Species differences in biliary excretion of benzo[a]pyrene

International Nuclear Information System (INIS)

Weyand, E.H.; Bevan, D.R.

1986-01-01

Biliary excretion of benzo[a]pyrene (B[a]P) was investigated in rats, hamsters, and guinea pigs following intratracheal administration. [ 3 H]-B[a]P, in amounts of approximately 150 ng or 350 μg, was instilled into lungs and amounts of radioactivity excreted in bile were monitored for six hrs following administration. Differences in biliary excretion of [ 3 H]-B[a]P and/or metabolites among species were observed at low doses but not at high doses. Six hours after instillation of a low dose of B[a]P, 70, 54, and 62% of the dose was excreted in bile of rats, hamsters, and guinea pigs, respectively. Upon administration of the higher dose of B[a]P, approximately 50% of the dose was excreted in bile in six hrs by all species. Thus, rats and guinea pigs exhibit differences in biliary excretion of low and high doses of B[a]P whereas hamsters do not. Profiles of phase II metabolites in rats and hamsters were similar at both low and high doses, with the majority of metabolites being glucuronides and thioether conjugates. However, differences in relative amounts of these conjugates were observed between the two doses, with a shift towards a greater proportion of glucuronides at the higher dose. Metabolites in bile from guinea pigs were primarily thioether conjugates, which accounted for 88% of metabolites at the low dose and 95% at the high dose

S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV

DEFF Research Database (Denmark)

Mortensen, R. W.; Corcoran, O.; Cornett, Claus

2001-01-01

Acyl-migrated isomers of drug beta -1-O-acyl glucuronides have been implicated in drug toxicity because they can bind to proteins. The acyl migration and hydrolysis of S-naproxen-beta -1-O-acyl glucuronide (S-nap-g) was followed by dynamic stopped-flow HPLC-H-1 NMR and HPLC methods. Nine first or...

FRET based integrated pyrene-AgNPs system for detection of Hg (II) and pyrene dimer: Applications to environmental analysis

Science.gov (United States)

Walekar, Laxman S.; Hu, Peidong; Vafaei Molamahmood, Hamed; Long, Mingce

2018-06-01

The integrated system of pyrene and cetyltrimethyl ammonium bromide (CTAB) capped silver nanoparticles (AgNPs) with a distance (r) of 2.78 nm has been developed for the detection of Hg (II) and pyrene dimer. The interaction between pyrene and AgNPs results in the fluorescence quenching of pyrene due to the energy transfer, whose mechanism can be attributed to the Forster Resonance Energy Transfer (FRET) supported by experimental observation and theoretical calculations. The developed probe shows a highly selective and sensitive response towards Hg (II) probably due to the amalgam formation, which results in the fluorescence recovery (90%) of pyrene and color change of solution from yellowish brown to colorless. The addition of Hg (II) may increase the distance between pyrene and AgNPs undergoes the 'FRET OFF' process. This system gives a selective response towards Hg (II) over other competing metal ions. Under the optimal condition, the system offers good linearity between 0.1 and 0.6 μg mL-1 with a detection limit of 62 ng mL-1. In addition, the system also provides an effective platform for detection of pyrene in its dimer form even at very low concentrations (10 ng mL-1) on the surface of AgNPs. Therefore, it could be used as effective alternatives for the detection of Hg (II) as well as pyrene simultaneously.

Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows.

Science.gov (United States)

Schwartz-Zimmermann, Heidi E; Hametner, Christian; Nagl, Veronika; Fiby, Iris; Macheiner, Lukas; Winkler, Janine; Dänicke, Sven; Clark, Erica; Pestka, James J; Berthiller, Franz

2017-12-01

The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC-MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of

Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism.

Science.gov (United States)

Gan, Jinping; Chen, Weiqi; Shen, Hong; Gao, Ling; Hong, Yang; Tian, Yuan; Li, Wenying; Zhang, Yueping; Tang, Yuwei; Zhang, Hongjian; Humphreys, William Griffith; Rodrigues, A David

2010-12-01

To further explore the mechanism underlying the interaction between repaglinide and gemfibrozil, alone or in combination with itraconazole. Repaglinide metabolism was assessed in vitro (human liver subcellular fractions, fresh human hepatocytes, and recombinant enzymes) and the resulting incubates were analyzed, by liquid chromatography-mass spectrometry (LC-MS) and radioactivity counting, to identify and quantify the different metabolites therein. Chemical inhibitors, in addition to a trapping agent, were also employed to elucidate the importance of each metabolic pathway. Finally, a panel of human liver microsomes (genotyped for UGT1A1*28 allele status) was used to determine the importance of UGT1A1 in the direct glucuronidation of repaglinide. The results of the present study demonstrate that repaglinide can undergo direct glucuronidation, a pathway that can possibly contribute to the interaction with gemfibrozil. For example, [³H]-repaglinide formed glucuronide and oxidative metabolites (M2 and M4) when incubated with primary human hepatocytes. Gemfibrozil effectively inhibited (∼78%) both glucuronide and M4 formation, but had a minor effect on M2 formation. Concomitantly, the overall turnover of repaglinide was also inhibited (∼80%), and was completely abolished when gemfibrozil was co-incubated with itraconazole. These observations are in qualitative agreement with the in vivo findings. UGT1A1 plays a significant role in the glucuronidation of repaglinide. In addition, gemfibrozil and its glucuronide inhibit repaglinide glucuronidation and the inhibition by gemfibrozil glucuronide is time-dependent. Inhibition of UGT enzymes, especially UGT1A1, by gemfibrozil and its glucuronide is an additional mechanism to consider when rationalizing the interaction between repaglinide and gemfibrozil. © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

Science.gov (United States)

Gill, Katherine L; Houston, J Brian; Galetin, Aleksandra

2012-04-01

Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CL(int, UGT)) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CL(int, UGT) on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CL(int, UGT) in different tissues. Although BSA increased CL(int, UGT) in all tissues, the extent was tissue- and drug-dependent. Scaled CL(int, UGT) in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min(-1) · g tissue(-1) in liver, kidney, and intestinal microsomes. Renal CL(int, UGT) (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CL(int, UGT) for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CL(int, UGT) (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CL(int, UGT) is particularly important for UGT1A9 substrates.

Removal of pyrene and benzo(a)pyrene micropollutant from water via adsorption by green synthesized iron oxide nanoparticles

Science.gov (United States)

Hassan, Saad S. M.; Abdel-Shafy, Hussein I.; Mansour, Mona S. M.

2018-03-01

Polycyclic aromatic hydrocarbons (PAHs) in water are classified as organic micropollutants, which are carcinogenic even in very low concentration (ppb). In this study the green synthesized iron oxide nanoparticles (IONPs) were green synthesized at room temperature by using pomegranate peel extract. The green synthesized IONPs were used for adsorbing benzo(a)pyrene and pyrene (PAHs) from water. Factors affecting the adsorption were investigated. These factors are: nanoparticles dose, pH, temperature, and initial concentration of PAHs. The overall results showed that the maximum adsorption capacities of IONPs towards pyrene and benzo(a)pyrene were 2.8 and 0.029 mg g-1, respectively. The thermodynamic study indicated an exothermic adsorption process of pyrene and benzo(a)pyrene. The kinetic and isotherm studies were carried out. The obtained data revealed that the adsorption process follows a pseudo-second order mechanism and obeys Langmuir isotherm model. In addition, the IONPs proved to be a potential candidate for the adsorption of pyrene and benzo(a)pyrene even after five cycles of use and regeneration. The investigation was extended using semi-pilot plant to remove the studied PAHs from artificially contaminated water. The results showed that the IONPs was capable to remove the pyrene and benzo (a) pyrene at the rate of 98.5 and 99%, respectively. It also can be used as disinfectant.

Direct radioimmunoassay of urinary estrogen and pregnanediol glucuronides during the menstrual cycle

Energy Technology Data Exchange (ETDEWEB)

Stanczyk, F.Z.; Miyakawa, I.; Goebelsmann, U.

1980-06-15

Assays measuring immunoreactive estrone glucuronide (E/sub 1/G), estradiol-3-glucuronide (E/sub 2/-3G), estradiol-17..beta..-glucuronide (E/sub 2/-17G), estriol-3-glucuronide (E/sub 3/-3G), estriol-16..cap alpha..-glucuronide (E/sub 3/-16G), and pregnanediol-3..cap alpha..-glucuronide (Pd-3G) directly in diluted urine were developed and validated. These estrogen and pregnanediol glucuronide fractions were measured in aliquots of 24-hour and overnight samples of urine collected daily from seven women for one menstrual cycle. Urinary hormone excretion was correlated with daily serum estradiol (E/sub 2/), progesterone (P), and lutenizing hormonee (LH) levels. A sharp midcycle LH peak preceded by a preovulatory rise in serum E/sub 2/ and followed by luteal phase serum P levels were noted in each of the seven apparently ovulatory cycles. Twenty-four-hour and overnight urinary excretion patterns of estrogen glucuronides were similar to those of serum E/sub 2/. Of the five estrogen glucuronide fractions tested, excretion of E/sub 2/-17G exhibited the earliest and steepest ascending slope of the preovulatory estrogen surge and correlated best with serum E/sub 2/ levels. Urinary excretion of E/sub 1/-G, E/sub 2/-3G, and E/sub 3/-16G also showed an early and steep preovulatory rise and preceded that of E/sub 3/-3G, whereas urinary excretion of E/sub 3/-3G exhibited the poorest correlation with serum E/sub 2/ concentrations. The urinary excretion of Pd-3G rose parallel to serum P levels and was markedly elevated 2 to 3 days after the midcycle LH peak in both 24-hour and overnight collections of urine. These results indicate that among the urinary estrogen conjugate fractions tested, E/sub 2/-17G is the one that most suitably predicts ovulation.

Direct radioimmunoassay of urinary estrogen and pregnanediol glucuronides during the menstrual cycle

International Nuclear Information System (INIS)

Stanczyk, F.Z.; Miyakawa, I.; Goebelsmann, U.

1980-01-01

Assays measuring immunoreactive estrone glucuronide (E 1 G), estradiol-3-glucuronide (E 2 -3G), estradiol-17β-glucuronide (E 2 -17G), estriol-3-glucuronide (E 3 -3G), estriol-16α-glucuronide (E 3 -16G), and pregnanediol-3α-glucuronide (Pd-3G) directly in diluted urine were developed and validated. These estrogen and pregnanediol glucuronide fractions were measured in aliquots of 24-hour and overnight samples of urine collected daily from seven women for one menstrual cycle. Urinary hormone excretion was correlated with daily serum estradiol (E 2 ), progesterone (P), and lutenizing hormonee (LH) levels. A sharp midcycle LH peak preceded by a preovulatory rise in serum E 2 and followed by luteal phase serum P levels were noted in each of the seven apparently ovulatory cycles. Twenty-four-hour and overnight urinary excretion patterns of estrogen glucuronides were similar to those of serum E 2 . Of the five estrogen glucuronide fractions tested, excretion of E 2 -17G exhibited the earliest and steepest ascending slope of the preovulatory estrogen surge and correlated best with serum E 2 levels. Urinary excretion of E 1 -G, E 2 -3G, and E 3 -16G also showed an early and steep preovulatory rise and preceded that of E 3 -3G, whereas urinary excretion of E 3 -3G exhibited the poorest correlation with serum E 2 concentrations. The urinary excretion of Pd-3G rose parallel to serum P levels and was markedly elevated 2 to 3 days after the midcycle LH peak in both 24-hour and overnight collections of urine. These results indicate that among the urinary estrogen conjugate fractions tested, E 2 -17G is the one that most suitably predicts ovulation

Sublethal toxicity and biotransformation of pyrene in Lumbriculus variegatus (Oligochaeta)

International Nuclear Information System (INIS)

Maeenpaeae, K.; Leppaenen, M.T.; Kukkonen, J.V.K.

2009-01-01

The aim of this work was to study the toxicity and biotransformation of polyaromatic hydrocarbon (PAH) pyrene in the oligochaete aquatic worm, Lumbriculus variegatus. PAHs are ubiquitous environmental pollutants that pose a hazard to aquatic organisms, and metabolizing capability is poorly known in the case of many invertebrate species. To study the toxicity and biotransformation of pyrene, the worm was exposed for 15 days to various concentrations of water-borne pyrene. The dorsal blood vessel pulse rate was used as a sublethal endpoint. Pyrene biotransformation by L. variegatus was studied and the critical body residues (CBR) were estimated for pyrene toxicity. The toxicokinetics of pyrene uptake was evaluated. A combination of radiolabeled ( 14 C) and nonlabeled pyrene was used in the exposures, and liquid scintillation counting (LSC) and high-pressure liquid chromatography were employed in both water and tissue residue analyses. The results showed that L. variegatus was moderately able to metabolize pyrene to 1-hydroxypyrene (1-HP), thus demonstrating that the phase-I-like oxidizing enzyme system metabolizes pyrene in L. variegatus. The amount of the 1-HP was 1-2% of the amount of pyrene in the worm tissues. The exposure to pyrene reduced the blood vessel pulse rate significantly (p < 0.05), showing that pyrene had a narcotic effect. The estimated CBRs remained constant during the exposure time, varying from 0.120 to 0.174 mmol pyrene/kg worm wet weight. The bioconcentration factors (BCF) decreased as exposure concentration increased. It was suggested that the increased toxicity of pyrene accounted for the decrease in BCFs by lowering the activity of the organism

Ultraviolet Radiation Increases the Toxicity of Pyrene, 1-Aminopyrene and 1-Hydroxypyrene to Human Keratinocytes

Directory of Open Access Journals (Sweden)

Huey-Min Hwang

2005-04-01

Full Text Available Over the past several years, a great deal of interest has been focused on the harmful effects of ultraviolet (UV radiation to human skin. UV light has been implicated in aging, sunburn and skin cancer. Few studies, however, have been done to determine the effects that UV light, in conjunction with other environmental contaminants, may have on human skin. Polycyclic Aromatic Hydrocarbons (PAHs are a class of compounds that have been reported to be toxic, mutagenic and carcinogenic to many eukaryotic organisms. UV light is also known to increase the toxicity of PAHs through photo-activation and photo-modification. The purpose of this study was to assess the effects of UV-A irradiated pyrene (Pyr, 1-aminopyrene (1-AP and 1-hydroxypyrene (1-HP on human keratinocytes, the skin primary site of UV irradiated PAH exposure. Our findings indicate that simultaneous treatment of human keratinocyte cell line, HaCaT, with 1.0μg/ml pyrene, 1-AP or 1-HP and 3.9 J/cm2/min UV-A light resulted in significant inhibition of cell proliferation. Approximately 100% of the cells died in the case of UV-A irradiated 1-AP and 1-HP. In the case of UV-A irradiated pyrene, more than 70% of the cells died, indicating that UV-A is able to transform these PAHs into more harmful intermediates.

Effects of Nereis diversicolor on the Transformation of 1-Methylpyrene and Pyrene

DEFF Research Database (Denmark)

Malmquist, Linus Mattias Valdemar; Christensen, Jan Henning; Selck, Henriette

and quantitative analyses of metabolites and parent compounds in worm tissue, water, and sediment were performed. Transformation of 1-methylpyrene generated the benzylic hydroxylated phase I product, 1-pyrenecarboxylic acid that comprised 90% of the total metabolites of 1-methylpyrene, and was mainly found......Transformation of nonsubstituted and alkyl-substituted polycyclic aromatic hydrocarbons (PAHs) by the benthic invertebrate Nereis diversicolor was compared in this study. Pyrene and 1-methylpyrene were used as model compounds for nonsubstituted and alkyl-substituted PAHs, respectively. Qualitative...... as the most prominent metabolite. Transformation of 1-methylpyrene (21% transformed) was more than 3 times as efficient as pyrene transformation (5.6% transformed). Because crude oils contain larger amounts of C1−C4-substituted PAHs than nonsubstituted PAHs, the rapid and efficient transformation of sediment...

Effects of Nereis diversicolor on the transformation of 1-Methylpyrene and Pyrene

DEFF Research Database (Denmark)

Malmquist, Linus Mattias Valdemar; Christensen, Jan H.; Selck, Henriette

2013-01-01

and quantitative analyses of metabolites and parent compounds in worm tissue, water, and sediment were performed. Transformation of 1-methylpyrene generated the benzylic hydroxylated phase I product, 1-pyrenecarboxylic acid that comprised 90% of the total metabolites of 1-methylpyrene, and was mainly found......Transformation of nonsubstituted and alkyl-substituted polycyclic aromatic hydrocarbons (PAHs) by the benthic invertebrate Nereis diversicolor was compared in this study. Pyrene and 1-methylpyrene were used as model compounds for nonsubstituted and alkyl-substituted PAHs, respectively. Qualitative...... as the most prominent metabolite. Transformation of 1-methylpyrene (21% transformed) was more than 3 times as efficient as pyrene transformation (5.6% transformed). Because crude oils contain larger amounts of C1−C4-substituted PAHs than nonsubstituted PAHs, the rapid and efficient transformation of sediment...

Radioimmunoassay of estriol-16-glucuronide using tritiated and radioiodinated radioligands: direct radioimmunoassay of urinary estriol-16-glucuronide during the menstrual cycle

International Nuclear Information System (INIS)

Stanczyk, F.Z.; Miyakawa, I.; Soares, J.R.; Goebelsmann, U.

1979-01-01

Estriol-16-glucuronide-[ 125 I]-iodohistamine (E 3 -16G-[ 125 ]) was prepared and utilized in a radioimmunoassay (RIA) in conjunction with anti-estriol-16-glucuronide-bovine serum albumin (E 3 -16G-BSA) serum (RIA No.1). This RIA was then compared with two other RIA methods employing [ 3 H]-labeled estriol-16-glucuronide (E 3 -16G) together with either anti-E 3 -16G-BAS serum (RIA No.2) or anti-estriol-16-glucuronide-2-azobenzoic acid-bovine serum albumin (E 3 -16G-2-BSA) serum (RIA No. 3). All three RIA's were accurate and precise, however, they differed in assay sensitivity and specificity. Most sensitive was RIA No.1 and least sensitive was RIA No.3. Both RIA's No.1 and 2 were less specific than RIA No.3. since unconjugated estriol and estrone 3-sulfate exhibited large and comparable cross-reactions in RIA's No.1 and 2, averaging 50% and 41% respectively. Furthermore, measurement of E 3 -16G in 10 different urine aliquots collected from non-pregnant women employing RIA's No. 1-3 showed that RIA's No. 1 and 2 yielded comparable results, however, the results obtained by RIA No.3 were, on the average, 26% lower than the mean of the values measured with RIA's No. 1 and 2. Consequently, RIA Bo.3 was used to measure daily 24-hour urinary E 3 -16G excretion in 7 women throughout an entire menstrual cycle. These data are in agreement with colorimetric and fluorimetric estimates of 24-h urinary estriol values throughout the menstrual cycle. The perovulatory rise of urinary E 3 -16G excretion, as quantitated by this RIA, is comparable to that of serum estradiol measured in the same 7 women, but peaks 1 to 2 days later than the serum estradiol surge. (author)

Patterns of 1-hydroxypyrene excretion in volunteers exposed to pyrene by the dermal route

Energy Technology Data Exchange (ETDEWEB)

Viau, C.; Vyskocil, A. [University of Montreal, Montreal, PQ (Canada)

1995-02-24

The urinary excretion profiles following exposure to pyrene were established in one psoriasic patient under treatment with a coal tar-based shampoo and in two other volunteers exposed to a single dose of 100{mu}1 creosote and, in a separate experiment, to five consecutive daily dermal applications of 500{mu}g pyrene on 200 cm{sup 2} of the inner face of the forearms. Timed micturitions were collected for up to 48 h following exposure. Both in the psoriasic patient and in the volunteers exposed to creosote, the excretion peaks between 10 and 15 h after application and first-order apparent half lives of 11.5-15 h can be calculated for the elimination phase. Compatible with these observations, repeated exposure to pyrene in the volunteers causes an increase in peak and trough urinary 1-hydroxypyrene (1-OHP) values for the first few days following the first exposure. These results suggest that the difference between beginning-of-shift/beginning of work week and beginning-of-shift/end of work week 1-OHP excretion should reflect the average exposure of the week in workers having a constant exposure to pyrene. The difference between the beginning and end-of-shift excretion values of a given day should reflect the exposure of that day but the maximum excretion would be attained a few hours after termination of exposure.

UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: I. Identification of polymorphisms in the 5'-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation.

Science.gov (United States)

Krishnaswamy, Soundararajan; Hao, Qin; Al-Rohaimi, Abdul; Hesse, Leah M; von Moltke, Lisa L; Greenblatt, David J; Court, Michael H

2005-06-01

UDP glucuronosyltransferase (UGT) 1A6 is a major isoform in human liver that glucuronidates numerous drugs, toxins, and endogenous substrates with high interindividual variability. The molecular basis for this variability remains unknown, although it likely involves genetic and environmental factors. Phenotype-genotype studies were conducted using a well characterized human liver bank (n = 54) and serotonin glucuronidation as a UGT1A6-specific phenotype marker. A positive moderate-to-heavy alcohol use history (>14 drinks per week) was the only demographic factor examined that correlated with phenotype and was associated with 2-fold higher serotonin glucuronidation (p g, -1310del5, and -652g-->a). Initial univariate analyses did not identify any significant phenotype-genotype associations. However, in livers without substantial alcohol exposure, 50% lower UGT1A6 mRNA levels (p = 0.026) were found in carriers of the linked S7A-enhancer polymorphisms compared with noncarriers but without significant effect on UGT1A6 protein content or glucuronidation activities. Three major haplotypes, including (*)1A (reference), (*)1B (-1535g-->a and -427g-->c), and (*)2 (-1710c-->g, -1310del5, -652g-->a, S7A, T181A, and R184S), were identified, accounting for 90% of alleles. No association of haplotype with any of the phenotype measures could be discerned. In conclusion, although the identified UGT1A6 polymorphisms did not explain the observed glucuronidation variability, there does seem to be a significant role for environmental factors associated with alcohol consumption.

Hepatic Disposition of Gemfibrozil and Its Major Metabolite Gemfibrozil 1-O-β-Glucuronide.

Science.gov (United States)

Kimoto, Emi; Li, Rui; Scialis, Renato J; Lai, Yurong; Varma, Manthena V S

2015-11-02

Gemfibrozil (GEM), which decreases serum triglycerides and low density lipoprotein, perpetrates drug-drug interactions (DDIs) with several drugs. These DDIs are primarily attributed to the inhibition of drug transporters and metabolic enzymes, particularly cytochrome P450 (CYP) 2C8 by the major circulating metabolite gemfibrozil 1-O-β-glucuronide (GG). Here, we characterized the transporter-mediated hepatic disposition of GEM and GG using sandwich-cultured human hepatocytes (SCHH) and transporter-transfect systems. Significant active uptake was noted in SCHH for the metabolite. GG, but not GEM, showed substrate affinity to organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1. In SCHH, glucuronidation was characterized affinity constants (Km) of 7.9 and 61.4 μM, and biliary excretion of GG was observed. Furthermore, GG showed active basolateral efflux from preloaded SCHH and ATP-dependent uptake into membrane vesicles overexpressing multidrug resistance-associated protein (MRP) 2, MRP3, and MRP4. A mathematical model was developed to estimate hepatic uptake and efflux kinetics of GEM and GG based on SCHH studies. Collectively, the hepatic transporters play a key role in the disposition and thus determine the local concentrations of GEM and more so for GG, which is the predominant inhibitory species against CYP2C8 and OATP1B1.

Pyrene degradation by yeasts and filamentous fungi.

Science.gov (United States)

Romero, M Cristina; Salvioli, Mónica L; Cazau, M Cecilia; Arambarri, A M

2002-01-01

The saprotrophic soil fungi Fusarium solani (Mart.) Sacc., Cylindrocarpon didymum (Hartig) Wollenw, Penicillium variabile Sopp. and the yeasts Rhodotorula glutinis (Fresenius) Harrison and Rhodotorula minuta (Saito) Harrison were cultured in mineral medium with pyrene. The remaining pyrene concentrations were periodically determined during 20 incubation days, using HPLC. To assess the metabolism of pyrene degradation we added 0.1 microCi of [4,5,9,10] 14C-pyrene to each fungi culture and measured the radioactivity in the volatile organic substances, extractable, aqueous phase, biomass and 14CO2 fractions. The assays demonstrated that F. solani and R. glutinis metabolized pyrene as a sole source of carbon. Differences in their activities at the beginning of the cultures disappeared by the end of the experiment, when 32 and 37% of the original pyrene concentration was detected, for the soil fungi and yeasts, respectively. Among the filamentous fungi, F. solani was highly active and oxidized pyrene; moreover, small but significant degradation rates were observed in C. didymum and P. variahile cultures. An increase in the 14CO2 evolution was observed at the 17th day with cosubstrate. R. glutinis and R. minuta cultures showed similar ability to biotransform pyrene, and that 35% of the initial concentration was consumed at the end of the assay. The same results were obtained in the experiments with or without glucose as cosubstrate.

Preparation of 1-pyrenebutyric acid and pyrene submicron dots by laser-induced molecular micro-jet implantation

International Nuclear Information System (INIS)

Pihosh, Y.; Goto, M.; Kasahara, A.; Tosa, M.

2009-01-01

Pyrene and 1-pyrenebuturic acid molecules were deposited on glass and copper substrates with the formation of submicron dots by laser-induced molecular micro-jet implantation through polar and non-polar liquid layers. The size of the smallest 1-pyrenebuturic acid molecules dots prepared on a glass substrate by implantation through water and diiodomethane was estimated to be about 400 nm and 300 nm at laser fluences of 235 J/cm 2 and 326 J/cm 2 , respectively. The fluorescence and the Raman spectra showed that the implanted 1-pyrenebutyric acid molecules did not decompose during the implantation process. The smallest size of a pyrene dot was 700 nm at the laser fluence of 378 J/cm 2 . However, the pyrene dots could be formed only by implantation through a water layer.

Tissue and species differences in the glucuronidation of glabridin with UDP-glucuronosyltransferases.

Science.gov (United States)

Guo, Bin; Fang, Zhongze; Yang, Lu; Xiao, Ling; Xia, Yangliu; Gonzalez, Frank J; Zhu, Liangliang; Cao, Yunfeng; Ge, Guangbo; Yang, Ling; Sun, Hongzhi

2015-04-25

Glabridin (GA) has gained wide application in the cosmetics and food industry. This study was performed to investigate its metabolic inactivation and elimination by glucuronidation by use of liver and intestine microsomes from humans (HLM and HIM) and rats (RLM and RIM), and liver microsomes from cynomolgus monkeys and beagle dogs (CyLM and DLM). Both hydroxyl groups at the C2 and C4 positions of the B ring are conjugated to generate two mono-glucuronides (M1 and M2). HIM, RIM and RLM showed the most robust activity in catalyzing M2 formation with intrinsic clearance values (Clint) above 2000 μL/min/mg, with little measurable M1 formation activity. DLM displayed considerable activity both in M1 and M2 formation, with Clint values of 71 and 214 μL/min/mg, respectively, while HLM and CyLM exhibited low activities in catalyzing M1 and M2 formation, with Clint values all below 20 μL/min/mg. It is revealed that UGT1A1, 1A3, 1A9, 2B7, 2B15 and extrahepatic UGT1A8 and 1A10 are involved in GA glucuronidation. Nearly all UGTs preferred M2 formation except for UGT1A1. Notably, UGT1A8 displayed the highest activity with a Clint value more than 5-fold higher than the other isoforms. Chemical inhibition studies, using selective inhibitors of UGT1A1, 1A9, 2B7 and 1A8, further revealed that UGT1A8 contributed significantly to intestinal GA glucuronidation in humans. In summary, this in vitro study demonstrated large species differences in GA glucuronidation by liver and intestinal microsomes, and that intestinal UGTs are important for the pathway in humans. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

False-positive ethyl glucuronide immunoassay screening caused by a propyl alcohol-based hand sanitizer.

Science.gov (United States)

Arndt, Torsten; Grüner, Joachim; Schröfel, Stefanie; Stemmerich, Karsten

2012-11-30

Urine ethyl glucuronide (EtG) is considered as a specific marker of recent ethanol consumption. We describe false-positive DRI(®) EIA EtG enzyme immunoassay results caused by propyl glucuronides in urine after using a propanol-based hand sanitizer. EtG screening was done with the DRI(®) EIA EtG assay (Microgenics), using a cut-off of 0.5 mg/L as recommended by the manufacturer and of 0.1 mg/L as demanded by the German Regulations for Reissuing Drivers Licenses. Confirmatory EtG analysis was done with the ClinMass(®) EtG LC-MS/MS testkit (Recipe), extended by the mass transitions 235.1→75.1, 235.1→85.1, and 235.1→113.1 for the detection of the 1- and 2-propyl glucuronides. Self-experiments were done by staff members of our lab (n=7), using 3 mL Sterillium(®) Classic Pure (30 g/100 g 1-propanol and 45 g/100 g 2-propanol) for hand sanitation every quarter of an hour for 8 h according to DIN EN 1500:2011-05 with and without an exhauster and by passive inhalation of the sanitizer vapor. Spot urine samples were taken immediately before and up to 24 h after the first sanitizer use. False-positive immunoassay results of up to 4 mg/L or 2.3 mg/g creatinine were obtained after normal use of the sanitizer and also after passive inhalation of the sanitizer vapor (up to 0.89 mg/L or 0.61 mg/g). Immunoassay results were positive even after 4-fold use of the sanitizer (up to 0.14 mg/L or 0.38 mg/g) and up to 6 h after the last sanitizer contact (maximum 0.63 mg/L and 0.33 mg/g for sanitizer users and 0.25 mg/g after passive inhalation). Spiking of EtG-free urine with 1-propyl glucuronide (Athena Environmental Sciences) between 0.05 and 10 mg/L clearly demonstrated a cross reaction of the immunoassay of approx. 10% as compared to EtG. LC-MS/MS of urines with a positive immunoassay EtG result did not show EtG signals, but distinct signals of 1-propyl glucuronide (n-propyl glucuronide) and 2-propyl glucuronide (iso-propyl glucuronide). An exhauster effectively prevented

Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity

Science.gov (United States)

Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

2013-01-01

Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

Direct detection of glucuronide metabolites of lidocaine in sheep urine.

Science.gov (United States)

Doran, Gregory S; Smith, Alistair K; Rothwell, Jim T; Edwards, Scott H

2018-02-15

The anaesthetic lidocaine is metabolised quickly to produce a series of metabolites, including several hydroxylated metabolites, which are further metabolised by addition of a glucuronic acid moiety. Analysis of these glucuronide metabolites in urine is performed indirectly by cleaving the glucuronic acid group using β-glucuronidase. However, direct analysis of intact glucuronide conjugates is a more straightforward approach as it negates the need for long hydrolysis incubations, and minimises the oxidation of sensitive hydrolysis products, while also distinguishing between the two forms of hydroxylated metabolites. A method was developed to identify three intact glucuronides of lidocaine in sheep urine using LC-MS/MS, which was further confirmed by the synthesis of glucuronide derivatives of 3OH-MEGX and 4OH-LIDO. Direct analysis of urine allowed the detection of the glucuronide metabolites of hydroxylidocaine (OH-LIDO), hydroxyl-monoethylglycinexylidide (OH-MEGX), and hydroxy-2,6-xylidine (OH-XYL). Analysis of urine before and after β-glucuronidase digestion showed that the efficiency of hydrolysis of these glucuronide metabolites may be underestimated in some studies. Analysis of urine in the current study from three different sheep with similar glucuronide metabolite concentrations resulted in different hydrolysis efficiencies, which may have been a result of different levels of substrate binding by matrix components, preventing enzyme cleavage. The use of direct analysis of intact glucuronides has the benefit of being less influenced by these matrix effects, while also allowing analysis of unstable metabolites like 4OH-XYL, which rapidly oxidises after hydrolysis. Additionally, direct analysis is less expensive and less time consuming, while providing more information about the status of hydroxylated metabolites in urine. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS

Directory of Open Access Journals (Sweden)

A. N. Glushkov

2016-01-01

Full Text Available Some genetic polymorphisms of CYP and GST enzymes metabolizing low-molecular weight xenobiotics may represent endogenous risk factors for carcinogenesis. However, possible relationships between the enzyme activities, amounts of carcinogen adducts and synthesis of anticarcinogen antibodies in humans (including cancer patients are still poorly studied. The purpose of this study was to identify possible associations between occurrence of antibodies against benzo[a]pyrene, and frequency of genetic polymorphisms of CYP1A1*2A, CYP1A2*1F, GSTT1, GSTM1 in healthy men and in lung cancer patients. Materials and methods. We have examined 203 men with non-small cell lung cancer and 267 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies to benzo[a]pyrene was performed. Analysis of polymorphic loci within CYP1A1 (rs4646903, CYP1A2 (rs762551, GSTP1 (rs1695, rs1138272 was performed by means of real-time PCR using TaqMan technology. Null-alleles of GSTM1 (del, GSTT1 (del genes were detected by multiplex PCR with real-time fluorescent assay. Results. Among the lung cancer patients, the proportion of cases with a high level of IgG antibodies to benzo[a]pyrene in carriers of GSTT1+ and GSTM1+ in conjunction with the CYP1A2*1F C allele was significantly greater than in AA homozygotes CYP1A2*1F. The risk of lung cancer was increased to 5.5 in carriers of CYP1A2*1F C allele combined with GSTT1+ and GSTM1+ at high levels of IgG antibodies to benzo [a] pyrene. In healthy male donors, we have not found differences between the incidence of low and high levels of IgG anti-benzo[a]pyrene antibodies in the carriers of certain CYP1A1*2A, CYP1A2*1F, GSTT1 and GSTM1 genotypes. Conclusions. We have first reported a relationship between CYP1 and GST gene polymorphisms and specific immune response to chemical carcinogens in lung cancer patients. Immunoassays of IgG antibodies to benzo[a]pyrene combined with molecular

25 years and still going strong: 2'-O-(pyren-1-yl)methylribonucleotides - versatile building blocks for applications in molecular biology, diagnostics and materials science.

Science.gov (United States)

Hrdlicka, Patrick J; Karmakar, Saswata

2017-11-29

Oligonucleotides (ONs) modified with 2'-O-(pyren-1-yl)methylribonucleotides have been explored for a range of applications in molecular biology, nucleic acid diagnostics, and materials science for more than 25 years. The first part of this review provides an overview of synthetic strategies toward 2'-O-(pyren-1-yl)methylribonucleotides and is followed by a summary of biophysical properties of nucleic acid duplexes modified with these building blocks. Insights from structural studies are then presented to rationalize the reported properties. In the second part, applications of ONs modified with 2'-O-(pyren-1-yl)methyl-RNA monomers are reviewed, which include detection of RNA targets, discrimination of single nucleotide polymorphisms, formation of self-assembled pyrene arrays on nucleic acid scaffolds, the study of charge transfer phenomena in nucleic acid duplexes, and sequence-unrestricted recognition of double-stranded DNA. The predictable binding mode of the pyrene moiety, coupled with the microenvironment-dependent properties and synthetic feasibility, render 2'-O-(pyren-1-yl)methyl-RNA monomers as a promising class of pyrene-functionalized nucleotide building blocks for new applications in molecular biology, nucleic acid diagnostics, and materials science.

Reactions of the hydrated electron with pyrene in lipid bilayer vesicles

International Nuclear Information System (INIS)

Schnecke, W.; Graetzel, M.; Henglein, A.

1977-01-01

Pyrene and some pyrene derivatives were solubilized in bilayer vesicles of lecithin and the rates of lecithin and the rates of reaction with the hydrated electron investigated. The concentration of the vesicles was 1.3 x 10 -7 M, that of pyrene 10 -6 - 10 -4 M. The rate constant decreases with increasing pyrene concentration. The effect is explained by the highly inhomogeneous distribution of pyrene molecules in the solutions. Only those pyrene molicules are reactive that reside close to the outer surface of the vesicles. The anions of pyrene formed disappear in a second order process. It is concluded that the anions are rapidly detached from their vesicular carriers and react with each other in the aqueous phase. Fluorescence, light scattering and electron microscopic investigations were also carried out to obtain information about the properties of the vesicles used. (orig.) [de

Higher urine 1-hydroxy pyrene glucuronide (1-OHPG) is associated with tobacco smoke exposure and drinking maté in healthy subjects from Rio Grande do Sul, Brazil Renato B. Fagundes ... [et al.

OpenAIRE

Fagundes, Renato Borges; Abnet, Christian C.; Strickland, Paul T.; Kamangar, Farin; Roth, Mark J.; Taylor, Philip R.; Dawsey, Sanford M.

2006-01-01

Background: The highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern B...

Effects of shape, size, and pyrene doping on electronic properties of graphene nanoflakes.

Science.gov (United States)

Kuamit, Thanawit; Ratanasak, Manussada; Rungnim, Chompoonut; Parasuk, Vudhichai

2017-11-25

Effects of size, shape, and pyrene doping on electronic properties of graphene nanoflakes (GNFs) were theoretically investigated using density functional theory method with PBE, B3PW91, and M06-2X functionals and cc-pVDZ basis set. Two shapes of zigzag GNFs, hexagonal (HGN) and rhomboidal (RGN), were considered. The energy band gap of GNF depends on shape and decreases with size. The HGN has larger band gap energy (1.23-3.96 eV) than the RGN (0.13-2.12 eV). The doping of pyrene and pyrene derivatives on both HGN and RGN was also studied. The adsorption energy of pyrene and pyrene derivatives on GNF does not depend on the shape of GNFs with energies between 21 and 27 kcal mol -1 . The substituent on pyrene enhances the binding to GNF but the strength does not depend on electron withdrawing or donating capability. The doping by pyrene and pyrene derivatives also shifts the HOMO and LUMO energies of GNFs. Both positive (destabilizing) and negative (stabilizing) shifts on HOMO and LUMO of GNFs were seen. The direction and magnitude of the shift do not follow the electron withdrawing and donating capability of pyrene substituents. However, only a slight shift was observed for doped RGN. A shift of 0.19 eV was noticed for HOMO of HGN doped with 1-aminopyrene (pyNH 2 ) and of 0.04 eV for LUMO of HGN doped with 1-pyrenecarboxylic acid (pyCOOH). Graphical Abstract HOMO and LUMO Energies of pyrene/pyrene derivatives doped Graphene Nanoflakes.

Synthesis, radiolabeling and biodistribution of a new opioid glucuronide derivative. Ethyl-morphine glucuronide (em-glu)

International Nuclear Information System (INIS)

Enginar, H.

2012-01-01

In current study, ethyl-morphine (em) was synthesized from the morphine and glucuronidated via enzymatic mechanism. The conjugated glucuronide ethyl-morphine (em-glu) was radiolabeled with 131 I using iodogen method. The quality control studies of radiolabeled compound ( 131 I-em-glu) were done with Thin Layer Radio Chromatography to confirm the radiolabeling efficiency. Biodistribution studies of 131 I labeled em-glu were run on healthy male Albino Wistar rats. The distribution figures demonstrated that 131 I-em-glu was eliminated through the small intestine, large intestine and accumulated in urinary bladder both receptor blocked and unblocked biodistribution studies. A greater uptake of the radiolabeled substance was observed in the m.pons, hypothalamus and mid brain than in the other branches of the rats' brains. (author)

A quencher-free molecular beacon design based on pyrene excimer fluorescence using pyrene-labeled UNA (unlocked nucleic acid)

DEFF Research Database (Denmark)

Karlsen, Kasper Kannegård; Okholm, Anders Hauge; Kjems, Jørgen

2013-01-01

A quencher-free molecular beacon capable of generating pyrene excimer fluorescence has been constructed using strategically positioned pyrene-UNA monomers. Hybridization of a fully complementary RNA target was accompanied by a pyrene excimer emission increase of more than 900%, and detection of RNA...

In vitro characterization of glucuronidation of vanillin: identification of human UDP-glucuronosyltransferases and species differences.

Science.gov (United States)

Yu, Jian; Han, Jing-Chun; Hua, Li-Min; Gao, Ya-Jie

2013-09-01

Vanillin is a food flavoring agent widely utilized in foods, beverages, drugs, and perfumes and has been demonstrated to exhibit multiple pharmacological activities. Given the importance of glucuronidation in the metabolism of vanillin, the UDP-glucuronosyltransferase conjugation pathway of vanillin was investigated in this study. Vanillin glucuronide was identified by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and a hydrolysis reaction catalyzed by β-glucuronidase. The kinetic study showed that vanillin glucuronidation by HLMs and HIMs followed Michaelis-Menten kinetics and the kinetic parameters were as follows: 134.9 ± 13.5 μM and 81.3 ± 11.3 μM for K(m) of HLMs and HIMs, 63.8 ± 2.0 nmol/min/mg pro and 13.4 ±2.0 nmol/min/mg pro for Vmax of HLMs and HIMs. All UDP-glucuronosyltransferase (UGT) isoforms except UGT1A4, 1A9, and 2B7 showed the capability to glucuronidate vanillin, and UGT1A6 exerted the higher V(max)/K(m) values than other UGT isoforms for the glucuronidation of vanillin when assuming expression of isoforms is similar in recombinant UGTs. Kinetic analysis using liver microsomes from six studied speices indicated that vanillin had highest affinity for the monkey liver microsomes enzyme (K(m)  = 25.6 ± 3.2 μM) and the lowest affinity for the mice liver microsomes enzyme (K(m)  = 149.1 ± 18.4 μM), and intrinsic clearance was in the following order: monkey > dog > minipig > mice > rat ~ human. These data collectively provided important information for understanding glucuronidation of vanillin. Copyright © 2012 John Wiley & Sons, Ltd.

Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model.

Science.gov (United States)

Jongeneelen, Frans; ten Berge, Wil

2012-08-01

simulations showed that the model-predicted concentrations of urinary pyrene and metabolites over time, as well as peak-concentrations and total excreted amount in different exposure scenarios of inhalation and transdermal exposure were in all comparisons within an order of magnitude. The model predicts that only a very small fraction is excreted in urine as parent pyrene and as free 1-OH-pyrene. The predominant urinary metabolite is 1-OH-pyrene-glucuronide. Enterohepatic circulation of 1-OH-pyrene-glucuronide seems the reason of the delayed release from the body. It appeared that urinary excretion of pyrene and pyrene-metabolites in humans is predictable with the PBTK-model. The model outcomes have a satisfying accuracy for early testing, in so-called 1st tier simulations and in range finding. This newly developed generic PBTK-model IndusChemFate is a tool that can be used to do early explorations of the significance of uptake of pyrene in the human body following industrial or environmental exposure scenarios. And it can be used to optimize the sampling time and urine sampling frequency of a biomonitoring program.

Synthesis of a radioiodinated antiestrogen glucuronide compound (TAM-G)

International Nuclear Information System (INIS)

Fazilet Zumrut Biber Muftuler; Perihan Unak; Cigdem Ichedef; Ilknur Demir

2011-01-01

Tamoxifen [TAM; ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine) has been used as an antiestrogen drug for treatment and prevention of human breast cancer. The aim of this study is conjugation of hydrophilic glucuronic acid to the starting substance TAM and labeling with 131 I using iodogen as oxidizing agent. The reactions are completed in three steps, including enzymatic reaction, with the following sub-steps; preparation of microsomal fraction from rat liver and subsequent purification of UDP-glucuronyl transferase (UDPGT), estimation of protein amount in microsomal samples and glucuronidation reaction. Synthesized glucuronide derivative (TAM-G) was purified using high performance liquid chromatography (HPLC). Mass spectroscopy of cold standard showed that the labeling most probably occurs in ortho position to the aromatic ring containing the ether group of TAM-G as expected. Radiochemical yield of the 131 I labeled TAM-G ([ 131 I]TAM-G) is determined by using Thin Layer Radio Chromatography (TLRC). The radiopharmaceutical potential of [ 131 I]TAM-G is examined by biodistribution studies that is run on normal female Albino Wistar rats. According to biodistribution results 131 I labeled TAM-G may be proposed as a new antiestrogen glucuronide imaging agent for breast and uterus. Electronic supplementary material. The online version of this article (doi:10.1007/s10967-010-0932-7) contains supplementary material, which is available to authorized users. (author)

Absorption and emission spectroscopic characterisation of a pyrene-flavin dyad

International Nuclear Information System (INIS)

Shirdel, J.; Penzkofer, A.; Prochazka, R.; Shen, Z.; Strauss, J.; Daub, J.

2007-01-01

The pyrene-flavin (isoalloxazine) dyad, PFD {C 44 H 31 N 5 O 5 ; CA Index name: 1-pyrenepropanoic acid, α-[[4,10-dihydro-2,4-dioxo-10- phenylbenzo[g]pteridin-3(2H)-yl)acetyl]amino]-, phenylmethyl ester (αR)-(9Cl); CA Registry number: 618907-57-6}, dissolved in either dichloromethane or acetonitrile is characterized by absorption and emission spectroscopy. Absorption cross-section spectra, stimulated emission cross-section spectra, fluorescence quantum distributions, quantum yields, and degrees of fluorescence polarisation are determined. The fluorescence decay after femtosecond pulse excitation is determined by fluorescence up-conversion. The ground-state absorption recovery is determined by picosecond pump and probe transmission measurements. The dye photo-stability is investigated by observation of absorption spectral changes due to prolonged blue-light excitation. The absorption spectrum of PFD dyad resembles the superposition of the absorption of isoalloxazine (flavin) and 1-methylpyrene. Long-wavelength photo-excitation of the flavin moiety causes fluorescence quenching by ground-state electron transfer from pyrene to isoalloxazine. Short-wavelength photo-excitation of the pyrene moiety causes (i) excited-state electron transfer from pyrene to isoalloxazine, and (ii) Foerster-type energy transfer from pyrene to flavin followed by ground-state electron transfer from pyrene to flavin.

Effects of oil dispersants on photodegradation of pyrene in marine water

Energy Technology Data Exchange (ETDEWEB)

Gong, Yanyan [Environmental Engineering Program, Department of Civil Engineering, Auburn University, Auburn, AL 36849 (United States); College of Environmental Science and Engineering, Nankai University, Tianjin 300071 (China); Fu, Jie [Environmental Engineering Program, Department of Civil Engineering, Auburn University, Auburn, AL 36849 (United States); O’Reilly, S.E. [U.S. Department of the Interior, Gulf of Mexico OCS, Office of Environment, New Orleans, LA 70123 (United States); Zhao, Dongye, E-mail: zhaodon@auburn.edu [Environmental Engineering Program, Department of Civil Engineering, Auburn University, Auburn, AL 36849 (United States)

2015-04-28

Highlights: • Oil dispersant enhances pyrene photodegradation in seawater. • Oil dispersant increases formation of superoxide radicals. • Pyrene photodegradation shows a two-stage kinetics and follows first-order rate law. • Pyrene is degraded mainly through electron transfer from excited pyrene to oxygen. • Higher ionic strength and temperature and lower HA favor pyrene photodegradation. - Abstract: This work investigated effects of a popular oil dispersant (Corexit EC9500A) on UV- or sunlight-mediated photodegradation of pyrene (a model polycyclic aromatic hydrocarbon) in seawater. The presence of 18 and 180 mg/L of the dispersant increased the first-order photodegradation rate by 5.5% and 16.7%, respectively, and reduced or ceased pyrene volatilization. By combining individual first-order rate laws for volatilization and photodegradation, we proposed an integrated kinetic model that can adequately predict the overall dissipation of pyrene from seawater. Mechanistic studies indicated that superoxide radicals played a predominant role in pyrene photodegradation, and the dispersant enhanced formation of superoxide radicals. 1-Hydroxypyrene was the main intermediate regardless of the dispersant, suggesting that electrons were transferred from excited pyrene to oxygen. In the presence of 18 mg/L of the dispersant, the photodegradation rate increased with increasing ionic strength and temperature, but decreased with increasing HA concentration, and remained independent of solution pH. The results are important in understanding roles of oil dispersants on environmental fate of persistent oil components in natural and engineered systems.

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene-derived aminophosphonates.

Science.gov (United States)

Lewkowski, Jarosław; Rodriguez Moya, Maria; Wrona-Piotrowicz, Anna; Zakrzewski, Janusz; Kontek, Renata; Gajek, Gabriela

2016-01-01

A large series of variously substituted amino(pyren-1-yl)methylphosphonic acid derivatives was synthesized using a modified aza-Pudovik reaction in 20-97% yields. The fluorescence properties of the obtained compounds were investigated revealing that N-alkylamino(pyren-1-yl)methylphosphonic derivatives are stronger emissive compounds than the corresponding N-aryl derivatives. N-Benzylamino(pyren-1-yl)methylphosphonic acid displayed strong fluorescence (ΦF = 0.68) in phosphate-buffered saline (PBS). The influence of a series of derivatives on two colon cancer cell lines HT29 and HCT116 was also investigated. The most promising results were obtained for N-(4-methoxyphenyl)amino(pyren-1-yl)methylphosphonate, which was found to be cytotoxic for the HCT116 cancer cell line (IC50 = 20.8 μM), simultaneously showing weak toxicity towards normal lymphocytes (IC50 = 230.8 µM).

