proteins, cellular and tissue changes, and reproductive success. Results revealed that eelpout captured in Stenungsund had significantly higher hepatic ethoxyresorufin O-deethylase activity, high levels of both cytochrome P4501A and diablo homolog mRNA, and high prevalence of dead larvae and nuclear damage in erythrocytes. Eelpout collected in Göteborg harbor displayed extensive macrovesicular steatosis, whereby the majority of hepatocytes were affected throughout the liver, which could indicate an effect on lipid metabolism. Results also indicate that eelpouts collected at polluted sites might have an affected immune system, with lower mRNA expression of genes involved in the innate immune system and a higher number of lymphocytes. Biomarker assessment also was performed on livers dissected from unborn eelpout larvae collected from the ovary of the females. No significant differences were noted, which might indicate that the larvae to some extent are protected from effects of environmental pollutants. In conclusion, usage of the selected set of biological markers, covering responses from gene to organism, has demonstrated site-specific biomarker patterns that provided a broad and comprehensive picture of the impact of environmental stressors.

  16. Fullerene-associated phenanthrene contributes to bioaccumulation but is not toxic to fish.

    PubMed

    Hu, Xialin; Li, Jing; Shen, Mohai; Yin, Daqiang

    2015-05-01

    The present study investigated the effects of aqueous fullerene suspensions (nC60 ) on the bioavailability and toxicity of phenanthrene (Phe) to junior carp (Cyprinus carpio). Bioaccumulation factors (BAFs) were calculated based on total as well as free concentrations of Phe. Equal BAF values were obtained with and without nC60 based on the total concentrations, whereas greater BAFs were found in the presence of nC60 when free Phe concentrations were applied. The results demonstrated that nC60 could act as a contaminant carrier to facilitate Phe bioaccumulation. The concentration-response relationship of induced hepatic 7-ethoxysorufin-O-deethylase activity was established in regard to the total and free concentrations of aqueous Phe solutions as well as the body residues. The concentration-response curves were reliant on the nC60 concentration when the total concentration of Phe was employed as a variable but were independent of nC60 presence when free concentration or body residue was employed as a variable, implying that the latter 2 parameters were more accurate in evaluating biological effects. Particles of C60 were mostly distributed in fish liver and intestines, which indicated the primary routine of uptake was through ingestion. Approximately 22% to 100% of the Phe-nC60 complex contributed to the bioaccumulation, whereas the complex did not contribute to the toxicity.

  17. Sensitivity of bald eagle (Haliaeetus leucocephalus) hepatocyte cultures to induction of cytochrome P4501A by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed

    Kennedy, Sean W; Jones, Stephanie P; Elliott, John E

    2003-01-01

    Graded doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were added to primary hepatocyte cultures of bald eagle (Haliaeetus leucocephalus) embryos to determine their sensitivity to induction of cytochrome P4501A (CYP1A) and porphyrin accumulation. No porphyrin accumulation was observed, but both CYP1A catalytic activity (using the ethoxyresorufin-O-deethylase (EROD) assay) and immunodetectable CYP1A were induced by relatively high concentrations of TCDD. Bald eagle hepatocytes were less sensitive to CYP1A induction than hepatocytes from any other avian species that we have studied to date. These in vitro results are in general agreement with recent assessments of field data, which indicate that bald eagles are relatively insensitive to some of the effects of TCDD and related compounds. Preparation of bald eagle hepatocytes was challenging because existing methods did not yield monolayers of cells. Here we describe details of a new method that was successful for bald eagle hepatocytes. This new method is used routinely in our laboratory to prepare hepatocyte cultures from birds for examination of various biochemical responses to environmental contaminants.

  18. Embryo toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the wood duck (Aix sponsa)

    USGS Publications Warehouse

    Augspurger, T.P.; Tillitt, D.E.; Bursian, S.J.; Fitzgerald, S.D.; Hinton, D.E.; Di Giulio, R.T.

    2008-01-01

    We examined the sensitivity of the wood duck (Aix sponsa) embryo to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by injecting the toxicant into their eggs. Six groups of wood duck eggs (n = 35 to 211 per trial) were injected with 0 to 4600 pg TCDD/g egg between 2003 and 2005. Injections were made into yolk prior to incubation, and eggs were subsequently incubated and assessed weekly for mortality. Significant TCDD-induced mortality was not observed through day 25 (90% of incubation). Liver, heart, eye, and brain histology were generally unremarkable. Hepatic ethoxyresorufin-O-deethylase activity, a biomarker of dioxin-like compound exposure, was induced by 12-fold in the 4600 pg/g treatment relative to controls. The median lethal dose for chicken (Gallus domesticus) eggs we dosed identically to wood duck eggs was about 100 pg/g, similar to other assessments of chickens. Among dioxin-like compound embryo lethality data for 15 avian genera, the wood duck 4600 pg/g no-observed-effect level ranks near the middle. Because no higher doses were tested, wood ducks may be like other waterfowl (order Anseriformes), which are comparatively tolerant to embryo mortality from polychlorinated dibenzo-p-dioxins and dibenzofurans when exposed by egg injection. ?? 2008 US Government.

  19. Weighing the evidence of ecological risk from PAHs contamination in the estuarine environment of Salina Cruz Bay, México.

    PubMed

    Salazar-Coria, L; Schifter, I; González-Macías, C

    2010-03-01

    Results of bulk-phase chemical measurements, toxicological tests combined with bioaccumulation measures in fishes, were used to evaluate the toxicity of the 16 USEPA priority polycyclic aromatic hydrocarbons from the sediment collected from eight stations of the Ventosa Estuarine System, located close to the main center of processing oil in the Mexican Pacific coast. Levels of the sum of polycyclic aromatic hydrocarbons varied from 22 to 6,850 microg kg(-1) dry weight. Based on sediment quality guidelines, the compounds with high environmental priority were acenaphtylene, acenaphtene, and phenanthrene. Acute toxicity tests with Vibrio fischeri and Daphnia magna as well as chronic toxicity with Panagrellus redivivus were performed. The quantification of hepatic ethoxyresorufin O-deethylase activity was used to assess the induction of the mixed function oxygenase system of brown trout. However, because it is often difficult to blend the results from such very different assays into a unified decision about the potential for impacts, a weight-of-evidence (WOE) approach to sediment quality investigations was followed. These assays provided measurement endpoints that could be used to develop an overall evaluation of the potential for environmental impacts from the oil processing operations. WOE provides a valuable tool for assessing the results of environmental investigations because it provides a framework for considering the strengths and weaknesses of environmental measurements, an approach for addressing uncertainty in the measurements, and documentation of the evaluation and its assumptions.

  20. Pharmacokinetic Interaction of Chrysin with Caffeine in Rats

    PubMed Central

    Noh, Keumhan; Oh, Do Gyeong; Nepal, Mahesh Raj; Jeong, Ki Sun; Choi, Yongjoo; Kang, Mi Jeong; Kang, Wonku; Jeong, Hye Gwang; Jeong, Tae Cheon

    2016-01-01

    Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism. PMID:27098862

  1. A point mutation (L1015F) of the voltage-sensitive sodium channel gene associated with lambda-cyhalothrin resistance in Apolygus lucorum (Meyer-Dür) population from the transgenic Bt cotton field of China.

    PubMed

    Zhen, Congai; Gao, Xiwu

    2016-02-01

    In China, the green mirid bug, Apolygus lucorum (Meyer-Dür), has caused severe economic damage to many kinds of crops, especially the cotton and jujubes. Pyrethroid insecticides have been widely used for controlling this pest in the transgenic Bt cotton field. Five populations of A. lucorum collected from cotton crops at different locations in China were evaluated for lambda-cyhalothrin resistance. The results showed that only the population collected from Shandong Province exhibited 30-fold of resistance to lambda-cyhalothrin. Neither PBO nor DEF had obvious synergism when compared the synergistic ratio between SS and RR strain which was originated from the Shandong population. Besides, there were no statistically significant differences (p>0.05) in the carboxylesterase, glutathione S-transferase, or 7-ethoxycoumarin O-deethylase activities between the Shandong population and the laboratory susceptible strain (SS). The full-length sodium channel gene named AlVSSC encoding 2028 amino acids was obtained by RT-PCR and rapid amplification of cDNA ends (RACE). One single point mutation L1015F in the AlVSSC was detected only in the Shandong population. Our results revealed that the L1015F mutation associated with pyrethroid resistance was identified in A. lucorum populations in China. These results will be useful for the rational chemical control of A. lucorum in the transgenic Bt cotton field. PMID:26821662

  2. Petroleum hydrocarbons, fluorescent aromatic compounds in fish bile and organochlorine pesticides from areas surrounding the spill of the Kab121 well, in the Southern Gulf of Mexico: a case study.

    PubMed

    Gold-Bouchot, G; Ceja-Moreno, V; Chan-Cocom, E; Zapata-Perez, O

    2014-01-01

    In October 2007, a light crude oil spill took place in the off shore Kab121 oil well, 32 km north of the mouth of the Grijalva River, Tabasco, Mexico. In order to estimate the possible effects of oil spill on the biota in the area surrounding the spilled well, the level of different fractions of petroleum hydrocarbons were measured in fish, as well as the concentration of some chlorinated hydrocarbons and PCBs. The organisms examined were cat fish (Ariopsis felis), in addition fluorescent aromatic compounds in bile, the contaminants above mentioned and their relationship with cyotochrome P-450 and Ethoxyresorufin-O-deethylase, Glutathion-S-Transferase and catalase activities in liver were determined. The concentration of most pollutants were low, except PAHs. Spatial distribution of these compounds, as well as most biomarkers, reflected the highest exposure of fish to pollutants in the area adjacent to well, as well as in the proximity of rivers. The profile of exposure to this environment was chronic in nature and not temporary.

  3. Toxic equivalency factors for tetra- through octachlorinated dibenzofurans in PLHC-1 fish hepatoma cell line

    SciTech Connect

    Tysklind, M.; Rappe, C.; Tillift, D.E.; Eriksson, L.

    1995-12-31

    Planar halogenated hydrocarbons (PHHs) elicit dioxin-like effects in fish at extremely low doses. However, the relative potencies of PHHs in fish differ from mammals in both absolute magnitude and relative rank order. Therefore, the relative potencies of polychlorinated dibenzofurans (PCDFs) were examined in PLHC-1 fish hepatoma cells. The response of PHHs in this cell line correlates with their toxicity to cause early life stage toxicity in fish. Twenty PCDFs were selected by means of a multivariate chemical characterization in combination with a 2{sup 4}-factorial design and separated into a 10 congener training set and 10 congener validation set. Toxic equivalency factors (TEFs) were determined for all 20 PCDF congeners based on ethoxyresorufin-O-deethylase (EROD) induction in the PLHC-1 cells. A quantitative structure-activity relation-ship (QSAR) model was constructed by partial least square modelling (PLS) of the physiochemical descriptor variables for the PCDFs in the training set and their EROD responses in the PLHC-1 cells. A predictive model was developed which accurately assessed the TEFs of the validation set of PCDFs. The model accounted for 87% (R{sup 2}) of the variance in TEFs and a cross-validated variance (Q{sup 2}) of 79%. From this QSAR, TEF values were predicted for all of the tetra through octa-chlorinated PCDFs in fish. Interestingly, there was a high degree of correlation among TEF values calculated in the PLHC-1 cells and the TEF values calculated in H411 E rat hepatoma cells.

  4. A toxic equivalency factor scale for polychlorinated dibenzofurans

    USGS Publications Warehouse

    Tysklind, M.; Tillitt, D.; Eriksson, L.; Lundgren, K.; Rappe, C.

    1994-01-01

    The ethoxyresorufin O-deethylase (EROD) induction of 20 polychiorinated dibenzofurans (PCDFs) was examined in the H4IIE rat hepatoma cell bioassay. The selection of the compounds tested was based on a multivariate chemical characterization laying the groundwork for covering the whole chemical series of PCDFs. The EROD induction potency was found to vary in ED50 values from 25 to 100,000,000 pg/mg, i.e., nearly seven orders of magnitude. The response of the bioassay was calibrated against the 2,3,7,8-tetrachlorodibenzo-p-dioxin, enabling the corresponding toxic equivalency factors (TEFs) to be calculated. In order to establish a quantitative structure-activity relationship (QSAR) for the TEF values, 37 physicochemical descriptor variables were used to chemically characterize the 87 tetra- to octachlorinated PCDFs. Using partial least-squares modeling on a training set of 10 congeners, a QSAR model with sound predictive power was obtained. The QSAR model was validated with a validation set of additional 10 congeners. The predicted TEFs indicate that a large number of congeners are potent EROD inducers.

  5. In vivo effects of environmental concentrations of produced water on the reproductive function of polar cod (Boreogadus saida).

    PubMed

    Geraudie, P; Nahrgang, J; Forget-Leray, J; Minier, C; Camus, L

    2014-01-01

    Offshore oil and gas drilling processes generate operational discharges such as produced water (PW), a complex mixture of seawater with polycyclic aromatic hydrocarbons (PAH) and alkylphenols (AP). Some of these compounds may interact with the endocrine system of marine organisms and alter reproductive functions. In this study, polar cod were exposed for up to 28 d to a mixture of PAH, alkylated PAH, and AP simulating the composition of North Sea PW, at low and high concentrations (1:2000 and 1:1000 dilution of the original concentrate, respectively). Potential adverse effects of PW on polar cod physiology were investigated through biomarkers of biotransformation (hepatic ethoxyresorufin O-deethylase [EROD] activity and bile PAH metabolites), endocrine disruption (plasma vitellogenin [VTG] levels and sex steroid concentrations), and gonad histology. Plasma sexual steroid levels in fish were not markedly affected by PW exposure, while higher plasma VTG concentrations were measured in females exposed to the high PW treatment for 7 and 28 d. In males exposed to the higher PW concentration, inhibition of spermatogenesis was observed after 28 d in addition to increase of melano-macrophage occurrence in testis. Females exposed to the high PW treatment for 21 d showed a significant increase of atresia incidence. Finally, a significant decrease in oocyte number was observed in high PW exposed female ovaries after 28 d of exposure.

  6. Yes, caffeine, ibuprofen, carbamazepine, novobiocin and tamoxifen have an effect on Corbicula fluminea (Müller, 1774).

    PubMed

    Aguirre-Martínez, Gabriela V; DelValls, Angel T; Laura Martín-Díaz, M

    2015-10-01

    Reports indicating the presence of pharmaceutical in fresh water environment in the ngL(-1) to µgL(-1) range are occurring with increasing frequency. It is also a fact that pharmaceuticals may produce adverse effects on aquatic organisms. Nevertheless, there is still a lack of knowledge regarding how these emergent contaminants may affect aquatic biota. The goal of this research was to evaluate the sublethal responses in Corbicula fluminea such as, general stress (lysosomal membrane stability [LMS]), biomarkers of phase I and II (etoxyresorufin O-deethylase [EROD], dibenzylfluorescein dealkylase [DBF], gluthathione-S-transferase [GST]), oxidative stress (gluthathione reductase [GR], gluthathione peroxidase [GPX], lipid peroxidation [LPO]), and biomarkers of effect (DNA damage) after 21 days of exposure to caffeine, ibuprofen, carbamazepine, novobiocin and tamoxifen at 0.1, 1, 5, 10, 15, 50µgL(-1). Environmental concentrations tested in this study caused general stress and produced changes on biomarkers tested. LMS, responses from phase I and II enzymatic activity, oxidative stress, and biomarker of effect represent important ecotoxicological information, and will provide a useful reference for the assessment of selected drugs and the effects which these compounds may have on aquatic invertebrates, using C. fluminea as a bioindicator species.

  7. Stressor identification and health assessment of fish exposed to wastewater effluents in Miho Stream, South Korea.

    PubMed

    Yeom, Dong-Hyuk; Lee, Soon-Ae; Kang, Gi Soo; Seo, Jinwon; Lee, Sung-Kyu

    2007-05-01

    This study evaluated the effects of an industrial wastewater treatment plant (IWTP) and a municipal wastewater treatment plant (MWTP) effluents on a variety of bioindicators ranging from biochemical, organism, and population-level responses in pale chub (Zacco platypus) and fish community structure. The Index of Biotic Integrity (IBI) indicated that the site upstream of these wastewater treatment plant discharges is in fair-good condition and downstream of the plant is in poor condition. The EROD (ethoxyresorufin-O-deethylase) activity, condition factor, and liver somatic index were significantly increased at the downstream site compared to those of the upstream site. The most significant change observed in pale chub population in the downstream site of the Miho Stream, relative to the upstream population, was the total absence of an younger age group. Stressors impacting the downstream site were identified as mostly organic or nutrient enrichment and habitat degradation associated with wastewater treatment plants. The results of causal analysis suggest that the primary causes affecting fish population in the downstream site are through both size-selective mortality caused by ammonia toxicity and recruitment failure caused by habitat degradation and reproduction problem due to an IWTP and MWTP effluents. PMID:17258278

  8. Signatures of contamination in invasive round gobies (Neogobius melanostomus): a double strike for ecosystem health?

    PubMed

    Marentette, Julie R; Gooderham, Krista L; McMaster, Mark E; Ng, Tania; Parrott, Joanne L; Wilson, Joanna Y; Wood, Chris M; Balshine, Sigal

    2010-10-01

    The invasive round goby has a recognised role in transferring contaminants through foodwebs, but little work has been done on contaminant impacts on round gobies themselves. Here we present the first case study of contaminant biomarkers and subpopulation structure variation in round gobies, in relation to habitat contamination, within a Canadian Area of Concern, Hamilton Harbour. Copper and cadmium were elevated in livers of fish from contaminated habitats. Although catch abundances were similar across sites, fish were smaller, a greater proportion of fish were female and more males were in reproductive condition in contaminated sites. Fish from contaminated areas showed more fin loss. Males from contaminated sites showed intersex gonads and genitalia. Ethoxyresorufin-o-deethylase (EROD) activity was higher in fish collected near polycyclic aromatic hydrocarbon (PAH)-rich sediments. The results indicate that contaminants impact the characteristics of round goby populations, which could affect ecosystems beyond toxicant biomagnification. This study also confirms that round gobies can be abundant in polluted habitats, which may draw predators-facilitating mobilisation of contaminants in foodwebs. PMID:20615549

  9. Cortisol metabolism in hepatocytes of rainbow trout treated with 3,3{prime},4,4{prime} tetrachlorobiphenyl

    SciTech Connect

    Vijayan, M.M.; Fiest, G.; Otto, D.; Moon, T.W.

    1995-12-31

    The objective of this study was to investigate the potential of hepatocytes for cortisol uptake and metabolism in 3,3{prime},4,4{prime}-tetrachlorobiphenyl (TCBP) treated trout. Two groups of rainbow trout (Oncorhynchus mykiss) were either given an intraperitoneal implant of peanut oil alone or peanut oil containing TCBP (10 mg.kg{sup {minus}1} body weight) and sampled six weeks later. The toxicant exposed fish had significantly lower condition factor and plasma glucose concentration, whereas plasma cortisol, protein and hepatocyte protein concentration and liver ethoxyresorufin-O-deethylase (EROD) activity were significantly higher in the TCBP compared to the sham group. There was no significant difference in plasma lactate and amino acid concentration, hepatocyte glycogen content or liver cytosolic cortisol binding affinity or capacity between the two groups. The uptake of [{sup 3}H] cortisol was significantly higher in the hepatocytes of TCBP treated fish compared to the sham fish. Also, there was enhanced catabolism of [{sup 3}H] cortisol by hepatocytes of TCBP treated fish; the major metabolite appeared to be tetrahydrocortisone. The results indicate that the potential for cortisol clearance is enhanced in hepatocytes of TCBP treated trout. The data also tend to suggest in vivo regulatory mechanisms that might possibly prevent the increased clearance of the hormone from circulation in toxicant exposed fish.

  10. Mechanistic studies of pericardial edema in early life stages (ELS) of medaka (Oryzias latipes)

    SciTech Connect

    Villalobos, S.A.; Fan, T.W.M.; Higashi, R.M.; Hinton, D.E.

    1995-12-31

    Pericardial edema (PE), a manifestation of developmental toxicity in fish ELS, may compromise stock recruitment and survival. However, the mechanism underlying this common lesion is unknown. Possible mechanisms for PE in ELS of medaka were studied by metabolic and morphologic methods. In the laboratory, medaka embryos readily develop PE after brief exposure to dioxin, trichloroethylene (TCE) soot extract, or thiobencarb. Histopathological analyses, regardless of agent, indicated widespread edema without cellular infiltrates in pericardial and peritoneal cavities and in subepithelial spaces of skin. Additionally, endothelia of sinus venosus and adjacent atrium were enlarged. Walls of dilated sinoatrial compartments showed subendothelial fluid accumulation. Ethoxyresorufin O-deethylase activity (indicator of CYPL A induction), considerably higher in embryos exposed to dioxin and TCE soot, was suppressed by thiobencarb. In vivo {sup 31}P nuclear magnetic resonance (NMR) spectroscopy of living embryos (pregastrula through hatching) previously treated with thiobencarb, showed a temporary depression of ATP and phosphocreatine levels, with an apparent transient alkalinization in intracellular (possibly yolk sac) pH. Results indicate that induction of CYP1A is not a requirement for development of PE, and that ionic imbalances and/or metabolic disorders following exposure may be causative factor(s).

  11. Toxicity assessment of environmental pollutant phenanthrene in clam Venerupis philippinarum using oxidative stress biomarkers.

    PubMed

    Zhang, Hui; Pan, Luqing; Tao, Yanxia

    2014-03-01

    The objective of this study was to assess potential toxic effects of phenanthrene (PHE) on tissues of clam Venerupis philippinarum using parameters of antioxidant defenses and oxidative stress. Antioxidant biomarkers including ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), and glutathione (GSH), as well as DNA damage and lipid peroxidation (LPO) in gills and digestive glands of V. philippinarum, were analyzed after a 1-, 3-, 6-, 10- and 15-day exposure to seawater containing PHE at concentrations of 2, 10, 50 μg/L. The results showed that the activity of most antioxidant enzymes was induced throughout the exposure period, and different trends were detected with time of exposure. The oxidative stress could be obviously caused in the gills and digestive glands under the experimental conditions. Overall, our results show that digestive glands are more sensitive to marine environmental stressors than gills, and GSH is proposed as potential useful biomarker as it showed good correlation with the target contaminant. This could provide useful information for toxic risk assessment of environmental pollutant PHE.

  12. In vivo effects of environmental concentrations of produced water on the reproductive function of polar cod (Boreogadus saida).

    PubMed

    Geraudie, P; Nahrgang, J; Forget-Leray, J; Minier, C; Camus, L

    2014-01-01

    Offshore oil and gas drilling processes generate operational discharges such as produced water (PW), a complex mixture of seawater with polycyclic aromatic hydrocarbons (PAH) and alkylphenols (AP). Some of these compounds may interact with the endocrine system of marine organisms and alter reproductive functions. In this study, polar cod were exposed for up to 28 d to a mixture of PAH, alkylated PAH, and AP simulating the composition of North Sea PW, at low and high concentrations (1:2000 and 1:1000 dilution of the original concentrate, respectively). Potential adverse effects of PW on polar cod physiology were investigated through biomarkers of biotransformation (hepatic ethoxyresorufin O-deethylase [EROD] activity and bile PAH metabolites), endocrine disruption (plasma vitellogenin [VTG] levels and sex steroid concentrations), and gonad histology. Plasma sexual steroid levels in fish were not markedly affected by PW exposure, while higher plasma VTG concentrations were measured in females exposed to the high PW treatment for 7 and 28 d. In males exposed to the higher PW concentration, inhibition of spermatogenesis was observed after 28 d in addition to increase of melano-macrophage occurrence in testis. Females exposed to the high PW treatment for 21 d showed a significant increase of atresia incidence. Finally, a significant decrease in oocyte number was observed in high PW exposed female ovaries after 28 d of exposure. PMID:24754392

  13. Toxicity of 2,4,4{prime}-trichlorobiphenyl in rats following 90-day dietary exposure

    SciTech Connect

    Chu, I.; Villeneuve, D.C.; Yagminas, A.; Lecavalier, P.; Poon, R.

    1996-10-25

    The toxicity of 2,4,4{prime}-trichlorobiphenyl (PCB 28) was investigated in rats after a 90-d dietary exposure. Groups of 10 male and 10 female weanling Sprague-Dawley rats were administered PCB 28 in the diet at 0, 0.05, 0.50, 5.0, or 50.0 ppm for 13 wk. Growth rate and food consumption were not affected by treatment, and no clinical signs of toxicity were observed. Mottled liver was noted in both control and PCB-treated males, but was found with increased incidence in the highest treatment group. Increased urinary ascorbic acid and hepatic microsomal ethoxyresorufin O-deethylase activity were observed in the 50.0 ppm group of both sexes. The vitamin A content in liver, lung, and kidney was not significantly affected by treatment. Analysis of brain biogenic amines showed a decreased dopamine concentration in the substantial nigra region of female rats receiving 0.5 ppm PCB 28 and higher doses. Female rats appeared top be more sensitive than males to the neurochemical effects of PCB 28. Dose-dependent histologic changes were observed in the thyroid and liver, with biologically significant changes occurring at 5.0 ppm and above. Based on these data, the no-observable-adverse-effect level (NOAEL) for this PCB congener was considered to be 0.5 ppm in diet or 36 {mu}g/kg body weight/d. 26 refs., 6 figs., 3 tabs.

  14. Active commuting to school

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Declines in physical activity levels have coincided with increasing rates of obesity in children. This is problematic because physical activity has been shown to attenuate weight gain in children. Active commuting to school is one way of increasing children's physical activity. However, given the hi...

  15. Home Activities for Fours.

    ERIC Educational Resources Information Center

    Ferguson-Florissant School District, Ferguson, MO.

    These home learning activity guides have been developed for parents to use with their 4-year-old children. Most of the activities require only household items that are often thrown away and can be recycled for learning activities. Some require no materials at all. The guides frequently begin with a discussion of home activities; progress through…

  16. [Positive Activities Campaign.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Prevention.

    This packet contains four pamphlets that are part of a campaign to encourage adults to provide and promote positive activities for youth and to serve as role models for young people. "Positive Activities: A Campaign for Youth" includes information on what positive activities are, how to get involved in helping to provide positive activities for…

  17. In vivo study of the effect of antiviral acyclic nucleotide phosphonate (R)-9-[2-(phosphonomethoxy)propyl]adenine (PMPA, tenofovir) and its prodrug tenofovir disoproxil fumarate on rat microsomal cytochrome P450.

    PubMed

    Anzenbacherová, E; Anzenbacher, P; Zídek, Z; Buchar, E; Kmonícková, E; Potmesil, P; Nekvindová, J; Veinlichová, A; Holý, A

    2008-01-01

    The total content of rat liver microsomal cytochrome P450 (CYP) significantly decreased after repeated i.p. administration of the antiviral agent tenofovir ((R)-9-[2-(phosphonomethoxy)propyl] adenine) and tenofovir disoproxil at a daily dose 25 mg/kg, although the content of liver microsomal protein did not change. The decrease of the CYP content was accompanied by concomitant increase of the amount of inactive CYP form, cytochrome P420. This effect was confirmed by a parallel study of the activities of selected CYP forms, CYP2E1 (p-nitrophenol hydroxylation) and CYP1A2 (7-ethoxyresorufin deethylation). The activity (expressed relatively to the protein content) of both CYP forms decreased significantly following the decrease of the total CYP. On the other hand, the CYP2E1 activity expressed relatively to the decreasing total CYP content remained unchanged. However, CYP1A2 activity also decreased when calculated relatively to the total native CYP content indicating lower stability of this form. Semiquantitative RT-PCR showed no significant changes in expression of major rat liver microsomal CYP forms after tenofovir treatment. In conclusion, repeated administration of tenofovir in higher doses led to significant decrease of the relative proportion of active liver microsomal CYPs accompanied by a conversion of these enzymes to the inactive form (CYP420) maintaining the sum of CYP proteins unchanged.

  18. Increasing Youth Physical Activity with Activity Calendars

    ERIC Educational Resources Information Center

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  19. Virucidal activity of an activated sludge supernatant.

    PubMed

    Rehn, Y; Schwartzbrod, L

    1993-09-01

    The virucidal activity of the activated sludge aqueous phase was studied from the time of initial inoculation with a poliovirus type 1 suspension and for durations of three and nine days. The mixtures were incubated in presence of a nutritive medium at 26 degrees C and samples were drawn at regular intervals of time for viral titration. The activated sludge supernatant (ASS) caused an important decrease of the titer of the poliovirus type 1 suspension especially after nine days of incubation. There was an average reduction of the viral titer of 79% after three days and 97% after nine days. When incubating the ASS with a nutritive medium before inoculating it, the viral decrease was much greater than when incubating without nutritive medium. When sterilizing the ASS before incubation and then inoculating it, no significant virucidal activity was observed (0% to 6%). Furthermore, when the ASS was subjected to a sterilization by filtration after incubation and was then inoculated, there existed a lower but not negligible viral inactivation (53% to 64%). The virucidal activity potentiality of the ASS is therefore due to microorganisms acting both directly as a support for viral particles adsorption and indirectly via the synthesis of substances with virucidal activity. When freezing and thawing the incubated ASS, and then sterilizing it by filtration before inoculation, the viral decrease reached 87% to 94%. This proves that the virucidal substances are only partly excreted by the microorganisms.

  20. Active magnetic regenerator

    DOEpatents

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  1. Preschoolers’ Physical Activity Behaviours

    PubMed Central

    Irwin, Jennifer D.; He, Meizi; Bouck, L. Michelle Sangster; Tucker, Patricia; Pollett, Graham L.

    2016-01-01

    Objectives To understand parents’ perspectives of their preschoolers’ physical activity behaviours. Methods A maximum variation sample of 71 parents explored their preschoolers’ physical activity behaviours through 10 semi-structured focus group discussions. Results Parents perceived Canada’s Physical Activity Guidelines for Children as inadequate; that their preschoolers get and need more than 30–90 minutes of activity daily; and that physical activity habits must be established during the preschool years. Nine barriers against and facilitators toward adequate physical activity were proposed: child’s age, weather, daycare, siblings, finances, time, society and safety, parents’ impact, and child’s activity preferences. Discussion The need for education and interventions that address current barriers are essential for establishing physical activity as a lifestyle behaviour during early childhood and, consequently, helping to prevent both childhood and adulthood obesity. PMID:16625802

  2. Balance Food and Activity

    MedlinePlus

    ... For Health Professionals Tools and Resources Promotional Materials Programming Materials Weight Management Nutrition Physical Activity Reduce Screen ... Training For Health Professionals Tools & Resources Promotional ... Programming Materials Weight Management Nutrition Physical Activity Reduce Screen ...

  3. Population Education. Awareness Activities.

    ERIC Educational Resources Information Center

    Brouse, Deborah E.

    1990-01-01

    Described are awareness activities that deal with human population growth, resources, and the environment. Activities include simulations, mathematical exercises, and discussions of the topic. Specific examples of what individuals can do to help are listed. (KR)

  4. Major operations and activities

    SciTech Connect

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development.

  5. Active Fire Mapping Program

    MedlinePlus

    ... Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS ... Data Web Services Latest Detected Fire Activity Other MODIS Products Frequently Asked Questions About Active Fire Maps ...

  6. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  7. Temporal induction of cytochrome P450 1A in the mirror carp (Cyprinus carpio) after administration of several polycyclic aromatic hydrocarbons

    SciTech Connect

    Weiden, M.E.J. Van Der; Hanegraaf, F.H.M.; Seinen, W.; Berg, M. Van Den . Research Inst. of Toxicology); Eggens, M.L. . Dept. of Ecotoxicology); Celander, M. . Dept. of Zoophysiology)

    1994-05-01

    High inductions of 7-ethoxyresorufin O-deethylation (EROD) activities, cytochrome P450 1A protein levels (P4501A), and total cytochrome P450 content (P450) were observed 1, 2, 5, and 14 d after a single i.p. injection of 99.5 [mu]mol/kg benzo[a]pyrene (BaP) and chrysene (Chrys). The highest inductions in EROD activities and P450 1A protein levels were seen 2 d after treatment, approximately 35- and 11-fold relative to the controls. Less pronounced increase of EROD activities and P4501A protein levels, approximately 3- to 10-fold and 6-fold, respectively, were observed after treatments with equimolar concentrations of fluoranthenes (Fluor) and pyrene (Pyr). Benzo[ghi]perylene (BghiP) and the carrier dimethyl sulfoxide (DMSO) did not affect these parameters. The highest concentrations of PAHs in the liver, equivalent to 2 to 25% of the dose, were found 1 or 2 d after treatment. The highest percentage of the dose in the liver was observed for Chrys, followed by BghiP, BaP, Fluor, and Pyr. Poor correlations were found between hepatic concentrations of PAHs and P450 1A increases, which might be attributed to the rapid metabolism of these compounds.

  8. Inhibition of human cytochrome P450 enzymes by the natural hepatotoxin safrole.

    PubMed

    Ueng, Yune-Fang; Hsieh, Chih-Hang; Don, Ming-Jaw

    2005-05-01

    The hepatotoxin, safrole is a methylenedioxy phenyl compound, found in sassafras oil and certain other essential oils. Recombinant cytochrome P450 (CYP, P450) and human liver microsomes were studied to investigate the selective inhibitory effects of safrole on human P450 enzymes and the mechanisms of action. Using Escherichia coli-expressed human P450, our results demonstrated that safrole was a non-selective inhibitor of CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP3A4 in the IC(50) order CYP2E1 < CYP1A2 < CYP2A6 < CYP3A4 < CYP2D6. Safrole strongly inhibited CYP1A2, CYP2A6, and CYP2E1 activities with IC(50) values less than 20 microM. Safrole caused competitive, non-competitive, and non-competitive inhibition of CYP1A2, CYP2A6 and CYP2E1 activities, respectively. The inhibitor constants were in the order CYP1A2 < CYP2E1 < CYP2A6. In human liver microsomes, 50 microM safrole strongly inhibited 7-ethoxyresorufin O-deethylation, coumarin hydroxylation, and chlorzoxazone hydroxylation activities. These results revealed that safrole was a potent inhibitor of human CYP1A2, CYP2A6, and CYP2E1. With relatively less potency, CYP2D6 and CYP3A4 were also inhibited.

  9. Inhibition of human and rat CYP1A1 enzyme by grapefruit juice compounds.

    PubMed

    Santes-Palacios, Rebeca; Romo-Mancillas, Antonio; Camacho-Carranza, Rafael; Espinosa-Aguirre, Jesús Javier

    2016-09-01

    Cytochrome P4501A1 is involved in the metabolism of carcinogenic polycyclic aromatic hydrocarbons; therefore, its inhibition interferes with the carcinogenesis process induced by these compounds in rats. The human and rat CYP1A1 differ by 21% in amino acid sequence, including the active site of the enzyme; this difference may be an important factor when results obtained using animal models are interpolated to humans. Based on its previously reported CYP inhibitory properties, we studied the effects of two molecules contained within grapefruit juice, naringenin and 6',7'-dihydroxybergamottin, on human and rat CYP1A1 activity. For this purpose, the kinetics of inhibition as well as computational simulations were used. Naringenin and 6',7'-dihydroxybergamottin were found to be competitive inhibitors of human and rat CYP1A1. Additionally, naringenin exerted a mixed type inhibition effect on rat CYP1A1. Computational docking showed that inhibitors might block the oxidation of 7-ethoxyresorufin by binding to the CYP1A1 active site. Our results demonstrate the differences in CYP inhibitory mechanisms for the same molecule when CYP from different species are considered. PMID:27444380

  10. Inhibition of human and rat CYP1A1 enzyme by grapefruit juice compounds.

    PubMed

    Santes-Palacios, Rebeca; Romo-Mancillas, Antonio; Camacho-Carranza, Rafael; Espinosa-Aguirre, Jesús Javier

    2016-09-01

    Cytochrome P4501A1 is involved in the metabolism of carcinogenic polycyclic aromatic hydrocarbons; therefore, its inhibition interferes with the carcinogenesis process induced by these compounds in rats. The human and rat CYP1A1 differ by 21% in amino acid sequence, including the active site of the enzyme; this difference may be an important factor when results obtained using animal models are interpolated to humans. Based on its previously reported CYP inhibitory properties, we studied the effects of two molecules contained within grapefruit juice, naringenin and 6',7'-dihydroxybergamottin, on human and rat CYP1A1 activity. For this purpose, the kinetics of inhibition as well as computational simulations were used. Naringenin and 6',7'-dihydroxybergamottin were found to be competitive inhibitors of human and rat CYP1A1. Additionally, naringenin exerted a mixed type inhibition effect on rat CYP1A1. Computational docking showed that inhibitors might block the oxidation of 7-ethoxyresorufin by binding to the CYP1A1 active site. Our results demonstrate the differences in CYP inhibitory mechanisms for the same molecule when CYP from different species are considered.

  11. Green Schools Activity Booklet.

    ERIC Educational Resources Information Center

    Sacramento Tree Foundation, CA.

    This collection of interdisciplinary hands-on activities covers a variety of topics related to trees and conservation. Twenty-four activities integrate the subjects of social studies, fine arts, science, language arts, math, geography, and music. Although activity instructions are not consistent they usually contain details on objectives and…

  12. Activity Sheets. Draft Copy.

    ERIC Educational Resources Information Center

    Duke Power Company, Educational Services Dept., Charlotte, NC.

    This document consists of energy vocabulary activities, three games, worksheets, laboratory activities/exercises, and an introductory classroom exercise designed to introduce energy concepts to students. Vocabulary activities focus on coal and energy consumption. The three games (with instructions) focus on various aspects of energy and energy…

  13. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Provides on-task activities to fill in unexpected extra moments in elementary classes. The activities require little preparation and take 5-15 minutes to complete. There are activities for math, language arts, social science, science, critical thinking, and computer. An outer space board game is also included. (SM)

  14. Climate Change: An Activity.

    ERIC Educational Resources Information Center

    Lewis, Garry

    1995-01-01

    Presents a segment of the Geoscience Education booklet, Climate Change, that contains information and activities that enable students to gain a better appreciation of the possible effects human activity has on the Earth's climate. Describes the Terrace Temperatures activity that leads students through an investigation using foraminifera data to…

  15. Active Learning Crosses Generations.

    ERIC Educational Resources Information Center

    Woodard, Diane K.

    2002-01-01

    Describes the benefits of intergenerational programs, highlighting a child care program that offers age-appropriate and mutually beneficial activities for children and elders within a nearby retirement community. The program has adopted High/Scope's active learning approach to planning and implementing activities that involve both generations. The…

  16. Activity Theory and Ontology

    ERIC Educational Resources Information Center

    Peim, Nick

    2009-01-01

    This paper seeks to re-examine Yrio Engestrom's activity theory as a technology of knowledge designed to enable positive transformations of specific practices. The paper focuses on a key paper where Engestrom defines the nature and present state of activity theory. Beginning with a brief account of the relations between activity theory and…

  17. Highlights of 1981 activities

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The highlights of NASA's 1981 activities are presented, including the results of the two flights of the space shuttle Columbia and the Voyager 2 encounter with Saturn. Accomplishments in the areas of space transportation operations; space science; aeronautical, energy, and space research and development; as well as space tracking, international activities, and 1981 launch activities are discussed.

  18. Measurement of Physical Activity.

    ERIC Educational Resources Information Center

    Dishman, Rod K.; Washburn, Richard A.; Schoeller, Dale A.

    2001-01-01

    Valid assessment of physical activity must be unobtrusive, practical to administer, and specific about physical activity type, frequency, duration, and intensity. Assessment methods can be categorized according to whether they provide direct or indirect (e.g., self-report) observation of physical activity, body motion, physiological response…

  19. FL Activities & Festivals.

    ERIC Educational Resources Information Center

    American Council on the Teaching of Foreign Languages, Hastings-on-Hudson, NY.

    A collection of student, class, and school foreign language activities suggests a variety of projects and describes three specific school efforts. The suggested activities include: (1) individual student efforts such as writing to pen-pals; (2) group activities such as a foreign language auction or sing-along; (3) group projects for the school…

  20. Technology Learning Activities I.

    ERIC Educational Resources Information Center

    International Technology Education Association, Reston, VA.

    This guide contains 30 technology learning activities. Activities may contain all or some of the following: an introduction, objectives, materials and equipment, challenges, limitations, notes and investigations, resources and references used, and evaluation ideas. Activity titles are: (1) Occupations in Construction Technology; (2) Designing a…

  1. Woodsy Owl Activity Guide.

    ERIC Educational Resources Information Center

    Forest Service (USDA), Washington, DC.

    This guide offers teachers and after-school group leaders 12 fun and engaging activities. Activities feature lessons on trees, water, wind, the earth, food, and waste. The activities are designed to help children aged 5-8 become more aware of the natural environment and fundamental conservation principles. Titles of children's books are embedded…

  2. Tea enhances insulin activity.

    PubMed

    Anderson, Richard A; Polansky, Marilyn M

    2002-11-20

    The most widely known health benefits of tea relate to the polyphenols as the principal active ingredients in protection against oxidative damage and in antibacterial, antiviral, anticarcinogenic, and antimutagenic activities, but polyphenols in tea may also increase insulin activity. The objective of this study was to determine the insulin-enhancing properties of tea and its components. Tea, as normally consumed, was shown to increase insulin activity >15-fold in vitro in an epididymal fat cell assay. Black, green, and oolong teas but not herbal teas, which are not teas in the traditional sense because they do not contain leaves of Camellia senensis, were all shown to increase insulin activity. High-performance liquid chromatography fractionation of tea extracts utilizing a Waters SymmetryPrep C18 column showed that the majority of the insulin-potentiating activity for green and oolong teas was due to epigallocatechin gallate. For black tea, the activity was present in several regions of the chromatogram corresponding to, in addition to epigallocatechin gallate, tannins, theaflavins, and other undefined compounds. Several known compounds found in tea were shown to enhance insulin with the greatest activity due to epigallocatechin gallate followed by epicatechin gallate, tannins, and theaflavins. Caffeine, catechin, and epicatechin displayed insignificant insulin-enhancing activities. Addition of lemon to the tea did not affect the insulin-potentiating activity. Addition of 5 g of 2% milk per cup decreased the insulin-potentiating activity one-third, and addition of 50 g of milk per cup decreased the insulin-potentiating activity approximately 90%. Nondairy creamers and soy milk also decreased the insulin-enhancing activity. These data demonstrate that tea contains in vitro insulin-enhancing activity and the predominant active ingredient is epigallocatechin gallate. PMID:12428980

  3. Vestibular activation of sympathetic nerve activity

    NASA Technical Reports Server (NTRS)

    Ray, C. A.; Carter, J. R.

    2003-01-01

    AIM: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well-established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure. CONCLUSION: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.

  4. Effect of different river flow rates on biomarker responses in common carp (Cyprinus carpio).

    PubMed

    Hackenberger, Branimir K; Velki, Mirna; Lončarić, Zeljka; Hackenberger, Davorka K; Ečimović, Sandra

    2015-02-01

    The present study investigated effects of different river flow rates on basal activities of selected biomarkers and the occurrence of oxidative stress in the common carp (Cyprinus carpio). Juvenile carp were exposed to different river flow rates (5-120 cm/s) by caging for 3 weeks. After this period, one half of the fish were sacrificed and used for analysis. The other half received a single intraperitoneal injection of 3-methylcholanthrene (3-MC) and after 6 days were sacrificed and used for analysis. In order to investigate whether the physical activity of carp in the environment will influence the condition status of carp, following biomarkers were measured - activities of glutathione S-transferase (GST), catalase (CAT) and ethoxyresorufin-O-deethylase (EROD) and concentration of protein carbonyls (PC). The results showed that different flow rates significantly influenced biochemical biomarkers. The basal activity of GST did not change significantly after exposure to different river flow rates, whereas the activity of CAT increased with increasing river flow rates. The application of 3-MC caused significant increases in GST and CAT activities, but there were no difference between 3-MC control and 3-MC different flow rates. The occurrence of oxidative stress as a result of exposure to increased physical activity, i.e. increased river flow rates, was confirmed by measurement of PC levels - the level of PC increased with increasing river flow rates. Measurement of EROD basal activity showed that at lower river flow rates the EROD activity increased and at higher river flow rates decreased towards control levels demonstrating a close relationship between oxidative stress, PC levels and EROD activity. Obviously, biomarker responses in carp of different condition status can differ substantially. It can be concluded that flow rate may be an important factor in biomonitoring of rivers using biomarkers and since at different locations river water flow rate can vary

  5. Effect of reduced food intake on toxicokinetics of halogenated organic contaminants in herring gull (Larus argentatus) chicks.

    PubMed

    Routti, Heli; Helgason, Lisa Bjørnsdatter; Arukwe, Augustine; Wolkers, Hans; Heimstad, Eldbjørg Sofie; Harju, Mikael; Berg, Vidar; Gabrielsen, Geir Wing

    2013-01-01

    The aim of the present study was to investigate how contaminant exposure and reduced food intake affect tissue distribution and biotransformation of halogenated organic contaminants (HOCs) in Arctic seabirds using herring gull (Larus argentatus) as a model species. Herring gull chicks were exposed for 44 d to cod liver oil containing a typical mixture of contaminants. Following exposure, food intake was reduced for a one-week period in a subgroup of the chicks. Polyclorinated biphenyls, organochlorine pesticides, and brominated flame retardants, as well as a wide range of hydroxy, methyl sulfone, and methoxy compounds were measured in liver, brain, and plasma samples. Additionally, phase I biotransformation enzyme activities and phase I and II messenger ribonucleic acid (mRNA) expression were investigated in the liver, brain, or both. Both contaminant exposure and reduced food intake had an increasing effect on the concentrations of HOCs and their metabolites. The HOC exposure and reduced food intake also led to increased 7-ethoxyresorufin-O-deethylation (EROD) activity, whereas mRNA expression of the biotransformation enzymes increased only following the reduced food intake. Tissue distribution of HOCs and their metabolites was not affected by either contaminant exposure or reduced food intake. In conclusion, the results indicate that biotransformation capacity and formation of HOC metabolites increase during reduced food intake. This finding supports the hypothesis that reduced food intake increases the susceptibility of Arctic animals to the effects of lipophilic HOCs.