Optical Sensing Properties of Pyrene-Schiff Bases toward Different Acids.

Science.gov (United States)

Babgi, Bandar A; Alzahrani, Asma

2016-07-01

A set of (4-substituted-phenyl)-pyren-1-ylmethylene-amine (PMA) was prepared by the reaction of pyrene-1-carboxaldehyde and the corresponding 4-substituted aniline. The structure of the PMA compounds were confirmed by spectroscopic data (IR, (1)HNMR, (13)CNMR, ISI-MS and elemental analysis. The structure of (4-bromo-phenyl)-pyren-1-ylmethylene-amine (BrPMA) was further confirmed by the single X-ray crystallography. The absorption and emission spectroscopic behaviors were investigated in variant acids. The compounds showed dramatic spectroscopic changes upon acidifying with strong acids and negligible effects when weak acids are used in the acidifications. Hence, the PMA compounds can be used as sensors to distinguish between weak and strong acids.

Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in a rat liver cell line

International Nuclear Information System (INIS)

Barhoumi, Rola; Mouneimne, Youssef; Ramos, Ernesto; Morisseau, Christophe; Hammock, Bruce D.; Safe, Stephen; Parrish, Alan R.; Burghardt, Robert C.

2011-01-01

Dynamic analysis of the uptake and metabolism of polycyclic aromatic hydrocarbons (PAHs) and their metabolites within live cells in real time has the potential to provide novel insights into genotoxic and non-genotoxic mechanisms of cellular injury caused by PAHs. The present work, combining the use of metabolite spectra generated from metabolite standards using multiphoton spectral analysis and an 'advanced unmixing process', identifies and quantifies the uptake, partitioning, and metabolite formation of one of the most important PAHs (benzo[a]pyrene, BaP) in viable cultured rat liver cells over a period of 24 h. The application of the advanced unmixing process resulted in the simultaneous identification of 8 metabolites in live cells at any single time. The accuracy of this unmixing process was verified using specific microsomal epoxide hydrolase inhibitors, glucuronidation and sulfation inhibitors as well as several mixtures of metabolite standards. Our findings prove that the two-photon microscopy imaging surpasses the conventional fluorescence imaging techniques and the unmixing process is a mathematical technique that seems applicable to the analysis of BaP metabolites in living cells especially for analysis of changes of the ultimate carcinogen benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide. Therefore, the combination of the two-photon acquisition with the unmixing process should provide important insights into the cellular and molecular mechanisms by which BaP and other PAHs alter cellular homeostasis.

Micellar enhanced spectrofluorimetric methods: application to the determination of pyrene

Energy Technology Data Exchange (ETDEWEB)

Singh, H.; Hinze, W.L.

1982-01-01

The effects of cationic hexadecyltrimethylammonium chloride (CTAC), nonionic polyoxyethylene(9.5)p-1,1,3,3-tetramethylbutylphenol, Triton X-100 (TX-100), and anionic sodium dodecylsulfate (NaLS) surfactant micelles upon the spectrofluorimetric determination of pyrene is described. It was found that the intensity of the pyrene fluorescence is enhanced from 3 to 16 times in the presence of the micellar systems. Possible reasons for this micellar induced enhanced fluorescence are discussed. The spectral parameters, fluorescence lifetimes, quantum yields, lower detection limits, and analytical figures of merit for pyrene in CTAC, NaLS, TX-100, ethanol, and water are compared. The detection limit of pyrene in the presence of micelles (approx. 1.0 x 10/sup -10/ M) is about an order of magnitude lower than that possible in alcohol alone. A brief discussion on the predicted general applicability of this new technique in fluorimetric analysis is also given. 4 figures, 2 tables.

Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants.

Science.gov (United States)

Krekels, Elke H J; van Ham, Saskia; Allegaert, Karel; de Hoon, Jan; Tibboel, Dick; Danhof, Meindert; Knibbe, Catherijne A J

2015-09-01

Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling approach. A population pharmacokinetic model was developed in NONMEM VI, based on paracetamol plasma concentrations from 54 preterm and term neonates and infants, and on paracetamol, paracetamol-glucuronide and paracetamol-sulphate amounts in urine from 22 of these patients. Patients received either a single intravenous propacetamol dose or up to 12 repeated doses. Paracetamol and metabolite disposition was best described with one-compartment models. The formation clearance of paracetamol-sulphate was 1.46 mL/min/kg(1.4), which was about 5.5 times higher than the formation clearance of the glucuronide of 0.266 mL/min/kg. The renal excretion rate constants of both metabolites was estimated to be 11.4 times higher than the excretion rate constant of unchanged paracetamol, yielding values of 0.580 mL/min/kg. Developmental changes were best described by bodyweight in linear relationships on the distribution volumes, the formation of paracetamol-glucuronide and the unchanged excretion of paracetamol, and in an exponential relationship on the formation of paracetamol-sulphate. There was no evidence for up-regulation or other time-varying changes in any of the model parameters. Simulations with this model illustrate how paracetamol-glucuronide recovery in urine increases over time due to the slower formation of this metabolite and in the absence of up-regulation. Developmental changes, described by bodyweight-based functions, rather than up-regulation, explain developmental changes in paracetamol disposition in neonates and infants.

Hepatocyte cotransport of taurocholate and bilirubin glucuronides: Role of microtubules

International Nuclear Information System (INIS)

Crawford, J.M.; Gollan, J.L.

1988-01-01

Modulation of bile pigment excretion by bile salts has been attributed to modification of canalicular membrane transport or a physical interaction in bile. Based on the observation that a microtubule-dependent pathway is involved in the hepatocellular transport of bile salts, the authors investigated the possibility that bilirubin glucuronides are associated with bile salts during intracellular transport. Experiments were conducted in intact rats (basal) or after overnight biliary diversion and intravenous reinfusion of taurocholate (depleted/reinfused). All rats were pretreated with intravenous low-dose colchicine or its inactive isomer lumicolchicine. Biliary excretion of radiolabeled bilirubin glucuronides derived from tracer [ 14 C]bilirubin-[ 3 H]bilirubin monoglucuronide (coinjected iv) was unchanged in basal rats but was consistently delayed in depleted/reinfused rats. This was accompanied by a significant shift toward bilirubin diglucuronide formation from both substrates. In basal Gunn rats, with deficient bilirubin glucuronidation, biliary excretion of intravenous [ 14 C]bilirubin monoglucuronide-[ 3 H]bilirubin diglucuronide was unaffected by colchicine but was retarded in depleted/reinfused Gunn rats. Colchicine had no effect on the rate of bilirubin glucuronidation in vitro in rat liver microsomes. They conclude that a portion of the bilirubin glucuronides generated endogenously in hepatocytes or taken up directly from plasma may be cotransported with bile salts to the bile canalicular membrane via a microtubule-dependent mechanism

Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver.

Science.gov (United States)

Papageorgiou, Ioannis; Freytsis, Marina; Court, Michael H

2016-10-01

Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3'-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression. We performed an unbiased miRNA whole transcriptome association analysis using a bank of human livers with known acetaminophen glucuronidation activities. Of 754 miRNAs evaluated, 9 miRNAs were identified that were significantly overexpressed (p2-fold) in livers with low acetaminophen glucuronidation activities compared with those with high activities. miR-375 showed the highest difference (>10-fold), and was chosen for further mechanistic validation. We demonstrated using in silico analysis and luciferase reporter assays that miR-375 has a unique functional binding site in the 3'-UTR of the aryl hydrocarbon receptor (AhR) gene. Furthermore overexpression of miR-375 in LS180 cells demonstrated significant repression of endogenous AhR protein (by 40%) and mRNA (by 10%), as well as enzyme activity and/or mRNA of AhR regulated enzymes including UGT1A1, UGT1A6, and CYP1A2, without affecting UGT2B7, which is not regulated by AhR. Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF. Published by Elsevier Inc.

Bioremediation of Pyrene-Contaminated Soils Using Biosurfactant

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Jorfi

2014-10-01

Full Text Available Background Polycyclic aromatic hydrocarbons (PAHs are persistence organic chemicals with proved carcinogenic and mutagenic hazards. These compounds are usually adsorbed in soils in vicinity of oil and gas industries. Bioremediation of PAHs contaminated soils is difficult due to hydrophobic nature of PAHs. Objectives The main purpose of the current study was to determine the pyrene removal efficiency in synthetically contaminated soil, using biosurfactant. Materials and Methods Four pure bacterial strains capable of pyrene degradation were isolated from contaminated soils via enrichment techniques. The soil samples were spiked with an initial pyrene concentration of 500 mg/kg and subjected to bioremediation using a mixed culture comprised of previously isolated strains, in addition to application of biosurfactant during 63 days. Results The pyrene removal efficiency in samples containing biosurfactant, without biosurfactant and controls, were 86.4%, 59.8% and 14%, respectively, after 63 days. The difference of pyrene removal efficiency between the biosurfactant-containing samples and the ones without it was significant (P < 0.05. Conclusions Application of rhamnolipid biosurfactant produced by Pseudomonas aeruginosa significantly improved pyrene removal in contaminated soils.

Autism and Phthalate Metabolite Glucuronidation

Science.gov (United States)

Stein, T. Peter; Schluter, Margaret D.; Steer, Robert A.; Ming, Xue

2013-01-01

Exposure to environmental chemicals may precipitate autism spectrum disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. To determine whether the efficiency of this pathway is compromised in children with ASD, we measured…

Evaluating pyrene toxicity on Arctic key copepod species Calanus hyperboreus

DEFF Research Database (Denmark)

Nørregaard, Rasmus Dyrmose; Nielsen, Torkel Gissel; Friis Møller, Eva

2014-01-01

was unaffected. The hatching success was also unaffected, although the total reproductive output was reduced with increased pyrene concentrations. Accumulation of pyrene in the copepods was higher in feeding than starving females and only trace amounts of the phase I metabolite 1-hydroxypyrene, were found...

Polymer solar cells based on poly(3-hexylthiophene) and fullerene: Pyrene acceptor systems

Energy Technology Data Exchange (ETDEWEB)

Cominetti, Alessandra; Pellegrino, Andrea; Longo, Luca [Research Center for Renewable Energies and Environment, Istituto Donegani, Eni S.p.A, Via Fauser 4, IT-28100 Novara (Italy); Po, Riccardo, E-mail: riccardo.po@eni.com [Research Center for Renewable Energies and Environment, Istituto Donegani, Eni S.p.A, Via Fauser 4, IT-28100 Novara (Italy); Tacca, Alessandra; Carbonera, Chiara; Salvalaggio, Mario [Research Center for Renewable Energies and Environment, Istituto Donegani, Eni S.p.A, Via Fauser 4, IT-28100 Novara (Italy); Baldrighi, Michele; Meille, Stefano Valdo [Dipartimento di Chimica, Materiali e Ingegneria Chimica “G. Natta”, Politecnico di Milano, via Mancinelli 7, IT-20131 Milano (Italy)

2015-06-01

The replacement of widely used fullerene derivatives, e.g. [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), with unfunctionalized C60 and C70 is an effective approach to reduce the costs of organic photovoltaics. However, solubility issues of these compounds have always represented an obstacle to their use. In this study, bulk-heterojunction solar cells made of poly(3-hexylthiophene) donor polymer, C60 or C70 acceptors and a pyrene derivative (1-pyrenebutiric acid butyl ester) are reported. Butyl 1-pyrenebutirate limits the aggregation of fullerenes and improves the active layer morphology, plausibly due to the formation of pyrene-fullerene complexes which, in the case of pyrene-C70, were also obtained in a crystalline form. Maximum power conversion efficiencies of 1.54% and 2.50% have been obtained using, respectively, C60 or C70 as acceptor. Quantum mechanical modeling provides additional insight into the formation of plausible supermolecular structures via π-π interactions and on the redox behaviour of pyrene-fullerene systems. - Highlights: • Pyrene derivatives favour the dispersion of unfunctionalized fullerenes. • Polymer solar cells with pyrene: C60 adduct as acceptor have efficiencies of 1.54%. • When C60 is substituted with C70 the efficiency is increased to 2.50%. • DFT calculations support the plausibility of the formation of pyrene: fullerene adducts. • The use of unfunctionalized fullerenes may decrease the costs of polymer solar cells.

Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

Energy Technology Data Exchange (ETDEWEB)

Bartlett, S.E.; Smith, M.T. (Department of Pharmacy, The University of Queensland (Australia)); Dood, P.R. (Clinical Research Centre, Royal Brisbane Hospital Foundation, Brisbane (Australia))

1994-07-01

Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of [sup 3]H-MK801 (non-competitive antagonist) and [sup 125]I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of [sup 3]H-muscimol (GABA receptor agonist), [sup 3]H-diazepam and [sup 3]H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA[sub A] receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of [sup 3]H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.).

Novel asymmetrical pyrene derivatives as light emitting materials: Synthesis and photophysics

International Nuclear Information System (INIS)

Li Yang; Wang Dong; Wang Lei; Li Zhengqiang; Cui Qing; Zhang Haiquan; Yang Huai

2012-01-01

A series of novel substituted pyrene derivatives with asymmetrical groups have been successfully synthesized in excellent yield. Structures of the asymmetrical compound were fully characterized by 1 H-NMR, IR spectroscopy and mass spectrometry. By introducing ethynyl functions to pyrene, we obtained highly efficient blue and green light emitting materials. It has been demonstrated that the emission characteristics of pyrene derivatives have been bathochromatically tuned in the visible region by extending the π-conjugation. The photophysical properties of these compounds were carefully examined in different organic solvents and different concentrations. The electrochemical properties and geometrical electronic structures of the new pyrene derivatives have been investigated by cyclic voltammograms and density functional theory (DFT) calculations. - Highlights: ► It is the first research about asymmetrial pyrene derivatives as highly efficient light emitting materials. ► The solvatochromism and concentration effect of the new compounds have been discussed. ► Furthermore, the electrochemical properties and geometrical electronic structures were also investigated in this paper.

Electronic Paramagnetic Resonance (EPR) of free radicals induced by X-rays in pyrene

International Nuclear Information System (INIS)

Moya Partiti, C.S. de.

1982-01-01

Pyrene single crystals C 16 H 10 , irradiated by X-rays, at room temperature, were studied by EPR technique, to determine free radicals formed by radiation. The angular dependence of EPR spectra was explained by the presence of two kinds of radicals with an aditional hydrogen: 2-H 2 pyrene and 3-H 2 pyrene. It was studied the isothermic decay of the EPR signal and two typical values for the activation energy were found = (1,9+-0,1) eV and (1,93+-0,03) eV. (author) [pt

Progress of pyrene-based organic semiconductor in organic field effect transistors

Institute of Scientific and Technical Information of China (English)

Yanbin; Gong; Xuejun; Zhan; Qianqian; Li; Zhen; Li

2016-01-01

Thanks to the pure blue emitting, high planarity, electron rich and ease of chemical modification, pyrene has been thoroughly investigated for applications in organic electronics such as organic light emitting diodes(OLEDs), organic field effect transistors(OFETs), and organic solar cells(OSCs). Especially, great progresses have been made of pyrene-based organic semiconductors for OFETs in past decades. Due to the difference of molecular structure, pyrene-based organic semiconductors are divided into three categories, pyrene as terminal group, pyrene as center core and fused pyrene derivatives. This minireview gives a brief introduction of the structure-property relationship and application in OFETs about most of pyrene-based semiconducting materials since 2006,illustrating that pyrene is a good building block to construct semiconductors with superior transport property for OFETs. Finally, we provide a summary concerning the methodology to improve the transport property of the pyrene-based semiconducting materials as well as an outlook.

Modulating the nanorods protrusion from poly(allylamine hydrochloride)-g-pyrene microcapsules by 1-pyrenesulfonic acid sodium salt.

Science.gov (United States)

Guan, Erjia; Wang, Tianxiang; Wang, Zhipeng; Gao, Changyou

2013-09-01

It was found previously that the Schiff base bonds in poly(allylamine hydrochloride)-g-pyrene (PAH-Py) microcapsules (MCs) are hydrolyzed at pH 2 within 1 h, leading to disassembly of the MCs and protrusion of pyrene aldehyde (Py) nanorods (NRs) on the capsule surface. Herein, we found a new way to modulate the protrusion of NRs by addition of 1-pyrenesulfonic acid sodium salt (PySO3Na). Along with the increase in PySO3Na to Py molar ratio in the MCs solution, the protrusion of NRs was progressively blocked and even inhibited at a ratio of 2.3, and at this condition, the microcapsules were stable under pH 2 for 24 h. After the composite microcapsules with excess PySO3Na were washed with a pH 10 solution and then incubated in a pH 2 solution, the NRs could be protruded from the MCs again. The fluorescence peak position of the PAH-Py/PySO3Na MCs gradually red-shifted with a decrease in pH value, and a sharp transition occurred at p H3.6, demonstrating the formation of pyrene excimers between the PySO3Na small molecules and the pendant Py groups on the PAH chain. The formed excimers take the role of blocking the self-assembly of cleaved Py molecules instead of inhibiting the hydrolysis of the Schiff base, whereas the MCs were stabilized by the charge interaction between PySO3Na and PAH backbone and the hydrophobic interaction between the pyrene rings. Copyright © 2013 Elsevier Inc. All rights reserved.

Identification of glucuronides as in vivo liver conjugates of seven cannabinoids and some of their hydroxy and acid metabolites.

Science.gov (United States)

Harvey, D J; Martin, B R; Paton, W D

1977-02-01

Glucuronide conjugates of cannabidiol (CBD), 7-hydroxy-CBD, propyl-CBD, cannabinol (CBN), 7-hydroxy-CBN, CBN-7-oic acid, propyl CBN and cannabichromene have been identified as major metabolites of CBD, CBN and their propyl homologues and of cannabichromene in mouse liver. Trace amounts of the glucuronide conjugates of delta1- and delta1(6)-tetrahydrocannabinol (THC) were also detected. Identification was made by combined gas-liquid chromatographic and mass spectrometric studies of the trimethylsilyl (TMS), d9-TMS and methyl ester-TMS derivatives of the glucuronides and the TMS derivatives of the product of the reduction of the metabolites with lithium aluminium deuteride.

Synthesis, crystal structure and aggregation-induced emission of a new pyrene-based compound, 3,3-diphenyl-2-[4-(pyren-1-ylphenyl]acrylonitrile

Directory of Open Access Journals (Sweden)

Bao-Xi Miao

2018-05-01

Full Text Available The title organic compound, C37H23N, crystallizing in the triclinic space group P\\overline{1}, has been designed, synthesized and characterized by single-crystal X-ray diffaction, MS, NMR and elemental analysis. There are alternating relatively strong and weak intermolecular π–π interactions between adjacent pyrene ring systems, forming a one-dimensional supramolecular structure. The compound is weakly fluorescent in THF solution, but it is highly emissive in the condensed phase, revealing distinct aggregation-induced emission (AIE characteristics.

Oral pharmacokinetics of baicalin, wogonoside, oroxylin A 7-O-β-d-glucuronide and their aglycones from an aqueous extract of Scutellariae Radix in the rat.

Science.gov (United States)

Cai, Yu; Li, Sai; Li, Ting; Zhou, Ruina; Wai, Alfred Tai-Seng; Yan, Ru

2016-07-15

Scutellariae Radix (SR) has been extensively prescribed in folk medicines due to its notable beneficial activities. The flavonoid glucuronides baicalin (BG), wogonoside (WG), oroxylin A 7-O-β-d-glucuronide (OG) and their aglycones baicalein, wogonin and oroxylin A, are the main components of the herb. So far, majority of previous studies failed to report the pharmacokinetics and none offered an explanation for the systemic exposures of these six flavonoids when the herbal extract was orally administered. In this study, when a SR extract was orally dosed to rats (800mg/kg, equivalent to BG 324.80, WG 124.00, OG 43.04, baicalein 25.36, wogonin 24.40, and oroxylin A 5.79mg/kg), all six flavonoids were detectable throughout the experimental period (48h) using an LC-MS/MS method with the Cmax and AUC0-48h of the glucuronides 10-130 times that of respective aglycones. As the lowest among the three glucuronides in the herb, OG was the most abundant in vivo, while the systemic exposure of wogonin was the highest amongst the three aglycones. The dose-normalized AUC0-48h descended in orders of OG/oroxylin A, WG/wogonin and BG/baicalein. Two di-conjugates of baicalein (BG glucuronide and BG glucoside), two BG isomers (minor BM1 and major BM2), and one WG isomer (wogonin 5-O-glucuronide) were detected in rat plasma. Semi-quantitation of the isomers with peak area data revealed that the AUPs (area under peak area ratio-time curves) of BG isomers were ∼3 times that of BG, yet the AUP of wogonin 5-O-glucuronide was only one seventh of WG. BM2, tentatively assigned as baicalein 6-O-glucuronide, was formed from both microbial isomerization of BG and hepatic glucuronidation of baicalein. Wogonin 5-O-glucuronide was only formed in hepatic glucuronidation of wogonin. Demethylated wogonin was observed in gut bacteria, offering an optional origin of BM1 apart from baicalein glucuronidation. Microbial isomerization of BG and extensive hepatic glucuronidation of baicalein to form BM2as

Pyrene-modified unlocked nucleic acids: synthesis, thermodynamic studies, and fluorescent properties

DEFF Research Database (Denmark)

Karlsen, Kasper K; Pasternak, Anna; Jensen, Troels B

2012-01-01

-UNA modifications were studied. It was found that incorporation of pyrene-UNA monomers increased duplex stability relative to UNA monomers, and thermodynamic studies revealed significant mismatch discriminative capabilities of the pyrene-UNA modified oligonucleotides. Furthermore, the steady-state fluorescence...... emission intensities of pyrene-UNA modified oligonucleotides were increased upon hybridization to DNA, which to the best of our knowledge is unprecedented for an acyclic pyrene modification in DNA. Interestingly, pyrene excimer emission was observed for single-stranded oligonucleotides containing three...

Mechanism-based inactivation of benzo[a]pyrene hydroxylase by aryl acetylenes and aryl olefins

International Nuclear Information System (INIS)

Gan, L.S.; Lu, J.Y.L.; Alworth, W.L.

1986-01-01

A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxgenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, 3-ethynylperylene, 2-ethynylfluorene, methyl 1-pyrenyl acetylene, cis- and trans-1-(2-bromovinyl)pyrene, and 1-allylpyrene serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo[a]pyrene hydroxylase, while 1-vinylpyrene and phenyl 1-pyrenyl acetylene do not cause a detectable suicide inhibition of benzo[a]pyrene hydroxylase. The mechanism-based loss of benzo[a]pyrene hydroxylase caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes (suicide destruction). The suicide inhibition by these aryl acetylenes therefore does not involve covalent binding to the heme moiety of the monooxygenase. Nevertheless, in the presence of NADPH, 3 H-labeled 1-ethynylpyrene becomes covalently attached to the cytochrome P-450 protein; the measured stoichiometry of binding is one 1-ethynylpyrene per P-450 heme unit. The authors conclude that the inhibition of benzo[a]pyrene hydroxylase produced by 1-ethynylpyrene may be related to the mechanism of suicide inhibition of P-450 activity by chloramphenicol rather than the mechanism of suicide destruction of P-450 previously described for acetylene and propyne

Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides

NARCIS (Netherlands)

Sesink, A.L.A.; Arts, I.C.W.; Boer, de V.C.J.; Breedveld, P.; Schellens, J.H.M.; Hollman, P.C.H.; Russel, F.G.M.

2005-01-01

The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides.

NARCIS (Netherlands)

Sesink, A.L.; Arts, I.C.; Boer, V.C. de; Breedveld, P.; Schellens, J.H.; Hollman, P.C.H.; Russel, F.G.M.

2005-01-01

The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

Photodegradation of polycyclic aromatic hydrocarbon pyrene by iron oxide in solid phase

International Nuclear Information System (INIS)

Wang, Y.; Liu, C.S.; Li, F.B.; Liu, C.P.; Liang, J.B.

2009-01-01

To better understand the photodegradation of polycyclic aromatic hydrocarbons (PAH) in solid phase in natural environment, laboratory experiments were conducted to study the influencing factors, kinetics and intermediate compound of pyrene photodegradation by iron oxides. The results showed that the pyrene photodegradation rate followed the order of α-FeOOH > α-Fe 2 O 3 > γ-Fe 2 O 3 > γ-FeOOH at the same reaction conditions. Lower dosage of α-FeOOH and higher light intensity increased the photodegradation rate of pyrene. Iron oxides and oxalic acid can set up a photo-Fenton-like system without additional H 2 O 2 in solid phase to enhance the photodegradation of pyrene under UV irradiation. All reaction followed the first-order reaction kinetics. The half-life (t 1/2 ) of pyrene in the system showed the higher efficiencies of using iron oxide as photocatalyst to degrade pyrene. Intermediate compound pyreno was found during photodegradation reactions by gas chromatography-mass spectrometry (GC-MS). The photodegradation efficiency for PAHs in this photo-Fenton-like system was also confirmed by using the contaminated soil samples. This work provides some useful information to understand the remediation of PAHs contaminated soils by photochemical techniques under practical condition

The endophytic bacterium Serratia sp. PW7 degrades pyrene in wheat.

Science.gov (United States)

Zhu, Xuezhu; Wang, Wanqing; Crowley, David E; Sun, Kai; Hao, Shupeng; Waigi, Michael Gatheru; Gao, Yanzheng

2017-03-01

This research was conducted to isolate polycyclic aromatic hydrocarbon-degrading (PAH-degrading) endophytic bacteria and investigate their potential in protecting plants against PAH contamination. Pyrene-degrading endophytic bacteria were isolated from plants grown in PAH-contaminated soil. Among these endophytic bacteria, strain PW7 (Serratia sp.) isolated from Plantago asiatica was selected to investigate the suppression of pyrene accumulation in Triticum aestivum L. In the in vitro tests, strain PW7 degraded 51.2% of the pyrene in the media within 14 days. The optimal biodegradation conditions were pH 7.0, 30 °C, and MS medium supplemented with additional glucose, maltose, sucrose, and peptones. In the in vivo tests, strain PW7 successfully colonized the roots and shoots of inoculated (E + ) wheat plants, and its colonization decreased pyrene accumulation and pyrene transportation from roots to shoots. Remarkably, the concentration of pyrene in shoots decreased much more than that in roots, suggesting that strain PW7 has the potential for protecting wheat against pyrene contamination and mitigating the threat of pyrene to human health via food consumption.

Trophic transfer of pyrene metabolites between aquatic invertebrates

International Nuclear Information System (INIS)

Carrasco Navarro, V.; Leppänen, M.T.; Kukkonen, J.V.K.; Godoy Olmos, S.

2013-01-01

The trophic transfer of pyrene metabolites was studied using Gammarus setosus as a predator and the invertebrates Lumbriculus variegatus and Chironomus riparius as prey. The results obtained by liquid scintillation counting confirmed that the pyrene metabolites produced by the aquatic invertebrates L. variegatus and C. riparius were transferred to G. setosus through the diet. More detailed analyses by liquid chromatography discovered that two of the metabolites produced by C. riparius appeared in the chromatograms of G. setosus tissue extracts, proving their trophic transfer. These metabolites were not present in chromatograms of G. setosus exclusively exposed to pyrene. The present study supports the trophic transfer of PAH metabolites between benthic macroinvertebrates and common species of an arctic amphipod. As some PAH metabolites are more toxic than the parent compounds, the present study raises concerns about the consequences of their trophic transfer and the fate and effects of PAHs in natural environments. - Highlights: ► The trophic transfer of pyrene metabolites between invertebrates was evaluated. ► Biotransformation of pyrene by L. variegatus and C. riparius is different. ► Metabolites produced by L. variegatus and C. riparius are transferred to G. setosus. ► Specifically, two metabolites produced by C. riparius were transferred. - Some of the pyrene metabolites produced by the model invertebrates L. variegatus and C. riparius are transferred to G. setosus through the diet, proving their trophic transfer.

High-mobility pyrene-based semiconductor for organic thin-film transistors.

Science.gov (United States)

Cho, Hyunduck; Lee, Sunyoung; Cho, Nam Sung; Jabbour, Ghassan E; Kwak, Jeonghun; Hwang, Do-Hoon; Lee, Changhee

2013-05-01

Numerous conjugated oligoacenes and polythiophenes are being heavily studied in the search for high-mobility organic semiconductors. Although many researchers have designed fused aromatic compounds as organic semiconductors for organic thin-film transistors (OTFTs), pyrene-based organic semiconductors with high mobilities and on-off current ratios have not yet been reported. Here, we introduce a new pyrene-based p-type organic semiconductor showing liquid crystal behavior. The thin film characteristics of this material are investigated by varying the substrate temperature during the deposition and the gate dielectric condition using the surface modification with a self-assembled monolayer, and systematically studied in correlation with the performances of transistor devices with this compound. OTFT fabricated under the optimum deposition conditions of this compound, namely, 1,6-bis(5'-octyl-2,2'-bithiophen-5-yl)pyrene (BOBTP) shows a high-performance transistor behavior with a field-effect mobility of 2.1 cm(2) V(-1) s(-1) and an on-off current ratio of 7.6 × 10(6) and enhanced long-term stability compared to the pentacene thin-film transistor.

The Uptake by Plants of Diethylstilboestrol and of Its Glucuronide

DEFF Research Database (Denmark)

Gregers Hansen, B.

1964-01-01

The uptake of diethylstilboestrol and its glucuronide by plants could, under certain circumstances, present a potential health hazard. The relative uptake of the two compounds has therefore been studied in rye grass, red clover, mushrooms, and maize in pot and water culture experiments. It is con......The uptake of diethylstilboestrol and its glucuronide by plants could, under certain circumstances, present a potential health hazard. The relative uptake of the two compounds has therefore been studied in rye grass, red clover, mushrooms, and maize in pot and water culture experiments...

Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation.

Directory of Open Access Journals (Sweden)

Pilar Galindo

Full Text Available BACKGROUND: Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3'-sulfate, Q3'S in spontaneously hypertensive rats (SHR. Q3GA and I3GA (1 mg/kg i.v., but not Q3'S, progressively reduced mean blood pressure (MBP, measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml. In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg induced a progressive decrease in MBP, which was also suppressed by SAL. CONCLUSIONS: Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect.

Metabolism of benzo(a)pyrene and identification of the major benzo(a)pyrene-DNA adducts in cultured human colon

DEFF Research Database (Denmark)

Autrup, Herman; Harris, Curtis C.; Trump, Benjamin F.

1978-01-01

The metabolism of benzo(a)pyrene in cultured human colon has been investigated. Nontumorous colonie tissue was collected at the time of either surgery or "immediate autopsy" from patients with or without colonic cancer. After 24 hr in culture the expiants were exposed to [3H]benzo(a)pyrene for an...

Tow-step degradation of pyrene by white-rot fungi and soil microorganisms

International Nuclear Information System (INIS)

Wische, C. in der; Martens, R.; Zadrazil, F.

1996-01-01

The effect of soil microorganisms on mineralization of 14 C-labelled pyrene by white-rot fungi in solid-state fermentation was investigated. Two strains of white-rot fungi, Dichomitus squalens and a Pleurotus sp., were tested. The fungi were incubated on milled wheat straw contaminated with [ 14 C]pyrene for 15 weeks. CO 2 and 14 CO 2 liberated from the cultures were determined weekly. To study the effect of soil microorganisms on respiration and [ 14 C]pyrene mineralization in different periods of fungal development, the fungal substrate was covered with soil at different times of incubation (after 0, 1, 3, 5, 7, 9 or 11 weeks). The two fungi showed contrasting ecological behaviour in competition with the soil microflora. Pleurotus sp. was highly resistant to microbial attack and had the ability to penetrate the soil. D. squalens was less competitive and did not colonize the soil. The resistance of the fungus was dependent on the duration of fungal preincubation. Mineralization of [ 14 C]pyrene by mixed cultures of D. squalens and soil microorganisms was higher than by the fungus or the soil microflora alone when soil was added after 3 weeks of incubation or later. With Pleurotus sp., the mineralization of [ 14 C]pyrene was enhanced by the soil microflora irrespective of the time of soil application. With D. squalens, which in pure culture mineralized less [ 14 C]pyrene than did Pleurotus sp., the increase of [ 14 C]pyrene mineralization caused by soil application was higher than with Pleurotus sp. (orig.)

Flow cytometric measurement of the metabolism of benzo [a] pyrene by mouse liver cells in culture

International Nuclear Information System (INIS)

Bartholomew, J.C.; Wade, C.G.; Dougherty, K.

1984-01-01

The metabolism of benzo[a]pyrene in individual cells was monitored by flow cytometry. The measurements are based on the alterations that occur in the fluorescence emission spectrum of benzo[a]pyrene when it is converted to various metabolities. Using present instrumentation the technique could easily detect 1 x 10/sup 6/ molecules per cells of benzo [a]pyrene and 1 x 10/sup 7/ molecules per cell of the diol epoxide. The analysis of C3H IOT 1/2 mouse fibroblasts growing in culture indicated that there was heterogeneity in the conversion of the parent compound into diol epoxide derivative suggesting that some variation in sensitivity to transformation by benzo[a]pyrene may be due to differences in cellular metabolism

A Novel Combination of Surfactant Addition and Persulfate-assisted Electrokinetic Oxidation for Remediation of Pyrene-Contaminated Soil

Directory of Open Access Journals (Sweden)

M. Abtahi

2018-03-01

Full Text Available Effect of surfactant addition on persulfate-assisted electrokinetic remediation of pyrene-spiked soil was studied. The influence of effective factors including voltage, surfactant addition, moisture content, and persulfate concentration on the removal of initial pyrene concentration of 200 mg kg–1 were investigated. A complete pyrene removal was observed for voltage of 1 V cm–1, saturated conditions, Tween 80 concentration of 20 mL kg–1, and persulfate concentration of 100 mg kg–1 after 24 h, corresponding to pyrene mineralization of 61 %, based on TPH analysis. The experimental results were best fitted with pseudo-first-order kinetic model with correlation coefficient of 0.968 and rate constant of 0.191 min−1. The main intermediates of pyrene degradation were benzene o-toluic acid, acetic, azulene, naphthalene and decanoic acid. Finally, an unwashed hydrocarbon-contaminated soil was subjected to persulfate-assisted electrokinetic remediation, and a TPH removal of 38 % was observed for the initial TPH content of 912 mg kg–1, under the selected conditions.

Percutaneous absorption of [14C]DDT and [14C]benzo[a]pyrene from soil

International Nuclear Information System (INIS)

Wester, R.C.; Maibach, H.I.; Bucks, D.A.; Sedik, L.; Melendres, J.; Liao, C.; DiZio, S.

1990-01-01

The objective was to determine percutaneous absorption of DDT and benzo[a]pyrene in vitro and in vivo from soil into and through skin. Soil (Yolo County 65-California-57-8; 26% sand, 26% clay, 48% silt) was passed through 10-, 20-, and 48-mesh sieves. Soil then retained by 80-mesh was mixed with [14C]-labeled chemical at 10 ppm. Acetone solutions at 10 ppm were prepared for comparative analysis. Human cadaver skin was dermatomed to 500 microns and used in glass diffusion cells with human plasma as the receptor fluid (3 ml/hr flow rate) for a 24-hr skin application time. With acetone vehicle, DDT (18.1 +/- 13.4%) readily penetrated into human skin. Significantly less DDT (1.0 +/- 0.7%) penetrated into human skin from soil. DDT would not partition from human skin into human plasma in the receptor phase (less than 0.1%). With acetone vehicle, benzo[a]pyrene (23.7 +/- 9.7%) readily penetrated into human skin. Significantly less benzo[a]pyrene (1.4 +/- 0.9%) penetrated into human skin from soil. Benzo[a]pyrene would not partition from human skin into human plasma in the receptor phase (less than 0.1%). Substantivity (skin retention) was investigated by applying 14C-labeled chemical to human skin in vitro for only 25 min. After soap and water wash, 16.7 +/- 13.2% of DDT applied in acetone remained absorbed to skin. With soil only 0.25 +/- 0.11% of DDT remained absorbed to skin. After soap and water wash 5.1 +/- 2.1% of benzo[a]pyrene applied in acetone remained absorbed to skin. With soil only 0.14 +/- 0.13% of benzo[a]pyrene remained absorbed to skin

Circularly Polarized Luminescence from a Pyrene-Cyclodextrin Supra-Dendron.

Science.gov (United States)

Zhang, Yuening; Yang, Dong; Han, Jianlei; Zhou, Jin; Jin, Qingxian; Liu, Minghua; Duan, Pengfei

2018-05-22

Soft nanomaterials with circularly polarized luminescence (CPL) have been currently attracting great interest. Here, we report a pyrene-containing π-peptide dendron hydrogel, which shows 1D and 2D nanostructures with varied CPL activities. It was found that the individual dendrons formed hydrogels in a wide pH range (3-12) and self-assembled into helices with pH-tuned pitches. Through chirality transfer, the pyrene unit could show CPL originated from both the monomer and excimer bands. When cyclodextrin was introduced, different supra-dendrons were obtained with β-cyclodextrin (PGAc@β-CD) and γ-cyclodextrin (PGAc@γ-CD) through host-guest interactions, respectively. Interestingly, the PGAc@β-CD and PGAc@γ-CD supra-dendrons self-assembled into 2D nanosheet and entangled nanofibers, respectively, showing cyclodextrin induced circularly polarized emission from both the monomer and excimer bands of the pyrene moiety. Thus, through a simple host-guest interaction, both the nanostructures and the chiroptical activities could be modulated.

Synthesis and Characterization of Novel Polythiophenes Containing Pyrene Chromophores: Thermal, Optical and Electrochemical Properties

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Bianca X. Valderrama-García

2016-01-01

Full Text Available A novel series of pyrene containing thiophene monomers TPM1–5 were synthesized and fully characterized by FTIR, MS, 1H- and 13C-NMR spectroscopy; their thermal properties were determined by TGA and DSC. These monomers were chemically polymerized using FeCl3 as oxidizing agent to give the corresponding oligomers TPO1–5 and they were electrochemically polymerized to obtain the corresponding polymer films deposited onto ITO. All oligomers exhibited good thermal stability, with T10 values between 255 and 299 °C, and Tg values varying from 36 to 39 °C. The monomers showed an absorption band at 345 nm due to the S0 → S2 transition of the pyrene group, whereas the fluorescence spectra showed a broad emission band arising from the “monomer” emission at 375–420 nm. The obtained polymers exhibited two absorption bands at 244 and 354 nm, due to the polythiophene and the pyrene moieties, respectively. The fluorescence spectra of polymers showed a broad “monomer” emission at 380–420 nm followed by an intense excimer emission band at 570 nm, due to the presence of intramolecular pyrene-pyrene interactions in these compounds.

Studies to further investigate the inhibition of human liver microsomal CYP2C8 by the acyl-β-glucuronide of gemfibrozil.

Science.gov (United States)

Jenkins, S M; Zvyaga, T; Johnson, S R; Hurley, J; Wagner, A; Burrell, R; Turley, W; Leet, J E; Philip, T; Rodrigues, A D

2011-12-01

In previous studies, gemfibrozil acyl-β-glucuronide, but not gemfibrozil, was found to be a mechanism-based inhibitor of cytochrome P450 2C8. To better understand whether this inhibition is specific for gemfibrozil acyl-β-glucuronide or whether other glucuronide conjugates are potential substrates for inhibition of this enzyme, we evaluated several pharmaceutical compounds (as their acyl glucuronides) as direct-acting and metabolism-dependent inhibitors of CYP2C8 in human liver microsomes. Of 11 compounds that were evaluated as their acyl glucuronide conjugates, only gemfibrozil acyl-β-glucuronide exhibited mechanism-based inhibition, indicating that CYP2C8 mechanism-based inhibition is very specific to certain glucuronide conjugates. Structural analogs of gemfibrozil were synthesized, and their glucuronide conjugates were prepared to further examine the mechanism of inhibition. When the aromatic methyl groups on the gemfibrozil moiety were substituted with trifluoromethyls, the resulting glucuronide conjugate was a weaker inhibitor of CYP2C8 and mechanism-based inhibition was abolished. However, the glucuronide conjugates of monomethyl gemfibrozil analogs were mechanism-based inhibitors of CYP2C8, although not as potent as gemfibrozil acyl-β-glucuronide itself. The ortho-monomethyl analog was a more potent inhibitor than the meta-monomethyl analog, indicating that CYP2C8 favors the ortho position for oxidation and potential inhibition. Molecular modeling of gemfibrozil acyl-β-glucuronide in the CYP2C8 active site is consistent with the ortho-methyl position being the favored site of covalent attachment to the heme. Moreover, hydrogen bonding to four residues (Ser100, Ser103, Gln214, and Asn217) is implicated.

A physiological toxicokinetic model for dermal absorption of waterborne pyrene by trout

Energy Technology Data Exchange (ETDEWEB)

Namdari, R.; Law, F.C.P. [Simon Fraser Univ., Burnaby, British Columbia (Canada)

1995-12-31

A physiologically-based toxicokinetic (PB-TK) model was developed to describe the disposition of pyrene in trout following a bolus injection into the dorsal aorta. In the present study, the PB-TK model was adapted for dermal absorption of waterborne pyrene by trout. A skin compartment with transdermal flux described mathematically by the permeability-area-concentration product was added to the PB-TK model to allow prediction of pyrene concentrations in target organs and blood on the basis of exposure concentration at the skin surface. Physiologically relevant parameters e.g., organ volume, blood flow rate, and tissue/blood partitioning coefficient which were derived from the model were similar to those reported in the previous publication. The dermal PB-TK model was validated by exposing the trunk of trout (400--500 g) to stagnant water containing 24 ppm pyrene in a specially designed chamber for 4 hr, 24 hr or 48 hr. The trout were sacrificed at the conclusion of pyrene exposure and the tissues analyzed for unchanged pyrene by HPLC. In separate experiments, trout were implanted with dorsal aorta cannuli before the trunks were exposed to stagnant water containing 24 ppm pyrene in the chamber for 4 hr. At specific time intervals during and after pyrene exposure, blood samples were withdrawn through the cannula and analyzed for pyrene by HPLC. The agreement between simulated and experimentally obtained values shows that this model is an appropriate tool to predict dermal absorption of waterborne pyrene by trout.

Investigation of benzo(a)pyrene-globin adducts

Energy Technology Data Exchange (ETDEWEB)

Wallin, H; Jeffre, A M; Santella, R M

1987-05-01

The nature of the adducts formed between benzo(a)pyrene (BP) and globin were investigated in animals treated with (/sup 3/H)BP. Modification levels on globin were determined by radioactivity measurements. Since BP tetraols can be released from benzo(a)pyrene diol epoxide modified protein and DNA by acid treatment, globin samples were treated with acid, released tetraols separated by HPLC and quantitated by scintillation counting. In addition, acid released material was measured in competitive enzyme linked immunosorbent assay (ELISA) using antibodies which recognize BP tetraols. Both measurements indicate that only 2% of bound radioactivity could be released as free BP tetraols. These studies indicate that benzo(a)pyrene diol epoxide may not be the major metabolite of BP involved in globin binding. (author). 14 refs.

Carcinogenicity of the environmental pollutants cyclopenteno-(cd)pyrene and cyclopentano(cd)pyrene in mouse skin

Energy Technology Data Exchange (ETDEWEB)

Cavalieri, E.; Rogan, E.; Toth, B.; Munhall, A.

1981-01-01

Cyclopenteno(cd)pyrene (CPEP) is a widespread environmental pollutant. This hydrocarbon and its 3,4-dihydro derivative, cyclopentano(cd)pyrene (CPAP), were tested on skin in a two-stage initiation-promotion experiment in CD-1 mice and by repeated application in Swiss mice. The biological effect of CPEP and CPAP was compared to that of benzo(a)-pyrene (BP). Nine-week-old female CD-1 mice in groups of 30 were treated every other day over a 20-day period at mini-dose levels of 0.18, 0.06 and 0.02 mumol of CPEP or CPAP in acetone. One group was treated with BP at the low mini-dose level. Initiation was followed by twice weekly application of tetradecanoyl phorbol acetate for 40 weeks. In the second experiments, nine-week-old female Swiss mice in groups of 30 were treated at dose levels of 1.8, 0.6 and 0.2 mumol CPEP or CPAP in acetone twice weekly for 30 weeks. One group was treated with BP at the low dose. CPAP was virtually inactive in both studies. In the initiation-promotion experiment CPEP was inactive at the low dose level, whereas BP exhibited significant tumorigenicity. At the medium and high doses CPEP showed weak, but statistically insignificant, tumorigenic activity. Repeated application of CPEP at the high, medium and low doses resulted in tumor incidences of 23, 37 and 57%, respectively. This reverse dose-response may be due to the relatively high cytotoxicity of CPEP, BP, which was compared to CPEP at the low dose, elicited tumors in 100% of the mice. Most of the CPEP-induced neoplasms were malignant and some metastasized to lungs and lymph nodes. The inactivity of CPAP suggests the carcinogenicity of CPEP is probably due to formation of the ultimate metabolite CPEP 3,4-oxide. In view of the abundance of CPEP in environmental and occupational pollutants, its moderately potent carcinogenicity may represent a potential health hazard.

Pyrene removal from contaminated soil using electrokinetic process combined with surfactant

Directory of Open Access Journals (Sweden)

Seyed Enayat Hashemi

2015-07-01

Full Text Available Background: Pyrene is one of the stable polycyclic aromatic hydrocarbons that is considered as an important pollutants, because of extensive distribution in the environment and carcinogenic and mutagenic properties. Among the various treatment techniques, electrokinetic method is an environmental- friendly process for organic and mineral pollutants adsorbed to soil with fine pore size the same as clay and low hydraulic conductivity soils. For improving the efficiency of pyrene removal from soil, soulobilization of pyrene from soil could be used by surfactants. Materials and Methods : In this study, clay soil was selected as model because of the specific properties. Combined method using surfactant and electrokinetic was applied for pyrene removal from soil. Experiments were designed using response surface methodology (RSM, and effect of three variables includes surfactant concentration, voltage and surfactant type were evaluated for pyrene removal from contaminated soil. Results: Pyrene removal using anionic surfactants(SDS and nonionic surfactants(TX100 as a solubilizing agents has high removal efficiency. In the optimum condition with 95% confidence coefficient, utilizing mixed surfactants of sodium dodecyl sulfate and triton X-100 with the same volume, induced of 18.54 volt and 6.53 percent surfactant concentration have 94.6% pyrene removal efficiency. Conclusion:: Results of this study shows that electrokinetic process combined with surfactant as solubilizing agent could be applied as an efficient method for treating the pyrene-contaminated soils.

Flow-through sensor based on derivative synchronous fluorescence spectrometry for the simultaneous determination of pyrene, benzo(e)pyrene and benzo(ghi)perylene in water

Energy Technology Data Exchange (ETDEWEB)

Canizares, P. [Cordoba Univ. (Spain). Dept. of Anal. Chem.; Luque de Castro, M.D. [Cordoba Univ. (Spain). Dept. of Anal. Chem.

1996-02-01

A flow-through/first derivative synchronous spectrofluorimetric sensor for the determination of PAH has been described. This sensor has been used for the simultaneous determination of PAH mixtures (pyrene, benzo(e)pyrene and benzo(ghi)perylene). Linear calibration ranges between 10 and 500 ng/ml with acceptable precision (repeatability, expressed as relative standard deviation, smaller than 4.6%, and sampling frequency of 12 h{sup -1}) have been obtained. The method has been applied to the determination of the target analytes in spiked water samples with excellent results (recoveries between 94 and 108%). (orig.)

Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers

DEFF Research Database (Denmark)

Villesen, Hanne H.; Kristensen, Kim; Hansen, Steen Honoré

2007-01-01

After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3-g......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

Coumarin–pyrene conjugate: Synthesis, structure and Cu-selective fluorescent sensing in mammalian kidney cells

Energy Technology Data Exchange (ETDEWEB)

Wani, Manzoor Ahmad [Department of Chemistry, Dr. H. S. Gour Central University Sagar, MP 470003 (India); Singh, Pankaj Kumar [Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016 (India); Pandey, Rampal, E-mail: rpvimlesh@gmail.com [Department of Chemistry, Dr. H. S. Gour Central University Sagar, MP 470003 (India); Pandey, Mrituanjay D., E-mail: mdpandey@dhsgsu.ac.in [Department of Chemistry, Dr. H. S. Gour Central University Sagar, MP 470003 (India)

2016-03-15

In this work, we report a coumarin–pyrene based fluorescent probes (E)-7-(diethylamino)-3-((pyren-1-ylimino)methyl)-2H-chromen-2-one (1) and (E)-7-(diethylamino)-3-((pyren-1-ylmethylimino)methyl)-2H-chromen-2-one (2) for the selective detection of Cu{sup 2+} ion. Receptor 1 upon binding with Cu{sup 2+} exhibited substantial fluorescence quenching as a detection response. Probe 1 induces green fluorescence in a cell lines derived from monkey kidney tissue and subsequent quenching of fluorescence in these cells manifest that 1 can probably be used as a potential fluorescent sensor for the detection of Cu{sup 2+} in biological samples too. However, 2 does not reveal any significant fluorescence change in presence of different metal ions. It is assumed that conjugation might be accountable for the discrete fluorescent behavior of 1 and 2.

Unlocked nucleic acids with a pyrene-modified uracil: Synthesis, hybridization studies, fluorescent properties and i-motif stability

DEFF Research Database (Denmark)

Perlíková, P.; Karlsen, K.K.; Pedersen, E.B.

2014-01-01

The synthesis of two new phosphoramidite building blocks for the incorporation of 5-(pyren-1-yl)uracilyl unlocked nucleic acid (UNA) monomers into oligonucleotides has been developed. Monomers containing a pyrene-modified nucleobase component were found to destabilize an i-motif structure at pH 5...... intensities upon hybridization to DNA or RNA. Efficient quenching of fluorescence of pyrene-modified UNA monomers was observed after formation of i-motif structures at pH 5.2. The stabilizing/destabilizing effect of pyrene-modified nucleic acids might be useful for designing antisense oligonucleotides...

Dual partitioning and attachment effects of rhamnolipid on pyrene biodegradation under bioavailability restrictions

International Nuclear Information System (INIS)

Congiu, Eleonora; Parsons, John R.; Ortega-Calvo, José-Julio

2015-01-01

We investigated the effects of different bioavailability scenarios on the rhamnolipid-enhanced biodegradation of pyrene by the representative polycyclic aromatic hydrocarbon degrader Mycobacterium gilvum VM552. This biosurfactant enhanced biodegradation when pyrene was provided in the form of solid crystals; no effect was observed when the same amount of the chemical was preloaded on polydimethylsiloxane (PDMS). An enhanced effect was observed when pyrene was sorbed into soil but not with the dissolved compound. Synchronous fluorescence spectrophotometry and liquid scintillation were used to determine the phase exchange of pyrene. We also investigated the phase distribution of bacteria. Our results suggest that the rhamnolipid can enhance the biodegradation of pyrene by micellar solubilization and increase diffusive uptake. These mechanisms increase substrate acquisition by bacterial cells at exposure concentrations well above the half-saturation constant for active uptake. The moderate solubilization of pyrene from PDMS by the rhamnolipid and the prevention of cell attachment may explain the lack of enhancement for pyrene-preloaded PDMS. - Highlights: • Rhamnolipid biosurfactant can enhance the biodegradation of pyrene. • The enhancement depends on how the bacteria are exposed to the pollutant. • Rhamnolipid stimulates if pyrene is provided by dissolution from crystals. • No effect is observed if pyrene is provided by partitioning from a silicone polymer. • This lack of effect is due to the balance between enhanced dissolution and decreased cell attachment. - Rhamnolipid-enhanced biodegradation of pyrene may depend on the exposure regime. Moderate solubilization from difficult matrices and prevention of cell attachment may have no effect

Conditions for effective removal of pyrene from an artificially contaminated soil using Pseudomonas aeruginosa 57SJ rhamnolipids

International Nuclear Information System (INIS)

Bordas, Francois; Lafrance, Pierre; Villemur, Richard

2005-01-01

The efficacy of a new rhamnolipid biosurfactants mixture to enhance the removal of pyrene from a soil artificially contaminated was investigated. The molar solubilization ratio (MSR) and the partition coefficient between the micelles and water (log K m ) were found to be 7.5 x 10 -3 and 5.7, respectively. From soil column studies, the pyrene removal increased linearly with the concentration of the injected biosurfactants solution above the effective critical micellar concentration (0.4 g L -1 ). Flushing with a 5.0 g L -1 biosurfactants solution increased the pyrene concentration in the effluent by 178 times. At high biosurfactants' concentrations (2.5 and 5.0 g L -1 ), the cumulative pyrene recovery reached 70%. This pyrene remobilization takes place independently of the soil organic carbon solubilization. This study provides a combination of batch and column experiments in order to find the conditions for effective soil remediation using a new rhamnolipids mixture. - The potential of newly isolated biosurfactants to mobilize PAHs from contaminated soils was evaluated from the determination in dynamic conditions of their effective critical micellar concentration

Flow cytometric measurement of the metabolism of benzo[a]pyrene by mouse liver cells in culture

International Nuclear Information System (INIS)

Bartholomew, J.C.; Wade, C.G.; Dougherty, K.K.

1984-01-01

The metabolism of benzo[a]pyrene in individual cells was monitored by flow cytometry. The measurements are based on the alterations that occur in the fluorescence emission spectrum of benzo[a]pyrene when it is converted to various metabolites. Using present instrumentation the technique could easily detect 1x10 6 molecules per cells of benzo[a]pyrene and 1x10 7 molecules per cell of the diol epoxide. The analysis of C3H IOT 1/2 mouse fibroblasts growing in culture indicated that there was heterogeneity in the conversion of the parent compound into diol epoxide derivatives suggesting that some variation in sensitivity to transformation by benzo[a]pyrene may be due to differences in cellular metabolism. The technique allows sensitive detection of metabolites in viable cells, and provides a new approach to the study of factors that influence both metabolism and transformation. (orig.)

Reactions of model compounds in the presence of pyrene and MoS sub 2 to simulate coprocessing

Energy Technology Data Exchange (ETDEWEB)

Ting, P.-S.; Curtis, C.W.; Cronauer, D.C. (Auburn University, Auburn, AL (USA). Chemical Engineering Dept.)

Catalytic reactions of pyrene using in situ generated MoS{sub 2} from molybdenum naphthenate and excess sulfur were evaluated in the presence of added model species, both hydrocarbons and heteroatomic species. The added hydrocarbons and heteroatomic compounds containing oxygen and sulfur had little effect on the hydrogenation of pyrene at either 400 or 425{degree}C, but quinoline at 400{degree}C reduced the hydrogenation of pyrene by half. Reactions at 425{degree}C also reduced the hydrogenation of pyrene by half regardless of the added model species. The added model species underwent different degrees of reaction: the hydrocarbons underwent little or no reaction, dibenzofuran showed little hydrodeoxygenation, dibenzothiophene yielded substantial hydrodesulfurization and quinoline was almost totally hydrodenitrogenated. The addition of quinoline at increasing concentration resulted in substantial lowering of pyrene hydrogenation and quinoline hydrodenitrogenation. Introduction of quinoline at a low concentration of 0.4 wt% gave a pyrene hydrogenation rate constant of 0.073 min{sup -1} at 400{degree}C while an increase in quinoline to 10.0 wt% yielded a rate constant of 0.020 min{sup -1}. 21 refs., 7 figs., 6 tabs.

Co-effects of pyrene and nitrate on the activity and abundance of soil denitrifiers under anaerobic condition.

Science.gov (United States)

Zhou, Zhi-Feng; Yao, Yan-Hong; Wang, Ming-Xia; Zuo, Xiao-Hu

2017-10-01

It has previously been confirmed that polycyclic aromatic hydrocarbons (PAHs) could be degraded by soil microbes coupling with denitrification, but the relationships among soil denitrifiers, PAHs, and nitrate under obligate anaerobic condition are still unclear. Here, co-effects of pyrene and nitrate on the activity and abundance of soil denitrifiers were investigated through a 45-day incubation experiment. Two groups of soil treatments with (N 30 ) and without (N 0 ) nitrate (30 mg kg -1 dry soil) amendment were conducted, and each group contained three treatments with different pyrene concentrations (0, 30, and 60 mg kg -1 dry soil denoted as P 0 , P 30 , and P 60 , respectively). The pyrene content, abundances of denitrification concerning genes (narG, periplasmic nitrate reductase gene; nirS, cd 1 -nitrite reductase gene; nirK, copper-containing nitrite reductase gene), and productions of N 2 O and CO 2 were measured at day 3, 14, 28, and 45, and the bacterial community structures in four represented treatments (N 0 P 0 , N 0 P 60 , N 30 P 0 , and N 30 P 60 ) were analyzed at day 45. The results indicated that the treatments with higher pyrene concentration had higher final pyrene removal rates than the treatments with lower pyrene concentration. Additionally, intensive emission of N 2 O was detected in all treatments only at day 3, but a continuous production of CO 2 was measured in each treatment during the incubation. Nitrate amendment could enhance the activity of soil denitrifiers, and be helpful for soil microbes to sustain their activity. While pyrene seemed had no influence on the productions of N 2 O and CO 2 , and amendment with pyrene or nitrate both had no obvious effect on abundances of denitrification concerning genes. Furthermore, it was nitrate but not pyrene had an obvious influence on the community structure of soil bacteria. These results revealed that, under anaerobic condition, the activity and abundance of soil denitrifiers both were

Circularly polarized luminescence of helically assembled pyrene π-stacks on RNA and DNA duplexes.

Science.gov (United States)

Nakamura, Mitsunobu; Ota, Fuyuki; Takada, Tadao; Akagi, Kazuo; Yamana, Kazushige

2018-05-01

In this report, we describe the circularly polarized luminescence (CPL) of the RNA duplexes having one to four 2'-O-pyrene modified uridines (Upy) and the DNA duplexes having two, four, and six pyrene modified non-nucleosidic linkers (Py). Both the pyrene π-stack arrays formed on the RNA and DNA double helical structures exhibited pyrene excimer fluorescence. In the pyrene-modified RNA systems, the RNA duplex having four Upys gives CPL emission with g lum value of <0.01 at 480 nm. The structure of pyrene stacks on the RNA duplex may be rigidly regulated with increase in the Upy domains, which resulted in the CPL emission. In the DNA systems, the pyrene-modified duplexes containing two and four Pys exhibited CPL emission with g lum values of <0.001 at 505 nm. The pyrene π-stack arrays presented here show CPL emission. However, the g lum values are relatively small when compared with our previous system consisting of the pyrene-zipper arrays on RNA. © 2018 Wiley Periodicals, Inc.

LC-H-1 NMR used for determination of the elution order of S-naproxen glucuronide isomers in two isocratic reversed-phase LC-systems

DEFF Research Database (Denmark)

Mortensen, R. W.; Corcoran, O.; Cornett, Claus

2001-01-01

. In both systems the elution order for the 2-, 3- and 4-O-acyl isomers corresponded with previously published results for 2-, 3-, and 4-fluorobenzoic acid glucuronide isomers determined by reversed phase HPLC-H-1 NMR [U.G. Sidelmann, S.H. Hansen, C. Gavaghan, A.W. Nicholls, H.A.J. Carless, J.C. Lindon, I...

Bioavailability and toxicity of pyrene in soils upon biochar and compost addition.

Science.gov (United States)

Bielská, Lucie; Kah, Melanie; Sigmund, Gabriel; Hofmann, Thilo; Höss, Sebastian

2017-10-01

The study investigates the role of biochar and/or compost in mitigating the toxic effects of pyrene in soils using reproduction of nematodes and porewater concentration as measures of pyrene toxicity and bioavailability, respectively. Two soils were spiked with increasing levels of pyrene to achieve a concentration-response relationship for the reproduction of Caenorhabditis elegans. The observed EC50 values (pyrene concentration causing 50% inhibition of reproduction) were 14mg/kg and 31mg/kg (dry mass) for these soils, corresponding to equilibrium porewater concentrations of 37μg/L and 47μg/L, respectively. Differences in organic carbon content were not sufficient to explain the variability in toxicity between the different soils. Soils causing a significant inhibition of reproduction were further amended with 10%-compost, 5%-biochar, or both, and the effects on reproduction and porewater concentration determined. Combined addition of compost and biochar was identified as the most effective strategy in reducing pyrene concentration in soil porewater, which was also partly reflected in soil toxicity. However, porewater concentrations predicted only 52% of pyrene toxicity to nematodes, pointing to particle-bound or dietary exposure pathways. Capsule: Amending pyrene-spiked soil with biochar and compost effectively reduced pyrene porewater concentrations and toxicity to nematodes, which were significantly related. Copyright © 2017 Elsevier B.V. All rights reserved.

Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.

Science.gov (United States)

Sell, David R; Nemet, Ina; Liang, Zhili; Monnier, Vincent M

2018-04-01

LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes. The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs). We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid. LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC). Advanced NMR techniques ( 1 H-NMR, 13 C-NMR, 1 H- 13 C HSQC, 1 H- 1 H TOCSY, 1 H- 13 C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1. To confirm this data, LW-1 was incubated with β-glycosidases (glucosidase, galactosidase, glucuronidase) and products were analyzed by LC-MS. Only glucuronidase could cleave the sugar from the parent molecule. These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications". Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.

Thermal properties and physicochemical behavior in aqueous solution of pyrene-labeled poly(ethylene glycol-polylactide conjugate

Directory of Open Access Journals (Sweden)

Chen WL

2015-04-01

Full Text Available Wei-Lin Chen,1,2 Yun-Fen Peng,1,3 Sheng-Kuo Chiang,1 Ming-Hsi Huang1–3 1National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; 2Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 3PhD Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, Taiwan Abstract: A fluorescence-labeled bioresorbable polymer was prepared by a coupling reaction of poly(ethylene glycol-polylactide (PEG-PLA with carboxyl pyrene, using N,N’-diisopropylcarbodiimide/1-hydroxy-7-azabenzotriazole (DIC/HOAt as a coupling agent and 4-dimethylaminopyridine (DMAP as a catalyst. The obtained copolymer, termed PEG-PLA-pyrene, was characterized using various analytical techniques, such as gel permeation chromatography (GPC, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS, proton nuclear magnetic resonance (1H-NMR, infrared spectroscopy (IR, differential scanning calorimetry (DSC, and thermogravimetric analysis (TGA, to identify the molecular structure and to monitor the thermal property changes before and after the reaction. The presence of a pyrene moiety at the end of polylactide (PLA did not alter the crystallization ability of the poly(ethylene glycol (PEG blocks, indicating that the conjugate preserved the inherent thermal properties of PEG-PLA. However, the presence of PEG-PLA blocks strongly reduced the melting of pyrene, indicating that the thermal characteristics were sensitive to PEG-PLA incorporation. Regarding the physicochemical behavior in aqueous solution, a higher concentration of PEG-PLA-pyrene resulted in a higher ultraviolet-visible (UV-vis absorbance and fluorescence emission intensity. This is of great interest for the use of this conjugate as a fluorescence probe to study the in vivo distribution as well as the internalization and intracellular localization of polymeric micelles

Isothermal annealing kinetics of X-irradiated pyrene by EPR

International Nuclear Information System (INIS)

Partiti, C.S.M.; Pontuschka, W.M.; Fazzio, A.; Piccini, A.

1989-07-01

The annealing behavior of X-irradiated stable free radicals found in Pyrene (C 16 H 10 ) single crystals was studied by EPR. Two processes of thermal decay kinetics were found, both with the same activation energy (1.9±0.1) ev. (author) [pt

Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

Energy Technology Data Exchange (ETDEWEB)

Ohara, Kazuaki, E-mail: Kazuaki_Ohara@kirin.co.jp [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Wakabayashi, Hideyuki [Laboratory for New Product Development, Kirin Beverage Company Limited, 1-17-1 Namamugi, Tsurumi-ku, Yokohama 230-8628 (Japan); Taniguchi, Yoshimasa [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Shindo, Kazutoshi [Department of Food and Nutrition, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681 (Japan); Yajima, Hiroaki [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Yoshida, Aruto [Central Laboratories for Key Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)

2013-11-29

Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXRα. •Q3GA induced ABCA1 via LXRα activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.

Stereo-selectivity and regio-selectivity in the metabolism of 7,8-dihydrobenzo[a]pyrene by cytochrome P450, epoxide hydrolase and hepatic microsomes from 3-methylcholanthrene-treated rats.

Science.gov (United States)

Adams, J D; Yagi, H; Levin, W; Jerina, D M

1995-03-30

The active site of cytochrome P450 1A1 has been probed with the substrate 7,8-dihydrobenzo[a]pyrene using a purified, reconstituted system composed of cytochrome P450 1A1, NADPH-cytochrome c reductase and lipid in the presence or absence of epoxide hydrolase. The turnover of the substrate was found to be 38 nmol/nmol of cytochrome P450/min. The metabolic products that were identified are: a phenolic 7,8-dihydrobenzo[a]pyrene (20-29%); 9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (17-28%); benzo[a]pyrene (12-19%); 7-hydroxy-7,8-dihydrobenzo[a]pyrene (13-16%); 8-hydroxy-7,8-dihydrobenzo[a]pyrene (7-15%); 3-hydroxybenzo[a]pyrene (7-15%); 4,5-epoxy-4,5,7,8-tetrahydrobenzo[a]pyrene (0-4%); and a triol of 7,8,9,10-tetrahydrobenzo[a]pyrene (0-4%). 9,10-Epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene undergoes rapid hydrolysis to cis- and trans-9,10-dihydroxy-dihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (2:1) by benzylic attack of water at C-10. Approximately 71% of the trans diols are derived from (+)-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, indicating that cytochrome P450 1A1 has more than a 2:1 preference for selective epoxidation of an enantiotopic face of 7,8-dihydrobenzo[a]pyrene. This stereo-selectivity agrees with the postulated stereo-selectivity predicted by a previously described active site model for cytochrome P450 1A1. Epoxide hydrolase in pure form or in hepatic microsomes catalyzes the hydrolysis of 9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, which is inhibited by 1,1,1-trichloropropane 2,3-oxide. The (+)-(9S,10R)-isomer of the epoxide is slightly preferred as a substrate over its enantiomer and is cleaved by benzylic and nonbenzylic attack. Only benzylic attack was found with (-)-(9R,10S)-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

Bis-pyrene-modified unlocked nucleic acids: synthesis, hybridization studies, and fluorescent properties

DEFF Research Database (Denmark)

Perlíková, Pavla; Ejlersen, Maria; Langkjaer, Niels

2014-01-01

Efficient synthesis of a building block for the incorporation of a bis-pyrene-modified unlocked nucleic acid (UNA) into oligonucleotides (DNA*) was developed. The presence of bis-pyrene-modified UNA within a duplex leads to duplex destabilization that is more profound in DNA*/RNA and less distinc......)uracil:pyrene exciplex emission in the single-stranded form. Such fluorescent properties enable the application of bis-pyrene-modified UNA in the development of fluorescence probes for DNA/RNA detection and for detection of deletions at specific positions....

PRACTICAL PREPARATION OF RESVERATROL 3-O-β-D-GLUCURONIDE

OpenAIRE

Jungong, Christian S.; Novikov, Alexei V.

2012-01-01

A practical synthesis of resveratrol 3-O-β-D-glucuronide, suitable for preparation of large quantities, was developed using selective deacetylation of resveratrol triacetate with ammonium acetate. A simplified procedure for large scale preparation of resveratrol is also reported.

Synthesis, physicochemical properties, and biological activity of bile acids 3-glucuronides: Novel insights into bile acid signalling and detoxification.

Science.gov (United States)

Mostarda, Serena; Passeri, Daniela; Carotti, Andrea; Cerra, Bruno; Colliva, Carolina; Benicchi, Tiziana; Macchiarulo, Antonio; Pellicciari, Roberto; Gioiello, Antimo

2018-01-20

Glucuronidation is considered an important detoxification pathway of bile acids especially in cholestatic conditions. Glucuronides are less toxic than the parent free forms and are more easily excreted in urine. However, the pathophysiological significance of bile acid glucuronidation is still controversial and debated among the scientific community. Progress in this field has been strongly limited by the lack of appropriate methods for the preparation of pure glucuronides in the amount needed for biological and pharmacological studies. In this work, we have developed a new synthesis of bile acid C3-glucuronides enabling the convenient preparation of gram-scale quantities. The synthesized compounds have been characterized in terms of physicochemical properties and abilities to modulate key nuclear receptors including the farnesoid X receptor (FXR). In particular, we found that C3-glucuronides of chenodeoxycholic acid and lithocholic acid, respectively the most abundant and potentially cytotoxic species formed in patients affected by cholestasis, behave as FXR agonists and positively regulate the gene expression of transporter proteins, the function of which is critical in human conditions related to imbalances of bile acid homeostasis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Conditions for effective removal of pyrene from an artificially contaminated soil using Pseudomonas aeruginosa 57SJ rhamnolipids

Energy Technology Data Exchange (ETDEWEB)

Bordas, Francois [Institut national de la recherche scientifique, Centre INRS-Eau-Terre-Environnement, Universite du Quebec, 2800 rue Einstein, C.P. 7500, Sainte-Foy, Quebec, G1V 4C7 (Canada)]. E-mail: francois.bordas@unilim.fr; Lafrance, Pierre [Institut national de la recherche scientifique, Centre Eau, Terre et Environnement, Universite du Quebec, 490, rue de la Couronne, Quebec, G1K 9A9 (Canada)]. E-mail: pierre_lafrance@inrs-ete.uquebec.ca; Villemur, Richard [Institut national de la recherche scientifique, Centre INRS-Institut Armand Frappier, Universite du Quebec, 531 bd des Prairies, Laval, Quebec, H7V 1B7 (Canada)]. E-mail: richard.villemur@inrs-iaf.uquebec.ca

2005-11-15

The efficacy of a new rhamnolipid biosurfactants mixture to enhance the removal of pyrene from a soil artificially contaminated was investigated. The molar solubilization ratio (MSR) and the partition coefficient between the micelles and water (log K {sub m}) were found to be 7.5 x 10{sup -3} and 5.7, respectively. From soil column studies, the pyrene removal increased linearly with the concentration of the injected biosurfactants solution above the effective critical micellar concentration (0.4 g L{sup -1}). Flushing with a 5.0 g L{sup -1} biosurfactants solution increased the pyrene concentration in the effluent by 178 times. At high biosurfactants' concentrations (2.5 and 5.0 g L{sup -1}), the cumulative pyrene recovery reached 70%. This pyrene remobilization takes place independently of the soil organic carbon solubilization. This study provides a combination of batch and column experiments in order to find the conditions for effective soil remediation using a new rhamnolipids mixture. - The potential of newly isolated biosurfactants to mobilize PAHs from contaminated soils was evaluated from the determination in dynamic conditions of their effective critical micellar concentration.

The effects of simultaneous application of plant growth regulators and bioaugmentation on improvement of phytoremediation of pyrene contaminated soils.

Science.gov (United States)

Rostami, Saeid; Azhdarpoor, Abooalfazl; Rostami, Majid; Samaei, Mohammad Reza

2016-10-01

Polycyclic aromatic hydrocarbons (PAHs) refer to a wide group of soil contaminants whose presence in the environment is a cause of concern. The present study aimed to evaluate the effects of Indole Acetic Acid (IAA) and Pseudomonas aeruginosa on the phytoremediation activities of sorghum bicolor and increase in pyrene removal efficiency in the soil. The initial concentration of pyrene was 150 and 300 mg kg(-1) in this experiment. The treatments included unplanted soil (T0), planted soil with sorghum (T1), planted soil with application of IAA (T2), planted soil with application of Pseudomonas sp. (T3), and planted soil with simultaneous application of IAA and Pseudomonas sp. (T4). The pyrene removal rate in the soil was measured every 30 days. Moreover, plant biomass and soil bacteria were measured after 90 days. The results showed that pyrene removal rate significantly increased in the planted treatments compared to the unplanted ones. After 90 days, at the initial concentration of 150-300 mg kg(-1), pyrene removal efficiency was 52-92% in T1-T4 and 35-47% in the unplanted treatment (T0). Application of IAA and Pseudomonas sp. significantly increased plant biomass, soil bacteria, and pyrene removal rate in T2, T3, and T4 compared to T1. Therefore, application of IAA in the planted treatments with sorghum could have a significant effect on increasing the removal efficiency of pyrene. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of pyrene labelling on the thermal stability of actin filaments

International Nuclear Information System (INIS)

Halasi, Szulamit; Papp, Gabor; Bugyi, Beata; Barko, Szilvia; Orban, Jozsef; Ujfalusi, Zoltan; Visegrady, Balazs

2006-01-01

The ability of actin to form filaments is fundamental to its biological function and often characterised by various methods in vitro. One of the most frequently used methods capitalises on the observation that the fluorescence emission of a pyrene label on the Cys-374 residue of actin is enhanced by a factor of ∼20 during polymerisation. This method inherently involves the chemical modification of actin monomers with pyrene. It was reported earlier that the pyrene labelling of actin monomers has only small effect on the polymerisation and depolymerisation rates of actin, indicating that the method is suitable to characterise the effect of actin-binding proteins or peptides on the polymerisation kinetics. In our present work we tested the effect of the pyrene labelling on the thermal denaturation of actin filaments by using the method of differential scanning calorimetry (DSC). By recording the heat denaturation profiles of unlabelled and pyrene labelled actin filaments we observed that pyrene labelling shifted the melting point (T m ) of actin filaments from 66 to 68 deg. C. A similar effect was detected in the presence of equimolar concentration of phalloidin where the T m shifted from 79 to 82 deg. C. We concluded that the observed pyrene labelling induced differences of the thermal denaturation of actin filaments were small. The DSC results, therefore, confirmed that the methods based on the measurements of pyrene intensity during actin polymerisation are suitable to characterise the polymerisation kinetics of actin under in vitro conditions

Pyrene Molecular Orbital Shuffle-Controlling Excited State and Redox Properties by Changing the Nature of the Frontier Orbitals.

Science.gov (United States)

Merz, Julia; Fink, Julian; Friedrich, Alexandra; Krummenacher, Ivo; Al Mamari, Hamad H; Lorenzen, Sabine; Haehnel, Martin; Eichhorn, Antonius; Moos, Michael; Holzapfel, Marco; Braunschweig, Holger; Lambert, Christoph; Steffen, Andreas; Ji, Lei; Marder, Todd B

2017-09-21

We show that by judicious choice of substituents at the 2- and 7-positions of pyrene, the frontier orbital order of pyrene can be modified, giving enhanced control over the nature and properties of the photoexcited states and the redox potentials. Specifically, we introduced a julolidine-like moiety and Bmes 2 (mes=2,4,6-Me 3 C 6 H 2 ) as very strong donor (D) and acceptor (A), respectively, giving 2,7-D-π-D- and unsymmetric 2,7-D-π-A-pyrene derivatives, in which the donor destabilizes the HOMO-1 and the acceptor stabilizes the LUMO+1 of the pyrene core. Consequently, for 2,7-substituted pyrene derivatives, unusual properties are obtained. For example, very large bathochromic shifts were observed for all of our compounds, and unprecedented green light emission occurs for the D/D system. In addition, very high radiative rate constants in solution and in the solid state were recorded for the D-π-D- and D-π-A-substituted compounds. All compounds show reversible one-electron oxidations, and Jul 2 Pyr exhibits a second oxidation, with the largest potential splitting (ΔE=440 mV) thus far reported for 2,7-substituted pyrenes. Spectroelectrochemical measurements confirm an unexpectedly strong coupling between the 2,7-substituents in our pyrene derivatives. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ovarian Hormone Estrone Glucuronide (E1G) quantification-impedimetric electrochemical spectroscopy approach

KAUST Repository

Zia, Asif I.; Mukhopadhyay, Subhas Chandra; Yu, Paklam; Al-Bahadly, Ibrahim H.; Yudhana, Anton; Gooneratne, Chinthaka Pasan; Kosel, Jü rgen

2013-01-01

A study was conducted on detection and concentration measurement of estrone glucuronide (E1G), an important metabolite of the ovarian hormone estradiol, by using Electrochemical Impedance Spectroscopy (EIS) technique. A miniature planar Inter-digital (ID) capacitive sensor fabricated on single crystal silicon substrate with sputtered gold electrodes coupled with EIS was used to measure conductivity, permeability and dielectric properties of the said hormone metabolite. A thin film of Silicon Nitride (50 um) was coated on the sensor as passivation layer to avoid Faradic currents through the sensor. Impedance spectrums were obtained with various concentrations of E1G in buffer solution by exposing the samples to electrical perturbations at certain frequency range. Relationship of sample conductance with E1G concentration was studied on basis Randle's equivalent circuit model and results were analyzed to deduce Constant Phase Equivalent (CPE) Circuit model in order to evaluate the double layer capacitance produced at the solution-electrode interface due to kinetic processes taking place in the electrochemical cell. The sensitivity of the sensor was evaluated against concentration. The result analysis confirmed that fabricated ID sensor together with EIS can provide a rapid and successful low cost sensing system which can help a lay user to determine peak time for feminine reproductive fertility at home without submitting samples for an expensive and time consuming laboratory test. © 2013 IEEE.

Ovarian Hormone Estrone Glucuronide (E1G) quantification-impedimetric electrochemical spectroscopy approach

KAUST Repository

Zia, Asif I.

2013-12-01

A study was conducted on detection and concentration measurement of estrone glucuronide (E1G), an important metabolite of the ovarian hormone estradiol, by using Electrochemical Impedance Spectroscopy (EIS) technique. A miniature planar Inter-digital (ID) capacitive sensor fabricated on single crystal silicon substrate with sputtered gold electrodes coupled with EIS was used to measure conductivity, permeability and dielectric properties of the said hormone metabolite. A thin film of Silicon Nitride (50 um) was coated on the sensor as passivation layer to avoid Faradic currents through the sensor. Impedance spectrums were obtained with various concentrations of E1G in buffer solution by exposing the samples to electrical perturbations at certain frequency range. Relationship of sample conductance with E1G concentration was studied on basis Randle\\'s equivalent circuit model and results were analyzed to deduce Constant Phase Equivalent (CPE) Circuit model in order to evaluate the double layer capacitance produced at the solution-electrode interface due to kinetic processes taking place in the electrochemical cell. The sensitivity of the sensor was evaluated against concentration. The result analysis confirmed that fabricated ID sensor together with EIS can provide a rapid and successful low cost sensing system which can help a lay user to determine peak time for feminine reproductive fertility at home without submitting samples for an expensive and time consuming laboratory test. © 2013 IEEE.

Aggregation induced emission enhancement of pyrene-appended Schiff base luminophore and its photovoltaic effect

Energy Technology Data Exchange (ETDEWEB)

Panda, Uttam; Roy, Suman; Mallick, Debashis [Department of Chemistry, Jadavpur University, Kolkata 700032 (India); Dalapati, Pradip [Condensed Matter Physics Research Center, Department of Physics, Jadavpur University, Kolkata 700032 (India); Biswas, Subir [Immunology Lab, Department of Zoology, University of Calcutta, Kolkata 700019 (India); Manik, Nabin Baran [Condensed Matter Physics Research Center, Department of Physics, Jadavpur University, Kolkata 700032 (India); Bhattacharyya, Arindam [Immunology Lab, Department of Zoology, University of Calcutta, Kolkata 700019 (India); Sinha, Chittaranjan, E-mail: c_r_sinha@yahoo.com [Department of Chemistry, Jadavpur University, Kolkata 700032 (India)

2016-07-15

Pyrene appended Schiff base, 1,3-bis-((E)-pyrene-1-ylmethyleneamino)propan-2-ol (HL), a fluorophore, shows aggregation induced emission enhancement upon addition of water in DMF (4:1, v/v) solution; the quantum yield (Φ) is increased by 0.034–0.450. Under illumination of solar radiation HL (10{sup −3} M) impregnated photovoltaic cell generates 4.4 mA/6.29 V electricity. DFT and TD-DFT computation of optimized geometry of HL has explained the photophysical properties.

IRIS Toxicological Review of Benzo[a]pyrene (Interagency ...

Science.gov (United States)

In January 2017, EPA finalized the IRIS assessment of Benzo[a]pyrene. The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science discussion materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Benzo[a]pyrene are posted on this site. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.

Biotransformation of the polycyclic aromatic hydrocarbon pyrene by the marine polychaete Nereis virens

DEFF Research Database (Denmark)

Jørgensen, Anne; Giessing, Anders M. B.; Rasmussen, Lene Juel

2005-01-01

In vivo and in vitro biotransformation of the polycyclic aromatic hydrocarbon (PAH) pyrene was investigated in the marine polychaete Nereis virens. Assays were designed to characterize phase I and II enzymes isolated from gut tissue. High-pressure liquid chromatography measurement of 1-hydroxypyr......In vivo and in vitro biotransformation of the polycyclic aromatic hydrocarbon (PAH) pyrene was investigated in the marine polychaete Nereis virens. Assays were designed to characterize phase I and II enzymes isolated from gut tissue. High-pressure liquid chromatography measurement of 1...

Inoculating wheat (Triticum aestivum L.) with the endophytic bacterium Serratia sp. PW7 to reduce pyrene contamination.

Science.gov (United States)

Zhu, Xuezhu; Wang, Wanqing; Sun, Kai; Lin, Xianghao; Li, Shuang; Waigi, Michael Gatheru; Ling, Wanting

2017-08-03

This research was conducted to find an optimal inoculation way for a pyrene-degrading endophytic Serratia sp. PW7 to colonize wheat for reducing pyrene contamination. Three inoculation ways, which are soaking seeds in inocula (TS), dipping roots of seedlings in inocula (TR), and spraying inocula on leaves of seedlings (TL), were used in this study. Inoculated seedlings and noninoculated seedlings (CK) were, respectively, cultivated in Hoagland solutions supplemented with pyrene in a growth chamber. The results showed that strain PW7 successfully colonized the inoculated seedlings in high numbers, and significantly promoted the growth of seedlings (TS and TR). More importantly, strain PW7 reduced pyrene levels in the seedlings and the Hoagland solutions. Compared to the noninoculated seedlings, the pyrene contents of the inoculated seedlings were decreased by 35.7-86.3% in the shoots and by 26.8-60.1% in the roots after 8-day cultivation. By comparing the efficiencies of decreasing pyrene residues, it can be concluded that TR was an optimal inoculation way for endophytic strains to colonize the inoculated plants and to reduce the pyrene contamination. Our findings provide an optimized inoculation way to reduce organic contamination in crops by inoculating plants with functional endophytic bacteria.

Pyrene-Phosphonate Conjugate: Aggregation-Induced Enhanced Emission, and Selective Fe3+ Ions Sensing Properties

Directory of Open Access Journals (Sweden)

Sachin D. Padghan

2017-08-01

Full Text Available A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE properties in water/acetonitrile (ACN solutions. Dynamic light scattering (DLS characterization revealed that the aggregates of receptor 1 at 80% water fraction have an average size of ≈142 nm. Field emission scanning electron microscopy (FE-SEM analysis confirmed the formation of spherical aggregates upon solvent evaporation. The sensing properties of receptor 1 were investigated by UV-vis, fluorescence emission spectroscopy, and other optical methods. Among the tested metal ions, receptor 1 is capable of recognizing the Fe3+ ion selectively. The changes in spectral measurements were explained on the basis of complex formation. The composition of receptor 1 and Fe3+ ions was determined by using Job’s plot and found to be 1:1. The receptor 1–Fe3+ complex showed a reversible UV-vis response in the presence of EDTA.

Synthesis of an estradiol glucuronide derivative and investigation of its radiopharmaceutical potential

International Nuclear Information System (INIS)

Biber, F.Z.; Unak, P.; Ertay, T.; Medine, E.I.; Zihnioglu, F.; Tasci, C.; Durak, H.

2006-01-01

The aim of the current study was to synthesize a derivative of estradiol glucuronide, which is able to be labeled with 99m Tc and to investigate its radiopharmaceutical potential using imaging and biodistribution studies. An estrogen derivative, β-estradiol (1,3,5,[10]-estratriene-3,17β-diol) attached to diethylenetriamine pentaacetic acid (DTPA) was synthesized in six steps. At the end of these steps a compound of estradiol and DTPA derivative called deoxy demethyl homoestradiolyl diethylenetriamine pentaacetic acid (ESTDTPA) was synthesized. Afterwards, this compound was reacted with UDP-glucuronyl transferase (UDPGT). Following the glucuronidation reaction, the product called deoxy demethyl homoestradiolyl diethylenetriamine pentaaceticacid-glucuronide (ESTDTPAG) was obtained. Synthesized products were purified using high performance liquid chromatography (HPLC). The identification of the purified products and impurities were also established using HPLC. Synthesized compound was labeled with 99m Tc. Thin layer radio chromatography (TLRC) technique was used to determine their radiochemical yields and stabilities. Labeling yield was over 96%. The biodistribution studies were performed on female Albino Wistar rats. The activity per gram tissue was calculated and time-activity curves were plotted. The target organs (tumor, as well as uterus, ovaries, adrenals and other ER containing tissues) retain the estradiol derivative longer than nontarget organs, but even these lost most of their activity within a few hours. In addition, the imaging studies were performed on normal and tumor bearing female Albino Wistar rats using Camstar XR/T gamma camera. In γ-scintigraphic imaging studies with 99m Tc-ESTDTPAG the breast tumors could be well visualized up to 24 h

Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

Science.gov (United States)

Dzobo, Kevin; Hassen, Naseeha; Senthebane, Dimakatso Alice; Thomford, Nicholas Ekow; Rowe, Arielle; Shipanga, Hendrina; Wonkam, Ambroise; Parker, M Iqbal; Mowla, Shaheen; Dandara, Collet

2018-04-17

Background: Environmental pollution such as exposure to pro-carcinogens including benzo-α-pyrene is becoming a major problem globally. Moreover, the effects of benzo-α-pyrene (BaP) on drug pharmacokinetics, pharmacodynamics, and drug resistance warrant further investigation, especially in cancer outpatient chemotherapy where exposure to environmental pollutants might occur. Method: We report here on the effects of benzo-α-pyrene on esophageal cancer cells in vitro, alone, or in combination with chemotherapeutic drugs cisplatin, 5-flurouracil, or paclitaxel. As the study endpoints, we employed expression of proteins involved in cell proliferation, drug metabolism, apoptosis, cell cycle analysis, colony formation, migration, and signaling cascades in the WHCO1 esophageal cancer cell line after 24 h of treatment. Results: Benzo-α-pyrene had no significant effect on WHCO1 cancer cell proliferation but reversed the effect of chemotherapeutic drugs by reducing drug-induced cell death and apoptosis by 30–40% compared to drug-treated cells. The three drugs significantly reduced WHCO1 cell migration by 40–50% compared to control and BaP-treated cells. Combined exposure to drugs was associated with significantly increased apoptosis and reduced colony formation. Evaluation of survival signaling cascades showed that although the MEK-ERK and Akt pathways were activated in the presence of drugs, BaP was a stronger activator of the MEK-ERK and Akt pathways than the drugs. Conclusion: The present study suggest that BaP can reverse the effects of drugs on cancer cells via the activation of survival signaling pathways and upregulation of anti-apoptotic proteins such as Bcl-2 and Bcl-xL. Our data show that BaP contribute to the development of chemoresistant cancer cells.

Microbial transformation of 6-nitrobenzo[a]pyrene

International Nuclear Information System (INIS)

Millner, G.C.; Fu, P.P.; Cerniglia, C.E.

1986-01-01

The fungal metabolism of the potent mutagenic and carcinogenic nitropolycyclic aromatic hydrocarbon (nitro-PAH) 6-nitrobenzo[a]pyrene (6-NO 2 -BaP) was investigated. Cunninghamella elegans was incubated with 6-NO 2 -BaP for periods ranging between 1 and 7 d, and the metabolites formed were separated by high-performance liquid chromatography and identified by their UV-visible absorption, mass, and 1 H nuclear magnetic resonance spectra. The results of the study indicate that C. elegans metabolized 6-NO 2 -BaP to glucoside and sulfate conjugates of 1- and 3-hydroxy 6-NO 2 -BaP and suggests that glycosylation and sulfation reactions may represent detoxification pathways in the fungal metabolism of nitro-PAHs. Experiments using [G- 3 H]-6-NO 2 -BaP indicated that C. elegans metabolized 62% of 6-NO 2 -BaP with 168 h. The data also indicated that the nitro group at the C-6 position of benzo[a]pyrene blocked metabolism at the regions peri to the nitro substituent (C-7, C-8 positions) and enhanced metabolism at the C-1 and C-3 positions. The ability of the fungus C. elegans to metabolize 6-NO 2 -BaP to biologically inactive compounds may have practical applications in the detoxification of nitro-PAH-contaminated wastes

The effect of caffeine on the reactions of the excited singlet state of pyrene in micellar sodium lauryl sulfate

Science.gov (United States)

Hashimoto, Shuichi; Thomas, J. Kerry

1984-08-01

The effect of caffeine on a few photo-induced reactions of pyrene in micellar sodium lauryl sulfate (NaLS) has been studied. In these systems caffeine complexes with the pyrene (K asso = 85 ± 10 M -1 and also with the other reactants, e.g. Cu 2+ or TI +. The efficiencies of reactions which involve contact, i.e. pyrene excimer formation, and quenching by TI + ions to give the triplet state of pyrene, are significantly reduced in the presence of caffeine, due to geometric inhibitions formed by the complexation processes. The kinetics of photo-induced electron transfer, e.g. between excited pyrene and Cu 2+, are not affected. However, the subsequent reactions of the products are modified and the yield of ionic products is markedly increased.

Equatorenes: synthesis and properties of chiral naphthalene, phenanthrene, chrysene, and pyrene possessing bis(1-adamantyl) groups at the peri-position.

Science.gov (United States)

Yamamoto, Koji; Oyamada, Naohiro; Xia, Sheng; Kobayashi, Yuta; Yamaguchi, Masahiko; Maeda, Hiroaki; Nishihara, Hiroshi; Uchimaru, Tadafumi; Kwon, Eunsang

2013-11-06

Chiral polycyclic aromatic hydrocarbons containing bis(1-adamantyl) groups at the peri-positions, named equatorenes, were synthesized in optically pure form starting from optically pure 4,5-bis(1-adamantyl)-8-methoxy-1-naphthol. A sequential Diels-Alder reaction of furan and arynes generated from 1,2-bromotriflates provided tricyclic and tetracyclic epoxides, and acid-catalyzed aromatization gave phenanthrol and chrysenol. Deoxygenation reactions involving the hydrogenolysis of triflates gave 1,8-bis(1-adamantyl)naphthalene, 1,10-bis(1-adamantyl)phenanthrene, and 1,12-bis(1-adamantyl)chrysene. 3,4-Bis(1-adamantyl)pyrene was synthesized from phenanthrol by Sonogashira coupling and Pt-catalyzed cyclization. Essentially no racemization occurred during the synthesis. X-ray analysis indicated the distorted naphthalene moiety possessing the peri-diadamantyl groups and the flat structure of the other benzene rings. UV-vis analysis of the equatorenes showed considerable redshifts compared with that of the corresponding achiral arenes. Electrochemical analysis of the naphthalene and pyrene indicated that the distortion decreased the highest occupied molecular orbital stability with no marked effect on the lowest unoccupied molecular orbital energy level, and the origin was discussed on the basis of calculation results.

High-efficiency pyrene-based blue light emitting diodes: Aggregation suppression using a calixarene 3D-scaffold

KAUST Repository

Chan, Khaileok

2012-01-01

An efficient blue light emitting diode based on solution processable pyrene-1,3-alt-calix[4]arene is demonstrated, providing a record current efficiency of 10.5 cd A -1 in a simple non-doped OLED configuration. Complete suppression of pyrene aggregation in the solid state is achieved by controlling chromophore dispersion using the 1,3-alt-calix[4]arene scaffold. © 2012 The Royal Society of Chemistry.

Multi step FRET among three laser dyes Pyrene, Acriflavine and Rhodamine B

International Nuclear Information System (INIS)

Saha, Jaba; Dey, Dibyendu; Roy, Arpan Datta; Bhattacharjee, D.; Hussain, Syed Arshad

2016-01-01

Fluorescence Resonance Energy Transfer (FRET) system using three dyes has been demonstrated. It has been observed that multi step energy transfer occurred from Pyrene to Rhodamine B via Acriflavine. Here Acriflavine acts as an antenna to receive energy from Pyrene and transfer the same to Rhodamine B. This multi step FRET system is advantageous compared to the conventional FRET as this can be used to study molecular level interaction beyond conventional FRET distance (1–10 nm) as well as studying multi-branched macromolecules. The introduction of clay enhances the FRET efficiencies among the dye pair, which is an advantage to make the multi step system more useful. Similar approach can be used for increasing FRET efficiencies by using other dyes. - Highlights: • Multi-step FRET occurred from Pyrene (Py) to Rhodamine B (RhB) via Acriflavine (Acf). • Acf acts as an antenna to receive energy from Py and to transfer energy to RhB. • Multi-step FRET can be used to study molecular level interaction beyond 1–10 nm. • Incorporation of nanoclay laponite enhances the energy transfer efficiency.

Charge-transfer excited state in pyrene-1-carboxylic acids adsorbed on titanium dioxide nanoparticles

Science.gov (United States)

Krawczyk, S.; Nawrocka, A.; Zdyb, A.

2018-06-01

The electronic structure of excited photosensitizer adsorbed at the surface of a solid is the key factor in the electron transfer processes that underlie the efficiency of dye-sensitized solar cells and photocatalysts. In this work, Stark effect (electroabsorption) spectroscopy has been used to measure the polarizability and dipole moment changes in electronic transitions of pyrene-1-carboxylic (PCA), -acetic (PAA) and -butyric (PBA) acids in ethanol, both free and adsorbed on colloidal TiO2, in glassy ethanol at low temperature. The lack of appreciable increase of dipole moment in the excited state of free and adsorbed PAA and PBA points that two or more single bonds completely prevent the expansion of π-electrons from the aromatic ring towards the carboxylic group, thus excluding the possibility of direct electron injection into TiO2. In free PCA, the pyrene's forbidden S0 → S1 transition has increased intensity, exhibits a long progression in 1400 cm-1 Ag mode and is associated with |Δμ| of 2 D. Adsorption of PCA on TiO2 causes a broadening and red shift of the S0 → S1 absorption band and an increase in dipole moment change on electronic excitation to |Δμ| = 6.5 D. This value increased further to about 15 D when the content of acetic acid in the colloid was changed from 0.2% to 2%, and this effect is ascribed to the surface electric field. The large increase of |Δμ| points that the electric field effect can not only change the energetics of electron transfer from the excited sensitizer into the solid, but can also shift the molecular electronic density, thus directly influencing the electronic coupling factor relevant for electron transfer at the molecule-solid interface.

Use of urinary pregnanediol 3-glucuronide to confirm ovulation.

Science.gov (United States)

Ecochard, R; Leiva, R; Bouchard, T; Boehringer, H; Direito, A; Mariani, A; Fehring, R

2013-10-01

Urinary hormonal markers may assist in increasing the efficacy of Fertility Awareness Based Methods (FABM). This study uses urinary pregnanediol-3a-glucuronide (PDG) testing to more accurately identify the infertile phase of the menstrual cycle in the setting of FABM. Secondary analysis of an observational and simulation study, multicentre, European study. The study includes 107 women and tracks daily first morning urine (FMU), observed the changes in cervical mucus discharge, and ultrasonography to identify the day of ovulation over 326 menstrual cycles. The following three scenarios were tested: (A) use of the daily pregnandiol-3a-glucuronide (PDG) test alone; (B) use of the PDG test after the first positive urine luteinizing hormone (LH) kit result; (C) use of the PDG test after the disappearance of fertile type mucus. Two models were used: (1) one day of PDG positivity; or (2) waiting for three days of PDG positivity before declaring infertility. After the first positivity of a LH test or the end of fertile mucus, three consecutive days of PDG testing over a threshold of 5μg/mL resulted in a 100% specificity for ovulation confirmation. They were respectively associated an identification of an average of 6.1 and 7.6 recognized infertile days. The results demonstrate a clinical scenario with 100% specificity for ovulation confirmation and provide the theoretical background for a future development of a competitive lateral flow assay for the detection of PDG in the urine. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of a UPLC–MS/MS method for determining ɣ-hydroxybutyric acid (GHB) and GHB glucuronide concentrations in hair and application to forensic cases

DEFF Research Database (Denmark)

Wang, Xin; Johansen, Sys Stybe; Linnet, Kristian

2016-01-01

We present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyric acid (GHB) and its glucuronide. The compounds were extracted from hair by incubation for 1.5 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8 % acetonitrile, pH 5.3). The co......We present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyric acid (GHB) and its glucuronide. The compounds were extracted from hair by incubation for 1.5 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8 % acetonitrile, pH 5...... to detection of exogenous exposure. To our knowledge, this is the first report to present GHB glucuronide in human hair....