  6. Modeling population-level effects of PCBs on largemouth bass using biomarkers

    SciTech Connect

    Jaworska, J.; Rose, K.A.; DeAngelis, D.L.; Adams, M.A.; Bevelheimer, M.

    1994-12-31

    Population-level effects of PCBs on largemouth bass Micropterus salmoides are simulated using a biomarker-based effects model coupled to an individual-based population model. The individual-based population model tracks individual fish through their daily processes of growth, feeding, mortality and spawning and is configured for Southeastern US reservoirs. The effects model uses relationships between biomarker levels and physiological variables of individual fish. PCB effects are imposed using relationships between EROD (7-ethoxyresorufin Odeethylation) activity and growth reduction and EROD levels in spawners and decreased fry survival. EROD activity measures the amount of P-450 cytochrome induced by PCB exposure. Using field observed EROD levels, one year simulations show that sublethal PCB effects on growth can directly result in increased young-of-the-year mortality by causing smaller sized fish at the end of the growing season, which suffer higher overwinter mortality. Imposing both growth and fry mortality effects produces more complicated results. Under some conditions, density-dependent growth due to lower fry survival can potentially offset PCB-induced reductions in growth. This approach provides a framework for quantitatively extrapolating molecular and other sub-organismal bioindicators to the population level.

  7. Effect of reduced food intake on toxicokinetics of halogenated organic contaminants in herring gull (Larus argentatus) chicks.

    PubMed

    Routti, Heli; Helgason, Lisa Bjørnsdatter; Arukwe, Augustine; Wolkers, Hans; Heimstad, Eldbjørg Sofie; Harju, Mikael; Berg, Vidar; Gabrielsen, Geir Wing

    2013-01-01

    The aim of the present study was to investigate how contaminant exposure and reduced food intake affect tissue distribution and biotransformation of halogenated organic contaminants (HOCs) in Arctic seabirds using herring gull (Larus argentatus) as a model species. Herring gull chicks were exposed for 44 d to cod liver oil containing a typical mixture of contaminants. Following exposure, food intake was reduced for a one-week period in a subgroup of the chicks. Polyclorinated biphenyls, organochlorine pesticides, and brominated flame retardants, as well as a wide range of hydroxy, methyl sulfone, and methoxy compounds were measured in liver, brain, and plasma samples. Additionally, phase I biotransformation enzyme activities and phase I and II messenger ribonucleic acid (mRNA) expression were investigated in the liver, brain, or both. Both contaminant exposure and reduced food intake had an increasing effect on the concentrations of HOCs and their metabolites. The HOC exposure and reduced food intake also led to increased 7-ethoxyresorufin-O-deethylation (EROD) activity, whereas mRNA expression of the biotransformation enzymes increased only following the reduced food intake. Tissue distribution of HOCs and their metabolites was not affected by either contaminant exposure or reduced food intake. In conclusion, the results indicate that biotransformation capacity and formation of HOC metabolites increase during reduced food intake. This finding supports the hypothesis that reduced food intake increases the susceptibility of Arctic animals to the effects of lipophilic HOCs. PMID:23060285

  8. Physical Activity and Albuminuria

    PubMed Central

    Robinson, Emily S.; Fisher, Naomi D.; Forman, John P.; Curhan, Gary C.

    2010-01-01

    Higher urinary albumin excretion predicts future cardiovascular disease, hypertension, and chronic kidney disease. Physical activity improves endothelial function so activity may reduce albuminuria. Among diabetics, physical activity decreases albuminuria. In nondiabetics, prior studies have shown no association. The authors explored the cross-sectional association between physical activity and albuminuria in 3,587 nondiabetic women in 2 US cohorts, the Nurses’ Health Study I in 2000 and the Nurses’ Health Study II in 1997. Physical activity was expressed as metabolic equivalents per week. The outcome was the top albumin/creatinine ratio (ACR) decile. Multivariate logistic regression was used. Secondary analyses explored the ACR association with strenuous activity and walking. The mean age was 58.6 years. Compared with women in the lowest physical activity quintile, those in the highest quintile had a multivariate-adjusted odds ratio for the top ACR decile of 0.65 (95% confidence interval (CI): 0.46, 0.93). The multivariate-adjusted odds ratio for the top ACR decile for those with greater than 210 minutes per week of strenuous activity compared with no strenuous activity was 0.61 (95% CI: 0.37, 0.99), and for those in the highest quintile of walking compared with the lowest quintile, it was 0.69 (95% CI: 0.47, 1.02). Greater physical activity is associated with a lower ACR in nondiabetic women. PMID:20133515

  9. Activated carbon from biomass

    NASA Astrophysics Data System (ADS)

    Manocha, S.; Manocha, L. M.; Joshi, Parth; Patel, Bhavesh; Dangi, Gaurav; Verma, Narendra

    2013-06-01

    Activated carbon are unique and versatile adsorbents having extended surface area, micro porous structure, universal adsorption effect, high adsorption capacity and high degree of surface reactivity. Activated carbons are synthesized from variety of materials. Most commonly used on a commercial scale are cellulosic based precursors such as peat, coal, lignite wood and coconut shell. Variation occurs in precursors in terms of structure and carbon content. Coir having very low bulk density and porous structure is found to be one of the valuable raw materials for the production of highly porous activated carbon and other important factor is its high carbon content. Exploration of good low cost and non conventional adsorbent may contribute to the sustainability of the environment and offer promising benefits for the commercial purpose in future. Carbonization of biomass was carried out in a horizontal muffle furnace. Both carbonization and activation were performed in inert nitrogen atmosphere in one step to enhance the surface area and to develop interconnecting porosity. The types of biomass as well as the activation conditions determine the properties and the yield of activated carbon. Activated carbon produced from biomass is cost effective as it is easily available as a waste biomass. Activated carbon produced by combination of chemical and physical activation has higher surface area of 2442 m2/gm compared to that produced by physical activation (1365 m2/gm).

  10. Physiologic activities of the contact activation system.

    PubMed

    Schmaier, Alvin H

    2014-05-01

    The plasma contact activation (CAS) and kallikrein/kinin (KKS) systems consist of 4 proteins: factor XII, prekallikrein, high molecular weight kininogen, and the bradykinin B2 receptor. Murine genetic deletion of factor XII (F12(-/-)), prekallikrein (Klkb1(-/-)), high molecular weight kininogen (Kgn1(-/-)) and the bradykinin B2 receptor (Bdkrb2(-/-)) yield animals protected from thrombosis. With possible exception of F12(-/-) and Kgn1(-/-) mice, the mechanism(s) for thrombosis protection is not reduced contact activation. Bdkrb2(-/-) mice are best characterized and they are protected from thrombosis through over expression of components of the renin angiotensin system (RAS) leading to elevated prostacyclin with vascular and platelet inhibition. Alternatively, prolylcarboxypeptidase, a PK activator and degrader of angiotensin II, when deficient in the mouse leads to a prothrombotic state. Its mechanism for increased thrombosis also is mediated in part by components of the RAS. These observations suggest that thrombosis in mice of the CAS and KKS are mediated in part through the RAS and independent of reduced contact activation. PMID:24759141

  11. Marine Biology Activities. Ocean Related Curriculum Activities.

    ERIC Educational Resources Information Center

    Pauls, John

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  12. Lightning Activities and Earthquakes

    NASA Astrophysics Data System (ADS)

    Liu, Jann-Yenq

    2016-04-01

    The lightning activity is one of the key parameters to understand the atmospheric electric fields and/or currents near the Earth's surface as well as the lithosphere-atmosphere coupling during the earthquake preparation period. In this study, to see whether or not lightning activities are related to earthquakes, we statistically examine lightning activities 30 days before and after 78 land and 230 sea M>5.0 earthquakes in Taiwan during the 12-year period of 1993-2004. Lightning activities versus the location, depth, and magnitude of earthquakes are investigated. Results show that lightning activities tend to appear around the forthcoming epicenter and are significantly enhanced a few, especially 17-19, days before the M>6.0 shallow (depth D< 20 km) land earthquakes. Moreover, the size of the area around the epicenter with the statistical significance of lightning activity enhancement is proportional to the earthquake magnitude.

  13. Thermally Activated Driver

    NASA Technical Reports Server (NTRS)

    Kinard, William H.; Murray, Robert C.; Walsh, Robert F.

    1987-01-01

    Space-qualified, precise, large-force, thermally activated driver (TAD) developed for use in space on astro-physics experiment to measure abundance of rare actinide-group elements in cosmic rays. Actinide cosmic rays detected using thermally activated driver as heart of event-thermometer (ET) system. Thermal expansion and contraction of silicone oil activates driver. Potential applications in fluid-control systems where precise valve controls are needed.

  14. Activated recombinant adenovirus proteinases

    SciTech Connect

    Anderson, C.W.; Mangel, W.F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  15. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  16. Active unilateral condylar hyperplasia.

    PubMed

    Luz, J G; de Rezende, J R; de Araújo, V C; Chilvarquer, I

    1994-01-01

    Two cases of active unilateral condylar hyperplasia which were treated with condylectomy alone are presented. The first case was an adult form and the other a juvenile form. Both were classified as active by using 99Tc bone scintigraphy. Clinical and radiographic features of both cases conformed to the hemimandibular hypertrophy type. Satisfactory facial symmetry and dental occlusion were achieved. Histopathological data confirmed the activity of the articular cartilage layers. PMID:8181091

  17. Activity in distant comets

    NASA Technical Reports Server (NTRS)

    Luu, Jane X.

    1992-01-01

    Activity in distant comets remains a mystery in the sense that we still have no complete theory to explain the various types of activity exhibited by different comets at large distances. This paper explores the factors that should play a role in determining activity in a distant comet, especially in the cases of comet P/Tempel 2, comet Schwassmann-Wachmann 1, and 2060 Chiron.

  18. Crew activities in space

    NASA Technical Reports Server (NTRS)

    Bluford, G. S., Jr.

    1981-01-01

    One of the mission requirements of the Space Shuttle is to serve as a working platform for experiments in space. Many of these experiments will be performed by crewmembers (mission specialists and payload specialists) in a general purpose laboratory called Spacelab. All nonexperiment-related activities or housekeeping activities will be done in the Orbiter, while most of the mission-related activities (experiments) will be done in Spacelab. In order for experimenters to design their experiments to best utilize the capabilities of the Orbiter, the Spacelab, and the crew, the working environment in the Orbiter and in Spacelab is described. In addition, the housekeeping activities required of the crew are summarized.

  19. Physical Activity and Cancer

    MedlinePlus

    ... of scientists, ranging from experts in basic biological science to those with expertise in community behavioral interventions to increase physical activity. This combination of scientists and expertise will ...

  20. NASA metrication activities

    NASA Technical Reports Server (NTRS)

    Vlannes, P. N.

    1978-01-01

    NASA's organization and policy for metrification, history from 1964, NASA participation in Federal agency activities, interaction with nongovernmental metrication organizations, and the proposed metrication assessment study are reviewed.

  1. The interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) and 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) in TCDD-induced porphyria

    SciTech Connect

    Yao, Cheng Catsby.

    1989-01-01

    Halogenated aryl hydrocarbon(HAH)-induced porphyria is caused by alteration of porphyrin metabolism and results in the accumulation of hepatic and urinary porphyrins. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (75 {mu}/kg) caused significant increases of hepatic porphyrin levels in C57BL/6 male, female and ovariectomized female, and C57BL/10 male mice 3 weeks after treatment. In contrast, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) was inactive at a dose of 750 {mu}mol/kg. Cotreatment with MCDF (750 {mu}mol/kg) and 2,3,7,8-TCDD (75 {mu}g/kg) resulted in partial antagonism of 2,3,7,8-TCDD-induced porphyrin accumulation in female but not in male mice. In female C57BL/6 mice, 2,3,7,8-TCDD-induced porphyria was accompanied by the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities and the inhibition of uroporphyrinogen decarboxylase (UROD) activity. MCDF (750 {mu}mol/kg) did not significantly affect these enzyme activities. In coadministration studies, MCDF partially antagonized 2,3,7,8-TCDD-induced hepatic porphyrin accumulation but did not affect the activities of hepatic AHH, EROD or UROD. These results demonstrate that the induction of the monooxygenase enzyme activities and the inhibition of UROD activity by 2,3,7,8-TCDD and the development of porphyria are not coordinately regulated in C57BL/6 female mice. In cultured chick embryo hepatocytes, 2,3,7,8-TCDD caused a significant increase in porphyrin levels and induced AHH and EROD activities. MCDF and Aroclor 1254 partially antagonized the 2,3,7,8-TCDD induced AHH and EROD activities but not the porphyrin accumulation.

  2. Active Flow Control Activities at NASA Langley

    NASA Technical Reports Server (NTRS)

    Anders, Scott G.; Sellers, William L., III; Washburn, Anthony E.

    2004-01-01

    NASA Langley continues to aggressively investigate the potential advantages of active flow control over more traditional aerodynamic techniques. This paper provides an update to a previous paper and describes both the progress in the various research areas and the significant changes in the NASA research programs. The goals of the topics presented are focused on advancing the state of knowledge and understanding of controllable fundamental mechanisms in fluids as well as to address engineering challenges. An organizational view of current research activities at NASA Langley in active flow control as supported by several projects is presented. On-center research as well as NASA Langley funded contracts and grants are discussed at a relatively high level. The products of this research are to be demonstrated either in bench-top experiments, wind-tunnel investigations, or in flight as part of the fundamental NASA R&D program and then transferred to more applied research programs within NASA, DOD, and U.S. industry.

  3. Activity Book: Ocean Ecology.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Presents a collection of activities to help elementary students study ocean ecology. The activities have students investigate ocean inhabitants, analyze animal adaptations, examine how temperature and saltiness affect ocean creatures, and learn about safeguarding the sea. Student pages offer reproducible learning sheets. (SM)

  4. [Field Learning Activities].

    ERIC Educational Resources Information Center

    Nolde Forest Environmental Education Center, Reading, PA.

    Seventy field activities, pertinent to outdoor, environmental studies, are described in this compilation. Designed for elementary and junior high school students, the activities cover many discipline areas--science, social studies, language arts, health, history, mathematics, and art--and many are multidisciplinary in use. Topics range from soil…

  5. Rainy Day Activities.

    ERIC Educational Resources Information Center

    Texas Child Care, 1997

    1997-01-01

    Experienced caregivers plan ahead for rainy days. This article describes specific rainy day activities for young children, such as books and crafts to learn about rain (rain in a jar, making a rainbow), simple cooking activities (taffy pull, cinnamon candy tea), and games (mummy wrap, hunt the thimble, rain lotto). (EV)

  6. Activities of the ILO.

    ERIC Educational Resources Information Center

    Labour Education, 1984

    1984-01-01

    Seven articles on International Labour Organization (ILO) activities cover study groups at ILO headquarters, a Philippine rural workers seminar, women's participation in Central American union activities, worksite courses in India, and seminars and symposia in Cape Verde, Mauritius, and Sierra Leone. (SK)

  7. Active Students in Webinars

    ERIC Educational Resources Information Center

    Kolås, Line; Nordseth, Hugo; Yri, Jørgen Sørlie

    2015-01-01

    To ensure student activity in webinars we have defined 10 learning tasks focusing on production and communication e.g. collaborative writing, discussion and polling, and investigated how the technology supports the learning activities. The three project partners in the VisPed-project use different video-conferencing systems, and we analyzed how it…

  8. The Activity of Trypsin

    ERIC Educational Resources Information Center

    Russo, Salvatore F.; Holzman, Tom

    1977-01-01

    Describes an experiment that illustrates the following points concerning the experimental determination of trypsin activity: (1) there is a difference in basing enzyme concentration on weight, absorbance, or active sites; and (2) the method of expressing enzyme concentration determines the value of specific, molecular, and catalytic center…

  9. Emotionally Intense Science Activities

    ERIC Educational Resources Information Center

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-01-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of…

  10. Games and Word Activities.

    ERIC Educational Resources Information Center

    Northwest Regional Educational Lab., Portland, OR.

    Games and word activities give children another way to integrate their learning and reinforce their literacy skills. They provide different and enjoyable contexts in which children can apply what they are learning. This booklet offers activities which provide a sampling of "fun" ways for tutors to support and supplement their tutees' classroom…

  11. Active Healthy Summer

    ERIC Educational Resources Information Center

    Elliott, Eloise

    2005-01-01

    Summer break is almost here for most elementary teachers and students. Warmer weather and additional free time to make choices create more opportunities to be physically active, whether home alone or out with friends and family. This article describes ways by which physical education specialists can encourage students' physical activity by…

  12. Coordinating Shared Activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley

    2004-01-01

    Shared Activity Coordination (ShAC) is a computer program for planning and scheduling the activities of an autonomous team of interacting spacecraft and exploratory robots. ShAC could also be adapted to such terrestrial uses as helping multiple factory managers work toward competing goals while sharing such common resources as floor space, raw materials, and transports. ShAC iteratively invokes the Continuous Activity Scheduling Planning Execution and Replanning (CASPER) program to replan and propagate changes to other planning programs in an effort to resolve conflicts. A domain-expert specifies which activities and parameters thereof are shared and reports the expected conditions and effects of these activities on the environment. By specifying these conditions and effects differently for each planning program, the domain-expert subprogram defines roles that each spacecraft plays in a coordinated activity. The domain-expert subprogram also specifies which planning program has scheduling control over each shared activity. ShAC enables sharing of information, consensus over the scheduling of collaborative activities, and distributed conflict resolution. As the other planning programs incorporate new goals and alter their schedules in the changing environment, ShAC continually coordinates to respond to unexpected events.

  13. Reflections on Activity Theory

    ERIC Educational Resources Information Center

    Bakhurst, David

    2009-01-01

    It is sometimes suggested that activity theory represents the most important legacy of Soviet philosophy and psychology. But what exactly "is" activity theory? The canonical account in the West is given by Engestrom, who identifies three stages in the theory's development: from Vygotsky's insights, through Leontiev's articulation of the…

  14. Obesity, Physical Activity - Children.

    ERIC Educational Resources Information Center

    Gilliam, Thomas B.

    Childhood obesity starts at a very early age, and preventive measures taken early enough may retard the development of fat cells. It appears that physical activity plays an important role in reducing obesity. The activity program must start early, in preschool days. It is felt that screening children for obesity when they first enter school and…

  15. Science World Activities Book.

    ERIC Educational Resources Information Center

    Wisconsin Academy of Sciences, Arts and Letters, Madison.

    This document consists of three sections. Section I contains 19 activities developed by master teachers for the Science World '84 summer science program. These activities focus on studies involving airplane controls, trash bag kites, computers, meteorology, compass orienteering, soils, aquatic ecosystems, bogs, and others. Objectives, materials…

  16. Peak Longevity Physical Activity

    Cancer.gov

    People who engage in three to five times the recommended minimum level of leisure-time physical activity derive the greatest benefit in terms of mortality reduction when compared with people who do not engage in leisure-time physical activity.

  17. ZOOMsci Activity Guide.

    ERIC Educational Resources Information Center

    Wade, Meredith

    This activity guide is based on the Public Broadcasting System's (PBS) program "ZOOM." It is designed for educators with activities that are categorized into three themes: (1) Things That Go, which includes "Air" which explores air pressure, "Rubber Bands" which discovers the potential energy of rubber bands, "Baking Soda and Vinegar" which…

  18. Active galactic nuclei

    PubMed Central

    Fabian, Andrew C.

    1999-01-01

    Active galactic nuclei are the most powerful, long-lived objects in the Universe. Recent data confirm the theoretical idea that the power source is accretion into a massive black hole. The common occurrence of obscuration and outflows probably means that the contribution of active galactic nuclei to the power density of the Universe has been generally underestimated. PMID:10220363

  19. Activation of fly ash

    DOEpatents

    Corbin, D.R.; Velenyi, L.J.; Pepera, M.A.; Dolhyj, S.R.

    1986-08-19

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  20. Laboratory Activities in Israel

    ERIC Educational Resources Information Center

    Mamlok-Naaman, Rachel; Barnea, Nitza

    2012-01-01

    Laboratory activities have long had a distinctive and central role in the science curriculum, and science educators have suggested that many benefits accrue from engaging students in science laboratory activities. Many research studies have been conducted to investigate the educational effectiveness of laboratory work in science education in…

  1. Curriculum Activities on Aging.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.; Benge, Nancy

    This paper contains learning activities on aging for use with elementary, high school, and university students in health, family relationships, social studies, and art courses. The activities are intended to help youth develop a more realistic understanding of the aging process and to become aware of both the problems and benefits associated with…

  2. Nutrition Activities Resource Guide.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Div. of Special Education.

    The resource guide suggests activities to help special education students make appropriate choices about their nutritional habits. It is explained that the activities can be infused into other curriculum areas. The guide consists of five themes and includes performance objectives for each: foods eaten at school (planning a school lunch, keeping a…

  3. Activation of fly ash

    DOEpatents

    Corbin, David R.; Velenyi, Louis J.; Pepera, Marc A.; Dolhyj, Serge R.

    1986-01-01

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  4. Learning Activities for Toddlers.

    ERIC Educational Resources Information Center

    Texas Child Care, 1996

    1996-01-01

    Suggests activities to help toddlers develop skills in the four important areas of self-help, creativity, world mastery, and coordination. Activities include hand washing, button practice, painting, movement and music, bubble making, creation of a nature mural, and a shoe print trail. (TJQ)

  5. Active and Healthy Schools

    ERIC Educational Resources Information Center

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  6. Calculator-Active Materials.

    ERIC Educational Resources Information Center

    Crow, Tracy, Ed.; Harris, Julia, Ed.