Blood-brain distribution of morphine-6-glucuronide in sheep

DEFF Research Database (Denmark)

Villesen, H H; Foster, D J R; Upton, R N

2006-01-01

At present there are few data regarding the rate and extent of brain-blood partitioning of the opioid active metabolite of morphine, morphine-6-glucuronide (M6G). In this study the cerebral kinetics of M6G were determined, after a short-term intravenous infusion, in chronically instrumented...

Synthesis of an estradiol glucuronide derivative and investigation of its radiopharmaceutical potential

Energy Technology Data Exchange (ETDEWEB)

Biber, F.Z. [Department of Nuclear Applications, Institute of Nuclear Sciences, Ege University, 35100 Bornova Izmir (Turkey)]. E-mail: fazilet.zumrut.biber@ege.edu.tr; Unak, P. [Department of Nuclear Applications, Institute of Nuclear Sciences, Ege University, 35100 Bornova Izmir (Turkey); Ertay, T. [Department of Nuclear Medicine, Faculty of Medicine, Dokuz Eylul University, Inciralti Izmir (Turkey); Medine, E.I. [Department of Nuclear Applications, Institute of Nuclear Sciences, Ege University, 35100 Bornova Izmir (Turkey); Zihnioglu, F. [Department of Biochemistry, Faculty of Sciences, Ege University, 35100 Bornova Izmir (Turkey); Tasci, C. [Department of Biochemistry, Faculty of Sciences, Ege University, 35100 Bornova Izmir (Turkey); Durak, H. [Department of Biochemistry, Faculty of Sciences, Ege University, 35100 Bornova Izmir (Turkey)

2006-07-15

The aim of the current study was to synthesize a derivative of estradiol glucuronide, which is able to be labeled with {sup 99m}Tc and to investigate its radiopharmaceutical potential using imaging and biodistribution studies. An estrogen derivative, {beta}-estradiol (1,3,5,[10]-estratriene-3,17{beta}-diol) attached to diethylenetriamine pentaacetic acid (DTPA) was synthesized in six steps. At the end of these steps a compound of estradiol and DTPA derivative called deoxy demethyl homoestradiolyl diethylenetriamine pentaacetic acid (ESTDTPA) was synthesized. Afterwards, this compound was reacted with UDP-glucuronyl transferase (UDPGT). Following the glucuronidation reaction, the product called deoxy demethyl homoestradiolyl diethylenetriamine pentaaceticacid-glucuronide (ESTDTPAG) was obtained. Synthesized products were purified using high performance liquid chromatography (HPLC). The identification of the purified products and impurities were also established using HPLC. Synthesized compound was labeled with {sup 99m}Tc. Thin layer radio chromatography (TLRC) technique was used to determine their radiochemical yields and stabilities. Labeling yield was over 96%. The biodistribution studies were performed on female Albino Wistar rats. The activity per gram tissue was calculated and time-activity curves were plotted. The target organs (tumor, as well as uterus, ovaries, adrenals and other ER containing tissues) retain the estradiol derivative longer than nontarget organs, but even these lost most of their activity within a few hours. In addition, the imaging studies were performed on normal and tumor bearing female Albino Wistar rats using Camstar XR/T gamma camera. In {gamma}-scintigraphic imaging studies with {sup 99m}Tc-ESTDTPAG the breast tumors could be well visualized up to 24 h.

Effect of bioaugmentation to enhance phytoremediation for removal of phenanthrene and pyrene from soil with Sorghum and Onobrychis sativa

Science.gov (United States)

2014-01-01

The use of plants to remove Poly-aromatic-hydrocarbons (PAHs) from soil (phytoremediation) is emerging as a cost-effective method. Phytoremediation of contaminated soils can be promoted by the use of adding microorganisms with the potential of pollution biodegradation (bioaugmentation). In the present work, the effect of bacterial consortium was studied on the capability of Sorghum and Onobrychis sativa for the phytoremediation of soils contaminated with phenanthrene and pyrene. 1.5 kg of the contaminated soil in the ratio of 100 and 300 mg phenanthrene and/or pyrene per kg of dry soil was then transferred into each pot (nine modes). The removal efficiency of natural, phytoremediation and bioaugmentation, separately and combined, were evaluated. The samples were kept under field conditions, and the remaining concentrations of pyrene and phenanthrene were determined after 120 days. The rhizosphere as well as the microbial population of the soil was also determined. Results indicated that both plants were able to significantly remove pyrene and phenanthrene from the contaminated soil samples. Phytoremediation alone had the removal efficiency of about 63% and 74.5% for pyrene and phenanthrene respectively. In the combined mode, the removal efficiency dramatically increased, leading to pyrene and phenanthrene removal efficiencies of 74.1% and 85.02% for Onobrychis sativa and 73.84% and 85.2% for sorghum, respectively. According to the results from the present work, it can be concluded that Onobrychis sativa and sorghum are both efficient in removing pyrene and phenanthrene from contamination and bioaugmentation can significantly enhance the phytoremediation of soils contaminated with pyrene and phenanthrene by 22% and 16% respectively. PMID:24406158

Baseline levels of benzo(a)pyrene in southern California mussels

Energy Technology Data Exchange (ETDEWEB)

Dunn, B P [Univ. of British Columbia, Vancouver; Young, D R

1976-12-01

Marine mussels accumulate the carcinogen benzo(a)-pyrene from contaminated environments. Baseline studies in California indicate that levels of the carcinogen in mussels are at or near zero, except in areas of human activity. This finding runs counter to previous suggestions that benzo(a)pyrene is widely distributed in marine organisms.

Nucleoside adducts from the in vitro reaction of benzo[a]pyrene-7,8-dihydrodiol 9,10-oxide or benzo[a]pyrene 4,5-oxide with nucleic acids.

Science.gov (United States)

Jennette, K W; Jeffrey, A M; Blobstein, S H; Beland, F A; Harvey, R G; Weinstein, I B

1977-03-08

The covalent binding of benzo[a]pyrene 4,5-oxide and benzo[a]pyrene-7,8-dihydrodiol 9,10-oxide isomer I and isomer II to nucleic acids in aqueous acetone solution has been investigated. Benzo[a]pyrene 4,5-oxide reacted preferentially with guanosine residues. On the other hand, benzo[a]pyrene-7,8-dihydrodiol 9,10-oxide isomer I and II reacted extensively with guanosine, adenosine, and cytidine residues. Time course studies showed that the reactivity of isomer I or isomer II with homopolyribonucleotides followed the order poly(G) greater than poly(A) greater than poly(C). Alkaline or enzymatic hydrolysis of the modified nucleic acids and subsequent chromatography on Sephadex LH-20 columns yielded benzo[a]pyrene-nucleotide adducts. These were enzymatically converted to the corresponding nucleosides which were resolved into several distinct components by high-pressure liquid chromatography. Evidence was obtained for the presence of multiple nucleoside adducts of guanosine, adenosine, cytidine, deoxyguanosine, deoxyadenosine, and deoxycytidine. The HPLC profiles of adducts formed with isomer I were different from the corresponding profiles of adducts formed with isomer II. Structural aspects of these nucleoside adducts are discussed.

Study of Necrosis in the Liver of Formaldehyde and Benzo(αPyrene Exposured-Mice

Directory of Open Access Journals (Sweden)

Ahmad Soni

2013-04-01

Full Text Available Formaldehyde and benzo(αpyrene are compounds that harmful for health. Misapplication of this compound has an impact in the form of organ damage in the body. This study aims to determine the impact of the treatment of the combined exposure of formaldehyde and benzo(αpyrene to cell necrosis in the liver of mice (Mus musculus. Treatment of formaldehyde dose of 25 mg/kg BW to mice was given orally every day for 60 days. Treatment of benzo(αpyrene via intraperitoneal injection at a dose of 250 mg/kg BW were given after 30 days of incubation with four times injection with one day interval. Liver organ histological preparations were made through the HE staining. Observations were made by using a microscope for liver organ preparations. The data obtained that is the percentage of cells necrosis and necrotic foci. This research used Completely Randomized Design (CRD with 95% confidence interval. Liver organ preparations observations indicate that the percentage of necrosis in the untreated control, benzo(αpyrene 250 mg/kg BW, formaldehyde 25 mg/kg BW, combination of formaldehyde 25 mg/kg BW with BaP in a row that is equal to 14.43% ± 0.91; 26.05% ± 3.75; 49.38% ± 2.66; 51.86 ± 1.73. The mean of necrotic foci in liver organ formed in the untreatment control, benzo(αpyrene 250 mg/kg BW, Formaldehyde 25 mg/kg BW, and the combination of formaldehyde 25 mg/kg BW with BaP in a row, equal to 1.3 ± 0,07; 1.63 ± 0.61; 2 ± 0.51, and 3.4 ± 0.76. This suggests that the combined treatment had the highest level of toxicity compared with other treatments.

Benzylic oxidation of gemfibrozil-1-O-beta-glucuronide by P450 2C8 leads to heme alkylation and irreversible inhibition.

Science.gov (United States)

Baer, Brian R; DeLisle, Robert Kirk; Allen, Andrew

2009-07-01

Gemfibrozil-1-O-beta-glucuronide (GEM-1-O-gluc), a major metabolite of the antihyperlipidemic drug gemfibrozil, is a mechanism-based inhibitor of P450 2C8 in vitro, and this irreversible inactivation may lead to clinical drug-drug interactions between gemfibrozil and other P450 2C8 substrates. In light of this in vitro finding and the observation that the glucuronide conjugate does not contain any obvious structural alerts, the current study was conducted to determine the potential site of GEM-1-O-gluc bioactivation and the subsequent mechanism of P450 2C8 inhibition (i.e., modification of apoprotein or heme). LC/MS analysis of a reaction mixture containing recombinant P450 2C8 and GEM-1-O-gluc revealed that the substrate was covalently linked to the heme prosthetic heme group during catalysis. A combination of mass spectrometry and deuterium isotope effects revealed that a benzylic carbon on the 2',5'-dimethylphenoxy group of GEM-1-O-gluc was covalently bound to the heme of P450 2C8. The regiospecificity of substrate addition to the heme group was not confirmed experimentally, but computational modeling experiments indicated that the gamma-meso position was the most likely site of modification. The metabolite profile, which consisted of two benzyl alcohol metabolites and a 4'-hydroxy-GEM-1-O-gluc metabolite, indicated that oxidation of GEM-1-O-gluc was limited to the 2',5'-dimethylphenoxy group. These results are consistent with an inactivation mechanism wherein GEM-1-O-gluc is oxidized to a benzyl radical intermediate, which evades oxygen rebound, and adds to the gamma-meso position of heme. Mechanism-based inhibition of P450 2C8 can be rationalized by the formation of the GEM-1-O-gluc-heme adduct and the consequential restriction of additional substrate access to the catalytic iron center.

Investigation on the photocatalytic degradation of pyrene on soil surfaces using nanometer anatase TiO2 under UV irradiation

International Nuclear Information System (INIS)

Dong Dianbo; Li Peijun; Li Xiaojun; Zhao Qing; Zhang Yinqiu; Jia Chunyun; Li Peng

2010-01-01

Photocatalytic degradation of pyrene on soil surfaces was investigated in the presence of nanometer anatase TiO 2 under a variety of conditions. After being spiked with pyrene, soil samples loaded with different amounts of TiO 2 (0%, 1%, 2%, 3%, and 4%, w/w) were exposed to UV irradiation for 25 h. The results indicated that the photocatalytic degradation of pyrene followed pseudo-first-order kinetics. TiO 2 accelerated the degradation of pyrene generally as indicated by the half-life reduction from 45.90 to 31.36 h, corresponding to the TiO 2 amounts from 0% to 4%, respectively. The effects of H 2 O 2 , light intensity and humic acids on the degradation of pyrene were also investigated. The degradation of pyrene increased along with increasing the concentration of H 2 O 2 , light intensity and the concentration of humic acids. All results indicated that the photocatalytic method in the presence of nanometer anatase TiO 2 was an advisable choice for the treatments of PAHs polluted soil in the future.

Role of glucuronidation for hepatic detoxification and urinary elimination of toxic bile acids during biliary obstruction.

Directory of Open Access Journals (Sweden)

Martin Perreault

Full Text Available Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in the overall BA detoxification by glucuronidation. Glucuronide (G, glycine, taurine conjugates, and unconjugated BAs were quantified in pre- and post-biliary stenting urine samples from 12 patients with biliary obstruction, using liquid chromatography-tandem mass spectrometry (LC-MS/MS. The same LC-MS/MS procedure was used to quantify intra- and extracellular BA-G in Hepatoma HepG2 cells. Bile acid-induced toxicity in HepG2 cells was evaluated using MTS reduction, caspase-3 and flow cytometry assays. When compared to post-treatment samples, pre-stenting urines were enriched in glucuronide-, taurine- and glycine-conjugated BAs. Biliary stenting increased the relative BA-G abundance in the urinary BA pool, and reduced the proportion of taurine- and glycine-conjugates. Lithocholic, deoxycholic and chenodeoxycholic acids were the most cytotoxic and pro-apoptotic/necrotic BAs for HepG2 cells. Other species, such as the cholic, hyocholic and hyodeoxycholic acids were nontoxic. All BA-G assayed were less toxic and displayed lower pro-apoptotic/necrotic effects than their unconjugated precursors, even if they were able to penetrate into HepG2 cells. Under severe cholestatic conditions, urinary excretion favors the elimination of amidated BAs, while glucuronidation allows the conversion of cytotoxic BAs into nontoxic derivatives.

Binding of benzo(a)pyrene and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrene to histones

International Nuclear Information System (INIS)

Sculley, T.B.; Zytkovicz, T.H.

1983-01-01

AKR-2B mouse embryo cells were incubated for 24 hr with [3H]benzo(a)pyrene, and the histones were isolated and analyzed using one- and two-dimensional gel electrophoresis and autoradiography. The results revealed that (a) histones H1, H2A, and H3 incorporated significant amounts of label whereas little or no label was associated with histones H2B and H4 and (b) electrophoresis of the histones in the Triton: acid: urea gel system caused labeled histones to have a slower migration than did the corresponding unlabeled histones. Additional studies such as incubation of (+/-)-7 beta,8 alpha-[3H]dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene with nuclei resulted in radioactive labeling of histones H1, H2A, H2B, and H3 and of high-mobility-group proteins HMG1 and HMG2. The low levels of label associated with histone H4 in the whole-cell and nuclear studies were further investigated by incubating isolated histones with (+/-)-7 beta,8 alpha-[3H]dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Under these conditions, negligible amounts of radioactivity were associated with H4, while significant labeling of H1, H2A, H2B, and H3 and other nuclear proteins was observed. The results suggest that factors other than the presence of suitable nucleophilic acceptor sites on the histones may be necessary for carcinogen binding

Selective protein adduct formation of diclofenac glucuronide is critically dependent on the rat canalicular conjugate export pump (Mrp2)

NARCIS (Netherlands)

Seitz, S.; Kretz-Rommel, A.; Oude Elferink, R. P.; Boelsterli, U. A.

1998-01-01

Previous work demonstrates that the reactive acyl glucuronide of the nonsteroidal antiinflammatory drug diclofenac forms selective protein adducts in the liver, which may play a causal role in the pathogenesis of diclofenac-associated liver toxicity. Because glucuronide conjugates can be exported

Pyrene based D-π-A architectures: synthesis, density functional theory, photophysics and electron transfer dynamics.

Science.gov (United States)

Kathiravan, Arunkumar; Srinivasan, Venkatesan; Khamrang, Themmila; Velusamy, Marappan; Jaccob, Madhavan; Pavithra, Nagaraj; Anandan, Sambandam; Velappan, Kandavelu

2017-01-25

Pyrene derivatives show immense potential as sensitizers for dye-sensitized solar cells (DSCs). Therefore, this work focuses on the impact of π-spacers on the photophysical, electrochemical and photovoltaic properties of pyrene based D-π-A dyes, since the insertion of π-spacers is one of the doable strategies to improve the light harvesting properties of the dye. In this respect, three new pyrene based D-π-A dyes have been synthesized and characterized by 1 H, 13 C NMR, and elemental analyses and EI-MS spectrometry. The selected π-spacers are benzene, thiophene and furan. Compared with a benzene spacer, the introduction of a heterocyclic ring spacer reduces the band gap of the dye and brings about the broadening of the absorption spectra to the longer wavelength region through intramolecular charge-transfer (ICT). Combined experimental and theoretical studies were performed to investigate the ICT process involved in the pyrene derivatives. The profound solvatochromism with increased nonradiative rate constants (k nr ) has been construed in terms of ICT from the pyrene core to rhodanine-3-acetic acid via conjugated π-spacers. Electrochemical data also reveal that the HOMO and LUMO energy levels are fine-tuned by incorporating different π-spacers between pyrene and rhodanine-3-acetic acid. On the basis of the optimized DSC test conditions, the best performance was found for PBRA, in which a benzene group is the conjugated π-spacer. The divergence in the photovoltaic behaviors of these dyes was further explicated by femtosecond fluorescence and electrochemical impedance spectroscopy.

In vitro Inhibitory Effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea, and Curcuma xanthorrhiza Extracts and Constituents on Human Liver Glucuronidation Activity.

Science.gov (United States)

Husni, Zulhilmi; Ismail, Sabariah; Zulkiffli, Mohd Halimhilmi; Afandi, Atiqah; Haron, Munirah

2017-07-01

Andrographis paniculata , Gynura procumbens , Ficus deltoidea and Curcuma xanthorrhiza are commonly consumed as herbal medicines. However their effects on human liver glucuronidation activity are not yet evaluated. In this study, we evaluate the inhibitory Effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza extracts and their constituents on human liver glucuronidation activity. Herbal extracts (aqueous, methanolic and ethanolic extracts) and their constituents were incubated with human liver microsomes with the addition of UDPGA to initiate the reaction. Working concentrations of herbal extracts and their constituents ranged from 10 μg/mL to 1000 μg/mL and 10 μM to 300 μM respectively. IC50 was determined by monitoring the decrement of glucuronidation activity with the increment of herbal extracts or phytochemical constituent's concentrations. All herbal extracts inhibited human liver glucuronidation activity in range of 34.69 μg/mL to 398.10 μg/mL whereas for the constituents, only xanthorrhizol and curcumin (constituents of Curcuma xanthorrhiza ) inhibited human liver glucuronidation activity with IC50 of 538.50 and 32.26 μM respectively. In the present study, we have proved the capabilities of Andrographis paniculata , Gynura procumbens , Ficus deltoidea and Curcuma xanthorrhiza to interfere with in vitro glucuronidation process in human liver microsomes. This study documented the capabilities of Andrographis paniculata , Gynura procumbens , Ficus deltoidea and Curcuma xanthorrhiza to inhibit human liver glucuronidation activity which may affect the metabolism of therapeutic drugs or hazardous toxicants that follow the same glucuronidation pathway. Abbreviations used: UGT: Uridine 5'-diphospho-glucuronosyltransferase; 4-MU: 4-methylumbelliferone; IC50: Half Maximal Inhibitory Concentration; Km: Michaelis constant; Vmax: Maximum velocity.

Relevance of urinary 3-hydroxybenzo(a)pyrene and 1-hydroxypyrene to assess exposure to carcinogenic polycyclic aromatic hydrocarbon mixtures in metallurgy workers.

Science.gov (United States)

Barbeau, Damien; Persoons, Renaud; Marques, Marie; Hervé, Claire; Laffitte-Rigaud, Gilbert; Maitre, Anne

2014-06-01

In metallurgy, workers are exposed to mixtures of polycyclic aromatic hydrocarbons (PAHs) in which some compounds are carcinogenic. Biomonitoring of PAH exposure has been performed by measuring urinary 1-hydroxypyrene (1-OHP), a metabolite of pyrene which is not carcinogenic. This study investigated the use of 3-hydroxybenzo(a)pyrene (3-OHBaP), a metabolite of benzo(a)pyrene (BaP) which is the main carcinogenic component in PAHs, to improve carcinogen exposure assessment. We included 129 metallurgy workers routinely exposed to PAHs during working hours. Urinary samples were collected at three sampling times at the beginning and at the end of the working week for 1-OHP and 3-OHBaP analyses. Workers in anode production showed greater exposure to both biomarkers than those in cathode or silicon production, with respectively, 71, 40, and 30% of 3-OHBaP concentrations exceeding the value of 0.4 nmol mol(-1) creatinine. No difference was observed between the 3-OHBaP levels found at the end of the penultimate workday shift and those at the beginning of the last workday shift. Within these plants, the 1-OHP/3-OHBaP ratios varied greatly according to the workers' activity and emission sources. Using linear regression between these two metabolites, the 1-OHP level corresponding to the guidance value for 3-OHBaP ranged from 0.7 to 2.4 µmol mol(-1) creatinine, depending on the industrial sector. This study emphasizes the interest of monitoring urinary 3-OHBaP at the end of the last workday shift when working week exposure is relatively steady, and the irrelevance of a single guideline value for 1-OHP when assessing occupational health risk. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Effect of sunlight irradiation on photocatalytic pyrene degradation in contaminated soils by micro-nano size TiO2

International Nuclear Information System (INIS)

Chang Chien, S.W.; Chang, C.H.; Chen, S.H.; Wang, M.C.; Madhava Rao, M.; Satya Veni, S.

2011-01-01

The enhanced catalytic pyrene degradation in quartz sand and alluvial and red soils by micro-nano size TiO 2 in the presence and absence of sunlight was investigated. The results showed that the synergistic effect of sunlight irradiation and TiO 2 was more efficient on pyrene degradation in quartz sand and red and alluvial soils than the corresponding reaction system without sunlight irradiation. In the presence of sunlight irradiation, the photooxidation (without TiO 2 ) of pyrene was very pronounced in alluvial and red soils and especially in quartz sand. However, in the absence of sunlight irradiation, the catalytic pyrene degradation by TiO 2 and the photooxidation (without TiO 2 ) of pyrene were almost nil. This implicates that ultra-violet (UV) wavelength range of sunlight plays an important role in TiO 2 -enhanced photocatalytic pyrene degradation and in photooxidation (without TiO 2 ) of pyrene. The percentages of photocatalytic pyrene degradation by TiO 2 in quartz sand, alluvial and red soils under sunlight irradiation were 78.3, 23.4, and 31.8%, respectively, at 5 h reaction period with a 5% (w/w) dose of the amended catalyst. The sequence of TiO 2 -enhanced catalytic pyrene degradation in quartz sand and alluvial and red soils was quartz sand > red soil > alluvial soil, due to different texture and total organic carbon (TOC) contents of the quartz sand and other two soils. The differential Fourier transform infrared (FT-IR) spectra of degraded pyrene in alluvial soil corroborate that TiO 2 -enhanced photocatalytic degradation rate of degraded pyrene was much greater than photooxidation (without TiO 2 ) rate of degraded pyrene. Based on the data obtained, the importance for the application of TiO 2 -enhanced photocatalytic pyrene degradation and associated organic contaminants in contaminated soils was elucidated. - Highlights: → Synergistic effect of sunlight irradiation and TiO 2 promoted degradation of pyrene. → Micro-nano size TiO 2 enhanced

Profiles of bile acids and their glucuronide and sulphate conjugates in the serum, urine and bile from patients undergoing bile drainage.

OpenAIRE

Takikawa, H; Beppu, T; Seyama, Y

1985-01-01

Bile acid profiles in serum, urine, and bile from patients undergoing bile drainage and the changes of serum bile acids after bile drainage were studied. Bile acids were separated into non-glucuronidate-non-sulphate, glucuronidated, and sulphated fractions and were measured by mass fragmentography using conjugates of deuterium labelled bile acids as internal standards. Glucuronidated and sulphated bile acids contribute 14-32% and 16-44% of serum bile acids, 4-11% and 61-82% of urine bile acid...

In vivo biological evaluation of 131I radiolabeled-paclitaxel glucuronide (131I-PAC-G)

International Nuclear Information System (INIS)

Aslan, O.; Biber Muftuler, F.Z.; Yurt Kilcar, A.; Ichedef, C.; Unak, P.

2012-01-01

Paclitaxel (PAC) is a natural occurring diterpene alkoloid originally isolated from the bark of Taxus Brevifolia. It is one of the most important antitumor agents for clinical treatment of ovarian, breast non-small cell lung and prostate cancers. It is known that these types of cancer cells have high β-glucuronidase enzyme which can catalyze the hydrolysis of glucuronides. This is why the synthesis compounds which undergo glucuronidation come into question in the imaging and therapy of these cancer cells. The aim of current study is conjugation of glucuronic acid (G) to the starting substance PAC, labeling with 131 I and to perform its in vivo biological evaluation. Glucuronic acid derived paclitaxel compound [paclitaxel-glucuronide (PAC-G)] was labeled with 131 I using iodogen method. According to thin layer radio chromatography (TLRC) method, the radiochemical yield of 131 I-PAC-G was 84.30 ± 7.40% (n=10). The biodistribution of 131 I-PAC-G in healthy female and male Wistar Albino rats has been investigated. Imaging studies on male Balb-C mice were performed by using the Kodak FX PRO in vivo Imaging System. The range of the breast/blood, breast/muscle; ovary/blood, ovary/muscle ratios is approximately between 1.29 and 11.34 in 240 min, and between 0.71 and 8.24 in 240 min for female rats. The prostate/blood and prostate/muscle ratio is between 1.94 and 6.95 in 30 min for male rats. All these experimental studies indicate that 131 I-PAC-G may potentially be used in breast, ovary and prostate tissues as an imaging agent. Also it is thought that 131 I-PAC-G bears a therapy potential because of the 131 I radionuclide and can be improved with further investigations. (orig.)

Systemic excretion of benzo(a)pyrene in the control and microsomally induced rat: the influence of plasma lipoproteins and albumin as carrier molecules

International Nuclear Information System (INIS)

Shu, H.P.; Bymun, E.N.

1983-01-01

In vitro studies have previously indicated that benzo(a)pyrene distributes primarily into the plasma lipoprotein fraction when incubated with whole plasma. Hydroxylated metabolites of benzo(a)pyrene distribute increasingly into the albumin fraction as the degree of metabolite hydroxylation increases. This report assesses the influence of plasma lipoproteins and albumin as carriers for benzo(a)pyrene on carcinogen excretion in the control and microsomally induced rat. Male Sprague-Dawley rats cannulated in the bile duct received i.v. injections of radiolabeled benzo(a)pyrene noncovalently bound to the very-low-density, low-density, or high-density lipoproteins in equimolar amounts. Bile was collected and measured for radioactivity. Cumulative biliary excretions of benzo(a)pyrene complexed with rat lipoproteins were 39.6 +/- 9.7 (S.D.), 24.6 +/- 1.3, and 21.2 +/- 8.8% for very low-density, low-density, and high-density lipoprotein, respectively. Values for excretion of benzo(a)pyrene complexed with rat or human lipoproteins were comparable. These data suggest that the transport molecule can effect a 2-fold difference in benzo(a)pyrene excretion under conditions of the present study. Thus, excretion increased as the degree of benzo(a)pyrene hydroxylation increased. The effect of microsomal enzyme induction on excretion of lipoprotein-bound benzo(a)pyrene was also assessed. Contrary to expectation, excretion of benzo(a)pyrene bound to the very-low-density, low-density, or high-density lipoproteins in Aroclor-induced rats was not greater than that of control animals. Hence, under the conditions of the present study, 60 to 80% of the injected benzo(a)pyrene and 50 to 60% of the injected benzo(a)pyrene metabolites were not excreted immediately in control or microsomally induced animals. This benzo(a)pyrene may represent a carcinogen pool that is slowly excreted

Androstanediol glucuronide isomers in normal men and women and in men infused with labeled dihydrotestosterone

International Nuclear Information System (INIS)

Rittmaster, R.S.; Thompson, D.L.; Listwak, S.; Loriaux, D.L.

1988-01-01

3 alpha-Androstanediol glucuronide (Adiol G) is a major metabolite of dihydrotestosterone (DHT). Adiol G actually represents 2 different compounds, since the glucuronide can be conjugated at the 3-carbon position (Adiol 3-G) or at the 17-carbon position (Adiol 17-G). To determine which glucuronide represents the predominant physiological DHT metabolite and which isomer is the major circulating form, we developed a RIA to directly measure Adiol 3-G in serum extracts. In 10 normal men, mean serum Adiol 3-G and total Adiol G levels were 4.44 +/- 0.49 (+/- SE) nmol/L (208 +/- 23 ng/dL) and 27.9 +/- 2.8 nmol/L (1310 +/- 129 ng/dL), respectively (13.9 +/- 3.0% of Adiol G was Adiol 3-G). In 10 normal women sampled during the early follicular phase, mean serum Adiol 3-G and total Adiol G levels were 2.64 +/- 0.64 nmol/L (124 +/- 30 ng/dL) and 14.9 +/- 1.5 nmol/L (697 +/- 69 ng/dL), respectively (17.4 +/- 3.6% of Adiol G was Adiol 3-G). In 4 normal men infused for 8 h with tritiated DHT, 17.4 +/- 3.4% of the resulting tritiated Adiol G was Adiol 3-G. These results indicate that Adiol 17-G is the predominant circulating form of Adiol G in normal men and women and that it is also the major Adiol G isomer derived from DHT

Sample preparation method for the combined extraction of ethyl glucuronide and drugs of abuse in hair.

Science.gov (United States)

Meier, Ulf; Briellmann, Thomas; Scheurer, Eva; Dussy, Franz

2018-04-01

Often in hair analysis, a small hair sample is available while the analysis of a multitude of structurally diverse substances with different concentration ranges is demanded. The analysis of the different substances often requires different sample preparation methods, increasing the amount of required hair sample. When segmental hair analysis is necessary, the amount of hair sample needed is further increased. Therefore, the required sample amount for a full analysis can quickly exceed what is available. To combat this problem, a method for the combined hair sample preparation using a single extraction procedure for analysis of ethyl glucuronide with liquid chromatography-multistage fragmentation mass spectrometry/multiple reaction monitoring (LC-MS 3 /MRM) and common drugs of abuse with LC-MRM was developed. The combined sample preparation is achieved by separating ethyl glucuronide from the drugs of abuse into separate extracts by fractionation in the solid-phase extraction step during sample clean-up. A full validation for all substances for the parameters selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, and recovery was successfully completed. The following drugs of abuse were included in the method: Amphetamine; methamphetamine; 3,4-methylenedioxy-N-methylamphetamine (MDMA); 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenedioxy-N-ethylamphetamine (MDE); morphine; 6-monoacetylmorphine; codeine; acetylcodeine; cocaine; benzoylecgonine; norcocaine; cocaethylene; methadone; 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and methylphenidate. In conclusion, as only 1 sample preparation is needed with 1 aliquot of hair, the presented sample preparation allows an optimal analysis of both ethyl glucuronide and of the drugs of abuse, even when the sample amount is a limiting factor. Copyright © 2017 John Wiley & Sons, Ltd.

Molecularly imprinted polystyrene–titania hybrids with both ionic and π–π interactions: a case study with pyrene butyric acid

International Nuclear Information System (INIS)

Selyanchyn, Roman; Lee, Seung-Woo

2013-01-01

We present hybrid films consisting of a composite prepared from polystyrene (PS) and titanium dioxide (titania; TiO 2 ) and molecularly imprinted with 1-pyrene butyric acid (PBA). The interaction of PBA with the polymer is shown to occur via binding of the carboxylic group to TiO 2 and hydrophobic interaction of the pyrene moiety with the PS network. We investigated the effects of the PS fraction on morphology, imprinting properties, and guest binding. The template could be completely removed by incubating the films in an acetonitrile solution of pyrene, which is due to the stronger π–π interaction between PBA and pyrene than the interaction between PBA and its binding site. A guest binding study with pyrene, 1-amino pyrene, pyr enemethanol, and anthracene-9-carboxylic acid showed that the hybrid films possessed selectivity and much higher binding capacity for PBA. This study demonstrates the first case of clear PS-assisted imprinting, where the π–π interaction of the template with a linear (non-crosslinked) polymer creates selective binding sites and enhances the binding capacity. This is a driving force for guest binding in addition to the interaction of the template/analyte with TiO 2 . All molecularly imprinted films displayed better binding, repeatability and reversibility compared to the respective non-imprinted films. (author)

Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

International Nuclear Information System (INIS)

Ba, Qian; Li, Junyang; Huang, Chao; Li, Jingquan; Chu, Ruiai; Wu, Yongning; Wang, Hui

2015-01-01

Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong to the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enriched through modular analysis. • Tissue- and time-specific pathways were identified

Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

Energy Technology Data Exchange (ETDEWEB)

Ba, Qian [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Li, Junyang; Huang, Chao [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Li, Jingquan; Chu, Ruiai [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Wu, Yongning, E-mail: wuyongning@cfsa.net.cn [Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Wang, Hui, E-mail: huiwang@sibs.ac.cn [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); School of Life Science and Technology, ShanghaiTech University, Shanghai (China)

2015-03-01

Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong to the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enriched through modular analysis. • Tissue- and time-specific pathways were identified.

Isolation and Identification of Pyrene Mineralizing Mycobacterium spp. from Contaminated and Uncontaminated Sources

International Nuclear Information System (INIS)

Lease, C.W.M; Bentham, R.H; Gaskin, S.E; Juhasz, A.L

2011-01-01

Mycobacterium isolates obtained from PAH-contaminated and uncontaminated matrices were evaluated for their ability to degrade three-, four- and five-ring PAHs. PAH enrichment studies were prepared using pyrene and inocula obtained from manufacturing gas plant (MGP) soil, uncontaminated agricultural soil, and faeces from Macropus fuliginosus (Western Grey Kangaroo). Three pyrene-degrading microorganisms isolated from the corresponding enrichment cultures had broad substrate ranges, however, isolates could be differentiated based on surfactant, phenol, hydrocarbon and PAH utilisation. 16S rRNA analysis identified all three isolates as Mycobacterium sp. The Mycobacterium spp. could rapidly degrade phenanthrene and pyrene, however, no strain had the capacity to utilise fluorene or benzo[a]pyrene. When pyrene mineralisation experiments were performed, 70-79% of added 14 C was evolved as 14 CO 2 after 10 days. The present study demonstrates that PAH degrading microorganisms may be isolated from a diverse range of environmental matrices. The present study demonstrates that prior exposure to PAHs was not a prerequisite for PAH catabolic activity for two of these Mycobacterium isolates.

How to link pyrene to its host lipid to minimize the extent of membrane perturbations and to optimize pyrene dimer formation

DEFF Research Database (Denmark)

Franova, M. D.; Repakova, J.; Holopainen, J. M.

2014-01-01

We study how lipid probes based on pyrene-labeling could be designed to minimize perturbations in lipid bilayers, and how the same design principles could be exploited to develop probes which gauge lipid dynamics primarily within a single lipid monolayer or between them. To this end, we use......, simulations suggest that formation of dimers is a slow process, where the rate is limited by both lateral diffusion and the dimerization process once the two probes are neighbors to one another. Typical lifetimes of pyrene dimers turn out be of the order of nanoseconds. The results are expected to pave...

Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-β-Glucuronide.

Science.gov (United States)

Varma, Manthena V S; Lin, Jian; Bi, Yi-an; Kimoto, Emi; Rodrigues, A David

2015-07-01

Gemfibrozil has been suggested as a sensitive cytochrome P450 2C8 (CYP2C8) inhibitor for clinical investigation by the U.S. Food and Drug Administration and the European Medicines Agency. However, gemfibrozil drug-drug interactions (DDIs) are complex; its major circulating metabolite, gemfibrozil 1-O-β-glucuronide (Gem-Glu), exhibits time-dependent inhibition of CYP2C8, and both parent and metabolite also behave as moderate inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. Additionally, parent and metabolite also inhibit renal transport mediated by OAT3. Here, in vitro inhibition data for gemfibrozil and Gem-Glu were used to assess their impact on the pharmacokinetics of several victim drugs (including rosiglitazone, pioglitazone, cerivastatin, and repaglinide) by employing both static mechanistic and dynamic physiologically based pharmacokinetic (PBPK) models. Of the 48 cases evaluated using the static models, about 75% and 98% of the DDIs were predicted within 1.5- and 2-fold of the observed values, respectively, when incorporating the interaction potential of both gemfibrozil and its 1-O-β-glucuronide. Moreover, the PBPK model was able to recover the plasma profiles of rosiglitazone, pioglitazone, cerivastatin, and repaglinide under control and gemfibrozil treatment conditions. Analyses suggest that Gem-Glu is the major contributor to the DDIs, and its exposure needed to bring about complete inactivation of CYP2C8 is only a fraction of that achieved in the clinic after a therapeutic gemfibrozil dose. Overall, the complex interactions of gemfibrozil can be quantitatively rationalized, and the learnings from this analysis can be applied in support of future predictions of gemfibrozil DDIs. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Investigation of biological destruction of benzo[a]pyrene andpolycyclic aromatic hydrocarbons of biochar in soil

Science.gov (United States)

Okunev, R. V.; Smirnova, E. V.; Sharipova, A. R.; Gilmutdinova, I. M.; Giniyatullin, K. G.

2018-01-01

The biological decomposition of benzo[a]pyrene in the concentrations exceeding the MAC (maximum permissible concentration) level in soils by 2, 5 and 10 times was studied in laboratory conditions. The gray forest soil samples were contaminated with benzo[a]pyrene and incubated in optimum for bacterial growth soil moisture for 30 and 60 days. The residual amount of contaminant was monitored by HPLC after extraction with acetone-cyclohexane (2:1). Soil microbial activity was evaluated by measuring basal respiration (BR) and substrate-induced respiration (SID) rates of the soil by gas chromatography. The results of the experiment showed that in 60 days the amount of benzo[a]pyrene in contaminated soils decreased; however, this time was not enough for complete decomposition of pollutant. In this case, benzo[a]pyrene has a negative effect on the BR and SIR rates. Soil contamination affected the BR rate only at high doses (10 MPC), whereas the SIR was a more sensitive indicator of the toxic effect of the pollutant and significantly reacts already at concentrations at the level of 2 MPC. The combination of PAHs isolated from biochar has a strong negative effect on the values of BR and SIR.

Dynamic changes in functional gene copy numbers and microbial communities during degradation of pyrene in soils

International Nuclear Information System (INIS)

Peng Jingjing; Cai Chao; Qiao Min; Li Hong; Zhu Yongguan

2010-01-01

This study investigates the dynamics of pyrene degradation rates, microbial communities, and functional gene copy numbers during the incubation of pyrene-spiked soils. Spiking pyrene to the soil was found to have negligible effects on the bacterial community present. Our results demonstrated that there was a significant difference in nidA gene copy numbers between sampling dates in QZ soil. Mycobacterium 16S rDNA clone libraries showed that more than 90% mycobacteria detected were closely related to fast-growing PAH-degrading Mycobacterium in pyrene-spiked soil, while other sequences related to slow-growing Mycobacterium were only detected in the control soil. It is suggested that nidA gene copy number and fast-growing PAH-degrading Mycobacterium could be used as indicators to predict pyrene contamination and its degradation activity in soils. - nidA gene and fast-growing PAH-degrading Mycobacterium can serve as indicators for pyrene contamination.

Analysis of ethyl glucuronide in human serum by capillary electrophoresis with sample self-stacking and indirect detection

Czech Academy of Sciences Publication Activity Database

Křivánková, Ludmila; Caslavska, J.; Malášková, Hana; Gebauer, Petr; Thormann, W.

2005-01-01

Roč. 1081, č. 1 (2005), s. 2-8 ISSN 0021-9673 R&D Projects: GA AV ČR IAA4031401 Institutional research plan: CEZ:AV0Z40310501 Keywords : ethyl glucuronide * capillary electrophoresis * serum Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.096, year: 2005

[Effect of different soil types on the remediation of copper-pyrene compound contaminated soils by EK-oxidation process].

Science.gov (United States)

Fan, Guang-Ping; Cang, Long; Zhou, Dong-Mei; Zhou, Li-Xiang

2011-11-01

The effect of different soil types (red soil,yellow-brown soil and black soil) on the electrokinetic (EK)-oxidation remediation of heavy metals-organic pollutant contaminated soil was studied in laboratory-scale experiments. Copper and pyrene were chosen as model pollutant, and 12% H2O2, 10% hydroxypropyl-beta-cyclodextrin and 0.01 mol x L(-1) NaNO3 solution were added into the anode and cathode cell. The applied voltage was 1 V x cm(-1). After 15 days of EK remediation, the removal rate of pyrene and copper in red soil, yellow-brown soil and black soil were 38.5%, 46.8%, 51.3% for pyrene and 85.0%, 22.6%, 24.1% for Cu, respectively. The high pH of black soil produced high electroosmotic flow and increased the exposure of oxidants and pollutants, meanwhile the low clay content was also conducive to the desorption of pyrene. The low pH and organic matter of red soil affected the chemical species distribution of Cu and increased its removal rate. It is concluded that soil pH, clay content and heavy metal speciation in soil are the dominant factors affecting the migration and removal efficiency of pollutants.

Pyrene absorption can be a convenient method for probing critical micellar concentration (cmc) and indexing micellar polarity.

Science.gov (United States)

Basu Ray, Gargi; Chakraborty, Indranil; Moulik, Satya P

2006-02-01

The critical micellar concentration (cmc) of both ionic and non-ionic surfactants can be conveniently determined from the measurements of UV absorption of pyrene in surfactant solution. The results on a number of surfactants have agreed with that realized from pyrene fluorescence measurements as well as that obtained following conductometric, tensiometric and calorimetric methods. The absorbance vs [surfactant] profiles for all the major UV spectral peaks of pyrene have been found to be sigmoidal in nature which were analyzed according to Sigmoidal-Boltzmann equation (SBE) to evaluate the cmcs of the studied surfactants. The difference between the initial and the final asymptotes (a(i) and a(f), respectively) of the sigmoidal profile, Delta a = (a(f)-a(i)) and the slope of the sigmoid, S(sig) have been observed to depend on the type of the surfactant. The Delta a has shown a linear correlation with the ratio of the fluorescence intensities of the first and the third vibronic peaks, I1/I3 of pyrene which is considered as a measure of the environmental polarity (herein micellar interior) of the probe (pyrene). Thus, Delta a values have the prospect for use as another index for the estimation of polarity of micellar interior.

High-Throughput LC-MS/MS Method for Direct Quantification of Glucuronidated, Sulfated and Free Enterolactone in Human Plasma

DEFF Research Database (Denmark)

Nørskov, Natalja; Kyrø, Cecilie; Olsen, Anja

2016-01-01

Sulfation and glucuronidation constitute a major pathway in humans and may play an important role in biological activity of metabolites including the enterolignan, enterolactone. Because the aromatic structure of enterolactone has similarities to steroid metabolites, it was hypothesized that ente......Sulfation and glucuronidation constitute a major pathway in humans and may play an important role in biological activity of metabolites including the enterolignan, enterolactone. Because the aromatic structure of enterolactone has similarities to steroid metabolites, it was hypothesized......−MS/MS and a fluoroimmunoassay; however, most of these methods measure the total concentration of enterolactone, without any specification of its conjugation pattern. Here for the first time we present a high-throughput LC−MS/MS method to quantify enterolactone in its intact form as glucuronide, sulfate, and free enterolactone....... The method has shown good accuracy and precision at low concentration and very high sensitivity, with LLOQ for enterolactone sulfate at 16 pM, enterolactone glucuronide at 26 pM, and free enterolactone at 86 pM. The short run time of 2.6 min combined with simple sample clean up and high sensitivity make...

Life history traits and the activity of antioxidative enzymes in Lymantria dispar L. (lepidoptera, lymantriidae) larvae exposed to benzo[a]pyrene.

Science.gov (United States)

Ilijin, Larisa; Mrdaković, Marija; Todorović, Dajana; Vlahović, Milena; Gavrilović, Anja; Mrkonja, Aleksandra; Perić-Mataruga, Vesna

2015-11-01

Increased presence of benzo[a]pyrene in the environment underlines the need for development of sensitive biomarkers for monitoring. Antioxidative enzymes could be used as early-warning signals because of their sensitivity and applicability. The activity of 2 antioxidative enzymes, superoxide dismutase (SOD) and catalase (CAT), were measured in midgut tissues of fifth instar Lymantria dispar larvae exposed to different concentrations of benzo[a]pyrene: 2 ng, 10 ng, 20 ng, 100 ng, 200 ng, and 2000 ng benzo[a]pyrene/g dry food weight. Larval development, larval mass, and relative growth rate were also monitored. The authors detected prolonged larval development, as well as reduced larval mass and relative growth rate in larvae exposed to all benzo[a]pyrene concentrations. The L. dispar midgut SOD activity was significantly increased, and 2 SOD isoforms were detected on native polyacrylamide gel electrophoresis in larvae fed on artificial diet supplemented with benzo[a]pyrene. In contrast, the control group had only 1 isoform. Catalase activity was significantly increased in all benzo[a]pyrene-treated larvae. Native gel electrophoresis showed that a switch in active CAT isoforms occurred after benzo[a]pyrene treatment. Thus, SOD and CAT in polyphagous herbivorous L. dispar larvae are very sensitive to low concentrations of benzo[a]pyrene. Therefore, they could be used as biomarkers for exposure and effects of this toxic polycyclic aromatic hydrocarbon. © 2015 SETAC.

Bioremediating silty soil contaminated by phenanthrene, pyrene ...

African Journals Online (AJOL)

sunny t

benzo(a)pyrene using Bacillus sp. and Pseudomonas sp.: Biosurfactant/Beta vulgaris ... potential human mutagens and carcinogens (Grimmer,. 1983). Chemical and ...... of naphthalene on zeolite from aqueous solution. J. Colloid Interf. Sci.

Bisphenol A glucuronidation in patients with Parkinson's disease.

Science.gov (United States)

Landolfi, Annamaria; Troisi, Jacopo; Savanelli, Maria Cristina; Vitale, Carmine; Barone, Paolo; Amboni, Marianna

2017-12-01

Bisphenol A (BPA) is a widely distributed estrogen-mimetic molecule, with well-established effects on the dopaminergic system. It can be found in canned food, dental sealants, thermal paper, etc. BPA undergoes liver conjugation with glucuronic acid and is subsequently excreted in the urine. In the present study we quantified the concentration of free and conjugated Bisphenol A in blood of patients affected by Parkinson Disease, using their spouses as controls. An interview was performed to determine possible confounders in BPA exposure. Free and conjugated BPA were quantified by gas chromatography coupled with mass spectrometry. Parkinson's Disease patients carried a statistically significant lower amount of conjugated Bisphenol A compared to controls. The two populations were mostly homogeneous in terms of exposure to possible Bisphenol A sources. The only exceptions were exposure to canned tuna and canned tomatoes PD patients consumed significantly more of both (pBisphenol A glucuronidation was found after stratification by typology of anti-Parkinson's drug taken and after conversion to the Levodopa Equivalent Daily Dose. BPA glucuronidation was decreased in patients with Parkinson disease. The possible unique mechanisms underlying Bisphenol A metabolism in PD patients deserve further elucidation. Moreover, further study is needed to assess a possible BPA role in Parkinson's Disease pathogenesis, due to its documented dopaminergic toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of 2,5-dimethyl-4-hydroxy-3[2H]-furanone beta-D-glucuronide as the major metabolite of a strawberry flavour constituent in humans.

Science.gov (United States)

Roscher, R; Koch, H; Herderich, M; Schreier, P; Schwab, W

1997-08-01

2,5-Dimethyl-4-hydroxy-3[2H]furanone (Furaneol, DMHF) [3658-77-3], an important flavour constituent of strawberry fruit, was administered to four male and two female volunteers using fresh strawberries as a natural DMHF source. The amount excreted was determined by measuring urinary levels of DMHF and DMHF glucuronide. DMHF glucuronide was synthesized and the structure elucidated by mens of 1H, 13C and two dimensional nuclear magnetic resonance, as well as mass spectral data. Identification and quantification of DMHF glucuronide in human urine were achieved after solid phase extraction on XAD-2 using reverse-phase reverse-phase HPLC with either on-line UV/VIS or electrospray tandem mass spectrometry detection. Male and female volunteers excreted 59-69% and 81-94%, respectively, of the DMHF dose (total of free and glycosidically bound DMHF in strawberries) as DMHF glucuronide in urine within 24 hr. The amount of DMHF excretion was independent of the dose size and the ratio of free to glycosidically bound forms of DMHF in strawberry fruit. DMHF, DMHF glucoside and its 6'-O-malonyl derivative, naturally occurring in strawberries, were not detected in human urine.

Species differences in the biotransformation of an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist: the effects of distinct glucuronide metabolites on overall compound disposition.

Science.gov (United States)

Shaffer, Christopher L; Gunduz, Mithat; Ryder, Tim F; O'Connell, Thomas N

2010-02-01

The metabolism and disposition of (1R,5S)-2,3,4,5-tetrahydro-7-(trifluoromethyl)-1,5-methano-1H-3-benzazepine (1), an alpha(4)beta(2) nicotinic acetylcholine receptor partial agonist, was investigated in Sprague-Dawley rats and cynomolgus monkeys receiving (1R,5S)-2,3,4,5-tetrahydro-7-(trifluoromethyl)-1,5-methano-1H-4[(14)C]-3- benzazepine hydrochloride ([(14)C]1) orally. Although both species chiefly (>or=62%) cleared 1 metabolically, species-specific dispositional profiles were observed for both 1 and total radioactivity. Radioactivity was excreted equally in the urine and feces of intact rats but largely (72%) in bile in bile duct-cannulated animals. In monkeys, radioactivity recoveries were 50-fold greater in urine than feces and minimal (<5%) in bile. Both species metabolized 1 similarly: four-electron oxidation to one of four amino acids or two lactams (minor) and glucuronide formation (major). In rats, the latter pathway predominantly formed an N-carbamoyl glucuronide (M6), exclusively present in bile (69% of dose), whereas in monkeys it afforded an N-O-glucuronide (M5), a minor biliary component (4%) but the major plasma (62%) and urinary (42%) entity. In rats, first-pass hepatic conversion of 1 to M6, which was confirmed in rat hepatocytes, and its biliary secretion resulted in the indirect enterohepatic cycling of 1 via M6 and manifested in double-humped plasma concentration-time curves and long t(1/2) for both 1 and total radioactivity. In monkeys, in which only M5 was formed, double-humped plasma concentration-time curves were absent, and moderate t(1/2) for both 1 and total radioactivity were observed. A seemingly subtle, yet critical, difference in the chemical structures of these two glucuronide metabolites considerably affected the overall disposition of 1 in rats versus monkeys.

Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vivo and in vitro

DEFF Research Database (Denmark)

Weinstein, I.B.; Jeffrey, A.M.; Jennette, K.W.

1976-01-01

Evidence has been obtained that a specific isomer of a diol epoxide derivative of benzo(a)pyrene, (+/-)-7 beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, is an intermediate in the binding of benzo(a)pyrene to RNA in cultured bovine bronchial mucosa. An adduct is for...

Monitoring of ovarian activity by measurement of urinary excretion rates of estrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part II: reliability of home testing.

Science.gov (United States)

Blackwell, Leonard F; Vigil, Pilar; Gross, Barbara; d'Arcangues, Catherine; Cooke, Delwyn G; Brown, James B

2012-02-01

The UNDP/WHO/World Bank/Special Programme of Research, Development and Research Training in Human Reproduction (Geneva) set up a study to determine whether it is feasible for women to monitor their ovarian activity reliably by home testing. Daily self-monitoring of urinary hormone metabolites for menstrual cycle assessment was evaluated by comparison of results obtained with the Home Ovarian Monitor by untrained users both at home and in study centres. Women collected daily data for urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) for two cycles, then the procedure was repeated in the women's local centre (in Chile, Australia or New Zealand) giving a total of 113 duplicate cycles. The tests were performed without the benefit of replicates or quality controls. The home and centre cycles were normalized and compared to identify assay errors, and the resulting home and centre menstrual cycle profiles were averaged. Reliable mean cycle profiles were obtained with the home and centre excretion rates agreeing to within 36 ± 21 nmol/24 h for E1G and 0.77 ± 0.28 µmol/24 h for baseline PdG values (1-5 µmol/24 h). The cycles had a mean length of 28.1 ± 3.1 days (n = 112; 5th and 95th percentiles: 24 and 35 days, respectively), a mean follicular phase of 14.8 ± 3.1 days (n = 107; 5th and 95th percentiles: 11 and 21 days) and a mean luteal phase length of 13.3 ± 1.5 days (n = 106; 5th and 95th percentiles: 11 and 17 days), calculated from the day of the LH peak. The study confirmed that the Ovarian Monitor pre-coated assay tubes worked well even in the hands of lay users, without standard curves, quality controls or replicates. Point-of-care monitoring to give reliable fertility data is feasible.

Inhalation but not transdermal resorption of hand sanitizer ethanol causes positive ethyl glucuronide findings in urine.

Science.gov (United States)

Arndt, Torsten; Schröfel, Stefanie; Güssregen, Brunhilde; Stemmerich, Karsten

2014-04-01

Ethyl glucuronide (EtG) in urine is considered a specific marker of recent ethanol consumption. There is an ongoing debate about whether inhalation or transdermal resorption of sanitizer ethanol is the underlying cause for positive EtG findings after hand disinfection. Desderman(®) pure (Schülke & Mayr GmbH, Norderstedt) with 78.2g 96% (v/v) ethanol/100g and approx. 10% 2-propanol was used for multiple hand disinfection without and under an exhauster. Simulating a common working day in a clinic, 5 co-workers of our lab used the sanitizer 32 fold within 8h and 2 persons were merely exposed to the sanitizer vapor but without any dermal sanitizer contact. Any additional ethanol intake or exposition was reliably excluded. Spot urine was collected at baseline, after 1, 2, 4, 6 … 14, and finally 24h after the first sanitizer use. A validated LC-MS/MS was used for MRM and MS(3) of EtG and qualitative analyses of ethyl sulfate and 2-propyl glucuronide. Multiple hand disinfection caused positive EtG findings of up to 2.1mg/L or 1.7mg/g creatinine in 4 out of 5 test persons and even of 0.6mg/L or 0.8mg/g for 2 controls which were merely exposed to the sanitizer vapor but without any sanitizer contact. EtG results between the clinical (0.5mg/g) and the forensic (0.1mg/g) cut-off were obtained even 6h after the last sanitizer exposition. An exhauster prevented the sanitizer vapor inhalation and reduced the EtG excretion to mostly below the detection limit of 0.02mg/g. The maximum value was 0.09mg/g. Ethyl sulfate and 2-propyl glucuronide (2-PpG) were detectable only in the EtG positive samples. 2-PpG is a metabolite of 2-propanol, which is quite frequently used in disinfectants. Thus, the detection of this substance can be used in cases of odd EtG results as an indicator of (unintended) sanitizer exposition. Ethanol from hand sanitizers is predominantly incorporated by the respiratory tract but not via the skin. It can cause a distinct ethyl glucuronide excretion and thus

Antioxidative Flavonol Glucuronides and Anti-HBsAg Flavonol from Rotala rotundifolia

Directory of Open Access Journals (Sweden)

Li-Jie Zhang

2011-10-01

Full Text Available Two new flavonol glucuronides, quercetin 3-O-β-d-2″-acetylglucuronide (1 and quercetin 3-O-β-d-2″-acetylglucuronide methyl ester (2, along with four known flavonoids (3-6 were isolated from the whole parts of Rotala rotundifolia. The structures of 1 and 2 were elucidated by application of various spectroscopic methods, including 1D and 2D NMR techniques. Biological evaluation showed that all of isolated flavonoid compounds have potent anti-oxidative activities by DPPH and superoxide anion methods, and kaempferol (3 and quercetin (4 exhibited significant anti-HBV activity assayed by anti-HBsAg production. The HPLC fingerprint with photodiode array detection (HPLC-DAD for quality control of R. rotundifolia partitioned EtOAc layer was also established.

Quantification of Cannabinoids and their Free and Glucuronide Metabolites in Whole Blood by Disposable Pipette Extraction and Liquid Chromatography Tandem Mass Spectrometry

Science.gov (United States)

Scheidweiler, Karl B.; Newmeyer, Matthew N.; Barnes, Allan J.; Huestis, Marilyn A.

2016-01-01

Identifying recent cannabis intake is confounded by prolonged cannabinoid excretion in chronic frequent cannabis users. We previously observed detection times ≤2.1 h for cannabidiol (CBD) and cannabinol (CBN) and THC-glucuronide in whole blood after smoking, suggesting their applicability for identifying recent intake. However, whole blood collection may not occur for up to 4 h during driving under the influence of drugs investigations, making a recent-use marker with a 6-8 h detection window helpful for improving whole blood cannabinoid interpretation. Other minor cannabinoids cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and its metabolite 11-nor-9-carboxy-THCV (THCVCOOH) might also be useful. We developed and validated a sensitive and specific liquid chromatography-tandem mass spectrometry method for quantification of THC, its phase I and glucuronide phase II metabolites, and 5 five minor cannabinoids. Cannabinoids were extracted from 200 μL whole blood via disposable pipette extraction, separated on a C18 column, and detected via electrospray ionization in negative mode with scheduled multiple reaction mass spectrometric monitoring. Linear ranges were 0.5-100 μg/L for THC and THCCOOH; 0.5-50 μg/L for 11-OH-THC, CBD, CBN, and THC-glucuronide; 1-50 μg/L for CBG, THCV, and THCVCOOH; and 5-500 μg/L for THCCOOH-glucuronide. Inter-day accuracy and precision at low, mid and high quality control (QC) concentrations were 95.1-113% and 2.4-8.5%, respectively (n=25). Extraction recoveries and matrix effects at low and high QC concentrations were 54.0-84.4% and −25.8-30.6%, respectively. By simultaneously monitoring multiple cannabinoids and metabolites, identification of recent cannabis administration or discrimination between licit medicinal and illicit recreational cannabis use can be improved. PMID:27236483

Charge recombination process in X-ray irradiated pyrene-doped polystyrene as studied by optically detected electron spin resonance and magnetic field dependence of the recombination fluorescence

International Nuclear Information System (INIS)

Okazaki, Masaharu; Tai, Yutaka; Toriyama, Kazumi

1993-01-01

The optically-detected ESR (ODESR) spectrum and magnetic field dependence on recombination fluorescence were observed for X-ray irradiated pyrene-doped polystyrene at temperatures of 242-348 K. The ODESR intensity as a function of the pyrene concentration, 0.1-8.9 wt%, showed an unusual minimum at about 1.0%. Two phases were separated in the magnetic field dependence of the fluorescence: one was sharp and saturates at fields of over 50 mT, while the other was broad with a dip at around 60-150 mT. The cause of this dip was naturally attributed to the ST -1 level crossing. The sharp magnetic field effect also showed a minimum at around a concentration of 1.0 wt%. These novel findings have been interpreted using a recombination model modified from the previous one for pyrene-doped ethylene-propylene rubber and polyethylene. The essential points of the present model are: (1) although electron hopping within the polystyrene molecule is rapid, electron transfer at the last step of recombination between the polystyrene anion and the pyrene cation proceeds at a moderate rate; (2) the hole-transfer rate in the polymer chain is moderate; (3) electron hopping between the doped pyrene molecules is very much dependent on the concentration; (4) hole hopping between the pyrenes is inhibited. (author)

3-Methylcholanthrene does not induce in vitro xenobiotic metabolism in spiny lobster hepatopancreas, or affect in vivo disposition of benzo(a)pyrene

Energy Technology Data Exchange (ETDEWEB)

James, M O; Little, P J

1984-01-01

Administration of 3-methylcholanthrene (10 mg/kg) i.m. to spiny lobsters, Panulirus argus, did not cause induction of the cytochrome P-450 content of hepatopancreas microsomes. The rate of oxidation of benzo(a)pyrene or 7-ethoxyresorufin in reductase-fortified preparations of hepatopancreas microsomes was the same for corn oil-treated or 3-methylcholanthrene-treated lobsters. Administration of 3-methylcholanthrene (10 mg/kg) i.m. to spiny lobsters one week prior to an i.v. dose of (/sup 14/C)benzo(a)pyrene (1 mg/kg) did not influence the disposition of the radiolabelled benzo(a)pyrene in lobsters. At one week after the dose of (/sup 14/C)benzo(a)pyrene, approximately 40% of the dose of (/sup 14/C)benzo(a)pyrene remained in the lobsters, regardless of treatment. The digestive tract (hepatopancreas, intestinal contents, stomach and intestine) contained most (86%) of the /sup 14/C remaining in the lobsters.

Determination of salbutamol and salbutamol glucuronide in human urine by means of liquid chromatography-tandem mass spectrometry

DEFF Research Database (Denmark)

Mareck, Ute; Guddat, Sven; Schwenke, Anne

2012-01-01

The determination of salbutamol and its glucuronide in human urine following the inhalative and oral administration of therapeutic doses of salbutamol preparations was performed by means of direct urine injection utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) and employing d(3...... glucuronide values between 8 and 15 ng/ml. The approach enabled the rapid determination of salbutamol and its glucuronic acid conjugate in human urine and represents an alternative to existing procedures since time-consuming hydrolysis or derivatization steps were omitted. Moreover, the excretion...

Use of positive ion fast atom bombardment mass spectrometry for rapid identification of a bile alcohol glucuronide isolated from cerebrotendinous xanthomatosis patients

International Nuclear Information System (INIS)

Dayal, B.; Salen, G.; Tint, G.S.; Shefer, S.; Benz, S.W.

1990-01-01

The identification of a major biliary and plasma bile alcohol glucuronide, 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol-3-0-beta-D-glucuronide, present in cerebrotendinous xanthomatosis (CTX) patients, was investigated by positive ion fast atom bombardment mass spectrometry (FAB-MS). The spectrum was characterized by abundant ions formed by attachment of a proton, [M + H]+, or of alkali ions, [M + Na]+ and [M + 39K]+, to the glucuronide salt. These ions allowed an unambiguous deduction of the molecular weight of the sample. It is suggested that FAB-MS could be used in the rapid diagnosis of CTX

In vivo biological evaluation of {sup 131}I radiolabeled-paclitaxel glucuronide ({sup 131}I-PAC-G)

Energy Technology Data Exchange (ETDEWEB)

Aslan, O.; Biber Muftuler, F.Z.; Yurt Kilcar, A.; Ichedef, C.; Unak, P. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

2012-07-01

Paclitaxel (PAC) is a natural occurring diterpene alkoloid originally isolated from the bark of Taxus Brevifolia. It is one of the most important antitumor agents for clinical treatment of ovarian, breast non-small cell lung and prostate cancers. It is known that these types of cancer cells have high {beta}-glucuronidase enzyme which can catalyze the hydrolysis of glucuronides. This is why the synthesis compounds which undergo glucuronidation come into question in the imaging and therapy of these cancer cells. The aim of current study is conjugation of glucuronic acid (G) to the starting substance PAC, labeling with {sup 131}I and to perform its in vivo biological evaluation. Glucuronic acid derived paclitaxel compound [paclitaxel-glucuronide (PAC-G)] was labeled with {sup 131}I using iodogen method. According to thin layer radio chromatography (TLRC) method, the radiochemical yield of {sup 131}I-PAC-G was 84.30 {+-} 7.40% (n=10). The biodistribution of {sup 131}I-PAC-G in healthy female and male Wistar Albino rats has been investigated. Imaging studies on male Balb-C mice were performed by using the Kodak FX PRO in vivo Imaging System. The range of the breast/blood, breast/muscle; ovary/blood, ovary/muscle ratios is approximately between 1.29 and 11.34 in 240 min, and between 0.71 and 8.24 in 240 min for female rats. The prostate/blood and prostate/muscle ratio is between 1.94 and 6.95 in 30 min for male rats. All these experimental studies indicate that {sup 131}I-PAC-G may potentially be used in breast, ovary and prostate tissues as an imaging agent. Also it is thought that {sup 131}I-PAC-G bears a therapy potential because of the {sup 131}I radionuclide and can be improved with further investigations. (orig.)

Pyrene As a New Detector for Determining the Composition of Silver Nanoparticle Dispersions in Aqueous Solutions

Science.gov (United States)

Romanovskaya, G. I.; Kazakova, S. Yu.; Koroleva, M. V.; Zuev, B. K.

2018-03-01

It is proposed that the fluorescence of monomeric molecules of pyrene in solid matrices or in concentrated micellar solutions be used as a detector for determining the compositional homogeneity of silver nanoparticle (NP) dispersions in aqueous solutions synthesized in different ways. It is found that the morphology of silver NPs affects the change in the fluorescence intensity of monomeric molecules of pyrene in a certain (violet or blue) region of the pyrene optical spectrum. The observed phenomenon is attributed to the resonance of electronic transitions in the monomeric molecules of pyrene in regions with plasmon oscillations in silver nanoparticles. A new way of obtaining fluorescent silver NPs is found.

Preparation and separation of the glucuronide and sulfate conjugates of thyroxine and triiodothyronine

International Nuclear Information System (INIS)

Hays, M.T.; Hsu, L.

1987-01-01

An enzymatic method for synthesis of labelled thyroxine glucuronide (T4G) and triiodothyronine glucuronide (T3G) from labelled thyroxine (T4) and triiodothyronine (T3) is presented. The synthetic glucuronides are completely digested by beta-glucuronidase, with recovery of the parent T4 or T3. They have distinctive elution patterns on HPLC and on Sephadex G25 chromatography, and can be clearly separated from T4 and T3 as well as from synthetic T4 sulfate (T4S) and T3 sulfate (T3S). On LH 20 chromatography, elution of T4G and T3G is intermediate between that of T4 and T3 and that of T4S and T3S. T3G can be well separated from other thyronines by HPLC alone, but T4G coelutes with rT3 on HPLC; these are then separated by adding a Sephadex G25 chromatography step. Biosynthetic 131 I-T3G and 125 I-T4G from the bile of a cat given 131 I-T3 and 125 I-T4 had similar HPLC chromatographic patterns to those of synthetic T3G and T4G. That the identified peaks from analysis of the bile were indeed T3G and T4G was confirmed by recovery of the parent T3 and T4 after beta-glucuronidase digestion

Rapid genotyping using pyrene-perylene locked nucleic acid complexes

DEFF Research Database (Denmark)

Kumar, Santhosh T.; Myznikova, Anna; Samokhina, Evgeniya

2013-01-01

We have developed an assay for single strand DNA and RNA detection which is based on novel pyrene-perylene FRET pairs attached to short LNA/DNA probes. The assay is based on ratiometric emission upon binding of target DNA/RNA by three combinations of fluorescent LNA/DNA reporter strands. Specific...... geometry of the pyrene fluorophore attached to the 2'-amino group of 2'-amino-LNA in position 4 allows for the first time to efficiently utilize dipole-dipole orientation parameter for sensing of single-nucleotide polymorphisms (SNPs) in nucleic acid targets by FRET. Using novel probes, SNP detection......-perylene FRET pairs, e.g., in imaging and clinical diagnostics....

Degradation of Polycyclic Aromatic Hydrocarbon Pyrene by Biosurfactant-Producing Bacteria Gordonia cholesterolivorans AMP 10

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Tri Handayani Kurniati

2016-12-01

Full Text Available Pyrene degradation and biosurfactant activity by a new strain identified as Gordonia cholesterolivorans AMP 10 were studied. The strain grew well and produced effective biosurfactants in the presence of glucose, sucrose, and crude oil. The biosurfactants production was detected by the decreased surface tension of the medium and emulsification activity.  Analysis of microbial growth parameters showed that AMP10 grew best at 50 µg mL-1 pyrene concentration, leading to 96 % degradation of pyrene within 7 days. The result of nested PCR analysis revealed that this isolate possessed the nahAc gene which encodes dioxygenase enzyme for initial degradation of Polycyclic Aromatic Hydrocarbon (PAH. Observation of both tensio-active and emulsifying activities indicated that biosurfactants which produced by AMP 10 when grown on glucose could lower the surface tension of medium from 71.3 mN/m to 24.7 mN/m and formed a stable emulsion in used lubricant oil with an emulsification index (E24 of 74%. According to the results, it is suggested that the bacterial isolates G. cholesterolivorans AMP10 are suitable candidates for bioremediation of PAH-contaminated environments.How to CiteKurniati, T. H.,  Rusmana, I. Suryani, A. & Mubarik, N. R. (2016. Degradation of Polycyclic Aromatic Hydrocarbon Pyrene by Biosurfactant-Producing Bacteria Gordonia cholesterolivorans AMP 10. Biosaintifika: Journal of Biology & Biology Education, 8(3, 336-343. 

Is THC-COOH-glucuronide a useful marker for Tetrahydrocannabinol (THC) in DUID cases?

DEFF Research Database (Denmark)

Telving, Rasmus; Hasselstrøm, Jørgen Bo; Andreasen, Mette Findal

Is THC-COOH-glucuronide a useful marker for Tetrahydrocannabinol (THC) in DUID cases? Retrospective data analysis on UPLC-HR-TOFMS data files from 2 years of DUID cases. Telving R.(rt@forens.au.dk)*, Hasselstrøm J.B., Andreasen M.F. Department of Forensic Medicine, Aarhus University (Denmark......). Introduction The physical and chemical nature of THC makes it difficult to include in traditional screening procedures along with other common legal and illegal drugs. Development of multi-component toxicological screening procedures that include THC is therefore a challenge but also highly desirable in high...... throughput laboratories. Aims The aim of the present study was to evaluate the detection of THC indirectly by detecting the presence of THC-COOH-glucuronide in whole blood from individuals suspected of driving under the influence of drugs (DUID). We will compare existing data from THC screening...

Charge-transfer interaction mediated organogels from 18β-glycyrrhetinic acid appended pyrene

Directory of Open Access Journals (Sweden)

Jun Hu

2013-12-01

Full Text Available We describe herein the two-component charge-transfer (CT interaction induced organogel formation with 18β-glycyrrhetinic acid appended pyrene (GA-pyrene, 3 as the donor, and 2,4,7-trinitrofluorenone (TNF, 4 as the acceptor. The use of TNF (4 as a versatile electron acceptor in the formation of CT gels is demonstrated through the formation of gels in a variety of solvents. Thermal stability, stoichiometry, scanning electron microscopy (SEM, optical micrographs, and circular dichroism (CD are performed on these CT gels to investigate their thermal and assembly properties. UV–vis, fluorescence, mass spectrometric as well as variable-temperature 1H NMR experiments on these gels suggest that the CT interaction is one of the major driving forces for the formation of these organogels.

Pyrene functionalized molecular beacon with pH-sensitive i-motif in a loop.

Science.gov (United States)

Dembska, Anna; Juskowiak, Bernard

2015-01-01

In this work, we present a spectral characterization of pH-sensitive system, which combines the i-motif properties with the spatially sensitive fluorescence signal of pyrene molecules attached to hairpin ends. The excimer production (fluorescence max. ∼480 nm) by pyrene labels at the ends of the molecular beacon is driven by pH-dependent i-motif formation in the loop. To illustrate the performance and reversible work of our systems, we performed the experiments with repeatedly pH cycling between pH values of 7.5±0.3 and 6.5±0.3. The sensor gives analytical response in excimer-monomer switching mode in narrow pH range (1.5 pH units) and exhibits high pH resolution (0.1 pH unit). Copyright © 2015 Elsevier B.V. All rights reserved.

Multi-step intramolecular excitation energy transfer in dendritic pyrene-phosphorus(V)porphyrin heptads

Energy Technology Data Exchange (ETDEWEB)

Hirakawa, Kazutaka, E-mail: hirakawa.kazutaka@shizuoka.ac.jp [Applied Chemistry and Biochemical Engineering Course, Department of Engineering, Graduate School of Integrated Science and Technology, Shizuoka University, Johoku 3-5-1, Naka-ku, Hamamatsu, Shizuoka 432-8561 (Japan); Department of Optoelectronics and Nanostructure Science, Graduate School of Science and Technology, Shizuoka University, Johoku 3-5-1, Naka-ku, Hamamatsu, Shizuoka 432-8561 (Japan); Segawa, Hiroshi [Department of Multi-Disciplinary Science - General Systems Studies, Graduate School of Arts and Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8904 (Japan); Research Center for Advanced Science and Technology, The University of Tokyo, Komaba 4-6-1, Meguro-ku, Tokyo 153-8904 (Japan)

2016-11-15

Dendritic heptad molecules in which four pyrenyl groups are connected at the central phosphorus atom of the edge-porphyrins of the center-to-edge type porphyrin trimers were synthesized to investigate a multi-step excitation energy transfer. As the central energy acceptor, two types porphyrins which one was phosphorus(V)tetraphenylporphyrin (H2) and another was its derivative substituted by butoxy groups at four para-position of meso-phenyl groups (H1) were used. In the photoexcited state of the pyrene units, the excitation energy transfer to the central-porphyrin unit was observed in toluene. The excitation energy transfer is considered to be through two pathways; one is a stepwise pathway through the edge-porphyrin unit and another is a direct excitation energy transfer to the central porphyrin. The direct excitation energy transfer from pyrenes to the edge-porphyrin and central-porphyrin were observed in the case for H1. From the excited state of the edge-porphyrins, the excitation energy transfer to the central-porphyrin occurs in the H1 case. In the H2 case, the excitation energy of central-porphyrin is higher than that of H1, and the electron transfer from edge-porphyrin to the central-porphyrin become predominant process. - Highlights: • Dendritic pyrene-porphyrin heptads were synthesized. • Excitation energy transfer occurs from the pyrenyl moiety to the phosphorus(V)porphyrin. • The stepwise and direct energy transfer pathways were observed. • The quantum yields of these energy transfer pathways could be determined.

Multi-step intramolecular excitation energy transfer in dendritic pyrene-phosphorus(V)porphyrin heptads

International Nuclear Information System (INIS)

Hirakawa, Kazutaka; Segawa, Hiroshi

2016-01-01

Dendritic heptad molecules in which four pyrenyl groups are connected at the central phosphorus atom of the edge-porphyrins of the center-to-edge type porphyrin trimers were synthesized to investigate a multi-step excitation energy transfer. As the central energy acceptor, two types porphyrins which one was phosphorus(V)tetraphenylporphyrin (H2) and another was its derivative substituted by butoxy groups at four para-position of meso-phenyl groups (H1) were used. In the photoexcited state of the pyrene units, the excitation energy transfer to the central-porphyrin unit was observed in toluene. The excitation energy transfer is considered to be through two pathways; one is a stepwise pathway through the edge-porphyrin unit and another is a direct excitation energy transfer to the central porphyrin. The direct excitation energy transfer from pyrenes to the edge-porphyrin and central-porphyrin were observed in the case for H1. From the excited state of the edge-porphyrins, the excitation energy transfer to the central-porphyrin occurs in the H1 case. In the H2 case, the excitation energy of central-porphyrin is higher than that of H1, and the electron transfer from edge-porphyrin to the central-porphyrin become predominant process. - Highlights: • Dendritic pyrene-porphyrin heptads were synthesized. • Excitation energy transfer occurs from the pyrenyl moiety to the phosphorus(V)porphyrin. • The stepwise and direct energy transfer pathways were observed. • The quantum yields of these energy transfer pathways could be determined.

Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein-Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects.

OpenAIRE

Radom, J; Salvayre, R; Levade, T; Douste-Blazy, L

1990-01-01

The uptake and intracellular metabolism of 4-(1-pyrene)butanoic acid (P4), 10-(1-pyrene)decanoic acid (P10) and 12-(1-pyrene)dodecanoic acid (P12) were investigated in cultured lymphoid cell lines from normal individuals and from a patient with multisystemic lipid storage myopathy (MLSM). The cellular uptake was shown to be dependent on the fatty-acid chain length, but no significant difference in the uptake of pyrene fatty acids was observed between MLSM and control lymphoid cells. After inc...

Effects of model traumatic injury on hepatic drug metabolism in the rat. IV. Glucuronidation.

Science.gov (United States)

Griffeth, L K; Rosen, G M; Rauckman, E J

1985-01-01

A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on hepatic glucuronidation activity. As was previously observed with hepatic oxidative drug metabolism, model trauma resulted in a significant decrease in the in vivo glucuronidation of chloramphenicol, with a 23% drop in clearance of this drug. The effect on in vivo pharmacokinetics appeared to result from a complex interaction between trauma's differential influences on conjugating enzyme(s), deconjugating enzyme(s), and hepatic UDP-glucuronic acid levels, as well as the relative physiological importance of these variables. Hepatic UDP-glucuronyltransferase activities towards both p-nitrophenol and chloramphenicol were elevated (44-54%) after model injury when measured in native hepatic microsomes. However, microsomes which had been "activated" by treatment with Triton X-100 showed no significant difference between control and traumatized animals. Serum beta-glucuronidase activities were elevated by 58%, while hepatic beta-glucuronidase rose by about 16%. Nevertheless, in vivo deconjugation showed no significant change. Model trauma also resulted in a 46% decrease in hepatic UDP-glucuronic acid content. Thus, the observed post-traumatic depression of in vivo chloramphenicol glucuronidation could be due either to a diminished availability of a necessary cofactor (UDP-glucuronic acid) or to an alteration in enzyme kinetics or function in vivo.

Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vitro and in vivo.

Science.gov (United States)

Weinstein, I B; Jeffrey, A M; Jennette, K W; Blobstein, S H; Harvey, R G; Harris, C; Autrup, H; Kasai, H; Nakanishi, K

1976-08-13

Evidence has been obtained that a specific isomer of a diol epoxide derivative of benzo(a)pyrene, (+/-)-7 beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, is an intermediate in the binding of benzo(a)pyrene to RNA in cultured bovine bronchial mucosa. An adduct is formed between position 10 of this derivative and the 2-amino group of guanine.

Gender and oral contraceptive steroids as determinants of drug glucuronidation: effects on clofibric acid elimination.

Science.gov (United States)

Miners, J O; Robson, R A; Birkett, D J

1984-01-01

The disposition of clofibric acid, a drug metabolised largely by glucuronidation, was studied in eight males, eight females and eight females receiving oral contraceptive steroids (OCS). Clofibric acid plasma clearance was not significantly different in males compared to the control female group but was 48% greater (P less than 0.01) in women receiving OCS compared to non-pill using females. This difference was due to an alteration in clofibric acid metabolic clearance as there were no differences between the groups in clofibric acid free fraction. Along with previous data the results suggest that induction of drug glucuronidation by OCS may be of clinical importance, although any sex-related differences are unlikely to be of clinical significance. PMID:6487463

Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants

NARCIS (Netherlands)

E.H.J. Krekels (Elke); S. Van Ham (Saskia); K.M. Allegaert (Karel); J.N. de Hoon; D. Tibboel (Dick); M. Danhof (Meindert); C.A.J. Knibbe (Catherijne)

2015-01-01

textabstractPurpose: Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling

Interaction of 1-pyrene sulfonic acid sodium salt with human serum albumin

Energy Technology Data Exchange (ETDEWEB)

Steblecka, Malgorzata, E-mail: gosia@mitr.p.lodz.pl; Wolszczak, Marian, E-mail: marianwo@mitr.p.lodz.pl; Szajdzinska-Pietek, Ewa, E-mail: espietek@mitr.p.lodz.pl

2016-04-15

Steady state and time-resolved techniques of optical spectroscopy were applied to examine the interaction between 1-pyrene sulfonic acid (PSA) sodium salt and human serum albumin (HSA). This work is directed towards finding a convenient fluorescent marker (or blocker) of hydrophobic binding sites within the protein, to be used in the in vitro studies of HSA−drug systems. The observed variation of PSA absorbance with HSA concentration was interpreted in terms of two possible probe/protein binding modes with the binding constants K{sub b,1}=(6.5±0.6)∙10{sup 6} M{sup −1} (a specific receptor site), and K{sub b,2}=(3.8±0.8)∙10{sup 5} M{sup −1} (non-specific binding of up to three probe molecules). The PSA fluorescence is quenched by the albumin (via both static and dynamic mechanisms), and also the HSA–Trp214 fluorescence is quenched by PSA (via resonance energy transfer). These results indicate that the probe is bound in the domain IIA of the secondary HSA structure. At lower [PSA]/[HSA] ratios the PSA fluorescence lifetime is longer than that in homogeneous buffer solutions (not containing HSA). Therefore, we conclude that lower affinity binding sites are distant from the tryptophan residue. This is confirmed by complementary studies on the transient T–T absorbance and on luminescence of the photosensitized singlet oxygen.

Solubility of Benzo[a]pyrene and Organic Matter of Soil in Subcritical Water

Directory of Open Access Journals (Sweden)

Svetlana Sushkova

2015-12-01

Full Text Available A dynamic subcritical water extraction method of benzo[a]pyrene from soils is under consideration. The optimum conditions for benzo[a]pyrene extraction from soil are described including the soil treatment by subcritical water at 250 °C and 100 atm for 30 min. The effectiveness of developed method was determined using the matrix spiking recovery technique. A comparative analysis was made to evaluate the results of benzo[a]pyrene extraction from soils using the subcritical water and organic solvents. The advantages of the subcritical water extraction involve the use of ecologically friendly solvent, a shorter time for the analysis and a higher amount of benzo[a]pyrene extracted from soil (96 %. The influence of subcritical water extraction on soil properties was measured the investigation of the processes occurring within soil under the influence the high temperature and pressure. Under appropriate conditions of the experiment there is the destruction of the soil organic matter while the composition of the soil mineral fraction remains practically unchanged.

Metabolic activation and DNA binding of benzo(a)pyrene in cultured human bronchus

DEFF Research Database (Denmark)

Yang, Shen K.; Gelboin, Harry V.; Trump, Benjamin F.

1977-01-01

. The predominant metabolite formed by human bronchus from the (-)-trans-7,8-diol is found by high-pressure liquid chromatographic analysis to be the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahy-drobenzo(a)pyrene. The results suggest that this diol-epoxide is the major benzo(a)pyrene metabolite bound...

Bioremediating silty soil contaminated by phenanthrene, pyrene ...

African Journals Online (AJOL)

... followed in the order of their increasing molecular weight. The synergy of the bacterial isolates and the biosurfactant produced from B. vulgaris agrowaste could be used in environmental bioremediation of PAHs even in silty soil. Keywords: Benz(a)anthracene, benzo(a)pyrene, bioremediation, biosurfactant, Beta vulgaris, ...

Selective binding of pyrene in subdomain IB of human serum albumin: Combining energy transfer spectroscopy and molecular modelling to understand protein binding flexibility

Science.gov (United States)

Ling, Irene; Taha, Mohamed; Al-Sharji, Nada A.; Abou-Zied, Osama K.

2018-04-01

The ability of human serum albumin (HSA) to bind medium-sized hydrophobic molecules is important for the distribution, metabolism, and efficacy of many drugs. Herein, the interaction between pyrene, a hydrophobic fluorescent probe, and HSA was thoroughly investigated using steady-state and time-resolved fluorescence techniques, ligand docking, and molecular dynamics (MD) simulations. A slight quenching of the fluorescence signal from Trp214 (the sole tryptophan residue in the protein) in the presence of pyrene was used to determine the ligand binding site in the protein, using Förster's resonance energy transfer (FRET) theory. The estimated FRET apparent distance between pyrene and Trp214 was 27 Å, which was closely reproduced by the docking analysis (29 Å) and MD simulation (32 Å). The highest affinity site for pyrene was found to be in subdomain IB from the docking results. The calculated equilibrium structure of the complex using MD simulation shows that the ligand is largely stabilized by hydrophobic interaction with Phe165, Phe127, and the nonpolar moieties of Tyr138 and Tyr161. The fluorescence vibronic peak ratio I1/I3 of bound pyrene inside HSA indicates the presence of polar effect in the local environment of pyrene which is less than that of free pyrene in buffer. This was clarified by the MD simulation results in which an average of 5.7 water molecules were found within 0.5 nm of pyrene in the binding site. Comparing the fluorescence signals and lifetimes of pyrene inside HSA to that free in buffer, the high tendency of pyrene to form dimer was almost completely suppressed inside HSA, indicating a high selectivity of the binding pocket toward pyrene monomer. The current results emphasize the ability of HSA, as a major carrier of several drugs and ligands in blood, to bind hydrophobic molecules in cavities other than subdomain IIA which is known to bind most hydrophobic drugs. This ability stems from the nature of the amino acids forming the binding

Effects of pyrene exposure and temperature on early development of two co-existing Arctic copepods

DEFF Research Database (Denmark)

Grenvald, Julie Cornelius; Nielsen, Torkel Gissel; Hjorth, Morten

2013-01-01

Oil exploration is expected to increase in the near future in Western Greenland. At present, effects of exposure to oil compounds on early life-stages of the ecologically important Calanus spp. are unknown. We investigated the effects of the oil compound pyrene, on egg hatching and naupliar...... with temperature at high pyrene concentration in C. finmarchicus. Both Calanus species were affected by pyrene exposure but C. finmarchicus was more sensitive compared to C. glacialis. Lowered growth rate and increased mortality of the naupliar stages entail reduced recruitment to copepod populations. Exposure...

Immunotoxicity effect of benzo[α]pyrene on scallop Chlamys farreri

Science.gov (United States)

Zhang, Lin; Pan, Luqing; Liu, Jing

2009-03-01

The toxic effects of benzo[ α]pyrene (B[ α]P) at different concentrations (0.1, 0.5, 1, 2.5 and 7.5 μgL-1) on scallop ( Chlamy farreri) immune system were studied. The results showed that B[ α]P had significant toxic effects on the haemocyte counts, neutral red uptake, phagocytosis, bacteriolytic and antibacterial activity ( P0.05). Thus, B[ α] has evident toxic effects on scallop immune system, which supports the view that a relationship exists between pollution and immunomodulation in aquatic organisms.

Photochemistry of pyrene with water at low temperature: study of atmospherical and astrochemical interest.

Science.gov (United States)

Guennoun, Zohra; Aupetit, Christian; Mascetti, Joëlle

2011-03-17

Photochemistry of a polyaromatic hydrocarbon, pyrene C(16)H(10), with water has been investigated at cryogenic temperatures. Photoprocessing of this species, performed at λ > 235 nm, in argon matrices, adsorbed onto amorphous water surfaces, and trapped in solid water, led to the formation of ketonic isomers, C(16)H(10)O, and possibly quinones. These species have been identified for the first time by infrared spectroscopy with the support of isotopic substitution experiments and DFT calculations. These oxidized pyrene-like species, of atmospherical and astrochemical interest, most likely arise from a tautomeric rearrangement of their analogous hydroxylated molecules, these latter being formed by reaction of water with pyrene cations.

Isolation and Identification of Pyrene-degrading Bacteria from Soils around Landfills in Shiraz and Their Growth Kinetic Assay

Directory of Open Access Journals (Sweden)

Farshid Kafilzadeh

2011-12-01

Full Text Available Background & Objectives: Pyrene is a kind of carcinogen hydrocarbon in environment and one of the top 129 pollutants as ranked by the U.S.Environmental Pretection Agency (USEPA. Today's commodious method that is considered by many researchers is the use of microorganisms to degrade these compounds from the environment. The goal of this research is separation and identification of the indigenous bacterias which are effective in decomposition of Pyrene hydrocarbon from soils around Shiraz Landfills. Isolated bacteria growth in the presence of different concentrations of the aforesaid organic pollutant was evaluated. Materials & Methods: Taking samples from Landfills were done after transportation them to the laboratory. The numbers of the bacterias were counted in a medium including Pyrene 0.6 g/l and in another medium without Pyrene. The isolated bacterias were separated by the enriched medium of hydrocarbon Pyrene and were recognized accordance with standards methods (specialty of colony, microscopic properties, fermentation of sugars and biochemical test.The kinetic growth of the separated bacterias was evaluated every 12 hours during 7 successive days. Results: It was reported that the numbers of the bacterias in the medium without Pyrene is more than those with Pyrene (cfu/g. The separated bacterias were included Bacillus spp., Pseudomonas spp., Micrococcus spp., Mycobacterium spp. These four isolated bacterias showed the best growth with Pyrene 0.6 g/l during third and fourth days. Conclusion: The separating bacterias, effecting in decomposition of PAH, make this possibility that the modern methods with more efficiency to be created for removing the carcinogen organic polluters from the environment. Moreover, the separated bacterias (relating to this research can be applied to develop the microbial population in the areas that polluted with Pyrene.

Impact of nitrogen-polycyclic aromatic hydrocarbons on phenanthrene and benzo[a]pyrene mineralisation in soil.

Science.gov (United States)

Anyanwu, Ihuoma N; Ikpikpini, Ojerime C; Semple, Kirk T

2018-01-01

When aromatic hydrocarbons are present in contaminated soils, they often occur in mixtures. The impact of four different (3-ring) nitrogen-containing polycyclic aromatic hydrocarbons (N-PAHs) on 12/14 C-phenanthrene and 12/14 C-benzo[a]pyrene (B[a]P) mineralisation in soil was investigated over a 90 d incubation period. The results revealed that both 12/14 C-phenanthrene and 12/14 C-benzo[a]pyrene showed no significant mineralisation in soils amended with 10mgkg -1 and 100mgkg -1 N-PAHs (p>0.05). However, increases in lag-phases and decreases in the rates and extents of mineralisation were observed, over time. Among the N-PAHs, benzo[h]quinoline impacted 14 C-phenanthrene mineralisation with extended and diauxic lag phases. Furthermore, 12/14 C-B[a]P and 14 C-benzo[a]pyrene-nitrogen-containing polycyclic aromatic hydrocarbons ( 14 C-B[a]P-N-PAHs) amended soils showed extensive lag phases (> 21 d); with some 14 C-B[a]P-N-PAH mineralisation recording polycyclic aromatic hydrocarbons (PAHs) and the impact was most likely the result of limited success in achieving absolute biodegradation of some PAHs in soil. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative determination of benzo[a]pyrene in foodstuffs using benzo[a]pyrene[G-3H

International Nuclear Information System (INIS)

Masuda, Yoshito; Shimamura, Kyoko; Yano, Hiroshige

1977-01-01

A method for quantitative determination of nano gram level of benzo(a)pyrene (BP) in foodstuffs using tritiated BP( 3 H-BP) was described. Extracts from foodstuffs, having been added a certain amount of 3 H-BP, were fractionated by column chromatography on Florisil, and thinlayer chromatography on acetylated cellulose. Concentration and radio activity of BP in the final fraction were determined by fluorescence spectrometry and liquid scintillation. Recovery ratio of each experiment was obtained by comparing the radio activities of added 3 H-BP and separated BP. Concentration of BP in the sample analyzed was calculated from the amount of isolated BP and the recovery ratio in each experiment. A quantitative limit of BP by this method was 0.2 ppb when 50 g of sample was used. By this method, contents of BO in each sample of Tenpura oil, salad oil, flour, and polished rice were determined as 0.6, 0.2, 0.1 and < 0.1 ppb on average, respectively. (auth.)

The nature of conducting materials by anodic coupling of pyrene

Energy Technology Data Exchange (ETDEWEB)

Zotti, G.; Schiavon, G. (Ist. di Polarografia ed Elettrochimica Preparativa, Consiglio Nazionale delle Ricerche, Padua (Italy))

1992-05-01

Polypyrenes from anodic coupling of pyrene in acetonitrile and 1,2-dichloroethane have been identified as the 1,1'-coupled dimer and tetramer, respectively, on the basis of electrochemical analysis and IR, UV-Vis and mass spectroscopies. Bipyrene and tetrapyrene are reversibly reduced at -2.27 and -2.15 V versus Ag/Ag{sup +}, respectively. Their electrochemical oxidation (at 0.96 and 0.87 V) is followed by further polymerization and ultimate degradation whereas iodine doping of tetrapyrene leads reversibly to a conducting adduct (6x10{sup -3} S/cm). (orig.).

Mechanism-based inactivation of cytochrome P-450 dependent benzo[a]pyrene hydroxylase activity by acetylenic and olefinic polycyclic arylhydrocarbons

International Nuclear Information System (INIS)

Gan, L.S.

1986-01-01

A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxygenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene (EP), 3-ethynylperylene (EPL), cis- and trans-1-(2-bromo-vinyl)pyrene (c-BVP and t-BVP), and 1-allylpyrene (AP) serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene (BP) hydroxylase, while 1-vinyl-pyrene (VP) and phenyl 1-pyrenyl acetylene (PPA) do not cause a detectable suicide inhibition of the BP hydroxylase. The mechanism-based loss of BP hydroxylase activity caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes. In the presence of NADPH, 3 H-labeled EP covalently attached to P-450 isozymes with a measured stoichiometry of one mole of EP per mole of the P-450 heme. The results of the effects of these aryl derivatives in the mammalian cell-mediated mutagenesis assay and toxicity assay show that none of the compounds examined nor any of the their metabolites produced in the incubation system are cytotoxic to V79 cells

The effect of pregnancy and estradiol-17 beta treatment on the biliary transport maximum of dibromosulfophthalein, and the glucuronide conjugates of 5-phenyl-5-p-hydroxyphenyl[14C]hydantoin and [14C]morphine in the isolated perfused rat liver

International Nuclear Information System (INIS)

Auansakul, A.C.; Vore, M.

1982-01-01

The biliary transport maximum (Tm) of three organic axions was determined in the isolated perfused livers of untreated female (control), estradiol-17 beta (E2)-treated female (1 mg/kg/day, s.c. for 14 days), and pregnant (19-21 days of gestation) rats. Dibromosulfophthalein (DBSP), 5-phenyl-5-p-hydroxyphenyl[ 14 C]hydantoin (HPPH) and [ 14 C]morphine were infused continuously into the perfusate for a total dose of 41.2, 18, or 40.5 mumol, respectively. The concentration of [ 14 C]HPPH and [ 14 C]morphine declined in the perfusate, whereas the concentrations of [ 14 C]HPPH glucuronide and [ 14 C]morphine glucuronide increased during the 90-min experiment, indicating that the rate of formation of the glucuronide exceeded its rate of excretion in bile. E2 treatment decreased the Tm (nmol/min/g liver) for [ 14 C]HPPH glucuronide and [ 14 C]morphine glucuronide but not for DBSP, whereas pregnancy decreased the Tm for all three organic anions. Pregnancy, and to a lesser extent E2 treatment, increased liver weight. When expressed per whole liver, the Tm was not altered by pregnancy for any of three organic anions. E2 treatment increased the Tm for DBSP, had no effect on the Tm for HPPH glucuronide and decreased the Tm for [ 14 C]morphine glucuronide. These data suggest the presence of multiple carriers for organic anions which are differentially affected by estrogen treatment and pregnancy

A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain

DEFF Research Database (Denmark)

Sverrisdóttir, Eva; Lund, Trine Meldgaard; Olesen, Anne Estrup

2015-01-01

Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can...... a detailed overview of the published human population pharmacokinetic-pharmacodynamic studies for morphine analgesia in addition to basic drug disposition and pharmacological properties of morphine and its analgesic active metabolite, morphine-6-glucuronide, that may help identify future covariates....... Furthermore, based on simulations from key pharmacokinetic-pharmacodynamic models, the contribution of morphine-6-glucuronide to the analgesic response in patients with renal insufficiency was investigated. Simulations were also used to examine the impact of effect-site equilibration half-life on time course...

PYRENE INTERCALATING NUCLEIC ACIDS WITH A CARBON LINKER

DEFF Research Database (Denmark)

Østergaard, Michael E.; Wamberg, Michael Chr.; Pedersen, Erik Bjerregaard

2011-01-01

geminally attached. Fluorescence studies of this intercalating nucleic acid with the pyrene moieties inserted as a bulge showed formation of an excimer band. When a mismatch was introduced at the site of the intercalator, an excimer band was formed for the destabilized duplexes whereas an exciplex band...