    1997-01-01

    This journal contains brief descriptions of calculator-active materials that were found using Resource Finder, the searchable online catalog of curriculum resources from the Eisenhower National Clearinghouse (ENC). It features both the calculators themselves and the activity books that are used with them. Among the calculators included are those…

  7. Activating Event Knowledge

    ERIC Educational Resources Information Center

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-01-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or…

  8. Bonus Activity Book. Peacemakers.

    ERIC Educational Resources Information Center

    Whitman, Betsy Blizard

    1992-01-01

    Activity book helps elementary students learn about peace and see themselves as peacemakers and peacekeepers. Students are introduced to literary and historical figures who have worked for peace and won the Nobel Peace Prize. Activities teach students that peace means more than calm situations or absence of war. (SM)

  9. Vegetable Soup Activities.

    ERIC Educational Resources Information Center

    Shepard, Mary; Shepard, Ray

    Vegetable Soup is a new children's television series whose purpose is to counter the negative and destructive effects of racial isolation. This manual gives detailed instructions for discussion of activities that are presented during the television series such as: crafts, games, recipes, language activities, and children's questions. A list of…

  10. Student Activities. Managing Liability.

    ERIC Educational Resources Information Center

    Bennett, Barbara; And Others

    This monograph suggests ways that college or university administrations can undertake a systematic and careful review of the risks posed by students' activities. Its purpose is to provide guidance in integrating the risk management process into a school's existing approaches to managing student organizations and activities. It is noted that no…

  11. Untangling occupation and activity.

    PubMed

    Pierce, D

    2001-01-01

    Activity and occupation are two core concepts of occupational therapy that are in need of differentiation. Occupation is defined here as a person's personally constructed, one-time experience within a unique context. Activity is defined as a more general, culturally shared idea about a category of action. The ways in which subjectivity and context are handled within the concepts of occupation and activity are keys to disentangling them. The proposed untangling of the two concepts into distinct definitions is congruent with their historical origins as well as with current definitional trends. Once occupation and activity are recognized as two separate and equally valuable concepts, they offer a rich set of theoretical relations for exploration. The clarity that will result from differentiating occupation and activity will enhance disciplinary discourse and research as well as enhance the intervention efficacy, moral surety, and political strength of the profession.

  12. Active element pattern

    NASA Astrophysics Data System (ADS)

    Pozar, D. M.

    1994-08-01

    This review article will discuss the use of the active element pattern for prediction of the scan performance of large phased array antennas. The introduction and application of the concept of the active element pattern goes back at least 30 years (1) -(6) , but the subject is generally not covered in modern antenna engineering textbooks or handbooks, and many contemporary workers are unfamiliar with this simple but powerful idea. In addition, early references on this subject do not provide a rigorous discussion or derivation of the active element pattern, relying instead on a more qualitative interpretation. The purpose of this communication is to make the technique of active element patterns more accessible to antenna engineers, and to provide a new derivation of the basic active element pattern relations in terms of scattering parameters.

  13. Potent and non-specific inhibition of cytochrome P450 by JM216, a new oral platinum agent.

    PubMed Central

    Ando, Y.; Shimizu, T.; Nakamura, K.; Mushiroda, T.; Nakagawa, T.; Kodama, T.; Kamataki, T.

    1998-01-01

    Bis-acetato-ammine-dichloro-cyclohexylamine-platinum (IV), JM216, is the first antineoplastic platinum compound that can be given to patients orally. Several phase II clinical trials of JM216 monotherapy have already been reported. However, no information on the potential drug interactions caused by JM216 is available. In this study, the capacity of JM216 to inhibit cytochrome P450 (CYP) in human liver microsomes was investigated by measuring the inhibition potential (IC50 and Ki) on prototype reactions. Specific substrates of CYP included testosterone (catalysed by CYP3A4), paclitaxel (CYP2C8), 7-ethoxyresorufin (CYP1A1, CYP1A2), coumarin (CYP2A6), aniline (CYP2E1) and (+/-)-bufuralol (CYP2D6). JM216 inhibited the catalytic activities of CYP isozymes. The IC50 values were between 0.3 microM and 10 microM, indicating strong and non-specific inhibitory effects of JM216. The inhibition occurred in a non-competitive manner, and the Ki value was 1.0 and 0.9 microM for metabolite formation of testosterone and paclitaxel respectively. Therefore, some in vivo studies should be conducted to determine whether or not there is a correlation between in vivo and in vitro results. PMID:9820175

  14. [Modeling of a three-dimensional structure of cytochrome P-450 1A2 and search for its new ligands].

    PubMed

    Belkina, N V; Skvortsov, V S; Ivanov, A S; Archakov, A I

    1998-01-01

    The substances inhibiting cytochrome P450 1A2 (CYP1A2) represent a perspective class of new drugs, which application in clinical practice can become the important part in preventive maintenance in oncology. The present work is devoted to computer modelling of 3-D structure of CYP1A2 and searching of new inhibitors by database mining. The modelling of CYP1A2 was done based on homology with 4 bacterial cytochromes P450 with known 3-D structure. For optimization of CYP1A2 active site structure the models of its complexes with characteristic substrates (caffeine and 7-ethoxyresorufin) were designed. These complexes were optimized by molecular dynamics simulation in water. The models of 24 complexes of CYP1A2 with known ligands with known Kd were designed by means of DockSearch and LeapFrog programs. 3D-QSAR model with good predictive force was created based on these complexes. On a final stage the search of knew CYP1A2 ligands in testing database (more than 23.000 substances from database Maybridge and 112 known CYP1A2 ligands from database Metabolite, MDL) was executed. 680 potential ligands of CYP1A2 with Kd values, comparable with known ones were obtained. This number has included 73 compounds from 112 known ligands, introduced in tested database as the internal control. PMID:9916262

  15. CYP 450 enzyme induction by chronic oral musk xylene in adult and developing rats.

    PubMed

    Suter-Eichenberger, R; Boelsterli, U A; Conscience-Egli, M; Lichtensteiger, W; Schlumpf, M

    2000-04-10

    Developmental and adult toxicity of musk xylene was studied in Long Evans (LE) rats fed with chow containing musk xylene (MX) in food pellets in concentrations of 1 mg, 10 mg, 33 mg, 100 mg and 1000 mg MX per 1 kg chow corresponding to a daily intake of 0.07-0.08 mg MX/kg up to 70-80 mg MX/kg body weight. Adult male and female rats were MX exposed for a minimum of 10 weeks before mating. Exposure continued throughout pregnancy, birth and lactation. The effects of MX on CYP1A1/1A2 were studied in liver microsomes by EROD (7-ethoxyresorufin-rosomes deethylase) for CYP1A1 and by MROD (methoxyresorufin-o-demethylase) for CYP1A2 activity and by Western blotting. MX induced these enzymes dose dependently in adult and developing rats at PN (postnatal day) 1 and 14. The lowest effective maternal dose was 2-3 mg MX/kg/day. Western blot data of CYP2B and CYP3A indicated the induction of both P450 enzyme proteins in developing rats at PN 14 at the higher dose of 70-80 mg MX/kg/day. In contrast, upon high MX exposure CYP2B but not CYP3A was found to be induced in adult first generation male and female rats, indicating differential sensitivity to MX in development.

  16. Identification of cytochrome P450 isoform involved in the metabolism of YM992, a novel selective serotonin re-uptake inhibitor, in human liver microsomes.

    PubMed

    Noguchi, K; Mera, A; Watanabe, T; Higuchi, S; Chiba, K

    2000-05-01

    1. In vitro studies were conducted to identify the hepatic cytochrome P450 isoform involved in the metabolism of YM992, ((S)-2-[[(fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride), a novel serotonin re-uptake inhibitor, in human liver microsomes. 2. Microsomes prepared from yeast expressing CYP1A1, CYP1A2 and CYP2D6 effectively metabolized YM992. A significant correlation was observed between the rate of YM992 metabolism and 7-ethoxyresorufin O-deethylation, CYP1A1/2 specific activity, in liver microsomes from 16 individual donors (r2 = 0.628, p < 0.001). Alpha-naphtoflavone and isosafrole, CYP1A1/2 inhibitors, suppressed the metabolism of YM992 in human liver microsomes in a concentration-dependent manner. 3. The metabolism of YM992 in human liver microsomes was inhibited by approximately 95% by antibodies which recognize both CYP1A1 and CYP1A2 whereas antibodies specific for CYP1A1 did not show inhibitory effects. 4. The same major metabolites, M6 and M7, were generated from YM992 after incubation with human liver microsomes and recombinant human CYP1A2. 5. These results suggest that the metabolism of YM992 in human liver microsomes is mainly catalysed by CYP1A2, and that YM992 might increase plasma concentration of concomitant drugs metabolized by CYP1A2 due to competitive inhibition.

  17. Functional expression and characterization of recombinant NADPH-P450 reductase from Malassezia globosa.

    PubMed

    Lee, Hwayoun; Park, Hyoung-Goo; Lim, Young-Ran; Lee, Im-Soon; Kim, Beom Joon; Seong, Cheul-Hun; Chun, Young-Jin; Kim, Donghak

    2012-01-01

    Malassezia globosa is a common pathogenic fungus that causes skin diseases including dandruff and seborrheic dermatitis in humans. Analysis of its genome identified a gene (MGL_1677) coding for a putative NADPH-P450 reductase (NPR) to support the fungal cytochrome P450 enzymes. The heterologously expressed recombinant M. globosa NPR protein was purified, and its functional features were characterized. The purified protein generated a single band on SDS-PAGE at 80.74 kDa and had an absorption maximum at 452 nm, indicating its possible function as an oxidized flavin cofactor. It evidenced NADPH-dependent reducing activity for cytochrome c or nitroblue tetrazolium. Human P450 1A2 and 2A6 were able to successfully catalyze the O-deethylation of 7- ethoxyresorufin and the 7-hydroxylation of coumarin, respectively, with the support of the purified NPR. These results demonstrate that purified NPR is an orthologous reductase protein that supports cytochrome P450 enzymes in M. globosa. PMID:22297231

  18. Differential potency of atropisomers of polychlorinated biphenyls on cytochrome P450 induction and uroporphyrin accumulation in the chick embryo hepatocyte culture.

    PubMed

    Rodman, L E; Shedlofsky, S I; Mannschreck, A; Püttmann, M; Swim, A T; Robertson, L W

    The atropisomers of 2,2',3,4,6-pentachlorobiphenyl (PeCB), 2,2',3,4,4',6-hexachlorobiphenyl (HeCB), and 2,2',3,3',4,4',6,6'-octachlorobiphenyl (OCB) were studied in the chick embryo hepatocyte culture to determine if chirality plays a role in the recognition events associated with the induction of cytochromes P450 and the accumulation of uroporphyrin (URO). Concentration-related induction of cytochrome P450 content, ethoxyresorufin-O-deethylase (EROD) and benzphetamine N-demethylase (BPDM) activities were measured. The rank order of potency for total cytochrome P450 induction was HeCB greater than OCB greater than or equal to PeCB. The (+)- and (-)-enantiomers of PeCB and OCB were of equal potencies as inducers of cytochromes P450, whereas the (+)-HeCB was greater than the (-)-HeCB. HeCB was a much more potent inducer of EROD activity than was either PeCB or OCB. EROD activity was induced to a much greater extent by the (+)-enantiomers of all compounds, with the (-)-enantiomers of PeCB and OCB being inactive. BPDM activity was induced by all three compounds in the order of OCB greater than or equal to HeCB greater than PeCB. The (-)-enantiomers were more potent inducers of BPDM activities than were the (+)-enantiomers, except for HeCB, in which the (+)- was more potent than the (-)-enantiomer. Analysis of porphyrin accumulation in cultures treated with delta-aminolevulinic acid revealed that (+)-HeCB caused the greatest percent URO accumulation, which also correlated with the greatest increase in EROD activity. All other enantiomers caused up to 47% URO accumulation, which did not correlate with an increase in EROD activity.

  19. Influence of recipient gender on intrasplenic fetal liver tissue transplants in rats: cytochrome P450-mediated monooxygenase functions.

    PubMed

    Lupp, Amelie; Hugenschmidt, Sabine; Rost, Michael; Müller, Dieter

    2004-05-01

    Rat livers display a sex-specific cytochrome P450 (P450) isoforms expression pattern with consecutive differences in P450-mediated monooxygenase activities, which have been shown to be due to a differential profile of growth hormone (GH) secretion. Parallel to previous investigations on P450 isoforms expression, the aim of the present study was to elucidate the influence of recipient gender on P450-mediated monooxygenase activities in intrasplenic liver tissue transplants in comparison to orthotopic liver. Fetal liver tissue suspensions of mixed gender were transplanted into the spleen of adult male or female syngenic recipients. Four months after grafting transplant-recipients and age-matched controls were treated with beta-naphthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX) or the vehicles and sacrificed 24 or 48 h thereafter. P450-dependent monooxygenase activities were assessed by a series of model reactions for different P450 subtypes in liver and spleen 9000 g supernatants. In spleens of male and female control rats only very low monooxygenase activities were detectable, whereas with most model reactions distinct activities were observed in transplant-containing organs. Livers and transplant-containing spleens from male rats displayed higher basal ethoxycoumarin O-deethylase and testosterone 2alpha-, 2beta-, 6beta-, 14alpha-, 15alpha-, 15beta-, 16alpha-, 16beta- and 17-hydroxylase activities than those from females. On the other hand, like the respective livers, spleens from female transplant-recipients demonstrated more pronounced p-nitrophenol- and testosterone 6alpha- and 7alpha-hydroxylase activities than those from male hosts. With nearly all model reactions gender-specific differences in inducibility by BNF, PB or DEX could be demonstrated in livers as well as in transplant-containing spleens. These results further confirm that the P450 system of intrasplenic liver tissue transplants and the respective orthotopic livers is similarly influenced

  20. Active optical zoom system

    DOEpatents

    Wick, David V.

    2005-12-20

    An active optical zoom system changes the magnification (or effective focal length) of an optical imaging system by utilizing two or more active optics in a conventional optical system. The system can create relatively large changes in system magnification with very small changes in the focal lengths of individual active elements by leveraging the optical power of the conventional optical elements (e.g., passive lenses and mirrors) surrounding the active optics. The active optics serve primarily as variable focal-length lenses or mirrors, although adding other aberrations enables increased utility. The active optics can either be LC SLMs, used in a transmissive optical zoom system, or DMs, used in a reflective optical zoom system. By appropriately designing the optical system, the variable focal-length lenses or mirrors can provide the flexibility necessary to change the overall system focal length (i.e., effective focal length), and therefore magnification, that is normally accomplished with mechanical motion in conventional zoom lenses. The active optics can provide additional flexibility by allowing magnification to occur anywhere within the FOV of the system, not just on-axis as in a conventional system.

  1. Emotionally Intense Science Activities

    NASA Astrophysics Data System (ADS)

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-08-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of each lesson were analysed to identify individual student's emotions. Results from two representative students are presented as case studies. Using a theoretical perspective drawn from theories of emotions founded in sociology, two assertions emerged. First, during the demonstration activity, students experienced the emotions of wonder and surprise; second, during a laboratory activity, students experienced the intense positive emotions of happiness/joy. Characteristics of these activities that contributed to students' positive experiences are highlighted. The study found that choosing activities that evoked strong positive emotional experiences, focused students' attention on the phenomenon they were learning, and the activities were recalled positively. Furthermore, such positive experiences may contribute to students' interest and engagement in science and longer term memorability. Finally, implications for science teachers and pre-service teacher education are suggested.

  2. Active touch sensing

    PubMed Central

    Prescott, Tony J.; Diamond, Mathew E.; Wing, Alan M.

    2011-01-01

    Active sensing systems are purposive and information-seeking sensory systems. Active sensing usually entails sensor movement, but more fundamentally, it involves control of the sensor apparatus, in whatever manner best suits the task, so as to maximize information gain. In animals, active sensing is perhaps most evident in the modality of touch. In this theme issue, we look at active touch across a broad range of species from insects, terrestrial and marine mammals, through to humans. In addition to analysing natural touch, we also consider how engineering is beginning to exploit physical analogues of these biological systems so as to endow robots with rich tactile sensing capabilities. The different contributions show not only the varieties of active touch—antennae, whiskers and fingertips—but also their commonalities. They explore how active touch sensing has evolved in different animal lineages, how it serves to provide rapid and reliable cues for controlling ongoing behaviour, and even how it can disintegrate when our brains begin to fail. They demonstrate that research on active touch offers a means both to understand this essential and primary sensory modality, and to investigate how animals, including man, combine movement with sensing so as to make sense of, and act effectively in, the world. PMID:21969680

  3. Biological activity of purpurogallin.

    PubMed

    Inamori, Y; Muro, C; Sajima, E; Katagiri, M; Okamoto, Y; Tanaka, H; Sakagami, Y; Tsujibo, H

    1997-05-01

    Purpurogallin showed antibacterial activity toward gram-positive bacteria. Strong activity against methicillin-resistant Staphylococcus aureus [minimal inhibitory concentration (MIC) against methicillin of 1600 micrograms/ml] was found, with MIC of 11.0 micrograms/ml. Purpurogallin inhibited the growth of all tested plants and decreased the chlorophyll content in the cotyledons of Brassica campestris subsp. rapa. It showed potent inhibitory activity against prolyl endopeptidase (the 50% inhibitory concentration was 1.6 x 10(-5) M), unlike its analogues, hinokitiol and tropolone.

  4. Physiological response of alligator gar juveniles (Atractosteus spatula) exposed to sub-lethal doses of pollutants.

    PubMed

    González, Carlos Aguilera; Cruz, Julio; Alfaro, Roberto Mendoza

    2015-08-01

    Alligator gar populations have declined because of overfishing, habitat loss and pollution. Over time, the exposure to different pollutants have affected these fishes as a consequence of their high trophic level, bottom-dwelling habits and long life span. In order to evaluate the physiological effects of pollutants on alligator gar, juveniles (6, 12 and 24 months) were exposed to sub-lethal doses of diazinon, β-naphthoflavone (BNF) and 17 β-estradiol (E2) by intraperitoneal injection. After 2 days of exposure, liver samples were taken to determine the activities of acetylcholinesterase, butyrylcholinesterase and carboxylesterase; alkaline and acid phosphatases (ALP and ACP); ethoxyresorufin o-deethylase (EROD); glutathione s-transferase (GST); superoxide dismutase (SOD), and vitellogenin (VTG) concentration. Two additional bioassays consisting on the exposure of compounds through water or food were performed and after 4 and 28 days, respectively, biomarkers were determined. All esterases were inhibited in organisms exposed to diazinon as well as in 6-months gar exposed to E2 and BNF. In contrast, ALP activity increased in gar exposed to diazinon and E2, while ACP activity did not show any variations. No EROD activity was registered after exposure to the different pollutants, despite being one of the most sensitive and common detoxification biomarkers used for fishes. GST activity reduction was detected when gar were exposed to E2 and BNF, while SOD activity increased after exposure to diazinon and E2. Finally, VTG levels were higher in animals exposed to E2 compared to other treatments. Overall, these results suggest that alligator gar juveniles have a low biotransformation metabolism and show that they are especially sensitive to those pollutants affecting the nervous system. PMID:25948055

  5. Biomarker responses in eelpouts from four coastal areas in Sweden, Denmark and Germany.

    PubMed

    Asker, Noomi; Albertsson, Eva; Wijkmark, Emma; Bergek, Sara; Parkkonen, Jari; Kammann, Ulrike; Holmqvist, Inger; Kristiansson, Erik; Strand, Jakob; Gercken, Jens; Förlin, Lars

    2016-09-01

    To increase our understanding of possible chemical impacts on coastal fish populations in the Baltic Sea, Kattegat and Skagerrak, the viviparous eelpout (Zoarces viviparus) was used as sentinel species in two major sampling campaigns (spring and autumn) in 16 different coastal sites. Condition factor (CF), liver somatic index (LSI), gonad somatic index (GSI) were measured and the activity of the hepatic enzymes ethoxyresorufin-O-deethylase (EROD), glutathione reductase GR), glutathione S-transferase (GST), catalase (CAT) and muscular activity of acetylcholinesterase (AChE) were assessed. PAH metabolites in bile were also analyzed. The most notable finding in the data set was the low EROD activity in eelpouts collected at the relatively polluted region in Germany compared to the other regions, which could be due to an inhibition of the CYP1A-system or to adaptation to chronic exposure of pollutants in this area. Additionally, low AChE activity was noted in the German region in the autumn campaign and low AChE activity detected in the Danish region in the spring campaign. These differences suggest possible season-specific differences in the use and release of AChE-inhibiting chemicals in the Danish and German regions. Clustering of biomarkers on site level indicated a relationship between CF and GSI and suggested that sites with a high CF contained eelpout that put a larger effort into their larvae development. Clustering of the oxidative stress markers GR, GST and CAT on the individual level reflected a possible coordinated regulation of these enzymes. Overall, the results support the importance of taking into account general regional differences and seasonal variation in biomarker activity when monitoring and assessing the effects of pollution. Despite the expected seasonal variation for most of the measured endpoint, several markers (GSI, EROD and CF) vary similarly between all selected sites in both spring and autumn. This suggests that the differences between

  6. Effect of swimming exercise and ethanol on rat liver P450-dependent monooxygenases.

    PubMed

    Ardies, C M; Zachman, E K; Koehn, B J

    1994-12-01

    The interactive effects of 6 wk of repeated swimming exercise and chronic ethanol consumption (36% of total calories) on the hepatic cytochrome P450-dependent monooxygenase system were studied utilizing four groups of male rats in a 2 x 2 factorial design. The sedentary-control (S/C), sedentary-ethanol (S/E), and swim-control (SW/C) groups received the same amount of food that the swim-ethanol (SW/E) group consumed. The swimming groups were trained to swim for 2 h.d-1, 5 d.wk-1. Significant main effects due to ethanol (P < 0.002) and exercise (P < 0.02) were observed for the enhanced cytochrome P450 content and cytochrome P450 reductase activity, respectively. In addition, significant main effects for ethanol (P < 0.001), exercise (P < 0.0001), and significant interaction effects (P < 0.005) on aniline p-hydroxylase activity and significant main effects for ethanol (P < 0.01), exercise (P < 0.01), and interaction effects (P < 0.04) on 7-ethoxycoumarin o-deethylase activity were observed. Because the SW/C treatment had no effect on any of the measured cytochrome P450 activities and the SW/E treatment enhanced P450 activities much more than the S/E treatment, the main effects observed for exercise are accounted for by the alterations produced by combining swimming with the ethanol treatment. Based on these results, repeated exercise combined with ethanol consumption produces a synergistic increase in ethanol-inducible cytochrome P450-dependent activities. PMID:7869878

  7. Early responses measured in the brachyuran crab Carcinus maenas exposed to carbamazepine and novobiocin: application of a 2-tier approach.

    PubMed

    Aguirre-Martínez, G V; Del Valls, T A; Martín-Díaz, M L

    2013-11-01

    One of the main consequences of the constant input of pharmaceuticals to the aquatic environment is that biota might develop unknown chronic effects, thus affecting their health even at low concentrations. The aim of this study is to evaluate the health status of Carcinus maenas employing a 2-tier approach, after 28 days of exposure to carbamazepine (CBZ) and novobiocin (NOV) at 0.1, 1, 10 and 50µgL(-1). Lysosomal membrane stability (LMS) is employed in tier 1. In tier 2 was applied a battery of biomarkers of exposure and effect (ethoxyresorufin O-deethylase (EROD), dibenzyl flourescein dealkylase (DBF), glutathione S-transferase (GST), glutathione peroxidase (GPx), lipid peroxidation (LPO) and DNA adducts) measured in gill, hepatopancreas, muscle and gonad tissues. Results show a dose-dependent effect. LMS in crabs exposed to environmental concentrations of pharmaceuticals was significantly lower compared to controls (p<0.05), indicating their stressed status. EROD activity was induced significantly (p<0.05) in all tissues by NOV (10-50µgL(-1)). DBF activity was induced significantly (p<0.05) in gill and hepatopancreas tissues by CBZ (10-50µgL(-1)). GST activity was activated in all tissues of crabs exposed to the highest concentrations tested (p<0.05). All tissues showed induction of GPX activity after exposure to selected drugs (p<0.05). LPO was activated in gill and hepatopancreas tissues by the pharmaceuticals at 50µgL(-1) (p<0.05). Crabs exposed to NOV (50µgL(-1)) presented DNA damage in gill and hepatopancreas tissues (p<0.05). Environmental concentrations of these pharmaceuticals have a measurable effect on the biomarkers studied. The 2-tier approach applied might be a suitable tool for the assessment of sublethal responses in crabs exposed to pharmaceuticals in the marine environment. PMID:23916015

  8. Furafylline is a potent and selective inhibitor of cytochrome P450IA2 in man.

    PubMed Central

    Sesardic, D; Boobis, A R; Murray, B P; Murray, S; Segura, J; de la Torre, R; Davies, D S

    1990-01-01

    1. Furafylline (1,8-dimethyl-3-(2'-furfuryl)methylxanthine) is a methylxanthine derivative that was introduced as a long-acting replacement for theophylline in the treatment of asthma. Administration of furafylline was associated with an elevation in plasma levels of caffeine, due to inhibition of caffeine oxidation, a reaction catalysed by one or more hydrocarbon-inducible isoenzymes of P450. We have now investigated the selectivity of inhibition of human monooxygenase activities by furafylline. 2. Furafylline was a potent, non-competitive inhibitor of high affinity phenacetin O-deethylase activity of microsomal fractions of human liver, a reaction catalysed by P450IA2, with an IC50 value of 0.07 microM. 3. Furafylline had either very little or no effect on human monooxygenase activities catalysed by other isoenzymes of P450, including P450IID1, P450IIC, P450IIA. Of particular interest, furafylline did not inhibit P450IA1, assessed from aryl hydrocarbon hydroxylase activity of placental samples from women who smoked cigarettes. 4. It is concluded that furafylline is a highly selective inhibitor of P450IA2 in man. 5. Furafylline was a potent inhibitor of the N3-demethylation of caffeine and of a component of the N1- and N7-demethylation. This confirms earlier suggestions that caffeine is a selective substrate of a hydrocarbon-inducible isoenzyme of P450 in man, and identifies this as P450IA2. Thus, caffeine N3-demethylation should provide a good measure of the activity of P450IA in vivo in man. 6. Although furafylline selectively inhibited P450IA2, relative to P450IA1, in the rat, this was at 1000-times the concentration required to inhibit the human isoenzyme, suggesting a major difference in the active site geometry between the human and the rat orthologues of P50IA2. PMID:2378786

  9. Effects of carbofuran on the sea bass (Dicentrarchus labrax L.): study of biomarkers and behaviour alterations.

    PubMed

    Hernández-Moreno, David; Pérez-López, Marcos; Soler, Francisco; Gravato, Carlos; Guilhermino, Lúcia

    2011-10-01

    The objective of this study was to investigate the acute effects of the pesticide carbofuran on the sea bass (Dicentrarchus labrax) using parameters at different levels of biological organisation (swimming behaviour and several biomarkers) and possible relationships between alterations found in different effect criteria. In a bioassay, sea bass juveniles were individually exposed to different doses of carbofuran (31, 63, 125 and 250 μg/L) for 96 h. At the end of the bioassay, the swimming performance and 11 biomarkers were determined. Biomarkers were: hepatosomatic index (HSI), lipid peroxidation (LPO), reduced glutathione and the activities of the enzymes ethoxyresorufin O-deethylase (EROD), glutathione S-transferases, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, brain acetylcholinesterase (AChE) and muscle cholinesterases (ChE). After 96 h of exposure, carbofuran induced a decrease of the swimming velocity and inhibition of EROD activity at all concentrations tested, and inhibition of muscle ChE and brain AChE activities at 250 μg/L. No relevant alterations in any of the other tested parameters were found. These results show that carbofuran induced adverse effects on fish by interfering with neurofunction, capability of detoxication and swimming velocity. In addition, positive and significant correlations between the swimming velocity and (i) brain AChE activity, (ii) muscle ChE activity and (iii) EROD activity suggest that the inhibition of these enzymes may somehow be related to the behavioural changes observed. Since these functions are determinant for the survival and performance of the fish in the wild, the findings of the present study suggest that adverse effects may occur in populations exposed to carbofuran if a sufficient number of animals is affected.

  10. Does the Clock Make the Poison? Circadian Variation in Response to Pesticides

    PubMed Central

    Hooven, Louisa A.; Sherman, Katherine A.; Butcher, Shawn; Giebultowicz, Jadwiga M.

    2009-01-01

    Background Circadian clocks govern daily physiological and molecular rhythms, and putative rhythms in expression of xenobiotic metabolizing (XM) genes have been described in both insects and mammals. Such rhythms could have important consequences for outcomes of chemical exposures at different times of day. To determine whether reported XM gene expression rhythms result in functional rhythms, we examined daily profiles of enzyme activity and dose responses to the pesticides propoxur, deltamethrin, fipronil, and malathion. Methodology/Principal Findings Published microarray expression data were examined for temporal patterns. Male Drosophila were collected for ethoxycoumarin-O-deethylase (ECOD), esterase, glutathione-S-transferase (GST), and, and uridine 5′-diphosphoglucosyltransferase (UGT) enzyme activity assays, or subjected to dose-response tests at four hour intervals throughout the day in both light/dark and constant light conditions. Peak expression of several XM genes cluster in late afternoon. Significant diurnal variation was observed in ECOD and UGT enzyme activity, however, no significant daily variation was observed in esterase or GST activity. Daily profiles of susceptibility to lethality after acute exposure to propoxur and fipronil showed significantly increased resistance in midday, while susceptibility to deltamethrin and malathion varied little. In constant light, which interferes with clock function, the daily variation in susceptibility to propoxur and in ECOD and UGT enzyme activity was depressed. Conclusions/Significance Expression and activities of specific XM enzymes fluctuate during the day, and for specific insecticides, the concentration resulting in 50% mortality varies significantly during the day. Time of day of chemical exposure should be an important consideration in experimental design, use of pesticides, and human risk assessment. PMID:19649249

  11. The effect of aspartame on rat brain xenobiotic-metabolizing enzymes.

    PubMed

    Vences-Mejía, A; Labra-Ruíz, N; Hernández-Martínez, N; Dorado-González, V; Gómez-Garduño, J; Pérez-López, I; Nosti-Palacios, R; Camacho Carranza, R; Espinosa-Aguirre, J J

    2006-08-01

    This study demonstrates that chronic aspartame (ASP) consumption leads to an increase of phase I metabolizing enzymes (cytochrome P450 (CYP)) in rat brain. Wistar rats were treated by gavage with ASP at daily doses of 75 and 125 mg/kg body weight for 30 days. Cerebrum and cerebellum were used to obtain microsomal fractions to analyse activity and protein levels of seven cytochrome P450 enzymes. Increases in activity were consistently found with the 75 mg/kg dose both in cerebrum and cerebellum for all seven enzymes, although not at the same levels: CYP 2E1-associated 4-nitrophenol hydroxylase (4-NPH) activity was increased 1.5-fold in cerebrum and 25-fold in cerebellum; likewise, CYP2B1-associated penthoxyresorufin O-dealkylase (PROD) activity increased 2.9- and 1.7-fold respectively, CYP2B2-associated benzyloxyresorufin O-dealkylase (BROD) 4.5- and 1.1-fold, CYP3A-associated erythromycin N-demethylase (END) 1.4- and 3.3-fold, CYP1A1-associated ethoxyresorufin O-deethylase (EROD) 5.5- and 2.8-fold, and CYP1A2-associated methoxyresorufin O-demethylase (MROD) 3.7- and 1.3-fold. Furthermore, the pattern of induction of CYP immunoreactive proteins by ASP paralleled that of 4-NHP-, PROD-, BROD-, END-, EROD- and MROD-related activities only in the cerebellum. Conversely, no differences in CYP concentration and activity were detected in hepatic microsomes of treated animals with respect to the controls, suggesting a brain-specific response to ASP treatment.

  12. Physiological response of alligator gar juveniles (Atractosteus spatula) exposed to sub-lethal doses of pollutants.

    PubMed

    González, Carlos Aguilera; Cruz, Julio; Alfaro, Roberto Mendoza

    2015-08-01

    Alligator gar populations have declined because of overfishing, habitat loss and pollution. Over time, the exposure to different pollutants have affected these fishes as a consequence of their high trophic level, bottom-dwelling habits and long life span. In order to evaluate the physiological effects of pollutants on alligator gar, juveniles (6, 12 and 24 months) were exposed to sub-lethal doses of diazinon, β-naphthoflavone (BNF) and 17 β-estradiol (E2) by intraperitoneal injection. After 2 days of exposure, liver samples were taken to determine the activities of acetylcholinesterase, butyrylcholinesterase and carboxylesterase; alkaline and acid phosphatases (ALP and ACP); ethoxyresorufin o-deethylase (EROD); glutathione s-transferase (GST); superoxide dismutase (SOD), and vitellogenin (VTG) concentration. Two additional bioassays consisting on the exposure of compounds through water or food were performed and after 4 and 28 days, respectively, biomarkers were determined. All esterases were inhibited in organisms exposed to diazinon as well as in 6-months gar exposed to E2 and BNF. In contrast, ALP activity increased in gar exposed to diazinon and E2, while ACP activity did not show any variations. No EROD activity was registered after exposure to the different pollutants, despite being one of the most sensitive and common detoxification biomarkers used for fishes. GST activity reduction was detected when gar were exposed to E2 and BNF, while SOD activity increased after exposure to diazinon and E2. Finally, VTG levels were higher in animals exposed to E2 compared to other treatments. Overall, these results suggest that alligator gar juveniles have a low biotransformation metabolism and show that they are especially sensitive to those pollutants affecting the nervous system.

  13. Algorithm-development activities

    NASA Technical Reports Server (NTRS)

    Carder, Kendall L.

    1994-01-01

    The task of algorithm-development activities at USF continues. The algorithm for determining chlorophyll alpha concentration, (Chl alpha) and gelbstoff absorption coefficient for SeaWiFS and MODIS-N radiance data is our current priority.

  14. Microglial Activation & Chronic Neurodegeneration

    PubMed Central

    Lull, Melinda E.; Block, Michelle L.

    2010-01-01

    Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurodegenerative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including TNFα, NO, IL1-β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (ex. LPS or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss over time. While the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s Disease. Here, we review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype. PMID:20880500

  15. Active noise reduction

    NASA Astrophysics Data System (ADS)

    Carter, J.

    1984-01-01

    Active Noise Reduction (ANR) techniques, singly and in combination with passive hearing protectors, offer the potential for increased sound protection, enhanced voice communications and improved wearability features for personnel exposed to unacceptable noise conditions. An enhanced closed loop active noise reduction system was miniaturized and incorporated into a standard Air Force flight helmet (HGU-26/P). This report describes the theory of design and operation, prototype configuration and operation, and electroacoustic performance and specifications for the ANR system. This system is theoretically capable of producing in excess of 30 decibels of active noise reduction. Electroacoustic measurements on a flat plate coupler demonstrated approximately 20 decibels of active noise reduction with the prototype unit. A performance evaluation of the integrated ANR unit will be conducted under laboratory and field conditions by government personnel to determine the feasibility of the system for use in military applications.

  16. Activities in Teaching Weather

    ERIC Educational Resources Information Center

    Tonn, Martin

    1977-01-01

    Presented is a unit composed of activities for teaching weather. Topics include cloud types and formation, simple weather instruments, and the weather station. Illustrations include a weather chart and instruments. A bibliography is given. (MA)

  17. Island Watershed Activity.

    ERIC Educational Resources Information Center

    Benson, Rod

    2003-01-01

    Describes a 90-minute "Island Watershed" activity to help earth science students understand the concept of the water cycle. Introduces a surface waters unit appropriate for students in grades 7-10. Includes watershed project guidelines. (Author/KHR)

  18. Authentic Listening Activities.

    ERIC Educational Resources Information Center

    Porter, Don; Roberts, Jon

    1981-01-01

    Discusses use of authentic listening experiences in second language classroom so that students will become involved in listening process demanded in authentic listening situations. Gives examples of sample classroom activities. (BK)

  19. French space activities

    NASA Technical Reports Server (NTRS)

    Blanc, R.

    1982-01-01

    The four main points of research and development of space programs by France are explained. The National Center of Space Studies is discussed, listing the missions of the Center and describing the activities of the staff.

  20. Creating Art Appreciation Activities.

    ERIC Educational Resources Information Center

    Heidt, Ann H.

    1986-01-01

    The experiences of college students enrolled as majors in elementary education in designing art appreciation activities for use in elementary classrooms are described. The college students had no art background. (RM)

  1. Active terahertz metamaterials

    SciTech Connect

    Chen, Hou-tong

    2009-01-01

    We demonstrate planar terahertz metamaterial devices enabling actively controllable transmission amplitude, phase, or frequency at room temperature via carrier depletion or photoexcitation in the semiconductor substrate or in semiconductor materials incorporated into the metamaterial structure.

  2. Planning activities in space

    NASA Technical Reports Server (NTRS)

    Chang, Kai-Hsiung

    1987-01-01

    Three aspects of planning activities in space are presented. These include generating plans efficiently, coordinating actions among multiple agents, and recovering from plan execution errors. Each aspect is discussed separately.

  3. A Big Gulp Activity.

    ERIC Educational Resources Information Center

    Kelly, Bruce

    1997-01-01

    Explains how to implement an activity in which students measure the volume of their oral cavities. Enables students to develop skills in estimation, measurement, connections, statistics, applying concepts and procedures, and communication. (DDR)

  4. PRESSURE ACTIVATED SEALANT TECHNOLOGY

    SciTech Connect

    Michael A. Romano

    2004-04-01

    The objective of this project is to develop new, efficient, cost effective methods of internally sealing natural gas pipeline leaks through the application of differential pressure activated sealants. In researching the current state of the art for gas pipeline sealing technologies we concluded that if the project was successful, it appeared that pressure activated sealant technology would provide a cost effective alternative to existing pipeline repair technology. From our analysis of current field data for a 13 year period from 1985 to 1997 we were able to identify 205 leaks that were candidates for pressure activated sealant technology, affirming that pressure activated sealant technology is a viable option to traditional external leak repairs. The data collected included types of defects, areas of defects, pipe sizes and materials, incident and operating pressures, ability of pipeline to be pigged and corrosion states. This data, and subsequent analysis, was utilized as a basis for constructing applicable sealant test modeling.

  5. Intercreativity: Mapping Online Activism

    NASA Astrophysics Data System (ADS)

    Meikle, Graham

    How do activists use the Internet? This article maps a wide range of activist practice and research by applying and developing Tim Berners-Lee's concept of ‘intercreativity' (1999). It identifies four dimensions of Net activism: intercreative texts, tactics, strategies and networks. It develops these through examples of manifestations of Net activism around one cluster of issues: support campaigns for refugees and asylum seekers.

  6. RMS active damping augmentation

    NASA Technical Reports Server (NTRS)

    Gilbert, Michael G.; Scott, Michael A.; Demeo, Martha E.

    1992-01-01

    The topics are presented in viewgraph form and include: RMS active damping augmentation; potential space station assembly benefits to CSI; LaRC/JSC bridge program; control law design process; draper RMS simulator; MIMO acceleration control laws improve damping; potential load reduction benefit; DRS modified to model distributed accelerations; accelerometer location; Space Shuttle aft cockpit simulator; simulated shuttle video displays; SES test goals and objectives; and SES modifications to support RMS active damping augmentation.

  7. Information Activities in Australia

    NASA Astrophysics Data System (ADS)

    Hanada, Takeyoshi

    The last few years have seen an explosive growth in database and computer networking activities in Australia. At present there are six major information networks in Australia, which carry more than 400 locally produced databases and many others from overseas. AUSINET databases are exemplified. MIDAS (Multi-mode International Data Aquisition System) provides lower cost access to overseas databases than before. The paper also gives brief outline of various bodies which relate to information and library policy in Australia and regional cooperative activities.

  8. RAVEN Quality Assurance Activities

    SciTech Connect

    Cogliati, Joshua Joseph

    2015-09-01

    This report discusses the quality assurance activities needed to raise the Quality Level of Risk Analysis in a Virtual Environment (RAVEN) from Quality Level 3 to Quality Level 2. This report also describes the general RAVEN quality assurance activities. For improving the quality, reviews of code changes have been instituted, more parts of testing have been automated, and improved packaging has been created. For upgrading the quality level, requirements have been created and the workflow has been improved.

  9. Low activation ferritic alloys

    DOEpatents

    Gelles, David S.; Ghoniem, Nasr M.; Powell, Roger W.

    1986-01-01

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  10. Low activation ferritic alloys

    DOEpatents

    Gelles, D.S.; Ghoniem, N.M.; Powell, R.W.

    1985-02-07

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  11. Tinnitus activities treatment.

    PubMed

    Tyler, Richard S; Gogel, Stephanie A; Gehringer, Anne K

    2007-01-01

    Tinnitus Activities Treatment includes counseling of the whole person, and considers individual differences and needs. We consider four areas: thoughts and emotions, hearing and communication, sleep, and concentration. We typically use Partial Masking Sound Therapy, with a noise or music set to the lowest level that provides relief. A picture-based approach facilitates engagement of the patient, and provides thorough and structured counseling. We engage the patient by including homework and activities to demonstrate understanding and facilitate progress. PMID:17956807

  12. Phytase activity in lichens.

    PubMed

    Higgins, Niall F; Crittenden, Peter D

    2015-10-01

    Phytase activity was investigated in 13 lichen species using a novel assay method. The work tested the hypothesis that phytase is a component of the suite of surface-bound lichen enzymes that hydrolyse simple organic forms of phosphorus (P) and nitrogen (N) deposited onto the thallus surface. Hydrolysis of inositol hexaphosphate (InsP6 , the substrate for phytase) and appearance of lower-order inositol phosphates (InsP5 -InsP1 ), the hydrolysis products, were measured by ion chromatography. Phytase activity in Evernia prunastri was compared among locations with contrasting rates of N deposition. Phytase activity was readily measurable in epiphytic lichens (e.g. 11.3 μmol InsP6 hydrolysed g(-1)  h(-1) in Bryoria fuscescens) but low in two terricolous species tested (Cladonia portentosa and Peltigera membranacea). Phytase and phosphomonoesterase activities were positively correlated amongst species. In E. prunastri both enzyme activities were promoted by N enrichment and phytase activity was readily released into thallus washings. InsP6 was not detected in tree canopy throughfall but was present in pollen leachate. Capacity to hydrolyse InsP6 appears widespread amongst lichens potentially promoting P capture from atmospheric deposits and plant leachates, and P cycling in forest canopies. The enzyme assay used here might find wider application in studies on plant root-fungal-soil systems.

  13. Physical activity and obesity.

    PubMed

    Tremblay, A

    1999-04-01

    The regular practice of physical activity promotes metabolic adaptations that facilitate the regulation of energy and fat balance. These effects are important for a better control of body weight in the obese individual and should enable him or her to involve adipose tissue to a lesser extent in this regulation. Physical activity favours a negative energy and fat balance, particularly if activities are prolonged and vigorous. The achievement of a negative energy and fat balance with physical activity also strongly depends on the nutritional context in which it is performed. In the long term, an active lifestyle and low-fat food habits are expected to induce a substantial body weight loss in the obese. This weight loss is progressively attenuated over time, presumably because of the decreased impact of a reduced adipose tissue mass on the regulation of energy and fat balance. For the obese individual complying with an activity programme and healthy food habits, a body weight loss of 10% is a realistic goal before the occurrence of resistance to further loss of body fat.

  14. ABB: active bandwidth broker

    NASA Astrophysics Data System (ADS)

    Wong, Kason; Law, Eddie

    2001-07-01

    In this paper, we shall discuss a novel design on the policy-based management for the Internet. This design deploys the concept of active networking. As opposed to the traditional network design, active network empowers network node with the ability to manipulate data and program code in packets, and configure the network properties according to the needs of different applications. The policy-based management can control network routers in order to realize end-to-end Quality of Service (QoS), such as differentiated and integrated services, across the Internet. For the moment, the Internet Engineering Task Force (IETF) has defined the framework of the policy-based management. It employs a simple client/server model that uses Common Open Policy Service (COPS) protocol to facilitate policy management and control. Our design of Active Bandwidth Broker (ABB) belongs to an active application. Our goals are to distribute centralized workload of the policy-based management over multiple active nodes in the active networks, introduce mobility of the bandwidth brokers, and allows load sharing to the policy-based management. This results a network-wide intelligent, highly available, and consistent QoS control that allows performance protection for voice, video and Internet business application while reducing costs for growing networks.