Topological analysis of the electron density and of the electron localization function of pyrene and its radicals

International Nuclear Information System (INIS)

Hernandez-Trujillo, Jesus; Garcia-Cruz, Isidoro; Martinez-Magadan, Jose Manuel

2005-01-01

The topological properties of the charge distribution of pyrene and the three derived monoradicals in their ground state and of didehydrogenated pyrenes in the lowest singlet and triplet electronic states are discussed in detail by means of the quantum theory of atoms in molecules (TAIM) and by the electron localization function (ELF). The non-equivalence of the fused aromatic rings of pyrene prevents one from anticipating the stability and reactivity of these species from the chemistry of didehydrogenated species derived from benzene only. Whereas some of these didehydrogenated molecules were found to display a diradical character in the singlet ground state, the topological analysis reveals that others correspond to normal closed shells. Using these theoretical tools, the energetic and geometric details of o-, m- and p-benzyne-like pyrene derivatives are explained

p53 Mutagenesis by Benzo[a]pyrene derived Radical Cations

Science.gov (United States)

Sen, Sushmita; Bhojnagarwala, Pratik; Francey, Lauren; Lu, Ding; Jeffrey Field, Trevor M. Penning

2013-01-01

Benzo[a]pyrene (B[a]P), a major human carcinogen in combustion products such as cigarette smoke and diesel exhaust, is metabolically activated into DNA-reactive metabolites via three different enzymatic pathways. The pathways are the anti-(+)-benzo[a]pyrene 7,8-diol 9, 10-epoxide pathway (P450/ epoxide hydrolase catalyzed) (B[a]PDE), the benzo[a]pyrene o-quinone pathway (aldo ketose reductase (AKR) catalyzed) and the B[a]P radical cation pathway (P450 peroxidase catalyzed). We used a yeast p53 mutagenesis system to assess mutagenesis by B[a]P radical cations. Because radical cations are short-lived, they were generated in situ by reacting B[a]P with cumene hydroperoxide (CuOOH) and horse radish peroxidase (HRP) and then monitoring the generation of the more stable downstream products, B[a]P-1,6-dione and B[a]P-3,6-dione. Based on the B[a]P-1,6 and 3,6-dione formation, approximately 4µM of radical cation was generated. In the mutagenesis assays, the radical cations produced in situ showed a dose-dependent increase in mutagenicity from 0.25 µM to 10 µM B[a]P with no significant increase seen with further escalation to 50 µM B[a]P. However, mutagenesis was 200-fold less than with the AKR pathway derived B[a]P, 7–8 dione. Mutant p53 plasmids, which yield red colonies, were recovered from the yeast to study the pattern and spectrum of mutations. The mutation pattern observed was G to T (31%) > G to C (29%) > G to A (14%). The frequency of codons mutated by the B[a]P radical cations was essentially random and not enriched at known cancer hotspots. The quinone products of radical cations, B[a]P-1,6-dione and B[a]P-3,6-dione were more mutagenic than the radical cation reactions, but still less mutagenic than AKR derived B[a]P-7,8-dione. We conclude that B[a]P radical cations and their quinone products are weakly mutagenic in this yeast-based system compared to redox cycling PAH o-quinones. PMID:22768918

Effect of Glucuronidation on the Potential of Kaempferol to Inhibit Serine/Threonine Protein Kinases

NARCIS (Netherlands)

Beekmann, Karsten; Haan, De Laura H.J.; Actis-Goretta, Lucas; Bladeren, Van Peter J.; Rietjens, Ivonne M.C.M.

2016-01-01

To study the effect of metabolic conjugation of flavonoids on the potential to inhibit protein kinase activity, the inhibitory effects of the dietary flavonol kaempferol and its major plasma conjugate kaempferol-3-O-glucuronide on protein kinases were studied. To this end, the inhibition of the

Bioremediation of Pyrene-Contaminated Soils Using Biosurfactant

OpenAIRE

Jorfi; Rezaee; Jaafarzadeh; Esrafili; Akbari; Moheb Ali

2014-01-01

Background Polycyclic aromatic hydrocarbons (PAHs) are persistence organic chemicals with proved carcinogenic and mutagenic hazards. These compounds are usually adsorbed in soils in vicinity of oil and gas industries. Bioremediation of PAHs contaminated soils is difficult due to hydrophobic nature of PAHs. Objectives The main purpose of the current study was to determine the pyrene removal efficiency in synthetically contaminated ...

Cancer risk estimation for mixtures of coal tars and benzo(a)pyrene

International Nuclear Information System (INIS)

Gaylor, D.W.; Culp, S.J.; Goldstein, L.S.; Beland, F.A.

2000-01-01

Two-year chronic bioassays were conducted by using B6C3F1 female mice fed several concentrations of two different mixtures of coal tars from manufactured gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain estimates of cancer potency of coal tar mixtures, by using conventional regulatory methods, for use in manufactured gas waste site remediation. A secondary purpose was to investigate the validity of using the concentration of a single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative risk for a coal tar mixture. The study has shown that BaP dominates the cancer risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In this case the most sensitive tissue site is the forestomach. Using low-dose linear extrapolation, the lifetime cancer risk for humans is estimated to be: Risk -4 (ppm coal tar in total diet) + 240 x 10 -4 (ppm BaP in total diet), based on forestomach tumors. If the BaP concentration in the coal tar mixture is less than 6,300 ppm, the more likely case, then lung tumors provide the largest estimated upper limit of risk, Risk -4 (ppm coal tar in total diet), with no contribution of BaP to lung tumors. The upper limit of the cancer potency (slope factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 x 10 -3 per microg per kg body weight per day from this Good Laboratory Practice (GLP) study compared with the current value of 7.3 x 10 -3 per microg per kg body weight per day listed in the US EPA Integrated Risk Information System

Differences in the covalent binding of benzo(a)pyrene, safrole, 1'-hydroxysafrole, and 4-aminobiphenyl to DNA of pregnant and non-pregnant mice

International Nuclear Information System (INIS)

Lu, L.W.; Disher, R.M.; Randerath, Kurt

1986-01-01

The effects of pregnancy on the covalent binding of several carcinogens to DNA were investigated in mice. Non-pregnant or timed-pregnant (18th day of gestation) ICR mice of similar age were treated with benzo(a)pyrene (BP, 200 μmol/kg), safrole (600 μmol/kg), 1'-hydroxysafrole (400 μmol/kg), 4-aminobiphenyl (4-ABP, 800 μmol/kg) or trioctanoin (4 ml/kg) per os. Tissue DNA adduct levels at 24 h after carcinogen treatment were analyzed via a 32 P-postabeling assay. Pregnancy lowered the binding of the ultimate carcinogenic metalolite of BP, 7β, 8α-dihydroxy-9, 10α-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE I), to liver and lung DNA by 29-41%, but not the binding of other metabolites. The binding of safrole and its proximate carcinogen, 1'-hydroxysafrole, to liver and kidney DNA was increased 2.3-3.5 fold. Pregnancy decreased the binding of 4-ABP to liver DNA by approx. 18% but increased its binding to kidney DNA by 67%. The results suggest that exposure to some genotoxic compounds especially those requiring conjugation reactions for metabolic activation, may be more hazardous during pregnancy than in the non-pregnant state (author)

Synthesis, characterization and photophysical study of ethynyl pyrene derivatives as promising materials for organic optoelectronics

Energy Technology Data Exchange (ETDEWEB)

Gama, Paola E.; Corrêa, Rodrigo J.; Garden, Simon J., E-mail: garden@iq.ufrj.br

2015-05-15

Two series of pyrene derivatives, phenylethynyl (4–6) and the previously unknown ethynylcyclohexanol (7–9), were prepared by Sonogashira cross-coupling reactions. The introduction of an increasing number of ethynyl substituents resulted in a progressive bathochromic shift in the absorption and emission spectra which culminated in an inversion of the nature of the first two excited states ({sup 1}L{sub a} and {sup 1}L{sub b}) of the tetra-substituted derivatives (6 and 9) relative to pyrene. In solution, only for the mono-cyclohexanolethynyl pyrene (7) a sufficiently concentrated solution could be obtained so as to observe the excimer. Additionally, the emission band ratio I{sub 1}/I{sub 3} for 7 was found to be moderately sensitive to the nature of the solvent and the ratio directly correlated with the Py scale. TDDFT calculations were used to explore the variation of the properties of the low lying excited states. Fluorescence emission in the solid state, with the appropriate choice of materials, covers the entire visible region of the electromagnetic spectrum due to static excimer emission. A massive red-shift for solid state photoluminescence from 9 resulted in emission at longer wavelength than the more highly conjugated 6. - Highlights: • Phenyl and cyclohexanol ethynylpyrene derivatives: photophysically compared. • Excimer formation and solvent dependent emission from cyclohexanolethynylpyrene. • Systematic red shifting of solid state photoluminescence from static excimers. • Massive red-shift in the solid state photoluminescence of 9. • TDDFT calculations: properties of the lowest singlet states, systematic comparison.

Enzymatic synthesis of pyrene-labeled polyphosphoinositides and their behavior in organic solvents and phosphatidylcholine bilayers

NARCIS (Netherlands)

Gadella, Th.W.J.; Moritz, A.; Westerman, J.; Wirtz, K.W.A.

1990-01-01

A method is reported for the synthesis of pyrene-labeled analogues of phosphatidylinositol 4-phosphate (Pyr-PIP) and phosphatidylinositol 4,5-bisphosphate (Pyr-PIP,) from sn-2-(pyrenyl-decanoy1)phosphatidylinositol (Pyr-PI) using partially purified PI and PIP kinase preparations. Phos-phorylation of

Effects of the antibiotic ciprofloxacin on the bacterial community structure and degradation of pyrene in marine sediment

International Nuclear Information System (INIS)

Naeslund, Johan; Hedman, Jenny E.; Agestrand, Cecilia

2008-01-01

The ecological consequences of antibiotics in the aquatic environment have been an issue of concern over the past years due to the potential risk for negative effects on indigenous microorganisms. Microorganisms provide important ecosystem services, such as nutrient recycling, organic matter mineralization and degradation of pollutants. In this study, effects of exposure to the antibiotic ciprofloxacin on the bacterial diversity and pollutant degradation in natural marine sediments were studied using molecular methods (T-RFLP) in combination with radiorespirometry. In a microcosm experiment, sediment spiked with 14 C-labelled pyrene was exposed to five concentrations of ciprofloxacin (0, 20, 200, 1000 and 2000 μg L -1 ) in a single dose to the overlying water. The production of 14 CO 2 (i.e. complete mineralization of pyrene) was measured during 11 weeks. Sediment samples for bacterial community structure analysis were taken after 7 weeks. Results showed a significant dose-dependent inhibition of pyrene mineralization measured as the total 14 CO 2 production. The nominal EC 50 was calculated to 560 μg L -1 , corresponding to 0.4 μg/kg d.w. sediment. The lowest effect concentration on the bacterial community structure was 200 μg L -1 , which corresponds to 0.1 μg/kg d.w. sediment. Our results show that antibiotic pollution can be a potential threat to both bacterial diversity and an essential ecosystem service they perform in marine sediment

Solid-phase microextraction (SPME) as a tool to predict the bioavailability and toxicity of pyrene to the springtail, Folsomia candida, under various soil conditions

DEFF Research Database (Denmark)

Styrishave, Bjarne; Mortensen, Mads; Krogh, Paul Henning

2008-01-01

The porewater concentrations of pyrene were estimated by a negligible depletive solid-phase microextraction (SPME) method. The effects of organic matter (OM) and soil aging on the bioavailability of pyrene in soil were investigated by generation of reproductive effect concentrations (EC50...... increased with increasing OM and aging of the soil. The increase of the OM content in the soil reduced the extractability of pyrene by SPME, as well as the toxicity of pyrene. An aging effect was demonstrated in Askov soil, EC50 values increased with increased contact time. The amounts of pyrene extracted...

Induction of secondary metabolism by environmental pollutants: metabolization of pyrene and formation of 6,8-dihydroxy-3-methylisocoumarin by Crinipellis stipitaria JK 364

International Nuclear Information System (INIS)

Lange, B.; Kremer, S.; Sterner, O.; Anke, H.

1995-01-01

In submerged cultures, when grown in the presence of pyrene, the saprophytic and plant inhabiting basidiomycete Crinipellis stipitaria was found to produce 6,8-dihydroxy-3-methyl-isocoumarin. The amount of 6,8-dihydroxy-3-methylisocoumarin formed depended on the concentration of pyrene in the medium. In cultures incubated without pyrene or with less than 2.5 mg/l no formation of 6,8-dihydroxy-3-methylisocoumarin was observed. Besides pyrene, chrysene, anotther four ring polycyclic aromatic hydrocarbon, induced isocoumarin formation whereas anthracene, phenanthrene or fluoranthene were not effective. During metabilization experiments with [4,5,9,10- 14 C]pyrene (0.4 mCi (14.8 kBq)/mmol), labelled 6,8-dihydroxy-3-methylsiocoumarin (specific activity 15 μCi (0.6 kBq)/mmol) was identified. When C. stipitaria JK 364 was incubated for 14 days with 5 μCi (0.2 kBq) sodium [2- 14 C]acetate and 10 mg/l pyrene, labelled 6,8-dihydroxy-3-methylisocoumarin was isolated from the culture. The results are in agreement with the polyketide origin of the isocoumarin and proof the breakdown of pyrene to acetate which is a central intermediate in the pathway from pyrene to 6,8-dihydroxy-3-methylisocoumarin. (orig.)

Metabolism of 1-fluoro-1,1,2-trichloroethane, 1,2-dichloro-1,1-difluoroethane, and 1,1,1-trifluoro-2-chloroethane.

Science.gov (United States)

Yin, H; Jones, J P; Anders, M W

1995-03-01

1-Fluoro-1,1,2-trichloroethane (HCFC-131a), 1,2-dichloro-1,1-difluoroethane (HCFC-132b), and 1,1,1-trifluoro-2-chloroethane (HCFC-133a) were chosen as models for comparative metabolism studies on 1,1,1,2-tetrahaloethanes, which are under consideration as replacements for ozone-depleting chlorofluorocarbons (CFCs). Male Fischer 344 rats were given 10 mmol/kg ip HCFC-131a or HCFC-132b or exposed by inhalation to 1% HCFC-133a for 2 h. Urine collected in the first 24 h after exposure was analyzed by 19F NMR and GC/MS and with a fluoride-selective ion electrode for the formation of fluorine-containing metabolites. Metabolites of HCFC-131a included 2,2-dichloro-2-fluoroethyl glucuronide, 2,2-dichloro-2-fluoroethyl sulfate, dichlorofluoroacetic acid, and inorganic fluoride. Metabolites of HCFC-132b were characterized as 2-chloro-2,2-difluoroethyl glucuronide, 2-chloro-2,2-difluoroethyl sulfate, chlorodifluoroacetic acid, chlorodifluoroacetaldehyde hydrate, chlorodifluoroacetaldehyde-urea adduct, and inorganic fluoride. HCFC-133a was metabolized to 2,2,2-trifluoroethyl glucuronide, trifluoroacetic acid, trifluoroacetaldehyde hydrate, trifluoroacetaldehyde-urea adduct, inorganic fluoride, and a minor, unidentified metabolite. With HCFC-131a and HCFC-132b, glucuronide conjugates of 2,2,2-trihaloethanols were the major urinary metabolites, whereas with HCFC-133a, a trifluoroacetaldehyde-urea adduct was the major urinary metabolite. Analysis of metabolite distribution in vivo indicated that aldehydic metabolites increased as fluorine substitution increased in the order HCFC-131a < HCFC-132b < HCFC-133a. With NADPH-fortified rat liver microsomes, HCFC-133a and HCFC-132b were biotransformed to trifluoroacetaldehyde and chlorodifluoroacetaldehyde, respectively, whereas HCFC-131a was converted to dichlorofluoroacetic acid. No covalently bound metabolites were detected by 19F NMR spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal monitoring of early pregnancy by a direct radioimmunoassay of steroid glucuronides in first morning urine

International Nuclear Information System (INIS)

Mendizabal, A.F.; Quiroga, S.; Farinati, Z.; Lahoz, M.; Nagle, C.

1984-01-01

The usefulness of the direct 4-hour radioimmunoassay of estriol-16-glucuronide (E 3 G) and pregnanediol-3-glucuronide (P 2 G) in first morning urine (FMU) for establishing a prognosis of the early pregnancy outcome was evaluated in 106 patients that became pregnant. Microaliquots of FMU were serially assayed from day 3 of the conception cycle until day 80 of pregnancy. The E 3 G and P 2 G profiles of 19 pregnancies which terminated in spontaneous abortion with either a diagnosis of the blighted ovum syndrome (n = 11) or presumption of a corpus luteum/trophoblast failure (n = 8) have been compared with those of clinically normal pregnancies (n = 87). Normal pregnancies displayed typical patterns of E 3 G and P 2 G development, while variations were observed in abortive events that reflected changes of the fetoplacental unit

Neonatal Maturation of Paracetamol (Acetaminophen) Glucuronidation, Sulfation, and Oxidation Based on a Parent-Metabolite Population Pharmacokinetic Model.

Science.gov (United States)

Cook, Sarah F; Stockmann, Chris; Samiee-Zafarghandy, Samira; King, Amber D; Deutsch, Nina; Williams, Elaine F; Wilkins, Diana G; Sherwin, Catherine M T; van den Anker, John N

2016-11-01

This study aimed to model the population pharmacokinetics of intravenous paracetamol and its major metabolites in neonates and to identify influential patient characteristics, especially those affecting the formation clearance (CL formation ) of oxidative pathway metabolites. Neonates with a clinical indication for intravenous analgesia received five 15-mg/kg doses of paracetamol at 12-h intervals (paracetamol, paracetamol-glucuronide, paracetamol-sulfate, and the combined oxidative pathway metabolites (paracetamol-cysteine and paracetamol-N-acetylcysteine) were simultaneously modeled in NONMEM 7.2. The model incorporated 259 plasma and 350 urine samples from 35 neonates with a mean gestational age of 33.6 weeks (standard deviation 6.6). CL formation for all metabolites increased with weight; CL formation for glucuronidation and oxidation also increased with postnatal age. At the mean weight (2.3 kg) and postnatal age (7.5 days), CL formation estimates (bootstrap 95% confidence interval; between-subject variability) were 0.049 L/h (0.038-0.062; 62 %) for glucuronidation, 0.21 L/h (0.17-0.24; 33 %) for sulfation, and 0.058 L/h (0.044-0.078; 72 %) for oxidation. Expression of individual oxidation CL formation as a fraction of total individual paracetamol clearance showed that, on average, fractional oxidation CL formation increased paracetamol and its metabolites in neonates. Maturational changes in the fraction of paracetamol undergoing oxidation were small relative to between-subject variability.

Tentative Structural Assignment of a Glucuronide Metabolite of Methyltestosterone in Tilapia Bile by Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry.

Science.gov (United States)

Nishshanka, Upul; Chu, Pak-Sin; Evans, Eric; Reimschuessel, Renate; Hasbrouck, Nicholas; Amarasinghe, Kande; Jayasuriya, Hiranthi

2015-06-24

Methyltestosterone (MT), a strong androgenic steroid, is not approved for use in fish aquaculture in the United States. It is used in the U.S. under an investigational new animal drug exemption (INAD) only during the early life stages of fish. There is a possibility that farmers feed fish with MT to enhance production for economic gains. Therefore, there is a need to develop methods for the detection of MT and its metabolite residues in fish tissue for monitoring purposes. Previously, our laboratory developed a liquid chromatography-quadrupole time-of-flight (LC-QTOF) method for characterization of 17-O-glucuronide metabolite (MT-glu) in bile of tilapia dosed with MT. The system used was an Agilent 6530 Q-TOF equipped with electrospray jet stream technology, operating in positive ion mode. Retrospective analysis of the data generated in that experiment by a feature-finding algorithm, combined with a search against an in-house library of possible MT-metabolites, resulted in the discovery of a major glucuronide metabolite of MT in the bile extracts. Preliminary data indicate it to be a glucuronide of a hydroxylated MT (OHMT-glu) which persists in tilapia bile for at least 2 weeks after dosing. We present the tentative structural assignment of the OHMT-glu in tilapia bile and time course of development. This glucuronide can serve as a marker to monitor illegal use of MT in tilapia culture.

Influence of particle characteristics and organic matter content on the bioavailability and bioaccumulation of pyrene by clams

International Nuclear Information System (INIS)

Verrengia Guerrero, N.R.; Taylor, M.G.; Wider, E.A.; Simkiss, K.

2003-01-01

An experimental model with artificial particles and humic acids describes bioavailability of sediment-bound pyrene to clams. - Hydrophobic chemicals are known to associate with sediment particles including those from both suspended particulate matter and bottom deposits. The complex and variable composition of natural particles makes it very difficult therefore, to predict the bioavailability of sediment-bound contaminants. To overcome these problems we have previously devised a test system using artificial particles, with or without humic acids, for use as an experimental model of natural sediments. In the present work we have applied this experimental technique to investigate the bioavailability and bioaccumulation of pyrene by the freshwater fingernail clam Sphaerium corneum. The uptake and accumulation of pyrene in clams exposed to the chemical in the presence of a sample of natural sediment was also investigated. According to the results obtained, particle surface properties and organic matter content are the key factors for assessing the bioavailability and bioaccumulation of pyrene by clams

Enzymatic synthesis of {sup 125/131}I labeled 8-hydroxyquinoline glucuronide and in vitro/in vivo evaluation of biological influence

Energy Technology Data Exchange (ETDEWEB)

Yesilagac, Reyhan [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey); Unak, Perihan, E-mail: perihan.unak@ege.edu.t [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey); Medine, E. Ilker; Ichedef, Cigdem A. [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey); Ertay, Turkan [Dokuz Eyluel University, Medical School, Department of Nuclear Medicine, Inciralti, Izmir (Turkey); Mueftueler, F.Z. Biber [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey)

2011-02-15

8-Hydroxyquinoline (8-OHQ) is a long-known molecule which due to its metal-complexation ability is frequently used for analysis. It is also called oxine. Oxine and derivatives have been investigated to process antitumor and antimicrobial activities. 8-Hydroxyquinolyl-glucuronide (8-OHQ-Glu) was enzymatically synthesized using microsome preparates separated from Hutu-80 cells, labeled with {sup 125}I to perform a radionuclide labeled prodrug and investigated of its biological affinities on Hutu-80 (human duodenum intestinal adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), Detroit 562 (human pharynx adenocarcinoma) cells and ACBRI 519 (primary human small intestine epithelial cells) in this work. UDP-glucuronyl transferase (UDPGT) rich microsome preparates, which are used for glucuronidation in enzymatic synthesis, were extracted from Hutu-80 cells. 8-OHQ-Glu components were labeled using iodogen method with {sup 125}I and {sup 131}I. Structural analyses were performed with LC/MS/MS, {sup 1}H NMR and {sup 13}C-MMR for identify and measure chemical constituents. Results confirmed expected molecular structure. 8-OHQ-Glu could successfully radioiodinated with {sup 125/131}I according to iodogen method. {sup 125}I-8-OHQ-glucuronide incorporated with human gastrointestinal cancer cells such as Detroit-562 (human pharynx adenocarcinoma) (12.6%), Caco-2 (human colorectal adenocarcinoma) (7.8%), Hutu- 80 (human duodenum intestinal adenocarcinoma) (9.5%) and ACBRI 519 (primary human small intestine epithelial cells) (6.40%). {sup 131}I-8-OHQ-Glu was tested in mice bearing subcutaneously implanted Caco-2 colorectal adenocarcinoma cells. The results demonstrated that radioiodinated 8-OHQ-Glu may be promising anticancer prodrug.

Formation of quinones by one-electron oxidation in the metabolism of benzo[a]pyrene and 6-fluorobenzo[a]pyrene

International Nuclear Information System (INIS)

Cavalieri, E.; Wong, A.; Cremonesi, P.; Warner, C.; Rogan, E.

1986-01-01

Metabolic activation of polycyclic aromatic hydrocarbons (PAH), as well as other chemical carcinogens, occurs by two major pathways: One-electron oxidation and two-electron oxidation, or monooxygenation. One-electron oxidation generates radical cations or radicals, depending on the molecule in which the oxidation occurs, whereas two-electron oxidation produces oxygenated metabolites. Radical cations of PAH are ultimate electrophilic metabolites capable of binding to cellular macromolecules to initiate the tumor process. In this paper the authors will provide evidence that one-electron oxidation is involved not only in PAH carcinogenesis, but also in the formation of certain metabolites. Metabolism of benzo[a]pyrene (BP) by cytochrome P-450 monooxygenase yields three classes of products: phenols, dihydrodiols and the quinones, 1,6-, 3,6- and 6,12- dione

Degradation of phenanthrene and pyrene using genetically engineered dioxygenase producing Pseudomonas putida in soil

Directory of Open Access Journals (Sweden)

Mardani Gashtasb

2016-01-01

Full Text Available Bioremediation use to promote degradation and/or removal of contaminants into nonhazardous or less-hazardous substances from the environment using microbial metabolic ability. Pseudomonas spp. is one of saprotrophic soil bacterium and can be used for biodegradation of polycyclic aromatic hydrocarbons (PAHs but this activity in most species is weak. Phenanthrene and pyrene could associate with a risk of human cancer development in exposed individuals. The aim of the present study was application of genetically engineered P. putida that produce dioxygenase for degradation of phenanthrene and pyrene in spiked soil using high-performance liquid chromatography (HPLC method. The nahH gene that encoded catechol 2,3-dioxygenase (C23O was cloned into pUC18 and pUC18-nahH recombinant vector was generated and transformed into wild P. putida, successfully. The genetically modified and wild types of P. putida were inoculated in soil and pilot plan was prepared. Finally, degradation of phenanthrene and pyrene by this bacterium in spiked soil were evaluated using HPLC measurement technique. The results were showed elimination of these PAH compounds in spiked soil by engineered P. putida comparing to dishes containing natural soil with normal microbial flora and inoculated autoclaved soil by wild type of P. putida were statistically significant (p0.05 but it was few impact on this process (more than 2%. Additional and verification tests including catalase, oxidase and PCR on isolated bacteria from spiked soil were indicated that engineered P. putida was alive and functional as well as it can affect on phenanthrene and pyrene degradation via nahH gene producing. These findings indicated that genetically engineered P. putida generated in this work via producing C23O enzyme can useful and practical for biodegradation of phenanthrene and pyrene as well as petroleum compounds in polluted environments.

Degradation of pyrene in soil and in vitro by a Bacillus lentus strain ...

African Journals Online (AJOL)

A bacterium isolated from an asphalt plant soil and identified as a strain of Bacillus lentus was tested in vitro and in sterilized and native soils for ability to survive and sustain pyrene degradation over a period of 63 days. The exponential growth rate in vitro was 0.049 d-1 and the doubling time 2.65 d. In the control flask ...

Association between mutation spectra and stable and unstable DNA adduct profiles in Salmonella for benzo[a]pyrene and dibenzo[a,l]pyrene

Energy Technology Data Exchange (ETDEWEB)

DeMarini, David M., E-mail: demarini.david@epa.gov [Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hanley, Nancy M.; Warren, Sarah H.; Adams, Linda D.; King, Leon C. [Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

2011-09-01

Highlights: {yields} Benzo[a]pyrene (BP) induces stable DNA adducts and mutations primarily at guanine. {yields} Dibenzo[a,l]pyrene (DBP) induces them primarily at adenine. {yields} BP induces abasic sites, but DBP does not in the Salmonella mutagenicity assay. {yields} Stable DNA adducts alone appear to account for the mutation spectrum of DBP. {yields} Stable DNA adducts and possibly abasic sites account for the mutation spectrum of BP. - Abstract: Benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) are two polycyclic aromatic hydrocarbons (PAHs) that exhibit distinctly different mutagenicity and carcinogenicity profiles. Although some studies show that these PAHs produce unstable DNA adducts, conflicting data and arguments have been presented regarding the relative roles of these unstable adducts versus stable adducts, as well as oxidative damage, in the mutagenesis and tumor-mutation spectra of these PAHs. However, no study has determined the mutation spectra along with the stable and unstable DNA adducts in the same system with both PAHs. Thus, we determined the mutagenic potencies and mutation spectra of BP and DBP in strains TA98, TA100 and TA104 of Salmonella, and we also measured the levels of abasic sites (aldehydic-site assay) and characterized the stable DNA adducts ({sup 32}P-postlabeling/HPLC) induced by these PAHs in TA104. Our results for the mutation spectra and site specificity of stable adducts were consistent with those from other systems, showing that DBP was more mutagenic than BP in TA98 and TA100. The mutation spectra of DBP and BP were significantly different in TA98 and TA104, with 24% of the mutations induced by BP in TA98 being complex frameshifts, whereas DBP produced hardly any of these mutations. In TA104, BP produced primarily GC to TA transversions, whereas DBP produced primarily AT to TA transversions. The majority (96%) of stable adducts induced by BP were at guanine, whereas the majority (80%) induced by DBP were at adenine

On the role of resonantly stabilized radicals in polycyclic aromatic hydrocarbon (PAH) formation: pyrene and fluoranthene formation from benzyl-indenyl addition.

Science.gov (United States)

Sinha, Sourab; Rahman, Ramees K; Raj, Abhijeet

2017-07-26

Resonantly stabilized radicals, such as propargyl, cyclopentadienyl, benzyl, and indenyl, play a vital role in the formation and growth of polycyclic aromatic hydrocarbons (PAHs) that are soot precursors in engines and flames. Pyrene is considered to be an important PAH, as it is thought to nucleate soot particles, but its formation pathways are not well known. This paper presents a reaction mechanism for the formation of four-ring aromatics, pyrene and fluoranthene, through the combination of benzyl and indenyl radicals. The intermediate species and transition structures involved in the elementary reactions of the mechanism were studied using density functional theory, and the reaction kinetics were evaluated using transition state theory. The barrierless addition of benzyl and indenyl to form the adduct, 1-benzyl-1H-indene, was found to be exothermic with a reaction energy of 204.2 kJ mol -1 . The decomposition of this adduct through H-abstraction and H 2 -loss was studied to determine the possible products. The rate-of-production analysis was conducted to determine the most favourable reactions for pyrene and fluoranthene formation. The premixed laminar flames of toluene, ethylbenzene, and benzene were simulated using a well-validated hydrocarbon fuel mechanism with detailed PAH chemistry after adding the proposed reactions to it. The computed and experimentally observed species profiles were compared to determine the effect of the new reactions for pyrene and fluoranthene formation on their concentration profiles. The role of benzyl and indenyl combination in PAH formation and growth is highlighted.

Effects of lactate and acetate on the determination of serum ethyl glucuronide by CZE

Czech Academy of Sciences Publication Activity Database

Mrázková, Michaela; Caslavska, J.; Thormann, W.; Křivánková, Ludmila

2006-01-01

Roč. 27, č. 23 (2006), s. 4772-4778 ISSN 0173-0835 R&D Projects: GA ČR GA203/05/2106; GA AV ČR IAA4031401; GA AV ČR IAA400310609 Institutional research plan: CEZ:AV0Z40310501 Keywords : acetate * CZE * ethyl glucuronide Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.101, year: 2006

A Pyrene-Linked Cavity within a β-Barrel Protein Promotes an Asymmetric Diels-Alder Reaction.

Science.gov (United States)

Himiyama, Tomoki; Taniguchi, Naomasa; Kato, Shunsuke; Onoda, Akira; Hayashi, Takashi

2017-10-23

A unique π-expanded reaction cavity tethering a polycyclic moiety which provides a platform for substrate binding was constructed within the robust β-barrel structure of nitrobindin (NB). NB variants with cavities of different sizes and shapes are coupled with N-(1-pyrenyl)maleimide (Pyr) to prepare a series of NB-Pyr conjugates. The orientation of the pyrene moiety is fixed within the cavity by the coupling reaction. The fluorescent quenching analysis of NB-Pyr indicates that azachalcone (aza), which is a dienophile for a Diels-Alder (DA) reaction, is efficiently incorporated within the pyrene-linked reaction cavity by the aromatic interaction. The DA reaction between aza and cyclopentadiene proceeds within the reaction cavity of NB-Pyr in the presence of Cu II ion in high yield and high enantio- and regioselectivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation and electrochemistry of a pyrene-linked iron terpyridine and its anodic redox polymer

International Nuclear Information System (INIS)

Lin, Hsiao-Chu; Straus, Daniel A.; Johnson, Victoria Anne; Lu, Jia E.; Lopez, Louise; Terrill, Roger H.

2012-01-01

An iron(II)bis-terpyridine complex bearing 4′ pendant pyrenyl groups on each ligand (Fe(tpySCH 2 -pyr) 2 2+ ) was synthesized, characterized electrochemically and was shown to form a novel redox polymer via anodic electropolymerization. Immersion of glassy carbon electrodes into dilute acetonitrile solutions of the complex and then into clean electrolyte established that the complex will physisorb onto glassy carbon at 0.1 monolayer coverage from 500 μM solution. Anodic cyclic voltammetry of the pyrenyl iron compound revealed well-resolved Fe(II/III) centered redox waves near 0.9 V and an irreversible, pyrene centered oxidation at ca. 1.1 V. The Fe(II/III) waves grew in magnitude over time and persisted in fresh complex-free electrolyte indicating a surface electropolymerization reaction most likely mediated via the pyrene pendant groups, and exhibiting facile charge transport through a ca. 100 nm polymer film. Spectroelectrochemical analysis of Fe(tpySCH 2 -pyr) 2 (OTf) 2 films grown on indium–tin oxide transparent electrodes confirmed the presence of a Fe(II/III) redox-active film that has a nearly Nernstian response, but with a small Fe(II) component that does not oxidize interfacially.

Hormonal monitoring of early pregnancy by a direct radioimmunoassay of steroid glucuronides in first morning urine

Energy Technology Data Exchange (ETDEWEB)

Mendizabal, A.F.; Quiroga, S.; Farinati, Z.; Lahoz, M.; Nagle, C.

1984-11-01

The usefulness of the direct 4-hour radioimmunoassay of estriol-16-glucuronide (E/sub 3/G) and pregnanediol-3-glucuronide (P/sub 2/G) in first morning urine (FMU) for establishing a prognosis of the early pregnancy outcome was evaluated in 106 patients that became pregnant. Microaliquots of FMU were serially assayed from day 3 of the conception cycle until day 80 of pregnancy. The E/sub 3/G and P/sub 2/G profiles of 19 pregnancies which terminated in spontaneous abortion with either a diagnosis of the blighted ovum syndrome (n = 11) or presumption of a corpus luteum/trophoblast failure (n = 8) have been compared with those of clinically normal pregnancies (n = 87). Normal pregnancies displayed typical patterns of E/sub 3/G and P/sub 2/G development, while variations were observed in abortive events that reflected changes of the fetoplacental unit.

Interactions of rice (Oryza sativa L.) and PAH-degrading bacteria (Acinetobacter sp.) on enhanced dissipation of spiked phenanthrene and pyrene in waterlogged soil.

Science.gov (United States)

Gao, Y; Yu, X Z; Wu, S C; Cheung, K C; Tam, N F Y; Qian, P Y; Wong, M H

2006-12-15

The effects of cultivation of rice (Oryza sativa L.) and PAH-degrading bacteria (Acinetobacter sp.) separately, and in combination, on the dissipation of spiked phenanthrene and pyrene (0, 50+50, 100+100, 200+200 mg kg(-1)) in waterlogged soil were studied using pot trials. The population of introduced PAH-degrading bacteria remained at 10(5) CFU g(-1) dry soil after 20 days of treatment with Acinetobacter sp. only, but increased to 10(6) when planted with rice simultaneously. Shoot and root biomass of rice when grown alone was adversely affected by spiked PAHs, but significantly increased by 2-55% and 8-409%, respectively, when inoculated with Acinetobacter sp.. Phenanthrene and pyrene concentrations in roots ranged from 1-27 and 20-98 mg kg(-1), respectively, while their concentrations in shoots were generally lower than 0.2 mg kg(-1). The dissipation of phenanthrene was mainly due to abiotic loss as 70-78% phenanthrene was lost from the control soil at the end of 80 days, while removal of 86-87% phenanthrene had been achieved after 40 days in the treatment co-cultivated with Acinetobacter sp. and rice. Compared with the control where only 6-15% of pyrene was removed from soil, a much higher dissipation of pyrene (43-62%) was attained for the treatments co-cultivated with Acinetobacter sp. and rice at the end of 80 days. The results demonstrated that co-cultivation of rice and PAH-degrading bacteria may have a great potential to accelerate the bioremediation process of PAH-contaminated soil under waterlogged conditions.

Influence of renal function on the elimination of morphine and morphine glucuronides

DEFF Research Database (Denmark)

Wolff, Jesper; Bigler, Dennis Richard; Christensen, C B

1988-01-01

plasma. No significant correlation was found between total body clearance of unconjugated morphine and 51Cr-EDTA clearance. However, patients with renal insufficiency had impaired elimination of morphine glucuronides, and the apparent clearance was significantly correlated with the 51Cr-EDTA clearance (r...... = 0.94, p less than 0.001). A relatively long terminal elimination of half-life of morphine was found in all patients (mean +/- SD: 9.2 +/- 2.5 h), irrespective of glomerular function....

Studies on the adsorption of naphthalene and pyrene from aqueous ...

African Journals Online (AJOL)

The effectiveness of dried ground orange peels in adsorbing naphthalene and pyrene from an aqueous stream has been investigated in terms of variation in concentration, adsorbent dosage, agitation time and particle size. Experimental batch data was correlated by Freundlich and Langmuir isotherm models.

Degradation of ¹³C-labeled pyrene in soil-compost mixtures and fertilized soil.

Science.gov (United States)

Adam, Iris K U; Miltner, Anja; Kästner, Matthias

2015-11-01

Polycyclic aromatic hydrocarbons (PAH) are toxic pollutants widely distributed in the environment due to natural and anthropogenic processes. In order to mitigate tar oil contaminations with PAH, research on improving bioremediation approaches, which are sometimes inefficient, is needed. However, the knowledge on the fate of PAH-derived carbon and the microbial degraders in particular in compost-supplemented soils is still limited. Here we show the PAH carbon turnover mass balance in microcosms with soil-compost mixtures or in farmyard fertilized soil using [(13)C6]-pyrene as a model PAH. Complete pyrene degradation of 100 mg/kg of soil was observed in all supplemented microcosms within 3 to 5 months, and the residual (13)C was mainly found as carbon converted to microbial biomass. Long-term fertilization of soil with farmyard manure resulted in pyrene removal efficiency similar to compost addition, although with a much longer lag phase, higher mineralization, and lower carbon incorporation into the biomass. Organic amendments either as long-term manure fertilization or as compost amendment thus play a key role in increasing the PAH-degrading potential of the soil microbial community. Phospholipid fatty acid stable isotope probing (PLFA-SIP) was used to trace the carbon within the microbial population and the amount of biomass formed from pyrene degradation. The results demonstrate that complex microbial degrader consortia rather than the expected single key players are responsible for PAH degradation in organic-amended soil.

Complexation (cucurbit[6]uril-pyrene): Thermodynamic and spectroscopic properties

Energy Technology Data Exchange (ETDEWEB)

Sueldo Occello, Valeria N.; Rossi, Rita H. de; Veglia, Alicia V., E-mail: aveglia@fcq.unc.edu.ar

2015-02-15

The influence of the macrocyclic compound cucurbit[6]uril (CB6) on the photophysical properties of the fluorophore pyrene (PYR) has been studied. Guest–host interaction was observed by UV–visible spectroscopy and spectrofluorimetry. The fluorescence of PYR was significantly increased in the presence of CB6. The binding equilibrium constants for the complex with 1:1 stoichiometry were determined in HCOOH 55% w/v. The values of the association constants, K{sub A}, and the fluorescence quantum yield ratios between complexed and free substrate, ϕ{sup PYR–CB6}/ϕ{sup PYR}, at different temperatures were (3.1±0.9)×10{sup 2} M{sup −1} and (5.1±0.2), (3.6±0.5)×10{sup 2} M{sup −1} and (5.9±0.1), (4.8±0.7)×10{sup 2} M{sup −1} and (5.5±0.1) at 15.0 °C, 25.0 °C and 40.0 °C, respectively. The enthalpic and entropic contributions to the complexation process were determined, yielding ΔS=(92±3) J mol{sup −1} K{sup −1} and ΔH=(13±1) kJ mol{sup −1}. From these results it can be concluded that the complex formation is mainly driven by the entropic term. The forces involved in the complexation are interpreted from the sign and magnitude of the thermodynamic parameters obtained. The partial inclusion of PYR or the formation of a suspended complex is proposed in base of all the data. The interaction is also demonstrated in the solid state by differential scanning calorimetric (DSC) measurements. - Highlights: • The cucurbit[6]uril (CB6) effects on the absorption and fluorescence of pyrene (PYR) were analyzed. • The association constant (K{sub A}) and the stoichiometry of the complex were determined. • The complex formation was confirmed by differential scanning calorimetry (DSC). • The thermodynamic parameters were determined. • The hydrophobic entropic contribution is the main driving force for the PYR–CB6 complex formation.

Forensic relevance of glucuronidation in phase-II-metabolism of alcohols and drugs.

Science.gov (United States)

Kaeferstein, Herbert

2009-04-01

Forensic toxicology means detecting toxic or pharmacologically active substances in body fluids and organs and the evaluation and judgement of the respective results. In the legal judgement, not only the taken in active drugs, but also their metabolites are to be included. Regarding metabolism one distinguishes phase-I- and phase-II-metabolism. In the phase-I-metabolism, active substances are converted by oxidation, reduction or hydrolysis, but influencing the polarity of more lipophilic substances often not decisively. The pharmacological activity is often preserved or even increased. In phase-II-metabolism a highly hydrophilic substance--mostly glucuronic acid--is coupled to the active substances or the respective phase-I-metabolites. This reaction step decisively increases hydrophilicity of lipophilic substances, thus enhancing renal elimination and often also abolishing pharmacologically and/or toxicologically effects. Nevertheless the interaction of different drugs and alcohols in glucuronidation and the glucuronides of phase-II-metabolism still do not play a substantial role in the forensic-toxicological analysis and interpretation of results so far. However, in vitro investigations since 1999 in our lab show that such interactions are not unlikely. For valid interpretation of complex cases in the future it may become necessary not only to quantify drugs and the phase-I-metabolites but also the phase-II-metabolites and discuss possible interactions in the metabolism.

Effects of Sludge-amendment on Mineralization of Pyrene and Microorganisms in Sludge and Soil

DEFF Research Database (Denmark)

Klinge, C; Gejlsbjerg, B; Ekelund, Flemming

2001-01-01

. Sludge-amendment enhanced the mineralization of pyrene in the soil compared to soil without sludge, and the most extensive mineralization was observed when the sludge was kept in a lump. The number of protozoa, heterotrophic bacteria and pyrene-mineralizing bacteria was much higher in the sludge compared...... to the soil. The amendment of sludge did not affect the number of protozoa and bacteria in the surrounding soil, which indicated that organic contaminants in the sludge had a little effect on the number of protozoa and bacteria in the surrounding soil...

Modulations of benzo[a]pyrene-induced DNA adduct, cyclin D1 and PCNA in oral tissue by 1,4-phenylenebis(methylene)selenocyanate

International Nuclear Information System (INIS)

Chen, Kun-Ming; Sacks, Peter G.; Spratt, Thomas E.; Lin, Jyh-Ming; Boyiri, Telih; Schwartz, Joel; Richie, John P.; Calcagnotto, Ana; Das, Arunangshu; Bortner, James; Zhao, Zonglin; Amin, Shantu; Guttenplan, Joseph; El-Bayoumy, Karam

2009-01-01

Tobacco smoking is an important cause of human oral squamous cell carcinoma (SCC). Tobacco smoke contains multiple carcinogens include polycyclic aromatic hydrocarbons typified by benzo[a]pyrene (B[a]P). Surgery is the conventional treatment approach for SCC, but it remains imperfect. However, chemoprevention is a plausible strategy and we had previously demonstrated that 1,4-phenylenebis(methylene)selenocyanate (p-XSC) significantly inhibited tongue tumors-induced by the synthetic 4-nitroquinoline-N-oxide (not present in tobacco smoke). In this study, we demonstrated that p-XSC is capable of inhibiting B[a]P-DNA adduct formation, cell proliferation, cyclin D1 expression in human oral cells in vitro. In addition, we showed that dietary p-XSC inhibits B[a]P-DNA adduct formation, cell proliferation and cyclin D1 protein expression in the mouse tongue in vivo. The results of this study are encouraging to further evaluate the chemopreventive efficacy of p-XSC initially against B[a]P-induced tongue tumors in mice and ultimately in the clinic.

Photodissociation of pyrene cations: structure and energetics from C16H10(+) to C14(+) and almost everything in between.

Science.gov (United States)

West, Brandi; Useli-Bacchitta, Francesca; Sabbah, Hassan; Blanchet, Valérie; Bodi, Andras; Mayer, Paul M; Joblin, Christine

2014-09-11

The unimolecular dissociation of the pyrene radical cation, C16H10(+•), has been explored using a combination of computational techniques and experimental approaches, such as multiple photon absorption in the cold ion trap Piège à Ions pour la Recherche et l'Etude de Nouvelles Espèces Astrochimiques (PIRENEA) and imaging photoelectron photoion coincidence spectrometry (iPEPICO). In total, 22 reactions, involving the fragmentation cascade (H, C2H2, and C4H2 loss) from the pyrene radical cation down to the C14(+•) fragment ion, have been studied using PIRENEA. Branching ratios have been measured for reactions from C16H10(+•), C16H8(+•), and C16H5(+). Density functional theory calculations of the fragmentation pathways observed experimentally and postulated theoretically lead to 17 unique structures. One important prediction is the opening of the pyrene ring system starting from the C16H4(+•) radical. In the iPEPICO experiments, only two reactions could be studied, namely, R1 C16H10(+•) → C16H9(+) + H (m/z = 201) and R2 C16H9(+) → C16H8(+•) + H (m/z = 200). The activation energies for these reactions were determined to be 5.4 ± 1.2 and 3.3 ± 1.1 eV, respectively.

Molecular mechanics and quantum mechanical modeling of hexane soot structure and interactions with pyrene

Directory of Open Access Journals (Sweden)

Kubicki JD

2000-09-01

Full Text Available Molecular simulations (energy minimizations and molecular dynamics of an n-hexane soot model developed by Smith and co-workers (M. S. Akhter, A. R. Chughtai and D. M. Smith, Appl. Spectrosc., 1985, 39, 143; ref. 1 were performed. The MM+ (N. L. Allinger, J. Am. Chem. Soc., 1977, 395, 157; ref. 2 and COMPASS (H. Sun, J. Phys. Chem., 1998, 102, 7338; ref. 3 force fields were tested for their ability to produce realistic soot nanoparticle structure. The interaction of pyrene with the model soot was simulated. Quantum mechanical calculations on smaller soot fragments were carried out. Starting from an initial 2D structure, energy minimizations are not able to produce the observed layering within soot with either force field. Results of molecular dynamics simulations indicate that the COMPASS force field does a reasonably accurate job of reproducing observations of soot structure. Increasing the system size from a 683 to a 2732 atom soot model does not have a significant effect on predicted structures. Neither does the addition of water molecules surrounding the soot model. Pyrene fits within the soot structure without disrupting the interlayer spacing. Polycyclic aromatic hydrocarbons (PAH, such as pyrene, may strongly partition into soot and have slow desorption kinetics because the PAH-soot bonding is similar to soot–soot interactions. Diffusion of PAH into soot micropores may allow the PAH to be irreversibly adsorbed and sequestered so that they partition slowly back into an aqueous phase causing dis-equilibrium between soil organic matter and porewater.

Two nitro derivatives of azabenzo[a]pyrene N-oxide: Electronic properties and their relation to mutagenic activity

Energy Technology Data Exchange (ETDEWEB)

Ostojić, Bojana D., E-mail: bostojic@chem.bg.ac.rs; Đorđević, Dragana S.

2015-03-21

Highlights: • Molecular properties of nitro isomers of azabenzo[a]pyrene N-oxide are investigated. • Stability, ionization potential, electron affinity, and polarizability are determined. • High quality DFT methods are employed. • Nitroreduction, oxidation, and polarizability are not crucial for mutagenicity. • Dipole moment and electronic charge distribution are important for characterization. - Abstract: The equilibrium geometries, relative energies, IR and Raman spectra, vertical ionization potentials (IP), vertical electron affinities (EA), dipole moments (μ), electronic dipole polarizabilities (α), and molecular electrostatic potentials (MEP) of two species that show very high mutagenicity, 1-nitro-6-azabenzo[a]pyrene N-oxide (1-N-6-ABPO) and 3-nitro-6-azabenzo[a]pyrene N-oxide (3-N-6-ABPO), are investigated by means of Density Functional Theory (DFT) using B3LYP functional with different basis sets. The 3-N-6-ABPO isomer was estimated to be much more mutagenic in Salmonella typhimurium tester strain TA98 (396 000 revertants/nmol) than 1-N-6-ABPO (36 100 revertants/nmol) (Fukuhara et al., 1992). The results show that for both isomers the structural, energetic, and vibrational properties are similar. The orientation of the nitro group with respect to the plane of the aromatic system as well as the nitroreduction and oxidation reaction and polarizability seem not be important for the determination of different mutagenic behavior of these isomers. However, the dipole moment of 3-N-6-ABPO is about 3 times that of 1-N-6-ABPO. The larger dipole moment and the different electronic charge distribution of 3-N-6-ABPO compared to 1-N-6-ABPO imply stronger electrostatic and inductive molecular interactions so that the active site of the enzyme involved in the mutagenic activation can more effectively bind 3-N-6-ABPO compared to 1-N-6-ABPO.

Naphthalene and pyrene degradation in contaminated soil as a ...

African Journals Online (AJOL)

The effect of soil particle size distribution and percent organic matter on the degradation rate of naphthalene and pyrene in a water medium of 7.05 ml/min at 27 ± 2oC in a soil reactor was studied. Analysis of the pattern of disappearance of these polycyclic aromatic hydrocarbons (PAHs) using various particle sizes showed ...