  15. Investigation of selective inhibitory effects of glycyrol on human CYP 1A1 and 2C9.

    PubMed

    Kim, Sun Joo; Kim, Su Jin; Hong, Miri; Choi, Hyun Gyu; Kim, Jeong Ah; Lee, Sangkyu

    2016-10-01

    1. Glycyrol is a coumarin derivative isolated from the roots of Glycyrrhiza uralensis called Gamcho in Korea and commonly used as a sweetener in oriental medicine. Glycyrol shows several biological activities, including anti-oxidative, anti-inflammatory, antibacterial, anti-angiogenic, and anti-allergenic properties. Although there have been studies on the biological effects of glycyrol, the inhibitory effects of glycyrol on cytochrome P450 (CYP) activities have not been investigated. 2. We investigated the inhibitory effects of glycyrol on the activities of CYP isoforms using a cocktail of probe substrates in pooled human liver microsome (HLM) and human recombinant cDNA-expressed CYPs. Glycyrol strongly inhibited CYP1A-mediated phenacetin O-deethylation and CYP2C9-mediated diclofenac 4'-hydroxylation in HLMs, which were the result of competitive inhibition as revealed by a Dixon plot. In addition, glycyrol showed selective inhibition of CYP1A1- and CYP1A2-catalyzed phenacetin O-deethylase activity with a half-maximal inhibitory concentration of (IC50) 1.3 and 16.1 μM in human recombinant cDNA-expressed CYP1A1 and CYP1A2, respectively. 3. Glycyrol decreased CYP2C9-catalyzed diclofenac 4'-hydroxylation activity with IC50 values of 0.67 μM in human recombinant cDNA-expressed CYP2C9. This is the first investigation of competitive inhibitory effects on CYP1A1 and CYP2C9 in HLMs. PMID:26750984

  16. The chlorinated AHR ligand 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) promotes reactive oxygen species (ROS) production during embryonic development in the killifish (Fundulus heteroclitus)

    USGS Publications Warehouse

    Arzuaga, Xabier; Wassenberg, Deena; Giulio, Richard D.; Elskus, Adria

    2006-01-01

    Exposure to dioxin-like chemicals that activate the aryl hydrocarbon receptor (AHR) can result in increased cellular and tissue production of reactive oxygen species (ROS). Little is known of these effects during early fish development. We used the fish model, Fundulus heteroclitus, to determine if the AHR ligand and pro-oxidant 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) can increase ROS production during killifish development, and to test a novel method for measuring ROS non-invasively in a living organism. The superoxide-sensitive fluorescent dye, dihydroethidium (DHE), was used to detect in ovo ROS production microscopically in developing killifish exposed to PCB126 or vehicle. Both in ovo CYP1A activity (ethoxyresorufin-o-deethylase, EROD) and in ovo ROS were induced by PCB126. In ovo CYP1A activity was inducible by PCB126 concentrations as low as 0.003 nM, with maximal induction occurring at 0.3 nM PCB126. These PCB126 concentrations also significantly increased in ovo ROS production in embryonic liver, ROS being detectable as early as 5 days post-fertilization. These data demonstrate that the pro-oxidant and CYP1A inducer, PCB126, increases both CYP1A activity and ROS production in developing killifish embryos. The superoxide detection assay (SoDA) described in this paper provides a semi-quantitative, easily measured, early indicator of altered ROS production that can be used in conjunction with simultaneous in ovo measurements of CYP1A activity and embryo development to explore functional relationships among biochemical, physiological and developmental responses to AHR ligands.

  17. Kinetics of mixed function oxygenase induction and retene excretion in retene-exposed rainbow trout (Oncorhynchus mykiss)

    SciTech Connect

    Fragoso, N.M.; Hodson, P.V.; Kozin, I.S.; Brown, R.S.; Parrott, J.L.

    1999-10-01

    The polycyclic aromatic hydrocarbon 7-isopropyl-1-methylphenanthrene (retene) induces mixed function oxygenase (MFO) activity of fish. Bile levels of retene and its metabolite(s) were measured in relation to exposure time, exposure concentration, and induction of MFO activity. Synchronous fluorescence spectrometry provided a rapid means of measuring the amount of retene present in the bile of exposed fish, whereas conventional fluorescence spectrometry was used to quantify the amount of retene metabolites. Based on bile analysis, increased retene exposure resulted in an increased uptake of retene and a curvilinear increase in hepatic MFO activity. Retene was present in the bile within 6 h of initial exposure. However, retene metabolite(s) only appeared in the bile after MFO induction had occurred, 12 h after exposure had commenced, suggesting that MFO activity is required for metabolism. Transfer of fish to clean water after 48 h of exposure resulted in a rapid decrease in the presence of retene and its metabolite(s) in the bile, with a calculated half-life of about 14 h. In vitro additions of retene directly to the ethoxyresorufin O-deethylase assay demonstrated that retene is capable of acting as a competitive inhibitor. Thus, retene contamination of postmitochondrial supernatant (S9 fraction) could result in false-negative results in the MFO assay. The MFO activity in extrahepatic tissues (gills, heart, and kidney) was not significantly induced with retene exposure. Thus, the major site of retene metabolism seems to be in the liver. These results confirm that retene is rapidly taken up, metabolized, and excreted by rainbow trout, and that retene metabolism and excretion are linked to hepatic MFO induction.

  18. Modulation of CYP1A1 and CYP1A2 hepatic enzymes after oral administration of Chios mastic gum to male Wistar rats.

    PubMed

    Katsanou, Efrosini S; Kyriakopoulou, Katerina; Emmanouil, Christina; Fokialakis, Nikolas; Skaltsounis, Alexios-Leandros; Machera, Kyriaki

    2014-01-01

    Chios mastic gum (CMG), a resin derived from Pistacia lentiscus var. chia, is known since ancient times for its pharmacological activities. CYP1A1 and CYP1A2 enzymes are among the most involved in the biotransformation of chemicals and the metabolic activation of pro-carcinogens. Previous studies referring to the modulation of these enzymes by CMG have revealed findings of unclear biological and toxicological significance. For this purpose, the modulation of CYP1A1 and CYP1A2 enzymes in the liver of male Wistar rats following oral administration of CMG extract (CMGE), at the levels of mRNA and CYP1A1 enzyme activity, was compared to respective enzyme modulation following oral administration of a well-known bioactive natural product, caffeine, as control compound known to involve hepatic enzymes in its metabolism. mRNA levels of Cyp1a1 and Cyp1a2 were measured by reverse transcription real-time polymerase chain reaction and their relative quantification was calculated. CYP1A1 enzyme induction was measured through the activity of ethoxyresorufin-O-deethylase (EROD). The results indicated that administration of CMGE at the recommended pharmaceutical dose does not induce significant transcriptional modulation of Cyp1a1/2 and subsequent enzyme activity induction of CYP1A1 while effects of the same order of magnitude were observed in the same test system following the administration of caffeine at the mean daily consumed levels. The outcome of this study further confirms the lack of any toxicological or biological significance of the specific findings on liver following the administration of CMGE. PMID:24950217

  19. Caged and wild fish: Induction of hepatic cytochrome P-450 (CYP1A1) as an environmental biomonitor

    SciTech Connect

    Haasch, M.L.; Lech, J.J. ); Prince, R.; Cooper, K.R. ); Wejksnora, P.J. )

    1993-05-01

    Hepatic monooxygenase activity can be induced by many different environmental chemical contaminants, and measurement of this activity has been proposed as an environmental biomonitor. Using in situ caged catfish and largemouth bass, and collected wild killifish, environmental induction of hepatic CYP1A1 was investigated using catalytic enzyme assays, regiospecific metabolism, immunodetection, and nucleic acid hybridization. The purpose of these studies was to evaluate these techniques for detection of CYP1A1 induction as a potential environmental biomonitor of environmental chemical contamination. Exposure of catfish in cages to polyaromatic hydrocarbon- (PAH-) and polychlorinated biphenyl- (PCB-) contaminated river water for two, four, or six weeks resulted in fourfold increases in ethoxyresorufin-O-deethylase (EROD) activity and three- and fivefold increases in immunoreactive CYP1A1 protein and hybridizable CYP1A1 mRNA, respectively, when compared to laboratory water control values. Hybridizable CYP1A1 mRNA in caged largemouth bass increased 5.1-fold at 1 d of exposure. Caged largemouth bass had 5-, 1.4-, and 0.8-fold increases at 3 d and 6-, 2.4-, 0.4-fold increases at 7 d of river water exposure in EROD, immunoreactive CYP1A1 protein, and CYP1A1 mRNA, respectively, when compared to laboratory water control values. Liver of killifish from a 2,3,7,8-tetrachlorodibenzo-p-dioxin-contaminated area had threefold higher EROD activity and similarly elevated immunoreactive CYP1A1 protein, a two- to fourfold increase in CYP1A1 mRNA, and a four- to eightfold increase in 6[beta]-hydroxyprogesterone activity, when compared to killifish livers sampled from a clean site.

  20. Investigation of selective inhibitory effects of glycyrol on human CYP 1A1 and 2C9.

    PubMed

    Kim, Sun Joo; Kim, Su Jin; Hong, Miri; Choi, Hyun Gyu; Kim, Jeong Ah; Lee, Sangkyu

    2016-10-01

    1. Glycyrol is a coumarin derivative isolated from the roots of Glycyrrhiza uralensis called Gamcho in Korea and commonly used as a sweetener in oriental medicine. Glycyrol shows several biological activities, including anti-oxidative, anti-inflammatory, antibacterial, anti-angiogenic, and anti-allergenic properties. Although there have been studies on the biological effects of glycyrol, the inhibitory effects of glycyrol on cytochrome P450 (CYP) activities have not been investigated. 2. We investigated the inhibitory effects of glycyrol on the activities of CYP isoforms using a cocktail of probe substrates in pooled human liver microsome (HLM) and human recombinant cDNA-expressed CYPs. Glycyrol strongly inhibited CYP1A-mediated phenacetin O-deethylation and CYP2C9-mediated diclofenac 4'-hydroxylation in HLMs, which were the result of competitive inhibition as revealed by a Dixon plot. In addition, glycyrol showed selective inhibition of CYP1A1- and CYP1A2-catalyzed phenacetin O-deethylase activity with a half-maximal inhibitory concentration of (IC50) 1.3 and 16.1 μM in human recombinant cDNA-expressed CYP1A1 and CYP1A2, respectively. 3. Glycyrol decreased CYP2C9-catalyzed diclofenac 4'-hydroxylation activity with IC50 values of 0.67 μM in human recombinant cDNA-expressed CYP2C9. This is the first investigation of competitive inhibitory effects on CYP1A1 and CYP2C9 in HLMs.

  1. Leflunomide Induces Pulmonary and Hepatic CYP1A Enzymes via Aryl Hydrocarbon Receptor.

    PubMed

    Patel, Ananddeep; Zhang, Shaojie; Paramahamsa, Maturu; Jiang, Weiwu; Wang, Lihua; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-12-01

    Emerging evidence indicates that the aryl hydrocarbon receptor (AhR) plays a crucial role in normal physiologic homeostasis. Additionally, aberrant AhR signaling leads to several pathologic states in the lung and liver. Activation of AhR transcriptionally induces phase I (CYP1A) detoxifying enzymes. Although the effects of the classic AhR ligands such as 3-methylcholanthrene and dioxins on phase 1 enzymes are well studied in rodent lung, liver, and other organs, the toxicity profiles limit their use as therapeutic agents in humans. Hence, there is a need to identify and investigate nontoxic AhR ligands not only to understand the AhR biology but also to develop the AhR as a clinically relevant therapeutic target. Leflunomide is a Food and Drug Administration-approved drug in humans that is known to have AhR agonist activity in vitro. Whether it activates AhR and induces phase 1 enzymes in vivo is unknown. Therefore, we tested the hypothesis that leflunomide will induce pulmonary and hepatic CYP1A enzymes in C57BL/6J wild-type mice, but not in AhR-null mice. We performed real-time reverse-transcription polymerase chain reaction analyses for CYP1A1/2 mRNA expression, western blot assays for CYP1A1/2 protein expression, and ethoxyresorufinO-deethylase assay for CYP1A1 catalytic activity. Leflunomide increased CYP1A1/A2 mRNA, protein, and enzymatic activities in wild-type mice. In contrast, leflunomide failed to increase pulmonary and hepatic CYP1A enzymes in AhR-null mice. In conclusion, we provide evidence that leflunomide induces pulmonary and hepatic CYP1A enzymes via the AhR.

  2. Walkability and Physical Activity

    PubMed Central

    Reis, Rodrigo Siqueira; Hino, Adriano Akira Ferreira; Rech, Cassiano Ricardo; Kerr, Jacqueline; Hallal, Pedro Curi

    2013-01-01

    Background Evidence from developing countries is limited on how income level for a given neighborhood is related to physical activity among its residents. Purpose The goal of the study was to examine the association between walkability and physical activity outcomes, and the effect of income on the relationship between walkability and physical activity in adults. Methods The Spaces for Physical Activity in Adults Study (ESPACOS Project) took place in Curitiba, Brazil. Data were collected in 2010 in 32 census tracts selected to vary in income and walkability, as measured by GIS. Participants were 697 individuals aged 18–65 years (52.0% were women) randomly sampled from the selected neighborhoods. The International Physical Activity Questionnaire was used to measure physical activity. All analyses were conducted in 2012. Results The proportion of those who walked for transportation for ≥150 minutes/week was 21.1% in low-walkability areas, and ranged from 33.5% to 35.0% in high-walkability areas. A total of 12.6% of residents were found to walk for leisure for ≥150 minutes/week; this result did not vary across quadrants of walkability and income level. The prevalence of leisure-time moderate-to-vigorous physical activity (MVPA) was 7.1–10.5 percentage points higher in high-compared to low-walkability areas. After adjusting for all individual confounders, walkability showed an independent association with walking for transport (OR=2.10, 95% CI=1.31, 3.37, p=0.002) and leisure-time MVPA (OR=1.57; 95% CI=1.06, 2.32; p=0.024). Neighborhood income level was independently associated with leisure-time MVPA (OR=1.70; 95% CI=1.06, 2.74, p=0.029). No association was found between walkability and walking for leisure. No interaction was found between walkability and neighborhood income level. Conclusions This study, among adults living in Curitiba, Brazil, confirms findings from studies of high-income countries showing that walkability is positively associated with

  3. Mechanochemically Active Soft Robots.

    PubMed

    Gossweiler, Gregory R; Brown, Cameron L; Hewage, Gihan B; Sapiro-Gheiler, Eitan; Trautman, William J; Welshofer, Garrett W; Craig, Stephen L

    2015-10-14

    The functions of soft robotics are intimately tied to their form-channels and voids defined by an elastomeric superstructure that reversibly stores and releases mechanical energy to change shape, grip objects, and achieve complex motions. Here, we demonstrate that covalent polymer mechanochemistry provides a viable mechanism to convert the same mechanical potential energy used for actuation in soft robots into a mechanochromic, covalent chemical response. A bis-alkene functionalized spiropyran (SP) mechanophore is cured into a molded poly(dimethylsiloxane) (PDMS) soft robot walker and gripper. The stresses and strains necessary for SP activation are compatible with soft robot function. The color change associated with actuation suggests opportunities for not only new color changing or camouflaging strategies, but also the possibility for simultaneous activation of latent chemistry (e.g., release of small molecules, change in mechanical properties, activation of catalysts, etc.) in soft robots. In addition, mechanochromic stress mapping in a functional robotic device might provide a useful design and optimization tool, revealing spatial and temporal force evolution within the robot in a way that might be coupled to autonomous feedback loops that allow the robot to regulate its own activity. The demonstration motivates the simultaneous development of new combinations of mechanophores, materials, and soft, active devices for enhanced functionality.

  4. Photon-activation therapy

    SciTech Connect

    Fairchild, R.G.; Bond, V.P.

    1982-01-01

    Photon Activation Therapy (PAT) is a technique in which radiation dose to tumor is enhanced via introduction of stable /sup 127/I in the form of iodinated deoxyuridine (IdUrd). Stimulation of cytotoxic effects from IdUrd is accomplished by activation with external (or implanted) radiation sources. Thus, accumulations of this nucleoside in actively competing cellpools do not preclude therapy in so far as such tissues can be excluded from the radiation field. Calculations show that 5% replacement of thymidine (Tyd) in tumor DNA should enhance the biological effectiveness of a given photon radiotherapy dose by a factor of approx. 3. Proportionally higher gains would result from higher replacements of Tyd and IdUrd. In addition, biological response is enhanced by chemical sensitization with IdUrd. The data indicate that damage from photon activation as well as chemical sensitization does not repair. Thus, at low dose rates, a further increase in therapeutic gain should accrue as normal tissues are allowed to repair and regenerate. A samarium-145 source has been developed for PAT, with activating x-ray energies of from 38 to 45 keV. Favorable clinical results can be expected through the use of IdUrd and protracted irradiations with low energy x-rays. In particular, PAT may provide unique advantages at selected sites such as brain, or head and neck tumors. (ERB)

  5. Mechanochemically Active Soft Robots.

    PubMed

    Gossweiler, Gregory R; Brown, Cameron L; Hewage, Gihan B; Sapiro-Gheiler, Eitan; Trautman, William J; Welshofer, Garrett W; Craig, Stephen L

    2015-10-14

    The functions of soft robotics are intimately tied to their form-channels and voids defined by an elastomeric superstructure that reversibly stores and releases mechanical energy to change shape, grip objects, and achieve complex motions. Here, we demonstrate that covalent polymer mechanochemistry provides a viable mechanism to convert the same mechanical potential energy used for actuation in soft robots into a mechanochromic, covalent chemical response. A bis-alkene functionalized spiropyran (SP) mechanophore is cured into a molded poly(dimethylsiloxane) (PDMS) soft robot walker and gripper. The stresses and strains necessary for SP activation are compatible with soft robot function. The color change associated with actuation suggests opportunities for not only new color changing or camouflaging strategies, but also the possibility for simultaneous activation of latent chemistry (e.g., release of small molecules, change in mechanical properties, activation of catalysts, etc.) in soft robots. In addition, mechanochromic stress mapping in a functional robotic device might provide a useful design and optimization tool, revealing spatial and temporal force evolution within the robot in a way that might be coupled to autonomous feedback loops that allow the robot to regulate its own activity. The demonstration motivates the simultaneous development of new combinations of mechanophores, materials, and soft, active devices for enhanced functionality. PMID:26390078

  6. Biological effects of polycyclic aromatic hydrocarbons (PAH) and their first metabolic products in in vivo exposed Atlantic cod (Gadus morhua).

    PubMed

    Pampanin, Daniela M; Le Goff, Jeremie; Skogland, Karianne; Marcucci, Cristian R; Øysæd, Kjell Birger; Lorentzen, Marianne; Jørgensen, Kåre B; Sydnes, Magne O

    2016-01-01

    The monitoring of the presence of polycyclic aromatic hydrocarbons (PAH) in the aquatic environment is a worldwide activity since some of these compounds are well-established carcinogens and mutagens. Contaminants in this class are in fact regarded as priority hazardous substances for environmental pollution (Water Framework Directive 2000/60/EC). In this study, Atlantic cod (Gadus morhua) was selected to assess in vivo effects of two PAH and their first metabolic products, namely, the corresponding trans-dihydrodiols, using biological markers. Fish were exposed for 1 wk to a single PAH (naphthalene or chrysene) and its synthetic metabolites ((1R,2R)-1,2-dihydronaphthalene-1,2-diol and (1R,2R)-1,2-dihydrochrysene-1,2-diol) by intraperitoneal injection in a continuous seawater flow system. After exposure, PAH metabolism including PAH metabolites in bile and ethoxyresorufin O-deethylase (EROD) activity, oxidative stress glutathione S-transferases (GST) and catalase (CAT) activities, and genotoxicity such as DNA adducts were evaluated, as well as general health conditions including condition index (CI), hepatosomatic index (HSI), and gonadosomatic index (GSI). PAH metabolite values were low and not significantly different when measured with the fixed-wavelength fluorescence screening method, while the gas chromatography-mass spectroscopy (GC-MS) method showed an apparent dose response in fish exposed to naphthalene. DNA adduct levels ≥0.16 × 10(-8) relative adduct level (RAL) were detected. It should be noted that 0.16 × 10(-8) RAL is considered the maximal acceptable background level for this species. The other biomarkers activities of catalase, GST, and EROD did not display a particular compound- or dose-related response. The GSI values were significantly lower in some chrysene- and in both naphthalene- and naphthalene diol-exposed groups compared to control. PMID:27484143

  7. Identification of cytochrome P4501A inducers in complex mixtures of PAHs

    SciTech Connect

    Villeneuve, D.; Crunkilton, R.; DeVita, W.

    1995-12-31

    An in vitro ethoxyresorufin-O-deethylase (EROD) assay was used to determine the ability of various PAHs and PAH mixtures to induce Ah receptor mediated cytochrome P4501A activity in PLHC-1 fish hepatoma cells. The purpose of this study was to identify the most potent inducers of a complement of thirteen separate PAHs and describe the interactions occurring in complex mixtures of the same. Analysis of individual PAHs at both equal concentrations and concentrations at which they were present in a model environmental sample showed chrysene, benzo(k)fluoranthene (BKF), benzo(b)fluoranthene, and benzo(a)anthracene to be the most potent cytochrome P4501A inducers of the thirteen PAHs tested. At equal concentrations, they yielded maximum EROD activities of 740, 380, 130, and 55 pmol/min/mg respectively. Although maximum activity was lower, 135, 75, 25, and 10 pmol/min/mg respectively, they remained the most potent inducers at model environmental concentrations, even at concentrations as little as 5% those of more abundant PAHs. Analysis of various mixtures of the thirteen PAHs provided evidence of complex interactions. The mixtures tested did not conform to an additive model generated from individual PAH analyses. Many PAHs, even those which caused little or no cytochrome P4501A induction individually, acted in an antagonistic manner in mixtures with more potent inducers. All mixtures lacking chrysene and/or BKF showed markedly lower induction than mixtures containing those compounds. Overall, this approach was a rapid and useful method for identifying Ah active PAHs and describing their interactions in complex mixtures. Such information could proved useful in efforts to understand biological effects of complex mixtures of PAHs in environmental samples.

  8. Effects of fatty acids on benzo[a]pyrene uptake and metabolism in human lung adenocarcinoma A549 cells.

    PubMed

    Barhoumi, Rola; Mouneimne, Youssef; Chapkin, Robert S; Burghardt, Robert C

    2014-01-01

    Dietary supplementation with natural chemoprotective agents is receiving considerable attention because of health benefits and lack of toxicity. In recent in vivo and in vitro experimental studies, diets rich in n-3 polyunsaturated fatty acids have been shown to provide significant anti-tumor action. In this investigation, the effects of control fatty acids (oleic acid (OA), linoleic acid (LA)) and n-3 PUFA, e.g., docosahexaenoic acid (DHA) on the uptake and metabolism of the carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP) was investigated in A549 cells, a human adenocarcinoma alveolar basal epithelial cell line. A549 cells activate BaP through the cytochrome P450 enzyme system to form reactive metabolites, a few of which covalently bind to DNA and proteins. Therefore, multiphoton microscopy spectral analysis combined with linear unmixing was used to identify the parent compound and BaP metabolites formed in cells, in the presence and absence of fatty acids. The relative abundance of select metabolites was associated with altered P450 activity as determined using ethoxyresorufin-O-deethylase activity in cells cultured in the presence of BSA-conjugated fatty acids. In addition, the parent compound within cellular membranes increases significantly in the presence of each of the fatty acids, with the greatest accumulation observed following DHA treatment. DHA treated cells exhibit significantly lower pyrene-like metabolites indicative of lower adducts including DNA adducts compared to control BSA, OA or LA treated cells. Further, DHA reduced the abundance of the proximate carcinogen BaP 7,8-dihydrodiol and the 3-hydroxybenzo[a]pyrene metabolites compared to other treatments. The significant changes in BaP metabolites in DHA treated cells may be mediated by the effects on the physicochemical properties of the membrane known to affect enzyme activity related to phase I and phase II metabolism. In summary, DHA is a highly bioactive chemo

  9. Effects of pentachlorophenol on the detoxification system in white-rumped munia (Lonchura striata).

    PubMed

    Jiang, Peng; Wang, Jianshe; Zhang, Jinguo; Dai, Jiayin

    2016-06-01

    Pentachlorophenol (PCP), a priority pollutant due to its persistence and high toxicity, has been used worldwide as a pesticide and biocide. To understand the adverse effects of PCP, adult male white-rumped munias (Lonchura striata) were orally administrated commercial PCP mixed with corn oil at dosages of 0, 0.05, 0.5, and 5mg/(kg·day) for 42day. Gas chromatography-mass spectrometry (GC-MS) analysis found that PCP was preferentially accumulated in the kidney rather than in the liver and muscle in all exposure groups. To examine the function of CYP1A in pollutant metabolism, we isolated two full-length cDNA fragments (designated as CYP1A4 and CYP1A5) from L. striata liver using reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. PCP induced the expression of CYP1A5, although no obvious change was observed in CYP1A4 expression. Furthermore, PCP significantly elevated the activities of ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase and decreased the activity of benzyloxy-trifluoromethyl-coumarin, with no significant responses observed in benzyloxyresorufin O-debenzylase. PCP induced significant changes in antioxidant enzyme (superoxide dismutase and catalase) activities and malondialdehyde content, but decreased glutathione peroxidase (GSH-Px) and glutathione S-transferase activities and GSH content in the liver of L. striata. The present study demonstrated that PCP had hepatic toxic effects by affecting CYP1As and anti-oxidative status. PMID:27266319

  10. Testing the ecotoxicology of vegetable versus mineral based lubricating oils: 2. Induction of mixed function oxidase enzymes in barramundi, Lates calcarifer, a tropical fish species.