3'-Pyrene-modified unlocked nucleic acids

DEFF Research Database (Denmark)

Ejlersen, Maria; Langkjær, Niels; Wengel, Jesper

2017-01-01

in the minor groove of DNA:DNA duplexes as confirmed by CD and UV/Vis absorption studies. Upon multiple incorporations of the monomer in single-stranded ONs, steady-state fluorescence emission studies revealed the formation of a pyrene excimer which in most cases was quenched upon duplex hybridization......, and fluorescence-based detection of mismatched hybridization was observed for some modified strand constitutions. Incorporation of the monomer in a triplex-forming oligonucleotide (TFO) strand lead to an increase of triplex melting temperature both at pH 6.0 and pH 7.0 for parallel triplexes - again an effect...

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs do not influence the urinary testosterone/epitestosterone glucuronide ratio

Directory of Open Access Journals (Sweden)

Jonas eLundmark

2013-05-01

Full Text Available The UDP Glucuronosyl Transferase (UGT enzymes are important in the pharmacokinetics, and conjugation, of a variety of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs as well as anabolic androgenic steroids (AAS. Testosterone glucuronidation capacity is strongly associated with a deletion polymorphism in the UGT2B17 gene. As the use of high doses of NSAIDs has been observed in athletes there is a risk for a drug-drug interaction that may influence the doping tests for AAS. In-vitro studies show inhibitory potential on UGT2B7, 2B15 and 2B17 enzymes by NSAIDs. The aim of this study was to investigate if concomitant use of NSAIDs and a single dose of testosterone enanthate would affect the excretion rate of testosterone and epitestosterone glucuronide (TG and EG as well as the T/E ratio, thereby affecting the outcome of the testosterone doping test.The study was designed as an open, randomized, cross-over study with subjects being their own control. The 23 healthy male volunteers, with either two, one or no allele (ins/ins, ins/del or del/del of the UGT2B17 gene, received the maximum recommended dose of NSAID (Ibuprofen or Diclofenac for six days. On day three, 500 mg of testosterone enanthate was administered. Spot urine samples were collected for 17 days. After a wash out period of four months the volunteers received 500 mg testosterone enanthate only, with subsequent spot urine collection for 14 days. The glucuronides of testosterone and epitestosterone were quantified. NSAIDs did not affect the excretion of TG or EG before the administration of testosterone. The concomitant use of NSAIDs and testosterone slightly increased the TG excretion while the EG excretion was less suppressed compared to testosterone use only. The effects of the NSAIDs on the TG and EG excretion did not differ between the UGT2B17 genotype groups. In conclusion, the outcome of testosterone doping tests does not seem to be affected by the use of NSAIDs.

Structures of benzo(a)pyrene-nucleic acid adducts formed in human and bovine bronchial explants

DEFF Research Database (Denmark)

Jeffrey, A.M.; Weinstein, I.B.; Jenette, K.W.

1977-01-01

PUBLICATION by Sims et al. of evidence that the 7,8-dihydrodiol-9,10-oxide of benzo(a)pyrene (BP) is a metabolic intermediate in the covalent binding of this ubiquitous polycyclic aromatic hydrocarbon to DNA in hamster embryo cells1 was followed by many related publications2. Grover et al. 3 also...

Phthalic acid and benzo[a]pyrene in soil-plant-water systems amended with contaminated sewage sludge

DEFF Research Database (Denmark)

Mougin, C.; Dappozze, F.; Brault, A.

2006-01-01

We studied the fate of C-14-labelled phthalic acid and benzo[a]pyrene applied to the soil by the way of contaminated sewage sludge in model ecosystems allowing the simultaneous assessment of physicochemical and biological descriptors. Here we show that the mineralisation of phthalic acid is highe......[a]pyrene is recalcitrant to biodegradation whatever the type of soil contamination. We show also that the chemicals present in the sludge are poorly transferred to soil leachates and plant seedlings....

A pyrene-benzthiazolium conjugate portraying aggregation induced emission, a ratiometric detection and live cell visualization of HSO_3"−

International Nuclear Information System (INIS)

Diwan, Uzra; Kumar, Virendra; Mishra, Rakesh K.; Rana, Nishant Kumar; Koch, Biplob; Singh, Manish Kumar; Upadhyay, K.K.

2016-01-01

The present study deals with the photophysical property of a pyrene-benzthiazolium conjugate R1, as a strong intramolecular charge transfer (ICT) probe exhibiting long wavelength emission in the red region. Unlike traditional planar polyaromatic hydrocarbons whose aggregation generally quenches the light emission, the pyrene based R1 was found to display aggregation-induced emission (AIE) property along with simultaneous increase in its quantum yield upon increasing the water content of the medium. The R1 exhibits high specificity towards HSO_3"−/SO_3"2"− by interrupting its own ICT producing there upon a large ratiometric blue shift of ∼220 nm in its emission spectrum. The lowest detection limit for the above measurement was found to be 8.90 × 10"−"8 M. The fluorescent detection of HSO_3"− was also demonstrated excellently by test paper strip and silica coated TLC plate incorporating R1. The live cell imaging of HSO_3"− through R1 in HeLa cells was studied using fluorescence microscopic studies. The particle size and morphological features of R1 and R1-HSO_3"− aggregates in aqueous solution were characterized by DLS along with SEM analysis.- Highlights: • A pyrene-benzthiazolium conjugate probe (R1) itself showed interesting phenomenon of an aggregation-induced emission (AIE). • R1 emits in the red channel and effectively utilized as a colorimetric and ratiometric fluorescent sensor for HSO_3"−. • The nano-dimensional spherical particles of R1 got enlarged upon its interaction with the HSO_3"−. • R1 can efficiently stain HSO_3"− in live cells and can be used for the on-spot detection of the same.

Cytochrome P450 1A1 (CYP1A1) protects against nonalcoholic fatty liver disease caused by Western diet containing benzo[a]pyrene in mice.

Science.gov (United States)

Uno, Shigeyuki; Nebert, Daniel W; Makishima, Makoto

2018-03-01

The Western diet contributes to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Benzo[a]pyrene (BaP), a prototypical environmental pollutant produced by combustion processes, is present in charcoal-grilled meat. Cytochrome P450 1A1 (CYP1A1) metabolizes BaP, resulting in either detoxication or metabolic activation in a context-dependent manner. To elucidate a role of CYP1A1-BaP in NAFLD pathogenesis, we compared the effects of a Western diet, with or without oral BaP treatment, on the development of NAFLD in Cyp1a1(-/-) mice versus wild-type mice. A Western diet plus BaP induced lipid-droplet accumulation in liver of Cyp1a1(-/-) mice, but not wild-type mice. The hepatic steatosis observed in Cyp1a1(-/-) mice was associated with increased cholesterol, triglyceride and bile acid levels. Cyp1a1(-/-) mice fed Western diet plus BaP had changes in expression of genes involved in bile acid and lipid metabolism, and showed no increase in Cyp1a2 expression but did exhibit enhanced Cyp1b1 mRNA expression, as well as hepatic inflammation. Enhanced BaP metabolic activation, oxidative stress and inflammation may exacerbate metabolic dysfunction in liver of Cyp1a1(-/-) mice. Thus, Western diet plus BaP induces NAFLD and hepatic inflammation in Cyp1a1(-/-) mice in comparison to wild-type mice, indicating a protective role of CYP1A1 against NAFLD pathogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Benzo[a]pyrene co-metabolism in the presence of plant root extracts and exudates: Implications for phytoremediation

International Nuclear Information System (INIS)

Rentz, Jeremy A.; Alvarez, Pedro J.J.; Schnoor, Jerald L.

2005-01-01

Benzo[a]pyrene, a high molecular weight (HMW) polycyclic aromatic hydrocarbon (PAH) was removed from solution by Sphingomonas yanoikuyae JAR02 while growing on root products as a primary carbon and energy source. Plant root extracts of osage orange (Maclura pomifera), hybrid willow (Salix albaxmatsudana), or kou (Cordia subcordata), or plant root exudates of white mulberry (Morus alba) supported 15-20% benzo[a]pyrene removal over 24 h that was similar to a succinate grown culture and an unfed acetonitrile control. No differences were observed between the different root products tested. Mineralization of 14 C-7-benzo[a]pyrene by S. yanoikuyae JAR02 yielded 0.2 to 0.3% 14 CO 2 when grown with plant root products. Collectively, these observations were consistent with field observations of enhanced phytoremediation of HMW PAH and corroborated the hypothesis that co-metabolism may be a plant/microbe interaction important to rhizoremediation. However, degradation and mineralization was much less for root product-exposed cultures than salicylate-induced cultures, and suggested the rhizosphere may not be an optimal environment for HMW PAH degradation by Sphingomonas yanoikuyae JAR02. - Bacterial benzo[a]pyrene cometabolism, a plant-microbe interaction affecting polycyclic aromatic hydrocarbon phytoremediation was demonstrated with Sphingomonas yanoikuyae JAR02 that utilized plant root extracts and exudates as primary substrates

Technique for controllable vapor-phase deposition of 1-nitro(14C)pyrene and other polycyclic aromatic hydrocarbons onto environmental particulate matter

International Nuclear Information System (INIS)

Lucas, S.V.; Lee, K.W.; Melton, C.W.; Lewtas, J.; Ball, L.M.

1991-01-01

To produce environmental particles fortified with a polycyclic aromatic hydrocarbon (PAH) for toxicology studies, an experimental apparatus was devised for deposition of the desired chemical species onto particles in a controlled and reproducible manner. The technique utilized consists of dispersion of the particles on a gaseous stream at a controlled rate, thermal vaporization of a solution of PAH, delivery of the vaporized PAH into the aerosol of particles at a controlled rate, subsequent condensation of the PAH onto the particles, and final recovery of the coated particles. The effectiveness of this approach was demonstrated by vapor-coating a 14 C-labeled PAH (1-nitro( 14 C)-pyrene) onto diesel engine exhaust particles that had previously been collected by tunnel dilution sampling techniques. Using the 14 C label as a tracer, the coated particles were characterized with respect to degree of coating, integrity of particle structure and absence of chemical decomposition of the coating substrate. The study demonstrates that the described method provides a controllable means for depositing a substance uniformly and with a high coating efficiency onto aerosolized particles. The technique was also used to vapor-coat benzo(a)pyrene onto diesel engine exhaust and urban ambient air particulate matter, and 2-nitrofluoranthene onto urban ambient air particulate matter. Coating efficiencies of about 400 micrograms/g particulate matter were routinely obtained on a single coating run, and up to 1200 micrograms/g (1200 ppm) were achieved after a second pass through the process. The coated particles were subsequently utilized in biological fate, distribution and metabolism studies

Synthesis, isolation and identification of glucuronides and mercapturic acids of a novel antiparasitic agent, licochalcone A

DEFF Research Database (Denmark)

Nadelmann, L.; Tjornelund, J.; Hansen, S. H.

1997-01-01

-glucuronide conjugate of a beta-hydroxylated Lica metabolite. The metabolites were identified by hplc-nmr (one and two-dimensional nmr) as well as hplc-ms. 3. At pH 8.5 Lica reacted with N-acetyl-L-cysteine giving the two epimeric conjugates, which were then isolated by preparative hplc and identified by one and two...

Synthesis and Evaluation of the Anti-Oxidant Capacity of Curcumin Glucuronides, the Major Curcumin Metabolites

OpenAIRE

Choudhury, Ambar K.; Raja, Suganya; Mahapatra, Sanjata; Nagabhushanam, Kalyanam; Majeed, Muhammed

2015-01-01

Curcumin metabolites namely curcumin monoglucuronide and curcumin diglucuronide were synthesized using an alternative synthetic approach. The anti-oxidant potential of these curcumin glucuronides was compared with that of curcumin using DPPH scavenging method and Oxygen Radical Absorbance Capacity (ORAC) assay. The results show that curcumin monoglucuronide exhibits 10 fold less anti-oxidant activity (DPPH method) and the anti-oxidant capacity of curcumin diglucuronide is highly attenuated co...

Measurement of urinary Benzo[a]pyrene tetrols and their relationship to other polycyclic aromatic hydrocarbon metabolites and cotinine in humans.

Science.gov (United States)

Hilton, Donald C; Trinidad, Debra A; Hubbard, Kendra; Li, Zheng; Sjödin, Andreas

2017-12-01

Biomonitoring of exposure to polycyclic aromatic hydrocarbons (PAHs) typically uses measurement of metabolites of PAHs with four or less aromatic rings, such as 1-hydroxypyrene, even though interest may be in exposure to larger and carcinogenic PAHs, such as benzo[a]pyrene (B[a]P). An improved procedure for measuring two tetrol metabolites of B[a]P has been developed. Using 2 mL urine, the method includes enzymatic deconjugation of the tetrol conjugates, liquid-liquid extraction, activated carbon solid phase extraction (SPE) and Strata-X SPE, and gas chromatography-electron capture negative ionization-tandem mass spectrometric determination. Limits of detection were 0.026 pg/mL (benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, BPT I-1) and 0.090 pg/mL (benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol, BPT II-1). We quantified BPT I-1 and BPT II-1 in urine from a volunteer who consumed one meal containing high levels of PAHs (barbequed chicken). We also measured urinary concentrations of BPT I-1 and BPT II-1 in smokers and nonsmokers, and compared these concentrations with those of monohydroxy PAHs (OH-PAHs) and cotinine. Urinary elimination of BPT I-1 and BPT II-1 as a function of time after dietary exposure was similar to that observed previously for OH-PAHs. While the median BPT I-1 concentration in smokers' urine (0.069 pg/mL) significantly differs from nonsmokers (0.043 pg/mL), BPT I-1 is only weakly correlated with cotinine. The urinary concentration of BPT I-1 shows a weaker relationship to tobacco smoke than metabolites of smaller PAHs, suggesting that other routes of exposure such as for example dietary routes may be of larger quantitative importance. Published by Elsevier Ltd.

Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer

Directory of Open Access Journals (Sweden)

Fan Yun

2014-01-01

Full Text Available Objective: The aim was to investigate the association between uridine diphosphate glucuronide transferase 1A1 (UGT1A1 gene promoter region polymorphism and irinotecan-related adverse effects and efficacy on recurrent and refractory small cell lung cancer (SCLC. Materials and Methods: A total of 31 patients with recurrent and refractory SCLC were enrolled in this study from June 2012 to August 2013 and received at least two cycles of single-agent irinotecan chemotherapy. The efficacy and adverse effects of irinotecan were evaluated. DNA was extracted from peripheral blood and direct sequencing method was employed to test UGT1A1FNx0128 polymorphism, thus analyzing the correlation between UGT1A1FNx0128 polymorphism and irinotecan-related side-effects and efficacy. Results: A total of 25 cases (80.6% were UGT1A1FNx0128 wild-type (TA 6 /(TA 6 ; 6 cases (19.4% were heterozygous mutant (TA 6 /(TA 7 , no homozygous mutant genotype (TA 7 /(TA 7 was found. The incidences of grade 3/4 neutropenia, diarrhea and thrombocytopenia were 35.5%, 25.8% and 22.6% in all the patients, respectively. The incidence of 3/4 adverse effects in patients with genotype (TA 6 /(TA 6 and heterozygous (TA 6 /(TA 7 had no statistical difference (P > 0.05 for all. The overall response rate (ORR was 32.3%. Median progression free survival (PFS and overall survival (OS were 4 months and 7.5 months in all patients, respectively. There was no statistical difference in ORR, PFS and OS between genotype (TA 6 /(TA 6 patients and heterozygous (TA 6 /(TA 7 patients. Conclusion: Irinotecan showed efficacy in patients with recurrent and refractory SCLC; UGT1A1 FNx01 28 polymorphism failed to predict the incidence of serious adverse effects and efficacy of irinotecan.

Does the Digestibility of Cyclodextrins Influence the In Vivo Absorption of Benzo[a] pyrene in Rats?

DEFF Research Database (Denmark)

Olesen, Niels Erik; Vana, Vasiliki; Holm, Rene

2016-01-01

-Cyclodextrin is digestible in contrast to b-cyclodextrins. This could potentially limit the sensitivity toward overdose, which was evaluated using benzo[a] pyrene in this study, in which rats were administered benzo[a] pyrene and different doses of the 2 cyclodextrins. Both cyclodextrins lowered the area under the curve......,000 at the concentration where a significant decrease in the absorption was observed. No difference was observed between the 2 cyclodextrins, so digestibility seemed less important. More interesting was that the decrease in absorption was relatively small when compared with literature values, suggesting that the effect...

Benzo[a]pyrene co-metabolism in the presence of plant root extracts and exudates: Implications for phytoremediation

Energy Technology Data Exchange (ETDEWEB)

Rentz, Jeremy A [Civil and Environmental Engineering, University of Iowa, Iowa City, IA 52242 (United States); Alvarez, Pedro J.J. [Civil and Environmental Engineering, Rice University, Houston, TX 77251 (United States); Schnoor, Jerald L [Civil and Environmental Engineering, University of Iowa, Iowa City, IA 52242 (United States)

2005-08-15

Benzo[a]pyrene, a high molecular weight (HMW) polycyclic aromatic hydrocarbon (PAH) was removed from solution by Sphingomonas yanoikuyae JAR02 while growing on root products as a primary carbon and energy source. Plant root extracts of osage orange (Maclura pomifera), hybrid willow (Salix albaxmatsudana), or kou (Cordia subcordata), or plant root exudates of white mulberry (Morus alba) supported 15-20% benzo[a]pyrene removal over 24 h that was similar to a succinate grown culture and an unfed acetonitrile control. No differences were observed between the different root products tested. Mineralization of {sup 14}C-7-benzo[a]pyrene by S. yanoikuyae JAR02 yielded 0.2 to 0.3% {sup 14}CO{sub 2} when grown with plant root products. Collectively, these observations were consistent with field observations of enhanced phytoremediation of HMW PAH and corroborated the hypothesis that co-metabolism may be a plant/microbe interaction important to rhizoremediation. However, degradation and mineralization was much less for root product-exposed cultures than salicylate-induced cultures, and suggested the rhizosphere may not be an optimal environment for HMW PAH degradation by Sphingomonas yanoikuyae JAR02. - Bacterial benzo[a]pyrene cometabolism, a plant-microbe interaction affecting polycyclic aromatic hydrocarbon phytoremediation was demonstrated with Sphingomonas yanoikuyae JAR02 that utilized plant root extracts and exudates as primary substrates.

A MONOCLONAL ANTIBODY-BETA-GLUCURONIDASE CONJUGATE AS ACTIVATOR OF THE PRODRUG EPIRUBICIN-GLUCURONIDE FOR SPECIFIC TREATMENT OF CANCER

NARCIS (Netherlands)

Haisma, Hidde; BOVEN, E; VANMUIJEN, M; DEJONG, J; VANDERVIJGH, WJF; PINEDO, HM

The anti-pan carcinoma monoclonal antibody (MAb) 323/A3, linked to E. coli-derived beta-glucuronidase (GUS) was used to study the tumour-site-selective activation of the prodrug Epirubicin-glucuronide (Epi-glu). Epi-glu was isolated from the urine of patients treated with Epirubicin (Epi) by

Pathological and biochemical changes in rat eyes exposed to gamma irradiation and benzo(A) pyrene and the protective role of glutathione and oltipraze

International Nuclear Information System (INIS)

Abd Elmaguid, A.; Naguib, N.I.; Saad, T.M.M.

2007-01-01

This study aims to evaluate the effect of exposure to carcinogenic compounds as benzo(a)pyrene in combination with other risk factor which is gamma irradiation on different eye tissues. The study was also conducted to evaluate the protective role of antioxidants such as glutathione and oltipraze before and during exposure to the risk factors. The first group of rats was kept as normal untreated control group. The second group was treated with oltipraze and glutathione for 14 days (positive control group). The third group was injected (i.p) with benzo(a)pyrene in three successive doses parallel with exposure to whole body gamma irradiation of 6 Gy divided in three successive doses ( 2 Gy/ day). The fourth group was treated with oltipraze and glutathione for 14 days then injected (i.p) with benzo(a)pyrene in the last 3 days of treatment in three successive doses parallel with exposure to the same whole body gamma irradiation as third group (6 Gy). Rat eyes were examined clinically every week. For histopathological and biochemical examinations, all groups were sacrificed at 1 month and 2 months after irradiation exposure and the eye tissues were examined by light microscope. The biochemical parameters such as lipid peroxides, SOD, GSH, GSH reductase and GSH peroxidase were estimated in blood and lens. Soluble and insoluble proteins were measured in lens only.The results showed that i.p injection of rats with benzo(a)pyrene and exposure to gamma irradiation caused alterations in eyes of rats clinically, histologically and biochemically. Animals that received glutathione and oltipraze and subjected to benzo(a)pyrene and radiation showed noticeable amelioration in the assayed parameters indicating their protective role as promising agents

Immobilization and stretching of 5'-pyrene-terminated DNA on carbon film deposited on electron microscope grid.

Science.gov (United States)

Loukanov, Alexandre; Filipov, Chavdar; Lecheva, Marta; Emin, Saim

2015-11-01

The immobilization and stretching of randomly coiled DNA molecules on hydrophobic carbon film is a challenging microscopic technique, which possess various applications, especially for genome sequencing. In this report the pyrenyl nucleus is used as an anchor moiety to acquire higher affinity of double stranded DNA to the graphite surface. DNA and pyrene are joined through a linker composed of four aliphatic methylene groups. For the preparation of pyrene-terminated DNA a multifunctional phosphoramidite monomer compound was designed. It contains pyrenylbutoxy group as an anchor moiety for π-stacking attachment to the carbon film, 2-cyanoethyloxy, and diisopropylamino as coupling groups for conjugation to activated oligonucleotide chain or DNA molecule. This monomer derivative was suitable for incorporation into automated solid-phase DNA synthesis and was attached to the 5' terminus of the DNA chain through a phosphodiester linkage. The successful immobilization and stretching of pyrene-terminated DNA was demonstrated by conventional 100 kV transmission electron microscope. The microscopic analysis confirmed the stretched shape of the negatively charged nucleic acid pieces on the hydrophobic carbon film. © 2015 Wiley Periodicals, Inc.

Studies on the analysis of benzo(a)pyrene and its metabolites in biological samples by using high performance liquid chromatography/fluorescence detection and gas chromatography/mass spectrometry

International Nuclear Information System (INIS)

Lee, Won; Hong, Jee Eun; Shin, Hye Seung; Pyo, Hee Soo; Kim, Yun Je

2003-01-01

An analytical method the determination of benzo(a)pyrene (BaP) and its hydroxylated metabolites, 1-hydroxybenzo(a)pyrene (1-OHBaP), 3-hydroxybenzo(a)pyrene (3-OHBaP), benzo(a)pyrene-4,5-dihydrodial(4,5-diolBaP) and benzo(a)pyrene-7,8-dihydrodiol (7,8-diolBaP), in rat urine and plasma has been developed by HPLC/FLD and GC/MS. The derivatization with alkyl iodide was employed to improve the resolution and the detection of two mono hydroxylated metabolites, 1-OHBaP and 3-OHBaP, in LC and GC. BaP and its four metabolites in spiked urine were successfully separated by gradient elution on reverse phase ODS C 18 column (4.6 mm I.D., 100 mm length, particle size 5μm) using a binary mixture of MeOH/H 2 O (85/15, v/v) as mobile phase after ethylation at 90 .deg. C for 10 min. The extraction recoveries of BaP and its metabolites in spiked samples with liquid-liquid extraction, which was better than solid phase extraction, were in the range of 90.3-101.6% in n-hexane for urine and 95.7-106.3% in acetone for plasma, respectively. The calibration curves has shown good linearity with the correlation coefficients (R 2 ) varying from 0.992 to 1.000 for urine and from 0.996 to 1.000 for plasma, respectively. The detection limits of all analytes were obtained in the range of 0.01-0.1 ng/mL for urine and 0.1-0.4ng/mL for plasma, respectively. The metabolites of BaP were excreted as mono hydroxy and dihydrodiol forms after intraperitoneal infection of 20 mg/kg of BaP to rats. The total amounts of BaP and four metabolites excreted in dosed rat urine were 3.79 ng over the 0 - 96 hr period from administration and the excretional recovery was less than 0.065% of the injection amounts of BaP. The proposed method was successfully applied to the determination of BaP and its hydroxylated metabolites in rat urine and plasma for the pharmacokinetic studies

Microplastic does not magnify the acute effect of PAH pyrene on predatory performance of a tropical fish (Lates calcarifer)

DEFF Research Database (Denmark)

Guven, Olgac; Bach, Lis; Munk, Peter

2018-01-01

Microplastic (MP) leads to widespread pollution in the marine ecosystem. In addition to the physical hazard posed by ingestion of microplastic particles, concern is also on their potential as vector for transport of hydrophobic contaminants. We studied experimentally the single and interactive...... effects of microplastic and pyrene, a polycyclic aromatic hydrocarbon, on the swimming behaviour and predatory performance of juvenile barramundi (Lates calcarifer). Juveniles (18+ days post hatch) were exposed to MPs, or pyrene (100nM), or combination of both and feeding rate and foraging activity...... no effect on feeding while swimming speed showed a significant decrease. Thus, our results confirm that short-time exposure to pyrene impacts performance of fish juveniles, while additional exposure to microplastic influenced their activity but not their feeding rate at the given conditions. Further studies...

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

International Nuclear Information System (INIS)

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

2011-01-01

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 [ 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 50 days of feeding 3 μg 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 AHR2α 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 P4501A

LC/MSMS STUDY OF BENZO[A]PYRENE-7,8-QUINONE ADDUCTION TO GLOBIN TRYPTIC PEPTIDES AND N-ACETYLAMINO ACIDS

Science.gov (United States)

Benzo[a]pyrene-7,8-quinone (BPQ) is regarded as a reactive genotoxic compound enzymatically formed from a xenobiotic precursor benzo[a]pyrene-7,8-diol by aldo-keto-reductase family of enzymes. Because BPQ, a Michael electrophile, was previously shown to react with oligonucleotide...

Synthesis of block copolymers derived from N-trityl-(S)-serine and pyrene end-labeled poly(methyl methacrylate) or poly(N-isopropylacrylamide) via ATRP

Energy Technology Data Exchange (ETDEWEB)

Buruiana, Emil C., E-mail: emilbur@icmpp.ro [Petru Poni Institute of Macromolecular Chemistry, 41A Gr. Ghica Voda Alley 700487, Iasi (Romania); Podasca, Viorica; Buruiana, Tinca [Petru Poni Institute of Macromolecular Chemistry, 41A Gr. Ghica Voda Alley 700487, Iasi (Romania)

2012-10-15

A new monomer bearing N-trityl-L-serine methyl ester in structure, methacryloyloxyethyl carbamoyloxy-N-trityl methyl serine (MTS), was prepared to be further polymerized by atom transfer radical polymerization (ATRP) with pyrene-endcapped poly(methyl methacrylate) (Py-PMMA-Br) or poly(N-isopropylacrylamide) (Py-PNIPA-Br). The resulting block copolymers, poly(methyl methacrylate-block-methacryloyloxyethyl carbamoyloxy-N-trityl methyl serine) (Py-PMMA-b-PMTS) and poly(N-isopropylacrylamide-block-methacryloyloxyethyl carbamoyloxy-N-trityl methyl serine (Py-PNIPA-b-PMTS) were characterized by {sup 1}H ({sup 13}C) NMR, ultraviolet, FTIR and fluorescence spectroscopy, thermal analysis, differential scanning calorimetry (DSC), atomic force microscopy (AFM), scanning electron microscopy (SEM), and gel permeation chromatography (GPC) measurements. The chemical composition in Py-PMMA-b-PMTS was estimated from the {sup 1}H NMR analysis that indicated a ratio of the repeating units of 46:19 (MMA:MTS). For the Py-PNIPA-b-PMTS the composition rate in the copolymer was 61:25 (NIPA:MTS). Quenching of the pyrene species with N,N-diethylaniline, nitrobenzene, nitrophenol, potassium iodide, p-nitrotoluene and tetracyanoquinodimethane (TCNQ) in DMF solution excited at 348 nm was evidenced, more efficiently being nitrophenol and TCNQ. In this case, the monomer emission at 388-409 nm underwent a significant decrease caused of an electron transfer from the electron-reach photoexcited pyrene molecule to the electron-deficient quenchers. - Highlights: Black-Right-Pointing-Pointer Diblock copolymers combine the fluorescence of pyrene-PMMA (PNIPA) with the characteristics of PMTS. Black-Right-Pointing-Pointer Such copolymers could be used for nitroderivatives detecting. Black-Right-Pointing-Pointer UV/vis and fluorescence measurements give a good correlation for LCST of Py-PNIPA-Br.

A pyrene-benzthiazolium conjugate portraying aggregation induced emission, a ratiometric detection and live cell visualization of HSO{sub 3}{sup −}

Energy Technology Data Exchange (ETDEWEB)

Diwan, Uzra; Kumar, Virendra [Department of Chemistry (Centre of Advanced Study), Faculty of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005 (India); Mishra, Rakesh K. [Photosciences and Photonics, Chemical Sciences and Technology Division, CSIR–National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram 695019 (India); Rana, Nishant Kumar; Koch, Biplob; Singh, Manish Kumar [Department of Zoology (Centre of Advanced Study), Faculty of Science, Banaras Hindu University, Varanasi 221005 (India); Upadhyay, K.K., E-mail: drkaushalbhu@yahoo.co.in [Department of Chemistry (Centre of Advanced Study), Faculty of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005 (India)

2016-07-27

The present study deals with the photophysical property of a pyrene-benzthiazolium conjugate R1, as a strong intramolecular charge transfer (ICT) probe exhibiting long wavelength emission in the red region. Unlike traditional planar polyaromatic hydrocarbons whose aggregation generally quenches the light emission, the pyrene based R1 was found to display aggregation-induced emission (AIE) property along with simultaneous increase in its quantum yield upon increasing the water content of the medium. The R1 exhibits high specificity towards HSO{sub 3}{sup −}/SO{sub 3}{sup 2−} by interrupting its own ICT producing there upon a large ratiometric blue shift of ∼220 nm in its emission spectrum. The lowest detection limit for the above measurement was found to be 8.90 × 10{sup −8} M. The fluorescent detection of HSO{sub 3}{sup −} was also demonstrated excellently by test paper strip and silica coated TLC plate incorporating R1. The live cell imaging of HSO{sub 3}{sup −} through R1 in HeLa cells was studied using fluorescence microscopic studies. The particle size and morphological features of R1 and R1-HSO{sub 3}{sup −} aggregates in aqueous solution were characterized by DLS along with SEM analysis.- Highlights: • A pyrene-benzthiazolium conjugate probe (R1) itself showed interesting phenomenon of an aggregation-induced emission (AIE). • R1 emits in the red channel and effectively utilized as a colorimetric and ratiometric fluorescent sensor for HSO{sub 3}{sup −}. • The nano-dimensional spherical particles of R1 got enlarged upon its interaction with the HSO{sub 3}{sup −}. • R1 can efficiently stain HSO{sub 3}{sup −} in live cells and can be used for the on-spot detection of the same.

Analysis and interpretation of specific ethanol metabolites, ethyl sulfate, and ethyl glucuronide in sewage effluent for the quantitative measurement of regional alcohol consumption.

Science.gov (United States)

Reid, Malcolm J; Langford, Katherine H; Mørland, Jørg; Thomas, Kevin V

2011-09-01

The quantitative measurement of urinary metabolites in sewage streams and the subsequent estimation of consumption rates of the parent compounds have previously been demonstrated for pharmaceuticals and narcotics. Ethyl sulfate and ethyl glucuronide are excreted in urine following the ingestion of alcohol, and are useful biomarkers for the identification of acute alcohol consumption. This study reports a novel ion-exchange-mediated chromatographic method for the quantitative measurement of ethyl sulfate and ethyl glucuronide in sewage effluent, and presents a novel calculation method for the purposes of relating the resulting sewage concentrations with rates of alcohol consumption in the region. A total of 100 sewage samples covering a 25-day period were collected from a treatment plant servicing approximately 500,000 people, and analyzed for levels of ethyl sulfate and ethyl glucuronide. The resulting data were then used to estimate combined alcohol consumption rates for the region, and the results were compared with alcohol related sales statistics for the same region. Ethyl glucuronide was found to be unstable in sewage effluent. Ethyl sulfate was stable and measurable in all samples at concentrations ranging from 16 to 246 nM. The highest concentrations of the alcohol biomarker were observed during weekend periods. Sixty one percent of the total mass of ethyl sulfate in sewage effluent corresponds to alcohol consumption on Friday and Saturday. Sales statistics for alcohol show that consumption in the region is approximately 6,750 kg/d. The quantity of ethyl sulfate passing through the sewage system is consistent with consumption of 4,900 to 7,800 kg/d.   Sewage epidemiology assessments of ethyl sulfate can provide accurate estimates of community alcohol consumption, and detailed examination of the kinetics of this biomarker in sewage streams can also identify time-dependent trends in alcohol consumption patterns. 2011 by the Research Society on Alcoholism.

Gambaran Histopatologik Payudara Mencit (Mus Musculus) Yang Diinduksi Benzo(α)pyrene Dan Diberikan Ekstrak Kunyit (Curcuma Longa L.)

OpenAIRE

Nansi, Eka M; Durry, Meilany F; Kairupan, Carla

2015-01-01

: Breast cancer (Carcinoma mammae) is one of the most common cancers affecting women. The etiology of breast cancer is still unknown, however, there are several important risk factors linked to the occurence of breast cancer, as follows: genetic, hormonal, and environmental. Polycyclic aromatic hydrocarbons (PHA) such as benzo(a)pyrene is a carcinogenic agent that can be found in the surrounding environment. It has been proven that benzo(a)pyrene can induce tumors in experimental animal model...

Photophysical and computational investigation of the intermolecular interactions of pyrene with phenothiazine and promazine

Energy Technology Data Exchange (ETDEWEB)

Güloğlu, Pınar; Acar, Nursel, E-mail: nursel.acar@ege.edu.tr

2016-10-20

Highlights: • Intermolecular interactions of pyrene with phenothiazine/promazine were investigated. • All investigated systems were optimized at ωB97XD/6-31G(d,p) level in gas phase. • The electronic transitions were determined using frontier orbitals. • Both Py–Pheno and Py–Prom are potential candidates for charge transfer systems. - Abstract: The intermolecular interactions between the pyrene (Py) (as acceptor) and phenothiazine (Pheno), promazine (Prom) (as donors) were investigated using UV/Vis absorption and fluorescence spectroscopy. Fluorescence quenching rate constants for Py–Pheno and Py–Prom systems have been calculated approximately 10{sup 10} M{sup −1} s{sup −1}, indicating diffusion controlled processes. A computational investigation has also been carried out in gas phase at ωB97XD/6-31G(d,p) level. Time-dependent density functional theory (TDDFT) was used to calculate the electronic transitions of molecules at B3LYP/6-311++G(d,p) level. Total electronic energies, complexation energies, free energy differences, excitation wavelengths, and HOMO–LUMO energy gaps are discussed in gas phase. Analyses of first excited singlet states have indicated charge transfers transitions between Py and Pheno, Prom through π–π stacking in gas phase at 433 nm and 466 nm, respectively. Due to its charge transfer character, Py–Pheno and Py–Prom systems seem to be appropriate models to investigate and design photosensitive materials.

Synthesis and photophysical properties of pyrene-functionalized nano-SiO{sub 2} hybrids in solutions and doped-PMMA thin films

Energy Technology Data Exchange (ETDEWEB)

Wu, Wen-Jie; He, Wen-Li; Yu, Hong-Yu [Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433 (China); Huang, Hong-Xiang [State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai 200433 (China); Chen, Meng [Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433 (China); Qian, Dong-Jin, E-mail: djqian@fudan.edu.cn [Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433 (China)

2017-01-15

Luminescent pyrene-functionalized nano-SiO{sub 2} (nano-SiO{sub 2}Pyr) hybrids were synthesized and characterized using thermogravimetry, infrared, UV–vis absorption and, X-ray photoelectron spectroscopy, as well as field emission transmission electron microscopy (FETEM). The organic substituents immobilized on the nano-SiO{sub 2}Pyr hybrids accounted for approximately 10% of the total weight. Polyethylene glycol 200 (PEG200) was found to be the most suitable solvent to suspend the nano-SiO{sub 2}Pyr hybrids compared to other commonly used organic solvents. FETEM images indicated an average SiO{sub 2} nanoparticle diameter of approximately 12 nm and a 1- to 2-nm thick organic species functionalization layer. Several emission peaks were recorded at wavelengths of 380–580 nm and were designated as emissions arising from either the monomer or excimer of the pyrene substituents. Excimer formation was concentration and solvent polarity dependent, with higher concentrations and a stronger solvent polarity benefiting excimer formation. Further, nano-SiO{sub 2}Pyr hybrids were doped in poly(methyl methacrylate) (PMMA) thin films; fluorescence spectra indicated that the excimer could be formed almost exclusively from neighboring nano-SiO{sub 2}Pyr hybrids. Time-resolved fluorescence decays revealed that the emission lifetimes of nano-SiO{sub 2}Pyr monomers and excimers were approximately 190 ns and 65–100 ns in the PEG200 solution, respectively, which was shortened to 0.45 ns to tens of ns in doped PMMA thin films, depending on the nano-hybrid concentration. Thus, the present study not only provides a method to prepare luminescent nano-materials but also a route to investigate excimer formation in solutions and thin films. - Highlights: • Luminescent pyrene-functionalized nano-SiO{sub 2}Pyr hybrids were prepared. • A 1- to 2- nm thick organic functionalization layer on nano-SiO{sub 2} was observed. • Formation of pyrene excimer was concentration and solvent

BODIPY-pyrene and perylene dyads as heavy atom-free singlet oxygen sensitizers

KAUST Repository

Filatov, Mikhail A.

2018-02-23

Dyads combining BODIPY as an electron acceptor and pyrene or perylene as electron donor subunits were prepared and studied their photophysical properties studied by steady-state and transient spectroscopy. Depending on the structure of the subunits and polarity of the media, the dyads show either bright fluorescence or photo-induced electron transfer (PeT) in solution. Charge-transfer (CT) states formed as a result of PeT and were found to yield triplet excited states of the BODIPY. In the presence of molecular oxygen, the dyads sensitize singlet oxygen (1O2) with quantum yields of up to 0.75.

BODIPY-pyrene and perylene dyads as heavy atom-free singlet oxygen sensitizers

KAUST Repository

Filatov, Mikhail A.; Karuthedath, Safakath; Polestshuk, Pavel M.; Callaghan, Susan; Flanagan, Keith J.; Wiesner, Thomas; Laquai, Fré dé ric; Senge, Mathias O.

2018-01-01

Dyads combining BODIPY as an electron acceptor and pyrene or perylene as electron donor subunits were prepared and studied their photophysical properties studied by steady-state and transient spectroscopy. Depending on the structure of the subunits and polarity of the media, the dyads show either bright fluorescence or photo-induced electron transfer (PeT) in solution. Charge-transfer (CT) states formed as a result of PeT and were found to yield triplet excited states of the BODIPY. In the presence of molecular oxygen, the dyads sensitize singlet oxygen (1O2) with quantum yields of up to 0.75.

Factors controlling benzo(a)pyrene concentration in aerosols in the urbanized coastal zone. A case study: Gdynia, Poland (Southern Baltic Sea).

Science.gov (United States)

Staniszewska, Marta; Graca, Bożena; Bełdowska, Magdalena; Saniewska, Dominika

2013-06-01

Annual study on the benzo(a)pyrene (BaP) concentration in aerosols in the coastal zone of the Gulf of Gdansk (southern Baltic) has been performed at Gdynia station. Combustion processes, especially domestic heating of both local and regional origin, were identified as the main sources of benzo(a)pyrene in this area. Concentrations observed during the heating season (mean 2.18 ng m(-3)) were significantly higher than these recorded in the non-heating season (mean 0.05 ng m(-3)). High benzo(a)pyrene concentrations were associated with low temperature and high humidity. Whereas high levels of precipitation usually decreased the BaP concentration in aerosols. The concentration of this factor in the studied area depended also on the wind direction and air masses trajectories. During heating season, continental air masses (coming from S, SE, SW) seemed to increase benzo(a)pyrene concentration, while maritime air masses (from N, NE, NW) caused its decrease. The differences in the BaP concentration resulting from potentially different emission levels of this compound during working and non-working days were not clearly pronounced.

Hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate, an active metabolite of di(2-ethylhexyl) phthalate, in humans, dogs, rats, and mice: an in vitro analysis using microsomal fractions.

Science.gov (United States)

Hanioka, Nobumitsu; Isobe, Takashi; Kinashi, Yu; Tanaka-Kagawa, Toshiko; Jinno, Hideto

2016-07-01

Mono(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di(2-ethylhexyl) phthalate (DEHP) and has endocrine-disrupting effects. MEHP is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the hepatic and intestinal glucuronidation of MEHP in humans, dogs, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of MEHP glucuronidation by liver microsomes followed the Michaelis-Menten model for humans and dogs, and the biphasic model for rats and mice. The K m and V max values of human liver microsomes were 110 µM and 5.8 nmol/min/mg protein, respectively. The kinetics of intestinal microsomes followed the biphasic model for humans, dogs, and mice, and the Michaelis-Menten model for rats. The K m and V max values of human intestinal microsomes were 5.6 µM and 0.40 nmol/min/mg protein, respectively, for the high-affinity phase, and 430 µM and 0.70 nmol/min/mg protein, respectively, for the low-affinity phase. The relative levels of V max estimated by Eadie-Hofstee plots were dogs (2.0) > mice (1.4) > rats (1.0) ≈ humans (1.0) for liver microsomes, and mice (8.5) > dogs (4.1) > rats (3.1) > humans (1.0) for intestinal microsomes. The percentages of the V max values of intestinal microsomes to liver microsomes were mice (120 %) > rats (57 %) > dogs (39 %) > humans (19 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward MEHP markedly differed among species, and imply that these species differences are strongly associated with the toxicity of DEHP.

Bis-Pyrene-Modified Unlocked Nucleic Acids: Synthesis, Hybridization Studies, and Fluorescent Properties

Czech Academy of Sciences Publication Activity Database

Perlíková, Pavla; Ejlersen, M.; Langkjaer, N.; Wengel, J.

2014-01-01

Roč. 9, č. 9 (2014), s. 2120-2127 ISSN 1860-7179 Grant - others:European Research Council(XE) FP7-268776 Institutional support: RVO:61388963 Keywords : fluorescence * nucleic acid hybridization * oligonucleotides * pyrenes * unlocked nucleic acids Subject RIV: CC - Organic Chemistry Impact factor: 2.968, year: 2014

Identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-COOH-glu) in hair by ultra-performance liquid chromatography tandem mass spectrometry as a potential hair biomarker of cannabis use.

Science.gov (United States)

Pichini, Simona; Marchei, Emilia; Martello, Simona; Gottardi, Massimo; Pellegrini, Manuela; Svaizer, Fiorenza; Lotti, Andrea; Chiarotti, Marcello; Pacifici, Roberta

2015-04-01

We developed and validated an ultra-high-pressure liquid chromatography-tandem mass spectrometry method to identify and quantify 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in hair of cannabis consumers. After hair washing with methyl alcohol and diethyl ether and subsequent addition of amiodarone as internal standard hair samples were treated with 500 μl VMA-T M3 buffer reagent for 1 h at 100 °C. After cooling, 10 μl VMA-T M3 extract were injected into chromatographic system. Chromatographic separation was carried out on a reversed phase column using a linear gradient elution with two solvents: 5 mM ammonium formate pH 3.0 (solvent A) and 0.1% formic acid in acetonitrile (solvent B). The flow rate was kept constant at 0.4 ml/min during the analysis. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring mode via positive electrospray ionization. Linear calibration curves were obtained for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide with correlation coefficients (r(2)) of 0.99 and a limit of quantification of 0.25 pg/mg hair. Analytical recovery was between 79.6% and 100.7% and intra- and inter-assay imprecision and inaccuracy were always lower than 15%. Ultra-high-pressure liquid chromatography-tandem mass spectrometry analysis of 20 different hair samples of cannabis consumers disclosed the presence of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in the range of 0.5-8.6 pg/mg hair. These data provided a good start to consider 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide as alternative hair biomarker of cannabis consumption. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein-Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects.

Science.gov (United States)

Radom, J; Salvayre, R; Levade, T; Douste-Blazy, L

1990-01-01

The uptake and intracellular metabolism of 4-(1-pyrene)butanoic acid (P4), 10-(1-pyrene)decanoic acid (P10) and 12-(1-pyrene)dodecanoic acid (P12) were investigated in cultured lymphoid cell lines from normal individuals and from a patient with multisystemic lipid storage myopathy (MLSM). The cellular uptake was shown to be dependent on the fatty-acid chain length, but no significant difference in the uptake of pyrene fatty acids was observed between MLSM and control lymphoid cells. After incubation for 1 h the distribution of fluorescent fatty acids taken up by the lymphoid cell lines also differed with the chain length, most of the fluorescence being associated with phospholipid and triacylglycerols. In contrast with P10 and P12, P4 was not incorporated into neutral lipids. When the cells were incubated for 24 h with the pyrene fatty acids, the amount of fluorescent lipids synthesized by the cells was proportional to the fatty acid concentration in the culture medium. After a 24 h incubation in the presence of P10 or P12, at any concentration, the fluorescent triacylglycerol content of MLSM cells was 2-5-fold higher than that of control cells. Concentrations of pyrene fatty acids higher than 40 microM seemed to be more toxic for mutant cells than for control cells. This cytotoxicity was dependent on the fluorescent-fatty-acid chain length (P12 greater than P10 greater than P4). Pulse-chase experiments permitted one to demonstrate the defect in the degradation of endogenously biosynthesized triacylglycerols in MLSM cells (residual activity was around 10-25% of controls on the basis of half-lives and initial rates of P10- or P12-labelled-triacylglycerol catabolism); MLSM lymphoid cells exhibited a mild phenotypic expression of the lipid storage (less severe than that observed in fibroblasts). P4 was not utilized in the synthesis of triacylglycerols, and thus did not accumulate in MLSM cells: this suggests that natural short-chain fatty acids might induce a lesser

Targeting Antibodies to Carbon Nanotube Field Effect Transistors by Pyrene Hydrazide Modification of Heavy Chain Carbohydrates

Directory of Open Access Journals (Sweden)

Steingrimur Stefansson

2012-01-01

Full Text Available Many carbon nanotube field-effect transistor (CNT-FET studies have used immobilized antibodies as the ligand binding moiety. However, antibodies are not optimal for CNT-FET detection due to their large size and charge. Their size can prevent ligands from reaching within the Debye length of the CNTs and a layer of charged antibodies on the circuits can drown out any ligand signal. In an attempt to minimize the antibody footprint on CNT-FETs, we examined whether pyrene hydrazide modification of antibody carbohydrates could reduce the concentration required to functionalize CNT circuits. The carbohydrates are almost exclusively on the antibody Fc region and this site-specific modification could mediate uniform antibody orientation on the CNTs. We compared the hydrazide modification of anti-E. coli O157:H7 polyclonal antibodies to pyrenebutanoic acid succinimidyl ester-coated CNTs and carbodiimide-mediated antibody CNT attachment. Our results show that the pyrene hydrazide modification was superior to those methods with respect to bacteria detection and less than 1 nM labeled antibody was required to functionalize the circuits.

Effect of eugenol on the mutagenicity of benzo[a]pyrene and the formation of benzo[a]pyrene-DNA adducts in the X-lacZ-transgenic mouse.

NARCIS (Netherlands)

Rompelberg, C.J.M.; Steenwinkel, M.J.S.T.; Asten, J.G. van; Delft, J.H.M. van; Baan, R.A.; Verhagen, H.

1996-01-01

To study the possible reduction by eugenol of the mutagenicity and genotoxicity of benzoja]pyrene (B[a]P) in vivo, the X-lacZ-transgenic mouse strain 40.6 (Muta(TM)Mouse) was used. Male mice were fed a diet containing 0.4% (w/w) eugenol or a control diet for 58 days. On day 10, half of the mice

Gender and oral contraceptive steroids as determinants of drug glucuronidation: effects on clofibric acid elimination.

OpenAIRE

Miners, J O; Robson, R A; Birkett, D J

1984-01-01

The disposition of clofibric acid, a drug metabolised largely by glucuronidation, was studied in eight males, eight females and eight females receiving oral contraceptive steroids (OCS). Clofibric acid plasma clearance was not significantly different in males compared to the control female group but was 48% greater (P less than 0.01) in women receiving OCS compared to non-pill using females. This difference was due to an alteration in clofibric acid metabolic clearance as there were no differ...