    PubMed

    Mercurio, Philip; Burns, Kathryn A; Cavanagh, Joanne

    2004-05-01

    An increasing number of vegetable-based oils are being developed as environmentally friendly alternatives to petroleum products. However, toxicity towards key tropical marine species has not been investigated. In this study we used laboratory-based biomarker induction experiments to compare the relative stress of a vegetable-based lubricating oil for marine 2-stroke engines with its mineral oil-based counterpart on tropical fish. The sub-lethal stress of 2-stoke outboard lubricating oils towards the fish Lates calcarifer (barramundi) was examined using liver microsomal mixed function oxidase (MFO) induction assays. This study is the first investigation into the use of this key commercial species in tropical North Queensland, Australia in stress assessment of potential hydrocarbon pollution using ethoxyresorufin O-deethylase (EROD) induction. Our results indicated that barramundi provide a wide range of inducible rates of EROD activity in response to relevant organic stressors. The vegetable- and mineral-based lubricants induced significant EROD activity at 1.0 mg kg(-1) and there was no significant difference between the two oil treatments at that concentration. At increasing concentrations of 2 and 3 mg kg(-1), the mineral-based lubricant resulted in slightly higher EROD activity than the vegetable-based lubricant. The EROD activity of control and treated barramundi are found to be within ranges for other species from temperate and tropical environments. These results indicate that vegetable-based lubricants may be less stressful to barramundi than their mineral counterparts at concentrations of lubricant > or =2 mg kg(-1). There is great potential for this species to be used in the biomonitoring of waterways around tropical North Queensland and SE Asia.

  11. Comparative toxicity of acephate in laboratory mice, white-footed mice and meadow voles

    USGS Publications Warehouse

    Rattner, B.A.; Hoffman, D.J.

    1983-01-01

    The LD50 (95% confidence limits) of the organophosphorus insecticide acephate was estimated to be 351, 380, and 321 mg/kg (295?416, 280?516, and 266?388 mg/kg) for CD-1 laboratory mice (Mus musculus), white-footed mice (Peromyscus leucopus noveboracensis), and meadow voles (Microtus pennsylvanicus), respectively. In a second study, these species were provided mash containing 0, 25, 100, and 400 ppm acephate for five days. Brain and plasma cholinesterase activities were reduced in a dose-dependent manner to a similar extent in the three species (inhibition of brain acetyl-cholinesterase averaged for each species ranged from 13 to 22% at 25 ppm, 33 to 42% at 100 ppm, and 56 to 57% at 400 ppm). Mash intake, body or liver weight, plasma enzyme activities (alkaline phosphatase, alanine and aspartate aminotransferase), hepatic enzyme activities (aniline hydroxylase, 7-ethoxycoumarin O-deethylase, and glutathione S-transferase), and cytochrome content (P-450 and b5) were not affected by acephate ingestion, although values differed among species. In a third experiment, mice and voles received 400 ppm acephate for 5 days followed by untreated food for up to 2 weeks. Mean inhibition of brain acetylcholin-esterase for the three species ranged from 47 to 58% on day 5, but by days 12 and 19, activity had recovered to 66 to 76% and 81 to 88% of concurrent control values. These findings indicate that CD-1 laboratory mice, white-footed mice, and meadow voles are equally sensitive to acephate when maintained under uniform laboratory conditions. Several factors (e.g., behavior, food preference, habitat) could affect routes and degree of exposure in the field, thereby rendering some species of wild rodents ecologically more vulnerable to organophosphorus insecticides.

  12. Comparative toxicity of acephate in laboratory mice, white-footed mice, and meadow voles

    USGS Publications Warehouse

    Rattner, B.A.; Hoffman, D.J.

    1984-01-01

    The LD50 (95% confidence limits) of the organophosphorus insecticide acephate was estimated to be 351, 380, and 321 mg/kg (295?416, 280?516, and 266?388 mg/kg) for CD-1 laboratory mice (Mus musculus), white-footed mice (Peromyscus leucopus noveboracensis), and meadow voles (Microtus pennsylvanicus), respectively. In a second study, these species were provided mash containing 0, 25, 100, and 400 ppm acephate for five days. Brain and plasma cholinesterase activities were reduced in a dose-dependent manner to a similar extent in the three species (inhibition of brain acetyl-cholinesterase averaged for each species ranged from 13 to 22% at 25 ppm, 33 to 42% at 100 ppm, and 56 to 57% at 400 ppm). Mash intake, body or liver weight, plasma enzyme activities (alkaline phosphatase, alanine and aspartate aminotransferase), hepatic enzyme activities (aniline hydroxylase, 7-ethoxycoumarin O-deethylase, and glutathione S-transferase), and cytochrome content (P-450 and b5) were not affected by acephate ingestion, although values differed among species. In a third experiment, mice and voles received 400 ppm acephate for 5 days followed by untreated food for up to 2 weeks. Mean inhibition of brain acetylcholin-esterase for the three species ranged from 47 to 58% on day 5, but by days 12 and 19, activity had recovered to 66 to 76% and 81 to 88% of concurrent control values. These findings indicate that CD-1 laboratory mice, white-footed mice, and meadow voles are equally sensitive to acephate when maintained under uniform laboratory conditions. Several factors (e.g., behavior, food preference, habitat) could affect routes and degree of exposure in the field, thereby rendering some species of wild rodents ecologically more vulnerable to organophosphorus insecticides.

  13. In situ exposure history modulates the molecular responses to carbamate fungicide Tattoo in bivalve mollusk.

    PubMed

    Falfushynska, Halina I; Gnatyshyna, Lesya L; Stoliar, Oksana B

    2013-04-01

    The aim of the present study was the investigation of the effect of in situ exposure history on the responses of freshwater mussels to thiocarbamate fungicide. Male bivalve mollusks Anodonta anatina (Unionidae) from polluted (A) and unpolluted (F) sites were subjected to 14 days of exposure to fungicide Tattoo (mixture of propamocarb and mancozeb, 91 μg L(-1)). When unexposed mussels were compared, chronic effect of toxic environment in site A was confirmed by oxidative stress indices (high levels of superoxide dismutase and catalase activities, lipid peroxidation, protein carbonyls and oxyradical production, low level of total glutathione (GSH)), genotoxicity (high levels of DNA-strand breaks and caspase-3 activity in digestive gland), and cytotoxicity (low lysosomal membrane stability in hemocytes), elevated vitellogenin-like proteins (Vtg-LP) concentration in gonads, high levels of Cu, Zn, Cd, metallothionein (MT)-bound metals (MT-Me) and MT-related thiol (MT-SH), and low ethoxyresorufin-O-deethylase (EROD) activity in digestive gland. The major differences in the responses of the two exposed groups were related to antioxidant defense and MT: in the group A, prominent oxidative stress response with the participation of MT-SH and GSH in the gills, EROD activation, but decrease of MT-Me level was shown, whereas in group F exposure provoked the elevation of MT-Me, caspase-3 and Vtg-LP values. Carbamate did not cause cholinesterase depletion and cytotoxicity. However, genotoxic and pro-oxidant effects (increased levels of hemocytes with micronuclei and nuclear abnormalities, DNA-strand breaks and oxyradical in digestive gland), were common responses for both the exposed groups. PMID:23306937

  14. Cytochrome P4501A biomarker indication of oil exposure in harlequin ducks up to 20 years after the Exxon Valdez oil spill

    USGS Publications Warehouse

    Esler, Daniel; Trust, Kimberly A.; Ballachey, Brenda E.; Iverson, Samuel A.; Lewis, Tyler L.; Rizzolo, Daniel; Mulcahy, Daniel M.; Miles, A. Keith; Woodin, Bruce R.; Stegeman, John J.; Henderson, John D.; Wilson, Barry W.

    2010-01-01

    Hydrocarbon-inducible cytochrome P4501A (CYP1A) expression was measured, as ethoxyresorufin-O-deethylase (EROD) activity, in livers of wintering harlequin ducks (Histrionicus histrionicus) captured in areas of Prince William Sound, Alaska, USA, oiled by the 1989 Exxon Valdez spill and in birds from nearby unoiled areas, during 2005 to 2009 (up to 20 years following the spill). The present work repeated studies conducted in 1998 that demonstrated that in harlequin ducks using areas that received Exxon Valdez oil, EROD activity was elevated nearly a decade after the spill. The present findings strongly supported the conclusion that average levels of hepatic EROD activity were higher in ducks from oiled areas than those from unoiled areas during 2005 to 2009. This result was consistent across four sampling periods; furthermore, results generated from two independent laboratories using paired liver samples from one of the sampling periods were similar. The EROD activity did not vary in relation to age, sex, or body mass of individuals, nor did it vary strongly by season in birds collected early and late in the winter of 2006 to 2007, indicating that these factors did not confound inferences about observed differences between oiled and unoiled areas. We interpret these results to indicate that harlequin ducks continued to be exposed to residual Exxon Valdez oil up to 20 years after the original spill. This adds to a growing body of literature suggesting that oil spills have the potential to affect wildlife for much longer time frames than previously assumed.

  15. Effect of honokiol on the induction of drug-metabolizing enzymes in human hepatocytes.

    PubMed

    Cho, Yong-Yeon; Jeong, Hyeon-Uk; Kim, Jeong-Han; Lee, Hye Suk

    2014-01-01

    Honokiol, 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol, an active component of Magnolia officinalis and Magnolia grandiflora, exerts various pharmacological activities such as antitumorigenic, antioxidative, anti-inflammatory, neurotrophic, and antithrombotic effects. To investigate whether honokiol acts as a perpetrator in drug interactions, messenger ribonucleic acid (mRNA) levels of phase I and II drug-metabolizing enzymes, including cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT), and sulfotransferase 2A1 (SULT2A1), were analyzed by real-time reverse transcription polymerase chain reaction following 48-hour honokiol exposure in three independent cryopreserved human hepatocyte cultures. Honokiol treatment at the highest concentration tested (50 μM) increased the CYP2B6 mRNA level and CYP2B6-catalyzed bupropion hydroxylase activity more than two-fold in three different hepatocyte cultures, indicating that honokiol induces CYP2B6 at higher concentrations. However, honokiol treatment (0.5-50 μM) did not significantly alter the mRNA levels of phase I enzymes (CYP1A2, CYP3A4, CYP2C8, CYP2C9, and CYP2C19) or phase II enzymes (UGT1A1, UGT1A4, UGT1A9, UGT2B7, and SULT2A1) in cryopreserved human hepatocyte cultures. CYP1A2-catalyzed phenacetin O-deethylase and CYP3A4-catalyzed midazolam 1'-hydroxylase activities were not affected by 48-hour honokiol treatment in cryopreserved human hepatocytes. These results indicate that honokiol is a weak CYP2B6 inducer and is unlikely to increase the metabolism of concomitant CYP2B6 substrates and cause pharmacokinetic-based drug interactions in humans.

  16. Population-related molecular responses on the effect of pesticides in Carassius auratus gibelio.

    PubMed

    Falfushynska, Halina I; Gnatyshyna, Lesya L; Stoliar, Oksana B

    2012-03-01

    The aim of this study was to evaluate population-related peculiarities of the adaptive responses of Carassius auratus gibelio. In order to do this, male specimens from polluted (B) and clean (Z) sites were exposed to commercial pesticides thiocarbamate Tatoo (9.1 μg·L(-1)and 91 μg·L(-1)) or tetrazine Apollo (2 μg·L(-1) and 10 μg·L(-1)) during fourteen days. The control fish from site B was distinguished by weakness of antioxidant defence (measured from superoxide dismutase and catalase activities, redox index of glutathione (GSH), superoxide anion (O(2)) and lipid peroxidation levels), imbalance of the concentrations of protein metallothionein (MT-SH) and MT-related metals (MT-Me) and neurotoxicity. Differences in glutathione-S-transferase activity in the liver and vitellogenin-like proteins in the serum were also showed between B and Z control groups. Common effects of pesticides were related to a decrease in GSH, an increase in O(2) production, ethoxyresorufin O-deethylase activity and hepatosomatic index. Apollo provoked particular elevation of MT-SH/MT-Me ratio. Population-related difference in the response was the activation of antioxidant defence in fish from site B and its inhibition in fish from site Z. The genotoxic effect of exposures was more expressed in fish from site B. Principal component analysis combine all exposed groups from site Z and control group from site B in one set, and separated each exposed group from site B. The main distinguishing index of each population selected by classification and regression tree analysis was MT-SH.

  17. The selective cytotoxicity of the alkenyl glucosinolate hydrolysis products and their presence in Brassica vegetables.

    PubMed

    Kadir, Nurul H A; David, Rhiannon; Rossiter, John T; Gooderham, Nigel J

    2015-08-01

    Cruciferous vegetable consumption correlates with reduced risk of cancer. This chemopreventative activity may involve glucosinolates and their hydrolysis products. Glucosinolate-derived isothiocyanates have been studied for their toxicity and chemopreventative properties, but other hydrolysis products (epithionitriles and nitriles) have not been thoroughly examined. We report that these hydrolysis products differ in their cytotoxicity to human cells, with toxicity most strongly associated with isothiocyanates rather than epithionitriles and nitriles. We explored mechanisms of this differential cytotoxicity by examining the role of oxidative metabolism, oxidative stress, mitochondrial permeability, reduced glutathione levels, cell cycle arrest and apoptosis. 2-Propenylisothiocyanate and 3-butenylisothiocyanate both inhibited cytochome P450 1A (CYP1A) enzyme activity in CYP expressing MCL-5 cells at high cytotoxic doses. Incubation of MCL-5 cells with non-cytotoxic doses of 2-propenylisothiocyanate for 24h resulted in a dose-dependent inhibition of ethoxyresorufin O-deethylase, yet failed to affect CYP1A1 mRNA expression indicating interference with enzyme activity rather than inhibition of transcription. Increased reactive oxygen species (ROS) production was observed only for 2-propenylisothiocyanate treatment. 2-Propenylisothiocyanate treatment lowered reduced glutathione levels whereas no changes were noted with 3,4-epithiobutylnitrile. Cell cycle analysis showed that 2-propenylisothiocyanate induced a G2/M block whereas other hydrolysis products showed only marginal effects. We found that 2-propenylisothiocyanate and 3-butenylisothiocyanate induced cell death predominantly via necrosis whereas, 3,4-epithiobutylnitrile promoted both necrosis and apoptosis. Thus the activity of glucosinolate hydrolysis products includes cytotoxicity that is compound-class specific and may contribute to their putative chemoprotection properties.

  18. Effect of honokiol on the induction of drug-metabolizing enzymes in human hepatocytes

    PubMed Central

    Cho, Yong-Yeon; Jeong, Hyeon-Uk; Kim, Jeong-Han; Lee, Hye Suk

    2014-01-01

    Honokiol, 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol, an active component of Magnolia officinalis and Magnolia grandiflora, exerts various pharmacological activities such as antitumorigenic, antioxidative, anti-inflammatory, neurotrophic, and antithrombotic effects. To investigate whether honokiol acts as a perpetrator in drug interactions, messenger ribonucleic acid (mRNA) levels of phase I and II drug-metabolizing enzymes, including cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT), and sulfotransferase 2A1 (SULT2A1), were analyzed by real-time reverse transcription polymerase chain reaction following 48-hour honokiol exposure in three independent cryopreserved human hepatocyte cultures. Honokiol treatment at the highest concentration tested (50 μM) increased the CYP2B6 mRNA level and CYP2B6-catalyzed bupropion hydroxylase activity more than two-fold in three different hepatocyte cultures, indicating that honokiol induces CYP2B6 at higher concentrations. However, honokiol treatment (0.5–50 μM) did not significantly alter the mRNA levels of phase I enzymes (CYP1A2, CYP3A4, CYP2C8, CYP2C9, and CYP2C19) or phase II enzymes (UGT1A1, UGT1A4, UGT1A9, UGT2B7, and SULT2A1) in cryopreserved human hepatocyte cultures. CYP1A2-catalyzed phenacetin O-deethylase and CYP3A4-catalyzed midazolam 1′-hydroxylase activities were not affected by 48-hour honokiol treatment in cryopreserved human hepatocytes. These results indicate that honokiol is a weak CYP2B6 inducer and is unlikely to increase the metabolism of concomitant CYP2B6 substrates and cause pharmacokinetic-based drug interactions in humans. PMID:25395831

  19. Effect of honokiol on the induction of drug-metabolizing enzymes in human hepatocytes.

    PubMed

    Cho, Yong-Yeon; Jeong, Hyeon-Uk; Kim, Jeong-Han; Lee, Hye Suk

    2014-01-01

    Honokiol, 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol, an active component of Magnolia officinalis and Magnolia grandiflora, exerts various pharmacological activities such as antitumorigenic, antioxidative, anti-inflammatory, neurotrophic, and antithrombotic effects. To investigate whether honokiol acts as a perpetrator in drug interactions, messenger ribonucleic acid (mRNA) levels of phase I and II drug-metabolizing enzymes, including cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT), and sulfotransferase 2A1 (SULT2A1), were analyzed by real-time reverse transcription polymerase chain reaction following 48-hour honokiol exposure in three independent cryopreserved human hepatocyte cultures. Honokiol treatment at the highest concentration tested (50 μM) increased the CYP2B6 mRNA level and CYP2B6-catalyzed bupropion hydroxylase activity more than two-fold in three different hepatocyte cultures, indicating that honokiol induces CYP2B6 at higher concentrations. However, honokiol treatment (0.5-50 μM) did not significantly alter the mRNA levels of phase I enzymes (CYP1A2, CYP3A4, CYP2C8, CYP2C9, and CYP2C19) or phase II enzymes (UGT1A1, UGT1A4, UGT1A9, UGT2B7, and SULT2A1) in cryopreserved human hepatocyte cultures. CYP1A2-catalyzed phenacetin O-deethylase and CYP3A4-catalyzed midazolam 1'-hydroxylase activities were not affected by 48-hour honokiol treatment in cryopreserved human hepatocytes. These results indicate that honokiol is a weak CYP2B6 inducer and is unlikely to increase the metabolism of concomitant CYP2B6 substrates and cause pharmacokinetic-based drug interactions in humans. PMID:25395831

  20. Biological responses to contaminants in darters (Etheostoma spp.) collected from rural and urban regions of the Grand River, ON, Canada.

    PubMed

    Diamond, Sam R; Sultana, Tamanna; Servos, Mark R; Metcalfe, Chris D

    2016-09-01

    Urban and agricultural activities may introduce chemical stressors, including contaminants of emerging concern (CECs) and current use pesticides (CUPs) into riverine systems. The objective of this study was to determine if fish collected from various sites in the Grand River, ON, Canada show biomarkers of exposure to these classes of contaminants, and if the biomarker patterns vary in fish collected from urbanized and agricultural sites. Female rainbow darters (Etheostoma caeruleum) and female fantail darters (Etheostoma flabellare) were collected from the Grand River in June, 2014 for biomarker analysis from two urbanized sites and three agricultural sites. Over the same period of time, Polar Organic Chemical Integrative Samplers (POCIS) were deployed for 2weeks at each site to monitor for the presence of CUPs and CECs. Data on the liver somatic index for darters indicate site-specific differences in this condition factor (p<0.05). Significant differences in the levels of thiobarbituric acid reactive substances (TBARS) in gill tissue (p<0.05) of darters collected from the various sites indicate site-specific differences in oxidative stress. The activities of ethoxyresorufin-O-deethylase (EROD) in the liver tissue of rainbow darters were significantly different between sites (p<0.05), indicating differences in exposure to chemicals that induce or inhibit CYP450 1A metabolic activity. Finally, acetylcholinesterase (AChE) activity in brain tissue was significantly different between rainbow darters collected from rural and urban sites (p<0.05). These data showing different impacts from chemical inputs related to land uses in the watershed may be useful in developing mitigation strategies to reduce impacts on fish and other aquatic organisms in receiving environments. PMID:26922905

  1. Toxicity of analytically cleaned pentabromodiphenylether after prolonged exposure in estuarine European flounder (Platichthys flesus), and partial life-cycle exposure in fresh water zebrafish (Danio rerio).

    PubMed

    Kuiper, Raoul V; Vethaak, A D; Cantón, Roćio F; Anselmo, Henrique; Dubbeldam, Marco; van den Brandhof, Evert-Jan; Leonards, Pim E G; Wester, Piet W; van den Berg, Martin

    2008-09-01

    Residues of polybrominated diphenylethers (PBDEs), extensively applied as flame retardants, are widely spread in the aquatic environment and biota. The present study investigates effects of the environmentally relevant lower brominated diphenylethers in two fish species in vivo under controlled laboratory conditions. Euryhaline flounder (Platichthys flesus) and freshwater zebrafish (Danio rerio) were exposed to a range of concentrations of a commercial pentabromodiphenylether mixture, DE-71. Chemical analysis of exposed fish showed a pattern of PBDE congeners that was very similar to that in wild fish. The resulting range included environmentally relevant, as well as higher levels. Animals were investigated histopathologically with emphasis on endocrine and reproductive organs. In zebrafish, hatching of embryos and larval development were assessed. Biochemical parameters were investigated in flounder as markers for suggested dioxin-like activity (ethoxyresorufin-O-deethylase=EROD), and activation of endogenous estrogen synthesis (gonad aromatase activity). Thyroid hormones were analyzed in plasma in both species. Benchmark analysis using internal PBDE concentrations showed a mild dose-dependent decrease of hepatic EROD and ovarian aromatase activities, and plasma thyroxin levels in flounder, and an increase of plasma thyroid hormone levels in zebrafish. These trends did not result in statistically significant differences from control fish, and major histopathological changes were not observed. Reproduction in zebrafish appeared to be the most sensitive parameter with statistically significantly reduced larval survival and non-significant indications for decreased egg production at internal levels that were more than 55 times the highest environmental recordings. The present results indicate limited risk for endocrine or reproductive effects of current environmental PBDE contamination in fish.

  2. Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China - A comprehensive perspective.

    PubMed

    Floehr, Tilman; Scholz-Starke, Björn; Xiao, Hongxia; Hercht, Hendrik; Wu, Lingling; Hou, Junli; Schmidt-Posthaus, Heike; Segner, Helmut; Kammann, Ulrike; Yuan, Xingzhong; Roß-Nickoll, Martina; Schäffer, Andreas; Hollert, Henner

    2015-12-15

    The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon receptor (AhR) agonists, have been widely detected in the Yangtze River, but only little research was yet done on AhR-mediated activities. Hence, in order to assess effects of organic pollution, with particular focus on AhR-mediated activities, several sites in the TGR area were examined applying the "triad approach". It combines chemical analysis, in vitro, in vivo and in situ investigations to a holistic assessment. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O-deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and phase II (glutathione-S-transferase) biotransformation enzymes, pollutant metabolites and histopathological alterations were studied in situ in P. vachellii. EROD induction was tested in vitro and in situ to evaluate possible relationships. Two sites, near Chongqing and Kaixian city, were identified as regional hot-spots and further investigated in 2013. The sediments induced in the in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic effects - particularly on the cardiovascular system. These endpoints could be significantly correlated to each other and respective chemical data. However, particle-bound pollutants showed only low bioavailability. The in situ investigations suggested a rather poor condition of P. vachellii, with histopathological alterations in liver and excretory kidney. Fish from Chongqing city exhibited significant hepatic EROD induction and obvious parasitic infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1

  3. Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China - A comprehensive perspective.

    PubMed

    Floehr, Tilman; Scholz-Starke, Björn; Xiao, Hongxia; Hercht, Hendrik; Wu, Lingling; Hou, Junli; Schmidt-Posthaus, Heike; Segner, Helmut; Kammann, Ulrike; Yuan, Xingzhong; Roß-Nickoll, Martina; Schäffer, Andreas; Hollert, Henner

    2015-12-15

    The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon receptor (AhR) agonists, have been widely detected in the Yangtze River, but only little research was yet done on AhR-mediated activities. Hence, in order to assess effects of organic pollution, with particular focus on AhR-mediated activities, several sites in the TGR area were examined applying the "triad approach". It combines chemical analysis, in vitro, in vivo and in situ investigations to a holistic assessment. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O-deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and phase II (glutathione-S-transferase) biotransformation enzymes, pollutant metabolites and histopathological alterations were studied in situ in P. vachellii. EROD induction was tested in vitro and in situ to evaluate possible relationships. Two sites, near Chongqing and Kaixian city, were identified as regional hot-spots and further investigated in 2013. The sediments induced in the in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic effects - particularly on the cardiovascular system. These endpoints could be significantly correlated to each other and respective chemical data. However, particle-bound pollutants showed only low bioavailability. The in situ investigations suggested a rather poor condition of P. vachellii, with histopathological alterations in liver and excretory kidney. Fish from Chongqing city exhibited significant hepatic EROD induction and obvious parasitic infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1

  4. Prenucleosomes and Active Chromatin

    PubMed Central

    Khuong, Mai T.; Fei, Jia; Ishii, Haruhiko; Kadonaga, James T.

    2016-01-01

    Chromatin consists of nucleosomes as well as nonnucleosomal histone-containing particles. Here we describe the prenucleosome, which is a stable conformational isomer of the nucleosome that associates with ~80 bp DNA. Prenucleosomes are formed rapidly upon the deposition of histones onto DNA and can be converted into canonical nucleosomes by an ATP-driven chromatin assembly factor such as ACF. Different lines of evidence reveal that there are prenucleosome-sized DNA-containing particles with histones in the upstream region of active promoters. Moreover, p300 acetylates histone H3K56 in prenucleosomes but not in nucleosomes, and H3K56 acetylation is found at active promoters and enhancers. These findings therefore suggest that there may be prenucleosomes or prenucleosome-like particles in the upstream region of active promoters. More generally, we postulate that prenucleosomes or prenucleosome-like particles are present at dynamic chromatin, whereas canonical nucleosomes are at static chromatin. PMID:26767995

  5. [Physical activity and obesity].

    PubMed

    Winkler, S; Hebestreit, A; Ahrens, W

    2012-01-01

    One reason for the high prevalence of overweight and obesity might be the differences in lifestyle compared to earlier decades, called the "obesogenic environment." With this, the decline in physical activity (PA) in favor of a sedentary lifestyle is assumed to play an important role. Physical activity or inactivity has a major impact on the development of overweight and obesity as well as on certain metabolic disorders. This review summarizes current scientific knowledge regarding the association between PA and overweight/obesity. The term "physical activity" is defined and different methods of its assessment are introduced. In addition, certain methods for the evaluation/operationalization of collected PA data are described. Finally, some epidemiological studies dealing with the associations between PA and overweight/obesity in children/adolescents as well as in adults are presented.

  6. Shared Activity Coordination

    NASA Technical Reports Server (NTRS)

    Clement, Bradley J.; Barrett, Anthony C.

    2003-01-01

    Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. In domains where agents have varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently reach consensus in real time. We briefly describe a largely unexplored class of real-time, distributed planning problems (inspired by interacting spacecraft missions), new challenges they pose, and a general approach to solving the problems. These problems involve self-interested agents that have infrequent communication but collaborate on joint activities. We describe a Shared Activity Coordination (SHAC) framework that provides a decentralized algorithm for negotiating the scheduling of shared activities in a dynamic environment, a soft, real-time approach to reaching consensus during execution with limited communication, and a foundation for customizing protocols for negotiating planner interactions. We apply SHAC to a realistic simulation of interacting Mars missions and illustrate the simplicity of protocol development.

  7. Stochastic optical active rheology

    NASA Astrophysics Data System (ADS)

    Lee, Hyungsuk; Shin, Yongdae; Kim, Sun Taek; Reinherz, Ellis L.; Lang, Matthew J.

    2012-07-01

    We demonstrate a stochastic based method for performing active rheology using optical tweezers. By monitoring the displacement of an embedded particle in response to stochastic optical forces, a rapid estimate of the frequency dependent shear moduli of a sample is achieved in the range of 10-1-103 Hz. We utilize the method to probe linear viscoelastic properties of hydrogels at varied cross-linker concentrations. Combined with fluorescence imaging, our method demonstrates non-linear changes of bond strength between T cell receptors and an antigenic peptide due to force-induced cell activation.

  8. SCOR announces new activities

    NASA Astrophysics Data System (ADS)

    Urban, Edward R., Jr.

    Roger Revelle had many good ideas during his long and productive career. One of them came to fruition in 1957 in the form of the Scientific Committee on Oceanic Research (SCOR), which the International Council for Science created as its first interdisciplinary body, to promote international activities in oceanography. Revelle served as SCOR's first president from 1957 to 1960. SCOR offers opportunities for scientists from different countries to cooperate in planning and executing international programs in ocean sciences. Over its 44 years in existence, SCOR has sponsored 120 working groups and has actively participated in many of the major international oceanographic projects. Thirty-six nations presently participate as SCOR members.

  9. Active cleaning technique device

    NASA Technical Reports Server (NTRS)

    Shannon, R. L.; Gillette, R. B.

    1973-01-01

    The objective of this program was to develop a laboratory demonstration model of an active cleaning technique (ACT) device. The principle of this device is based primarily on the technique for removing contaminants from optical surfaces. This active cleaning technique involves exposing contaminated surfaces to a plasma containing atomic oxygen or combinations of other reactive gases. The ACT device laboratory demonstration model incorporates, in addition to plasma cleaning, the means to operate the device as an ion source for sputtering experiments. The overall ACT device includes a plasma generation tube, an ion accelerator, a gas supply system, a RF power supply and a high voltage dc power supply.

  10. Cosmogenic activation of materials

    SciTech Connect

    Amare, J.; Beltran, B.; Carmona, J.M.; Cebrian, S.; Garcia, E.; Irastorza, I.G.; Gomez, H.; Luzon, G.; Martinez, M.; Morales, J.; Ortiz de Solorzano, A.; Pobes, C.; Puimedon, J.; Rodriguez, A.; Ruz, J.; Sarsa, M. L.; Torres, L.; Villar, J.A.; Capelli, S.; Capozzi, F.

    2005-09-08

    The problem of cosmogenic activation produced at sea level in materials typically used in underground experiments looking for rare events is being studied. Several nuclear data libraries have been screened looking for relevant isotope production cross-sections and different codes which can be applied to activation studies have been reviewed. The excitation functions for some problems of interest like production of 60Co and 68Ge in germanium and production of 60Co in tellurium have been obtained taking into account both measurements and calculations and a preliminary estimate of the corresponding rates of production at sea level has been performed.

  11. Optical activity and evolution.

    PubMed

    Khasanov, M M; Gladyshev, G P

    1980-09-01

    It is noted that the chemical reactions occurring in rarefied cosmic clouds (molecular concentration less than or approximately to 10(2) cm-3) differ from similar laboratory reactions by the much greater effect on the outcome of external force fields. In this light it is hypothesized that the synthesis of optically active substances may occur in the outer space under the conjoint stereospecific effect of a magnetic and other molecule-orienting field. It is further conjectured that the optically active substances of the Solar System had been produced in the course of its formation out of the primal rarefield cloud.

  12. Activated carbon material

    DOEpatents

    Evans, A. Gary

    1978-01-01

    Activated carbon particles for use as iodine trapping material are impregnated with a mixture of selected iodine and potassium compounds to improve the iodine retention properties of the carbon. The I/K ratio is maintained at less than about 1 and the pH is maintained at above about 8.0. The iodine retention of activated carbon previously treated with or coimpregnated with triethylenediamine can also be improved by this technique. Suitable flame retardants can be added to raise the ignition temperature of the carbon to acceptable standards.

  13. Inflammasomes and Their Activation

    PubMed Central

    Khare, Sonal; Luc, Nancy; Dorfleutner, Andrea; Stehlik, Christian

    2011-01-01

    The innate immune system relies on the recognition of pathogens by pattern recognition receptors as a first line of defense and to initiate the adaptive immune response. Substantial progress has been made in defining the role of Nod (nucleotide-binding oligimerization domain)-like receptors and AIM2 (absent in melanoma 2) as pattern recognition receptors that activate inflammasomes in macrophages. Inflammasomes are protein platforms essential for the activation of inflammatory caspases and subsequent maturation of their pro-inflammatory cytokine substrates and induction of pyroptosis. This paper summarizes recent developments regarding the function of Nod-like receptors in immunity and disease. PMID:21083527

  14. Space construction activities

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The Center for Space Construction at the University of Colorado at Boulder was established in 1988 as a University Space Engineering Research Center. The mission of the Center is to conduct interdisciplinary engineering research which is critical to the construction of future space structures and systems and to educate students who will have the vision and technical skills to successfully lead future space construction activities. The research activities are currently organized around two central projects: Orbital Construction and Lunar Construction. Summaries of the research projects are included.

  15. Active seismic experiment

    NASA Technical Reports Server (NTRS)

    Kovach, R. L.; Watkins, J. S.; Talwani, P.

    1972-01-01

    The Apollo 16 active seismic experiment (ASE) was designed to generate and monitor seismic waves for the study of the lunar near-surface structure. Several seismic energy sources are used: an astronaut-activated thumper device, a mortar package that contains rocket-launched grenades, and the impulse produced by the lunar module ascent. Analysis of some seismic signals recorded by the ASE has provided data concerning the near-surface structure at the Descartes landing site. Two compressional seismic velocities have so far been recognized in the seismic data. The deployment of the ASE is described, and the significant results obtained are discussed.

  16. [Adolescents' physical activity].

    PubMed

    Pagaeva, E K; Misho, P -A; Zhanin, A; Chanturishvili, T P; Pagaeva, K I

    2006-01-01

    The paper defines the parameters reflecting the physical activity of adolescents and their correlation with health and a risk of behavioral disorders, bad habits, and cravings. A total of 9499 Georgian adolescents aged 14-18 years, the senior (9th-llth-form) pupils, selected through two-step cluster sampling were surveyed. The pupils anonymously filled in special questionnaires. This yielded the parameters reflecting the intensity of physical activity of the adolescents and the latter's going in for sports. The parameters were shown to have a beneficial effect on health, including mental health, and on the magnitude of unhealthy behavior.

  17. EPAct Transportation Regulatory Activities

    SciTech Connect

    2011-11-21

    The U.S. Department of Energy's (DOE) Vehicle Technologies Program manages several transportation regulatory activities established by the Energy Policy Act of 1992 (EPAct), as amended by the Energy Conservation Reauthorization Act of 1998, EPAct 2005, and the Energy Independence and Security Act of 2007 (EISA).

  18. Active-bridge oscillator

    DOEpatents

    Wessendorf, Kurt O.

    2001-01-01

    An active bridge oscillator is formed from a differential amplifier where positive feedback is a function of the impedance of one of the gain elements and a relatively low value common emitter resistance. This use of the nonlinear transistor parameter h stabilizes the output and eliminates the need for ALC circuits common to other bridge oscillators.

  19. Antifungal activity of diethyldithiocarbamate.

    PubMed

    Allerberger, F; Reisinger, E C; Söldner, B; Dierich, M P

    1989-10-01

    Sodium diethyldithiocarbamate (DTC) was evaluated for its ability to combat four different species of fungi in vitro. Using a microtiter-broth-dilution method we were able to demonstrate an antifungal activity against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Mucor mucedo in doses achievable by intravenous administration in man.

  20. Activities of the ILO.

    ERIC Educational Resources Information Center

    Labour Education, 1986

    1986-01-01

    Discusses the Workers' Education Branch of the ILO (International Labour Organisation), which has been developing workers' education activities in Africa, Asia, and Latin America for the purpose of assisting rural workers' organizations in identifying and developing plans to overcome their own major organizational and financial problems. (CT)

  1. Activities of the ILO.

    ERIC Educational Resources Information Center

    Enevoldsen, Niels; And Others

    1981-01-01

    A series of articles reviews educational activities of the International Labour Organisation (ILO), including international seminars on workers' education, a study of women workers, trade union training courses at the ILO Turin Centre, and the importance of information dissemination to trade unions. (SK)

  2. Valuing Families. Activity Guide.

    ERIC Educational Resources Information Center

    Glashagel, Jerry; Glashagel, Char

    Developed as a resource for family life education, this activity guide can be used to lead experiential learning situations for intergenerational groups by a counselor, in a course, in a family organization like the YMCA, or in the home. The goals of this guide are to increase the self-esteem of each person and to strengthen the family as a human…

  3. Classroom Speaking Activities.

    ERIC Educational Resources Information Center

    Shuying, Yang

    1999-01-01

    Because most language teaching in China is focused on national tests, language is treated as a knowledge subject and development of communicative abilities is often ignored. This article describes activities that one English-as-a-Foreign-Language teacher used to teach oral English to university students in China. (Author/VWL)

  4. Ocean Drilling Simulation Activity.

    ERIC Educational Resources Information Center

    Telese, James A.; Jordan, Kathy

    The Ocean Drilling Project brings together scientists and governments from 20 countries to explore the earth's structure and history as it is revealed beneath the oceans' basins. Scientific expeditions examine rock and sediment cores obtained from the ocean floor to learn about the earth's basic processes. The series of activities in this…

  5. Physical Education Activities

    ERIC Educational Resources Information Center

    Russo, Letty P.

    1978-01-01

    Described are three physical activity games designed to help young children develop a sense of mastery over their bodies: (which will in turn improve their self concepts): a poem to be acted out, Simon Says, and a story play to be acted out. (DLS)

  6. Sexual activity and aging.

    PubMed

    Ni Lochlainn, Mary; Kenny, Rose Anne

    2013-08-01

    Sexuality is an important component of emotional and physical intimacy that men and women experience throughout their lives. Research suggesting that a high proportion of men and women remain sexually active well into later life refutes the prevailing myth that aging and sexual dysfunction are inexorably linked. Age-related physiological changes do not render a meaningful sexual relationship impossible or even necessarily difficult. Many of these physiological changes are modifiable. There are various therapeutic options available to patients to achieve maximum sexual capacity in old age. This article reviews the prevalence of sexual activity among older adults, the problems these adults encounter with sexual activity, and the role of the health care professional in addressing these problems. The physiological sex-related changes that occur as part of the normal aging process in men and women are reviewed, as well as the effect of age-related physical and psychological illness on sexual function. The attitudes and perceptions of the media and general public toward sexual activity and aging are summarized. An understanding of the sexual changes that accompany the aging process may help general practitioners and other doctors to give practical and useful advice on sexuality as well as refute the misconception that aging equates to celibacy. A thorough awareness of this aspect of older people's quality of life can raise meaningful expectations for aging patients. PMID:23540950

  7. Discovering Columbus: Classroom Activities.

    ERIC Educational Resources Information Center

    Moulden, Rick

    1992-01-01

    Presents learning activities concerning Christopher Columbus and his voyages. Includes lessons requiring students to (1) write a pledge of allegiance to the world; (2) examine the Americas before Columbus; (3) prepare a newscast on Columbus' arrival in the Americas; (4) imagine being a Native American encountering Columbus; and (5) explore what…

  8. Nutrition. Learning Activity Package.

    ERIC Educational Resources Information Center

    Lee, Carolyn

    This learning activity package on nutrition is one of a series of 12 titles developed for use in health occupations education programs. Materials in the package include objectives, a list of materials needed, a list of definitions, information sheets, reviews (self evaluations) of portions of the content, and answers to reviews. These topics are…

  9. Highlights of 1978 activities

    NASA Technical Reports Server (NTRS)

    1978-01-01

    General highlights of NASA's activities for 1978 are presented. The highlights are categorized into topics such as space science, space transportation systems, space and terrestrial applications, environment, technology utilization, aeronautics, space research and technology, energy programs, and international. A list of the 1978 launches including: (1) launch date; (2) payload designation; (3) launch vehicle; (4) launch site and (5) mission remarks is also presented.

  10. Arsenic activation neutron detector

    DOEpatents

    Jacobs, E.L.

    1980-01-28

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5-MeV neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  11. Arsenic activation neutron detector

    DOEpatents

    Jacobs, Eddy L.

    1981-01-01

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5 Mev neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  12. Activating silent argonautes.

    PubMed

    Kidwell, Mary Anne; Doudna, Jennifer A

    2013-07-01

    Multiple Argonaute proteins are implicated in gene silencing by RNA interference (RNAi), but only one is known to be an endonuclease that can cleave target mRNAs. Chimeric Argonaute proteins now reveal an unexpected mechanism by which mutations distal to the catalytic center can unmask intrinsic catalytic activity, results hinting at structurally mediated regulation. PMID:23984440

  13. Highlights of 1976 activities

    NASA Technical Reports Server (NTRS)

    Fitzpatrick, M.

    1976-01-01

    Highlights of NASA's 1976 activities are summarized. Sixteen successful launches were made. Two landings of Viking spacecraft on Mars and rollout of the space shuttle orbiter are reviewed. Applications of aerospace science to education, health care, and community services are also discussed.

  14. Educating for Political Activity

    ERIC Educational Resources Information Center

    Chitty, Clyde

    2010-01-01

    The term "political activity" can be interpreted in a myriad of different ways, but in this paper, it is taken to mean involvement in a variety of campaigns around issues affecting the way we live and the sort of society we want to live in. At a time when support for the main political parties has never been weaker, it is essential that teachers…

  15. Geology: The Active Earth.

    ERIC Educational Resources Information Center

    Braus, Judy, Ed.

    1987-01-01

    Ranger Rick's NatureScope is a creative education series dedicated to inspiring in children an understanding and appreciation of the natural world while developing the skills they will need to make responsible decisions about the environment. The topic of this issue is "Geology: The Active Earth." Contents are organized into the following…

  16. Environmental Chemistry Activities.

    ERIC Educational Resources Information Center

    Jackland, Thomas; And Others

    The authors of this curriculum supplement believe in a laboratory approach to chemistry and express the feeling that environmental chemistry provides the students an opportunity to apply theoretical chemistry to important practical problems. There are eighteen activities presented, each accompanied with behavioral objectives, one or more suggested…

  17. Regional Activities Division. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on library network activities in Canada, the Third World, Japan, Malaysia, Brazil, and Sweden which were presented at the 1982 International Federation of Library Associations (IFLA) conference include: (1) "Canada: A Voluntary and Flexible Network," a review by Guy Sylvestre of the political, social, and economic structures affecting…

  18. Classification of Physical Activity

    PubMed Central

    Turksoy, Kamuran; Paulino, Thiago Marques Luz; Zaharieva, Dessi P.; Yavelberg, Loren; Jamnik, Veronica; Riddell, Michael C.; Cinar, Ali

    2015-01-01

    Physical activity has a wide range of effects on glucose concentrations in type 1 diabetes (T1D) depending on the type (ie, aerobic, anaerobic, mixed) and duration of activity performed. This variability in glucose responses to physical activity makes the development of artificial pancreas (AP) systems challenging. Automatic detection of exercise type and intensity, and its classification as aerobic or anaerobic would provide valuable information to AP control algorithms. This can be achieved by using a multivariable AP approach where biometric variables are measured and reported to the AP at high frequency. We developed a classification system that identifies, in real time, the exercise intensity and its reliance on aerobic or anaerobic metabolism and tested this approach using clinical data collected from 5 persons with T1D and 3 individuals without T1D in a controlled laboratory setting using a variety of common types of physical activity. The classifier had an average sensitivity of 98.7% for physiological data collected over a range of exercise modalities and intensities in these subjects. The classifier will be added as a new module to the integrated multivariable adaptive AP system to enable the detection of aerobic and anaerobic exercise for enhancing the accuracy of insulin infusion strategies during and after exercise. PMID:26443291

  19. Physical Activities for Preschool.

    ERIC Educational Resources Information Center

    Adkins, Dorothy C.; And Others

    The underlying premise of the University of Hawaii Physical Activities for Preschool curriculum is that important contributions to a positive self-concept are made by motor independence and a realistic body image. Program objectives include: (1) the development of strength, endurance, and flexibility in skills that involve the muscles,…

  20. Shark Tagging Activities.

    ERIC Educational Resources Information Center

    Current: The Journal of Marine Education, 1998

    1998-01-01

    In this group activity, children learn about the purpose of tagging and how scientists tag a shark. Using a cut-out of a shark, students identify, measure, record data, read coordinates, and tag a shark. Includes introductory information about the purpose of tagging and the procedure, a data sheet showing original tagging data from Tampa Bay, and…