Low Cotinine Glucuronidation Results in Higher Serum and Saliva Cotinine in African American Compared to White Smokers.

Science.gov (United States)

Murphy, Sharon E; Sipe, Christopher J; Choi, Kwangsoo; Raddatz, Leah M; Koopmeiners, Joseph S; Donny, Eric C; Hatsukami, Dorothy K

2017-07-01

Background: Tobacco exposure is often quantified by serum or saliva concentrations of the primary nicotine metabolite, cotinine. However, average cotinine concentrations are higher in African Americans (AA) compared with Whites with similar smoking levels. Cotinine is metabolized by UGT2B10 and CYP2A6, and low UGT2B10 activity is common in AA, due to the prevalence of a UGT2B10 splice variant. Methods: UGT2B10 activity was phenotyped in 1,446 smokers (34% AA) by measuring the percentage of cotinine excreted as a glucuronide. Urinary total nicotine equivalents (TNE), the sum of nicotine and 6 metabolites, were determined to quantify smoking dose, and cotinine and 3'-hydroxycotinine were quantified in saliva (study 1) or serum (study 2). Results: Ninety-seven smokers (78% AA) were null for UGT2B10 activity, and the saliva and serum cotinine levels, after adjustment for TNE and cigarettes per day (CPD), were 68% and 48% higher in these smokers compared with nonnull smokers ( P smokers, but with additional adjustment for UGT2B10 activity, there were no significant differences in saliva and serum cotinine concentrations between these two groups. Conclusions: UGT2B10 activity significantly influences plasma cotinine levels, and higher cotinine concentrations in AA versus White smokers (after adjustment for smoking dose) result from lower levels of UGT2B10-catalyzed cotinine glucuronidation by AA. Impact: UGT2B10 activity or genotype should be considered when using cotinine as a tobacco exposure biomarker, particularly in populations such as AA with high frequencies of UGT2B10 nonfunctional variants. Cancer Epidemiol Biomarkers Prev; 26(7); 1093-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Human hair follicle benzo(a)pyrene and benzo(a)pyrene 7, 8-diol metabolism: effect of exposure to a coal tar-containing shampoo

Energy Technology Data Exchange (ETDEWEB)

Merk, H.F.; Mukhtar, H.; Kaufmann, I.; Das, M.; Bickers, D.R.

1987-01-01

Hair follicles are a readily available source of human epithelial tissue and offer an excellent system with which to study carcinogen metabolism in human populations. In this study hair follicles were employed to measure the metabolism of benzo(a)pyrene (BP), benzo(a)pyrene - 7,8-diol (BP 7,8-diol) and the enzyme mediated binding of /sup 3/H-BP to DNA. The effect of human exposure to a crude coal tar (CCT) - containing shampoo, a preparation rich in polycyclic aromatic hydrocarbons (PAHs on these parameters was also evaluated. It was found that aryl hydrocarbon hydroxylase (AHH) activity increased after use of the shampoo and enhancement of enzyme-mediated binding of BP to DNA was detected in most subjects. Hair follicles were shown to convert BP to several metabolic species and BP, 7,8-diol was also metabolised. Clotrimazole, a known inhibitor of the metabolism of BP was found to inhibit AHH and the metabolism of BP and BP 7,8-diol in human hair follicles, as were other imidazole compounds. The studies show that hair follicles represent an accessible tissue suitable for assessing the extent of PAH carcinogen metabolism in human subjects. Furthermore enzyme activity critical to cancer induction by PAHs was shown to be inducible following the use of a CCT-containing shampoo. Imidazole compounds were shown to be possible effective anti-carcinogens in human populations. 29 refs.

Effect of dietary factors on mutagenesis, metabolism, and binding to DNA of benzo[a]pyrene and benzo[a]pyrene 7,8-dihydrodiol

International Nuclear Information System (INIS)

Vance, R.E.

1988-01-01

Ellagic acid (EA), a naturally occurring plant phenol, at concentrations of 5 to 50 μg/plate, inhibited rate liver S9 protein dependent benzo[a]pyrene (B[a]P)-induced mutagenesis in Salmonella typhimurium TA 100 by 30-81% and B[a]P 7,8-dihydrodiol (DHD)-induced mutagenesis by 29 to 75%. EA did not significantly affect the metabolism of B[a]P or B[a]P 7,8-DHD as determined by high performance liquid chromatographic analysis of the organosoluble fraction and by the quantification of water-soluble conjugates. At these concentrations EA inhibited the covalent binding of [ 3 H] B[a]P and [ 3 H] B[a]P 7,8-DHD metabolites to calf thymus DNA by 5 to 42% and 27 to 64%, respectively. Formation of benzo[a]pyrene 7,8-dihydrodiol-9,10-epoxide:deoxyguanosine (BPDE:dG) adducts was inhibited by 13 to 56% for B[a]P for B[a]P and 11 to 38% for B[a]P 7,8-DHD. These results suggest that the antimutagenic effect of EA and its inhibition of B[a]P and B[a]P 7,8-DHD metabolite-binding to DNA is not due to the inhibition of S9-mediated metabolism of these compounds. The inhibitory effect may be by previously described scavenging mechanism or by a DNA-affinity binding mechanism that prevents BPDE:DNA adduct formation

Photoinduced toxicity of three polycyclic aromatic hydrocarbons (fluoranthene, pyrene, and naphthalene) to the duckweed Lemna gibba L. G-3

International Nuclear Information System (INIS)

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

1994-01-01

The authors recently demonstrated that light dramatically enhances the hazards of three polycyclic aromatic hydrocarbons (PAHs), anthracene, phenanthrene, and benzo[a]pyrene, to the duckweed Lemna gibba L. G-3 (X.-D. Huang, D. G. Dixon, and B. M. Greenberg, 1993, Environ. Toxicol. Chem., 12, 1067-1077). To extend this research, growth and chlorosis were used as end points to assess the photoinduced toxicity of three additional PAHs, fluoranthene, pyrene, and naphthalene, to L. gibba in the presence of simulated solar radiation (a light source with a UV-B: UV-A:visible light ratio equivalent to that of sunlight). The phytotoxicity of these three PAHs was photoactivated, with ultraviolet radiation being the only spectral region that enhanced the harmful effects of the chemicals. Dose-response curves based on chemical concentration and light intensity revealed that the order of phytotoxic strength was fluoranthene > pyrene > naphthalene. To explore whether photomodification (in addition to photosensitization) of fluoranthene, pyrene, and naphthalene could contribute to photoinduced toxicity, the chemicals were irradiated prior to (as opposed to simultaneously with) application to the plans. The rates of photomodification of the three PAHs were rapid enough for the photooxidized compounds to contribute to toxicity, and the photomodified PAHs were more toxic than the parent compounds. As well, toxicity could be correlated to photomodification; impacts increased in parallel with the extent of photomodification

Dispersion state and humic acids concentration-dependent sorption of pyrene to carbon nanotubes

NARCIS (Netherlands)

Zhang, X.; Kah, M.; Jonker, M.T.O.; Hofmann, T.

2012-01-01

Sonication and humic acids (HA) are known to disperse carbon nanotube (CNT) suspensions, but potential effects on sorption of chemicals to CNTs remain poorly understood. We applied a passive sampling method to investigate the influence of dispersion/aggregation on sorption of pyrene to CNTs.

A simple LC-MS/MS method facilitated by salting-out assisted liquid-liquid extraction to simultaneously determine trans-resveratrol and its glucuronide and sulfate conjugates in rat plasma and its application to pharmacokinetic assay.

Science.gov (United States)

Qiu, Zhixia; Yu, Jiaojiao; Dai, Yu; Yang, Yue; Lu, Xiaoyu; Xu, Jiaqiu; Qin, Zhiying; Huang, Fang; Li, Ning

2017-11-01

A simple LC-MS/MS method facilitated by salting-out assisted liquid-liquid extraction (SALLE) was applied to simultaneously investigate the pharmacokinetics of trans-resveratrol (Res) and its major glucuronide and sulfate conjugates in rat plasma. Acetonitrile-methanol (80:20, v/v) and ammonium acetate (10 mol L -1 ) were used as extractant and salting-out reagent to locate the target analytes in the supernatant after the aqueous and organic phase stratification, then the analytes were determined via gradient elution by LC-MS/MS in negative mode in a single run. The analytical method was validated with good selectivity, acceptable accuracy (>85%) and low variation of precision (extraction efficiency of target glucuronide and sulfate conjugates (>80%). The method was successfully applied to determine Res and its four conjugated metabolites in rat after Res administration (intragastric, 50 mg kg -1 ; intravenous, 10 mg kg -1 ). The systemic exposures to Res conjugates were much higher than those to Res (AUC 0-t , i.v., 7.43 μm h; p.o., 8.31 μm h); Res-3-O-β-d-glucuronide was the major metabolite (AUC 0-t , i.v., 66.1 μm h; p.o., 333.4 μm h). The bioavailability of Res was estimated to be ~22.4%. The reproducible SALLE method simplified the sample preparation, drastically improved the accuracy of the concomitant assay and gave full consideration of extraction recovery to each target analyte in bio-samples. Copyright © 2017 John Wiley & Sons, Ltd.

An evaluation of the DRI-ETG EIA method for the determination of ethyl glucuronide concentrations in clinical and post-mortem urine.

Science.gov (United States)

Turfus, Sophie C; Vo, Tu; Niehaus, Nadia; Gerostamoulos, Dimitri; Beyer, Jochen

2013-06-01

A commercial enzyme immunoassay for the qualitative and semi-quantitative measurement of ethyl glucuronide (EtG) in urine was evaluated. Post-mortem (n=800), and clinical urine (n=200) samples were assayed using a Hitachi 902 analyzer. The determined concentrations were compared with those obtained using a previously published liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of EtG and ethyl sulfate. Using a cut-off of 0.5 µg/ml and LC-MS/MS limit of reporting of 0.1 µg/ml, there was a sensitivity of 60.8% and a specificity of 100% for clinical samples. For post-mortem samples, sensitivity and specificity were 82.4% and 97.1%, respectively. When reducing the cut-off to 0.1 µg/ml, the sensitivity and specificity were 83.3% and 100% for clinical samples whereas for post-mortem samples the sensitivity and specificity were 90.3 % and 88.3 %, respectively. The best trade-offs between sensitivity and specificity for LC-MS/MS limits of reporting of 0.5 and 0.1 µg/ml were achieved when using immunoassay cut-offs of 0.3 and 0.092 µg/ml, respectively. There was good correlation between quantitative results obtained by both methods but analysis of samples by LC-MS/MS gave higher concentrations than by enzyme immunoassay (EIA), with a statistically significant proportional bias (P<0.0001, Deming regression) for both sample types. The immunoassay is reliable for the qualitative and semi-quantitative presumptive detection of ethyl glucuronide in urine. Copyright © 2012 John Wiley & Sons, Ltd.

Long Range Polymer Chain Dynamics of Highly Flexible Polysiloxane in Solution Probed by Pyrene Excimer Fluorescence

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Janine L. Thoma

2018-03-01

Full Text Available A poly(dimethylsiloxane-co-(3-aminopropylmethylsiloxane polymer (PDMS with 20.3 mol % of (3-aminopropylmethyl siloxane monomer has been labeled randomly with 1-pyreneacetyl groups to generate a series of polysiloxanes (Py-PDMS with pyrenyl contents ranging from 0.7 mol % to 5.2 mol % of the total number of structural units. The remainder of the amino groups were acetylated to avoid intra-chain quenching of the excited singlet states of pyrene via exciplex formation with free amino groups while allowing the formation of excimers to proceed. The fluorescence spectra and temporal decays of the Py-PDMS samples were acquired in tetrahydrofuran (THF, N,N-dimethylformamide (DMF, and dioxane. blob, the average rate constant for intra-chain pyrene excimer formation, was determined from the analysis of the fluorescence decays. blob was found to equal 1.16 (±0.13 × 109, 1.14 (±0.12 × 109, and 0.99 (±0.10 × 109 s−1 in THF, DMF, and dioxane, respectively, at room temperature. They are the largest values found to date for any polymeric backbone in these solvents. The qualitative relationship found here between blob and the chemical structures of the polymers indicates that the luminescence characteristics of randomly labeled polymers is a very useful method to probe the long range dynamics of chains of almost any polymer that is amenable to substitution by a lumophore.

Nitration of benzo[a]pyrene adsorbed on coal fly ash particles by nitrogen dioxide: role of thermal activation.

Science.gov (United States)

Kristovich, Robert L; Dutta, Prabir K

2005-09-15

Nitration of benzo[a]pyrene (BaP) by nitrogen dioxide (NO2) adsorbed on the surface of thermally activated coal fly ash and model aluminosilicate particles led to the formation of nitrobenzo[a]pyrenes as verified by extraction and gas chromatography/mass spectrometry (GC/MS). In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was utilized to follow the nitration reaction on the surface of zeolite Y. Nitrobenzo[a]pyrene formation was observed along with the formation of nitrous acid and nitrate species. The formation of the BaP radical cation was also observed on thermally activated aluminosilicate particles by electron spin resonance (ESR) spectroscopy. On the basis of GC/MS, DRIFTS, and ESR spectroscopy results, a mechanism of nitration involving intermediate BaP radical cations generated on thermally activated aluminosilicate particles is proposed. These observations have led to the hypothesis that nitration of adsorbed polyaromatic hydrocarbons on coal fly ash by reaction with nitrogen oxides can occur in the smokestack, but with the aging of the fly ash particles, the extent of the nitration reaction will be diminished.

Effect of benzo[a]pyrene on the production of vascular endothelial growth factor by human eosinophilic leukemia EoL-1 cells.

Science.gov (United States)

Gu, Jie; Chan, Lai-Sheung; Wong, Chris Kong-Chu; Wong, Ngok-Shun; Wong, Chun-Kwok; Leung, Kok-Nam; Mak, Naiki K

2011-01-01

Benzo[a]pyrene (BaP) has been shown to affect both the development and response of T and B cells in the immune system. However, the effect of BaP on other immune cells, such as eosionophils, is unknown. In this study, we investigated the effect of BaP on the production of vascular endothelial growth factor (VEGF) using an in vitro eosinophilic EoL-1 cell and human umbilical vein endothelial cell (HUVEC) co-culture system. EoL-1-conditioned medium was found to promote the growth of HUVEC in a time-dependent manner. The growth stimulating activity was due to the production of VEGF by the EoL-1 cells. The production of VEGF was correlated with the enhanced expression of the phosphorylated form of extracellular signal-regulated kinases (p-ERKs) and the upregulated expression of VEGF mRNA. Furthermore, BaP-induced expression of VEGF mRNA was reduced by the ERK inhibitor PD98059. Results from this study suggested that BaP might affect the growth of endothelial cells through the modulation of VEGF production by eosinophils.

On the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene in volcano exhausts.

Science.gov (United States)

Ilnitsky, A P; Belitsky, G A; Shabad, L M

1976-05-01

The content of benzo(a)pyrene in the juvenile ashes of the volcano Tyatya (Kunashir Island, Kuriles) and in the soil, vegetation and volcanic mud collected near volcanos in Kamchatka was studied. It was concluded that volcanic activity does not play a large role in forming the background level of this carcinogen in the human environment.

Tetraaryl pyrenes: photophysical properties, computational studies, crystal structures, and application in OLEDs

KAUST Repository

El-Assaad, Tarek H.; Auer, Manuel; Castañ eda, Raul; Hallal, Kassem M.; Jradi, Fadi M.; Mosca, Lorenzo; Khnayzer, Rony S.; Patra, Digambara; Timofeeva, Tatiana V.; Bredas, Jean-Luc; List-Kratochvil, Emil J. W.; Wex, Brigitte; Kaafarani, Bilal R.

2015-01-01

Pyrene was derivatized in positions 1, 3, 6, and 8 to yield a series of nine tetraarylpyrenes for which absorption, emission, emission lifetimes and solvatochromism in solution were determined. The fluorescence quantum yields in thin films and crystalline state, electrochemistry, and quantum-chemical calculations were completed for the series along with the X-ray crystal structure analysis of compounds 1, 2, 4, 5, 7, and 9. Compounds 2, 3, 4 as well as 7 were identified as the most suitable candidates for OLED application. Notably, in an unoptimized single-layer device geometry, these compounds exhibited blue electroluminescence coupled with impressively low turn-on voltages and high maximum luminances such as 2.8 V and 13 542 cd m-2 at 8.2 V for compound 2, respectively. © The Royal Society of Chemistry 2016.

Tetraaryl pyrenes: photophysical properties, computational studies, crystal structures, and application in OLEDs

KAUST Repository

El-Assaad, Tarek H.

2015-10-15

Pyrene was derivatized in positions 1, 3, 6, and 8 to yield a series of nine tetraarylpyrenes for which absorption, emission, emission lifetimes and solvatochromism in solution were determined. The fluorescence quantum yields in thin films and crystalline state, electrochemistry, and quantum-chemical calculations were completed for the series along with the X-ray crystal structure analysis of compounds 1, 2, 4, 5, 7, and 9. Compounds 2, 3, 4 as well as 7 were identified as the most suitable candidates for OLED application. Notably, in an unoptimized single-layer device geometry, these compounds exhibited blue electroluminescence coupled with impressively low turn-on voltages and high maximum luminances such as 2.8 V and 13 542 cd m-2 at 8.2 V for compound 2, respectively. © The Royal Society of Chemistry 2016.

Applications of PDMS partitioning methods in the study of biodegradation of pyrene in the

DEFF Research Database (Denmark)

Tejeda-Agredano, MC; Gouliarmou, Varvara; Ortega-Calvo, JJ

Although there are reports on the inhibition of anthropogenic organic chemicals biodegradation due to binding to dissolved humic substances (HS), there is an increasing body of evidence pointing to an enhancing effect in the case of hydrophobic chemicals, like pyrene. The addition of humic fracti...

Transplantation of hamster lung lesions induced by 239PuO2 or benz(a)pyrene

International Nuclear Information System (INIS)

McDonald, K.E.; Sanders, C.L.

1980-01-01

None(0%) of 1000 recipients of lung lesions for 239 PuO 2 -exposed hamsters that were transplanted into other hamsters' cheek pouches, developed tumors, whereas 90% of transplants from benz(a)pyrene-induced lung lesions were malignant

Urinary Excretion of Buprenorphine, Norbuprenorphine, Buprenorphine-Glucuronide, and Norbuprenorphine-Glucuronide in Pregnant Women Receiving Buprenorphine Maintenance Treatment

Science.gov (United States)

Kacinko, Sherri L.; Jones, Hendree E.; Johnson, Rolley E.; Choo, Robin E.; Concheiro-Guisan, Marta; Huestis, Marilyn A.

2011-01-01

BACKGROUND Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women. We investigated BUP and metabolite disposition in urine from women maintained on BUP during the second and third trimesters of pregnancy and postpartum. METHODS We measured BUP, norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and NBUP-Gluc concentrations in 515 urine specimens collected thrice weekly from 9 women during pregnancy and postpartum. Specimens were analyzed using a fully validated liquid chromatography-mass spectrometry method with limits of quantification of 5 µg/L for BUP and BUP-Gluc and 25 µg/L for NBUP and its conjugated metabolite. We examined ratios of metabolites across trimesters and postpartum to identify possible changes in metabolism during pregnancy. RESULTS NBUP-Gluc was the primary metabolite identified in urine and exceeded BUP-Gluc concentrations in 99% of specimens. Whereas BUP-Gluc was identified in more specimens than NBUP, NBUP exceeded BUP-Gluc concentrations in 77.9% of specimens that contained both analytes. Among all participants, the mean BUP-Gluc:NBUP-Gluc ratio was significantly higher in the second trimester compared to the third trimester, and there were significant intrasubject differences between trimesters in 71% of participants. In 3 women, the percent daily dose excreted was higher during pregnancy than postpregnancy, consistent with other data indicating increased renal elimination of drugs during pregnancy. CONCLUSIONS These data are the first to evaluate urinary disposition of BUP and metabolites in a cohort of pregnant women. Variable BUP excretion during pregnancy may indicate metabolic changes requiring dose adjustment during later stages of gestation. PMID:19325013

Development and Uses of Offline and Web-Searchable Metabolism Databases - The Case of Benzo[a]pyrene.

Science.gov (United States)

Rendic, Slobodan P; Guengerich, Frederick P

2018-01-01

The present work describes development of offline and web-searchable metabolism databases for drugs, other chemicals, and physiological compounds using human and model species, prompted by the large amount of data published after year 1990. The intent was to provide a rapid and accurate approach to published data to be applied both in science and to assist therapy. Searches for the data were done using the Pub Med database, accessing the Medline database of references and abstracts. In addition, data presented at scientific conferences (e.g., ISSX conferences) are included covering the publishing period beginning with the year 1976. Application of the data is illustrated by the properties of benzo[a]pyrene (B[a]P) and its metabolites. Analysis show higher activity of P450 1A1 for activation of the (-)- isomer of trans-B[a]P-7,8-diol, while P4501B1 exerts higher activity for the (+)- isomer. P450 1A2 showed equally low activity in the metabolic activation of both isomers. The information collected in the databases is applicable in prediction of metabolic drug-drug and/or drug-chemical interactions in clinical and environmental studies. The data on the metabolism of searched compound (exemplified by benzo[a]pyrene and its metabolites) also indicate toxicological properties of the products of specific reactions. The offline and web-searchable databases had wide range of applications (e.g. computer assisted drug design and development, optimization of clinical therapy, toxicological applications) and adjustment in everyday life styles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hepatitis B spliced protein (HBSP) promotes the carcinogenic effects of benzo [alpha] pyrene by interacting with microsomal epoxide hydrolase and enhancing its hydrolysis activity

International Nuclear Information System (INIS)

Chen, Jin-Yan; Chen, Wan-Nan; Jiao, Bo-Yan; Lin, Wan-Song; Wu, Yun-Li; Liu, Ling-Ling; Lin, Xu

2014-01-01

The risk of hepatocellular carcinoma (HCC) increases in chronic hepatitis B surface antigen (HBsAg) carriers who often have concomitant increase in the levels of benzo[alpha]pyrene-7,8-diol-9,10-epoxide(±) (BPDE)-DNA adduct in liver tissues, suggesting a possible co-carcinogenesis of Hepatitis B virus (HBV) and benzo[alpha]pyrene in HCC; however the exact mechanisms involved are unclear. The interaction between hepatitis B spliced protein (HBSP) and microsomal epoxide hydrolase (mEH) was confirmed using GST pull-down, co-immunoprecipitation and mammalian two-hybrid assay; the effects of HBSP on mEH-mediated B[alpha]P metabolism was examined by high performance liquid chromatography (HPLC); and the influences of HBSP on B[alpha]P carcinogenicity were evaluated by bromodeoxyuridine cell proliferation, anchorage-independent growth and tumor xenograft. HBSP could interact with mEH in vitro and in vivo, and this interaction was mediated by the N terminal 47 amino acid residues of HBSP. HBSP could greatly enhance the hydrolysis activity of mEH in cell-free mouse liver microsomes, thus accelerating the metabolism of benzo[alpha]pyrene to produce more ultimate carcinnogen, BPDE, and this effect of HBSP requires the intact HBSP molecule. Expression of HBSP significantly increased the formation of BPDE-DNA adduct in benzo[alpha]pyrene-treated Huh-7 hepatoma cells, and this enhancement was blocked by knockdown of mEH. HBSP could enhance the cell proliferation, accelerate the G1/S transition, and promote cell transformation and tumorigenesis of B[alpha]P-treated Huh-7 hepatoma cells. Our results demonstrated that HBSP could promote carcinogenic effects of B[alpha]P by interacting with mEH and enhancing its hydrolysis activity

Benzo[a]pyrene induces intercellular adhesion molecule-1 through a caveolae and aryl hydrocarbon receptor mediated pathway

International Nuclear Information System (INIS)

Oesterling, Elizabeth; Toborek, Michal; Hennig, Bernhard

2008-01-01

Toxicologic and epidemiologic studies have linked benzo[a]pyrene (B[a]P) exposure with cardiovascular diseases such as atherosclerosis. The mechanisms of action leading to these diseases have not been fully understood. One key step in the development of atherosclerosis is vascular endothelial dysfunction, which is characterized by increased adhesiveness. To determine if B[a]P could lead to increased endothelial adhesiveness, the effects of B[a]P on human endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression was investigated. B[a]P was able to increase ICAM-1 protein only after pretreatment with the aryl hydrocarbon receptor (AhR) agonist β-naphthoflavone (β-NF). Knockdown of AhR by siRNA or treatment with AhR antagonist α-naphthoflavone (α-NF) eliminated the induction of ICAM-1 from B[a]P, confirming the necessity of AhR in this process. Likewise, B[a]P only increased monocyte adhesion to the vascular endothelium when cells were pretreated with β-NF. Experiments were done to define a signaling mechanism. B[a]P increased phosphorylation of MEK and p38-MAPK, and inhibitors to these proteins blunted the ICAM-1 induction. B[a]P was also able to increase AP-1 DNA binding and phosphorylation of cJun. Phosphorylation of cJun was disrupted by MEK and p38-MAPK inhibitors linking the signaling cascade. Finally, the importance of membrane microdomains, caveolae, was demonstrated by knockdown of the structural protein caveolin-1. Disruption of caveolae eliminated the B[a]P-induced ICAM-1 expression. These data suggest a possible pro-inflammatory mechanism of action of B[a]P involving caveolae, leading to increased vascular endothelial adhesiveness, and this inflammation may be a critical step in the development of B[a]P-induced atherosclerosis

Deposition of ethyl glucuronide in WHP rat hair after chronic ethanol intake.

Science.gov (United States)

Małkowska, Anna; Szutowski, Mirosław; Dyr, Wanda

2012-01-01

This study investigated the relationship between ethanol intake in rats and the resulting level of ethyl glucuronide (EtG) in rat hair. Rats (n = 50) consumed a 10% ethanol solution for 4 weeks, then EtG was extracted from samples of their hair using a novel extraction procedure involving freezing and thawing. The EtG concentration was measured using gas chromatography and mass spectrometry. The animals voluntarily drank ethanol, with daily consumption in most rats exceeding 5 g/kg b.w. The silylated EtG was stable for at least 28 h. The limit of detection was 0.03 ng/mg, and the limit of quantification was 0.1 ng/mg. Hair samples from rats that consumed ethanol had EtG levels ranging from 0.17-20.72 ng/mg in female rats and 0.15-13.72 ng/mg in males. There was a correlation between the amount of alcohol consumed and the EtG levels in hair from female (p < 0.01), but not male, rats. The method presented allows detection and quantification of EtG in rat hair. We also observed differences in EtG deposition in male and female rats.

Luminescence quenching by heavy metal ions of probes based on anthracene, pyrene, and eosin in human serum albumin

Science.gov (United States)

Naumova, E. V.; Melnikov, A. G.; Melnikov, G. V.

2013-05-01

Fluorescence and phosphorescence quenching processes of polar and non-polar luminescent probes associated with human serum albumin (HSA) in phosphate buffer at pH 7.4 were studied. Stern-Volmer quenching constants of anthracene and pyrene fluorescence and eosin phosphorescence and rate constants for quenching of eosin triplet states were determined. The polarity index of pyrene bound to HSA was obtained as a function of thallium nitrate concentration. The influences of structural changes in the proteins that were stimulated by heavy-metal salts and of screening of protein charges by salt ions on quenching processes of singlet and triplet states of the probes were found.

Effect of Organic Solvents and Biologically Relevant Ions on the Light-Induced DNA Cleavage by Pyrene and Its Amino and Hydroxy Derivatives

Directory of Open Access Journals (Sweden)

Hongtao Yu

2002-09-01

Full Text Available Abstract: Polycyclic aromatic hydrocarbons (PAHs are a class of carcinogenic compounds that are both naturally and artificially produced. Many PAHs are pro-carcinogens that require metabolic activation. Recently, it has been shown that PAH can induce DNA single strand cleavage and formation of PAH-DNA covalent adduct upon irradiation with UVA light. The light-induced DNA cleavage parallels phototoxicity in one instance. The DNA photocleavage efficiency depends on the structure of the PAHs. This article reports the effect of both organic solvents and the presence of biologically relevant ions, Na+, Mg2+, Ca2+, K+, Fe3+, Cu2+, Zn+2, Mn2+, and I-, on the light-induced DNA cleavage by pyrene, 1-hydroxypyrene and 1-aminopyrene. Since both 1-hydroxypyrene (0.6 μM and 1-aminopyrene (6 μM dissolve well in the minimum organic solvents used (2% methanol, dimethylsulfoxide, and dimethylformamide, increasing the amount of the organic solvent resulted in the decrease of the amount of DNA single strand cleavage caused by the combination effect of 1-hydroxy or 1-aminopyrene and UVA light. The result with the less watersoluble pyrene shows that increase of the amount of the organic solvent can increase the amount of DNA single strand DNA photocleavage cause by the combination of pyrene and UVA light. Therefore, there are two effects by the organic solvents: (i to dissolve PAH and (ii to quench DNA photocleavage. The presence of Fe3+ and Zn2+ enhances, while the presence of Ca2+ and Mn2+ inhibits the DNA photocleavage caused by 1-aminopyrene and UVA light. Other metal ions have minimal effect. This means that the effect of ions on DNA photocleavage by PAHs is complex. The presence of KI enhances DNA photocleavage. This indicates that the triplet-excited state of 1-aminopyrene is involved in causing DNA cleavage

In vitro inhibitory effects of major bioactive constituents of Andrographis paniculata, Curcuma longa and Silybum marianum on human liver microsomal morphine glucuronidation: A prediction of potential herb-drug interactions arising from andrographolide, curcumin and silybin inhibition in humans.

Science.gov (United States)

Uchaipichat, Verawan

2018-02-01

This study aimed to investigate the liver microsomal inhibitory effects of silybin, silychristin, andrographolide, and curcumin by using morphine as an in vitro UGT2B7 probe substrate, and predict the magnitude of the herb-drug interaction arising from these herbal constituents' inhibition in vivo. Studies were performed in the incubation with and without bovine serum albumin (BSA). Andrographolide and curcumin showed a marked inhibition on morphine 3- and 6-glucuronidation with IC 50 of 50&87 and 96&111 μM, respectively. In the presence of 2%BSA, andrographolide also showed a strong inhibition on morphine 3- and 6-glucuronidation (IC 50 4.4&21.6 μM) whereas curcumin showed moderate inhibition (IC 50 338&333 μM). In the absence and presence of 2%BSA, morphine 3- and 6-glucuronidation was moderately inhibited by silybin (IC 50 583&862 and 1252&1421 μM, respectively), however was weakly inhibited by silychristin (IC 50 3527&3504 and 1124&1530 μM, respectively). The K i of andrographolide, curcumin and silybin on morphine 3- and 6-glucuronidation were 7.1&9.5, 72.7&65.2, and 224.5&159.7 μM, respectively, while the respective values generated from the system containing 2%BSA were 2.4&3.1, 96.4&108.8, and 366.3&394.5 μM. Using the in vitro and in vivo extrapolation approach, andrographolide was herbal component that may have had a potential interaction in vivo when it was co-administered with morphine. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Human Metabolite Lamotrigine-N(2)-glucuronide Is the Principal Source of Lamotrigine-Derived Compounds in Wastewater Treatment Plants and Surface Water.

Science.gov (United States)

Zonja, Bozo; Pérez, Sandra; Barceló, Damià

2016-01-05

Wastewater and surface water samples, extracted with four solid-phase extraction cartridges of different chemistries, were suspect-screened for the anticonvulsant lamotrigine (LMG), its metabolites, and related compounds. LMG, three human metabolites, and a LMG synthetic impurity (OXO-LMG) were detected. Preliminary results showed significantly higher concentrations of OXO-LMG in wastewater effluent, suggesting its formation in the wastewater treatment plants (WWTPs). However, biodegradation experiments with activated sludge demonstrated that LMG is resistant to degradation and that its human metabolite lamotrigine-N(2)-glucuronide (LMG-N2-G) is the actual source of OXO-LMG in WWTPs. In batch reactors, LMG-N2-G was transformed, following pseudo-first-order kinetics to OXO-LMG and LMG, but kinetic experiments suggested an incomplete mass balance. A fragment ion search applied to batch-reactor and environmental samples revealed another transformation product (TP), formed by LMG-N2-G oxidation, which was identified by high-resolution mass spectrometry. Accounting for all TPs detected, a total mass balance at two concentration levels in batch reactors was closed at 86% and 102%, respectively. In three WWTPs, the total mass balance of LMG-N2-G ranged from 71 to 102%. Finally, LMG-N2-G and its TPs were detected in surface water samples with median concentration ranges of 23-139 ng L(-1). The results of this study suggest that glucuronides of pharmaceuticals might also be sources of yet undiscovered, but environmentally relevant, transformation products.

REDUCTION OF BENZO (A PYRENE IN CHARCOAL GRILLED DUCK MEAT BY MARINATING WITH ANDALIMAN (Zanthoxylum acanthopodium, DC FRUIT JUICE

Directory of Open Access Journals (Sweden)

K. Sinaga

2016-12-01

Full Text Available The effect of andaliman fruit juice marination on the amounts of benzo (a pyrene in charcoal grilled duck meat were investigated in this research. Completely randomized design was used to determine the effect of 4 treatments of andaliman fruit juice concentration (w/v. Twenty four duck meat samples were devided into 4 treatment groups, those were 0% (I, 10% (II, 20% (III and 30% (IV. Each group consisted of 6 samples. Total Fat, Tio Barbituric Acid (TBA value and antioxidant activity were measured from all samples. The result showed there was no effect on total fat of duck meat. Antioxidant activity was 18.60 %, 18.06 %, 19.99 % and 7.54 % for andaliman fruit juice of 10%, 20%, 30% and 0%, respectively. TBA value was 1.03 %, 0.89 %, 0.09 % and 0.10 % for treatment II, III, IV and I, respectively. Antioxidant activity of andaliman fruit was decreased the amounts of Benzo (a pyrene of duckmeat. Charcoal duck meat without andaliman fruit produced 787 ng, it was higher than charcoal duck meat with andaliman fruit (295 ng.

Benzo[a]pyrene in urban environments of eastern Moscow: pollution levels and critical loads

Science.gov (United States)

Kasimov, Nikolay S.; Kosheleva, Natalia E.; Nikiforova, Elena M.; Vlasov, Dmitry V.

2017-02-01

Polycyclic aromatic hydrocarbons (PAHs), particularly benzo[a]pyrene (BaP), are toxic compounds emitted from various anthropogenic sources. Understanding the BaP concentrations, dynamics and decomposition in soil is required to assess the critical loads of BaP in urban environments. This study is the first attempt to evaluate all major input and output components of benzo[a]pyrene (BaP) balance and to calculate the permissible load on the urban environment in different land-use zones in the Eastern district of Moscow. BaP contamination of the snow cover in the Eastern district of Moscow was related to daily BaP fallout from the atmosphere. In 2010, the mean content of the pollutant in the snow dust was 1942 ng g-1, whereas the average intensity of its fallout was 7.13 ng m-2 per day. Across the territory, BaP winter fallout intensities varied from 0.3 to 1100 ng m-2 per day. The average BaP content in the surface (0-10 cm) soil horizons was 409 ng g-1, which is 83 times higher than the local background value and 20 times higher than the maximum permissible concentration (MPC) accepted in Russia. The variations in soil and snow BaP concentrations among different land-use zones were examined. A significant contribution of BaP from the atmosphere to urban soils was identified. Based on the measurements of BaP atmospheric fallout and BaP reserves in the soils, the critical loads of BaP for the land-use zones in the Eastern district were calculated for different values of degradation intensity and different exposure times. It was established that at an annual degradation intensity of 1-10 %, ecologically safe BaP levels in the soils of all land-use zones, excluding the agricultural zone, will only be reached after many decades or centuries.

A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

DEFF Research Database (Denmark)

Syed, Muzeeb; Srinivas, Nuggehally R

2016-01-01

Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the an...

beta-Glucuronidase-resistant bilirubin glucuronide isomers in cholestatic liver disease--determination of bilirubin metabolites in serum by means of high-pressure liquid chromatography

NARCIS (Netherlands)

Jansen, P. L.

1981-01-01

"Direct reacting bilirubin" in serum of patients with cholestatic liver disease and in serum of bile duct-ligated rats consists of a complex mixture of bilirubin metabolites. These metabolites were studied by means of high-pressure liquid chromatography. Bilirubin glucuronides in normal bile are

Liquid chromatographic determination of microcystins in water samples following pre-column excimer fluorescence derivatization with 4-(1-pyrene)butanoic acid hydrazide.

Science.gov (United States)

Hayama, Tadashi; Katoh, Kenji; Aoki, Takayoshi; Itoyama, Miki; Todoroki, Kenichiro; Yoshida, Hideyuki; Yamaguchi, Masatoshi; Nohta, Hitoshi

2012-11-28

A method to measure the concentrations of microcystins (MCs) in water samples has been developed by incorporating pre-column fluorescence derivatization and liquid chromatography (LC). A solid-phase extraction for pretreatment was used to extract the MCs in water samples. The MCs were derivatized with excimer-forming 4-(1-pyrene)butanoic acid hydrazide (PBH). The MCs could then be detected by fluorescence after separation with a pentafluorophenyl (PFP)-modified superficially porous (core shell) particle LC column. The derivatization reactions of MCs with PBH proceeded easily in the presence of 4,6-dimethoxy-1,3,5-triazin-2-yl-4-methylmorpholinium (DMT-MM) as a condensation reagent, and the resulting derivatives could be easily separated on the PFP column. The derivatives were selectively detected at excimer fluorescence wavelengths (440-540 nm). The instrument detection limit and the instrument quantification limit of the MCs standards were 0.4-1.2 μg L(-1) and 1.4-3.9 μg L(-1), respectively. The method was validated at 0.1 and 1.0 μg L(-1) levels in tap and pond water samples, and the recovery of MCs was between 67 and 101% with a relative standard deviation of 11%. The proposed method can be used to quantify trace amounts of MCs in water samples. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of Green Tea Catechins and Hydrolyzable Tannins on Benzo[a]pyrene-Induced DNA Adducts and Structure–Activity Relationship

OpenAIRE

Cao, Pengxiao; Cai, Jian; Gupta, Ramesh C.

2010-01-01

Green tea catechins and hydrolyzable tannins are gaining increasing attention as chemopreventive agents. However, their mechanism of action is poorly understood. We investigated the effects of four green tea catechins and two hydrolyzable tannins on microsome-induced benzo[a]pyrene (BP)–DNA adducts and the possible structure–activity relationship. BP (1 μM) was incubated with rat liver microsomes and DNA in the presence of the test compound (1–200 μM) or vehicle. The purified DNA was analyzed...

STUDYING THE INFLUENCE OF THE PYRENE INTERCALATOR TINA ON THE STABILITY OF DNA i-MOTIFS

DEFF Research Database (Denmark)

El-Sayed, Ahmed A.; Pedersen, Erik Bjerregaard; Khaireldin, Nahid A.

2012-01-01

Certain cytosine-rich (C-rich) DNA sequences can fold into secondary structures as four-stranded i-motifs with hemiprotonated base pairs. Here we synthesized C-rich TINA-intercalating oligonucleotides by inserting a nonnucleotide pyrene moiety between two C-rich regions. The stability of their i-...

32P-postlabeling assay in mice of transplacental DNA damage induced by the environmental carcinogens safrole, 4-aminobiphenyl, and benzo(a)pyrene

International Nuclear Information System (INIS)

Lu, L.J.; Disher, R.M.; Reddy, M.V.; Randerath, K.

1986-01-01

Transplacental exposure of fetuses to carcinogens is known to induce tumors in the offspring, often with a high incidence and short latency. While covalent adduction of DNA appears to be essential for tumor initiation, little is known about the binding of carcinogens to the DNA of fetal tissues. A sensitive 32 P-postlabeling method enabled us to study the binding of the environmental carcinogens safrole (600 mumol/kg p.o.), 4-aminobiphenyl (800 mumol/kg), and benzo(a)pyrene (200 mumol/kg) to the DNA of various maternal and fetal tissues after administration of test carcinogens to pregnant ICR mice on day 18 of gestation. The results show that these carcinogens bound to the DNA of maternal and fetal liver, lung, kidney, heart, brain, intestine, skin, maternal uterus, and placenta, with organ-specific quantitative and qualitative differences. It was possible for the first time to analyze DNA adduct patterns in minute amounts of tissue, for example those available from fetal heart. The covalent binding index 24 h after safrole treatment was estimated for the different organs and ranged from 0.1 to 247 and 0.1 to 5.8 for maternal and fetal DNA, respectively. Covalent binding index values of 0.2 to 13 and 0.1 to 0.3 for maternal and fetal DNA, respectively, were found for 4-aminobiphenyl. Benzo(a)pyrene treatment yielded covalent binding index values of 0.6 to 6.5 and 0.3 to 0.7 for maternal and fetal DNA, respectively. In both maternal and fetal tissues, safrole exhibited preferential binding to liver DNA. 4-Aminobiphenyl bound preferentially to DNA of maternal liver and kidney but showed no preference among fetal tissues. Benzo(a)pyrene exhibited weak tissue preference in both maternal and fetal organs

Inhibitory Effects of Commonly Used Herbal Extracts on UDP-Glucuronosyltransferase 1A4, 1A6, and 1A9 Enzyme Activities

Science.gov (United States)

Mohamed, Mohamed-Eslam F.

2011-01-01

The aim of this study was to investigate the effect of commonly used botanicals on UDP-glucuronosyltransferase (UGT) 1A4, UGT1A6, and UGT1A9 activities in human liver microsomes. The extracts screened were black cohosh, cranberry, echinacea, garlic, ginkgo, ginseng, milk thistle, saw palmetto, and valerian in addition to the green tea catechin epigallocatechin gallate (EGCG). Formation of trifluoperazine glucuronide, serotonin glucuronide, and mycophenolic acid phenolic glucuronide was used as an index reaction for UGT1A4, UGT1A6, and UGT1A9 activities, respectively, in human liver microsomes. Inhibition potency was expressed as the concentration of the inhibitor at 50% activity (IC50) and the volume in which the dose could be diluted to generate an IC50-equivalent concentration [volume/dose index (VDI)]. Potential inhibitors were EGCG for UGT1A4, milk thistle for both UGT1A6 and UGT1A9, saw palmetto for UGT1A6, and cranberry for UGT1A9. EGCG inhibited UGT1A4 with an IC50 value of (mean ± S.E.) 33.8 ± 3.1 μg/ml. Milk thistle inhibited both UGT1A6 and UGT1A9 with IC50 values of 59.5 ± 3.6 and 33.6 ± 3.1 μg/ml, respectively. Saw palmetto and cranberry weakly inhibited UGT1A6 and UGT1A9, respectively, with IC50 values >100 μg/ml. For each inhibition, VDI was calculated to determine the potential of achieving IC50-equivalent concentrations in vivo. VDI values for inhibitors indicate a potential for inhibition of first-pass glucuronidation of UGT1A4, UGT1A6, and UGT1A9 substrates. These results highlight the possibility of herb-drug interactions through modulation of UGT enzyme activities. Further clinical studies are warranted to investigate the in vivo extent of the observed interactions. PMID:21632963

Inhibitory Effects of Diclofenac on Steroid Glucuronidation In Vivo Do Not Affect Hair-Based Doping Tests for Stanozolol.

Science.gov (United States)

Zachár, Gergely; Deshmukh, Naved I K; Petróczi, Andrea; Székely, Andrea D; Shah, Iltaf; Barker, James; Naughton, Declan P

2017-06-12

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3'-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair, which holds considerable advantages over urinalysis for anti-doping tests.

Effect of various chemicals on the metabolism of benzo(a)pyrene by cultured rat colon

DEFF Research Database (Denmark)

Autrup, Herman; Harris, Curtis C.; Fugaro, Steven

1977-01-01

The effect of various co- and anti-carcinogens of colon carcinogenesis on the metabolism of benzo(a)pyrene (BP) in cultured rat colon is reported. Rat colon enzymatically converted BP into metabolites which bind to cellular macromolecules i.e., DNA and protein. Activity of aryl hydrocarbon...

Menadione Suppresses Benzo(α)pyrene-Induced Activation of Cytochromes P450 1A: Insights into a Possible Molecular Mechanism.

Science.gov (United States)

Sidorova, Yulia A; Perepechaeva, Maria L; Pivovarova, Elena N; Markel, Arkady L; Lyakhovich, Vyacheslav V; Grishanova, Alevtina Y

2016-01-01

Oxidative reactions that are catalyzed by cytochromes P450 1A (CYP1A) lead to formation of carcinogenic derivatives of arylamines and polycyclic aromatic hydrocarbons (PAHs), such as the widespread environmental pollutant benzo(α)pyrene (BP). These compounds upregulate CYP1A at the transcriptional level via an arylhydrocarbon receptor (AhR)-dependent signaling pathway. Because of the involvement of AhR-dependent genes in chemically induced carcinogenesis, suppression of this signaling pathway could prevent tumor formation and/or progression. Here we show that menadione (a water-soluble analog of vitamin K3) inhibits BP-induced expression and enzymatic activity of both CYP1A1 and CYP1A2 in vivo (in the rat liver) and BP-induced activity of CYP1A1 in vitro. Coadministration of BP and menadione reduced DNA-binding activity of AhR and increased DNA-binding activity of transcription factors Oct-1 and CCAAT/enhancer binding protein (C/EBP), which are known to be involved in negative regulation of AhR-dependent genes, in vivo. Expression of another factor involved in downregulation of CYP1A-pAhR repressor (AhRR)-was lower in the liver of the rats treated with BP and menadione, indicating that the inhibitory effect of menadione on CYP1A is not mediated by this protein. Furthermore, menadione was well tolerated by the animals: no signs of acute toxicity were detected by visual examination or by assessment of weight gain dynamics or liver function. Taken together, our results suggest that menadione can be used in further studies on animal models of chemically induced carcinogenesis because menadione may suppress tumor formation and possibly progression.

Pyrene synthesis in circumstellar envelopes and its role in the formation of 2D nanostructures

Science.gov (United States)

Zhao, Long; Kaiser, Ralf I.; Xu, Bo; Ablikim, Utuq; Ahmed, Musahid; Joshi, Dharati; Veber, Gregory; Fischer, Felix R.; Mebel, Alexander M.

2018-05-01

For the past decades, the hydrogen-abstraction/acetylene-addition (HACA) mechanism has been instrumental in attempting to untangle the origin of polycyclic aromatic hydrocarbons (PAHs) as identified in carbonaceous meteorites such as Allende and Murchison. However, the fundamental reaction mechanisms leading to the synthesis of PAHs beyond phenanthrene (C14H10) are still unknown. By exploring the reaction of the 4-phenanthrenyl radical (C14H9•) with acetylene (C2H2) under conditions prevalent in carbon-rich circumstellar environments, we show evidence of a facile, isomer-selective formation of pyrene (C16H10). Along with the hydrogen-abstraction/vinylacetylene-addition (HAVA) mechanism, molecular mass growth processes from pyrene may lead through systematic ring expansions not only to more complex PAHs, but ultimately to 2D graphene-type structures. These fundamental reaction mechanisms are crucial to facilitate an understanding of the origin and evolution of the molecular universe and, in particular, of carbon in our Galaxy.

A Pyrene- and Phosphonate-Containing Fluorescent Probe as Guest Molecule in a Host Polymer Matrix

Directory of Open Access Journals (Sweden)

Jacqueline Marchand-Brynaert

2013-02-01

Full Text Available New host-guest materials have been prepared by incorporation of a home-made organic probe displaying a pyrene motif and a phosphonate function into a regular amphiphilic copolymer. Using powder X-Ray diffraction, photoluminescence and FT-IR spectroscopy, we have been able to study the non-covalent interactions between the host matrix and the guest molecule in the solid state. Interestingly, we have shown that the matrix directs the guest spatial localization and alters its properties. Thanks to the comparison of pyrene vs. N-pyrenylmaleimide derivatives, the influence of the chemical nature of the guest molecules on the non-covalent interactions with the host have been studied. In addition, using polyethylene glycol as a reference host, we have been able to evidence a true matrix effect within our new insertion materials. The phosphonated guest molecule appears to be a novel probe targeting the hydrophilic domain of the host copolymer.

Benzo(a)pyrene parallel measurements in PM1 and PM2.5 in the coastal zone of the Gulf of Gdansk (Baltic Sea) in the heating and non-heating seasons.

Science.gov (United States)

Lewandowska, Anita Urszula; Staniszewska, Marta; Witkowska, Agnieszka; Machuta, Magdalena; Falkowska, Lucyna

2018-05-05

Parallel measurements of PM 1 and PM 2.5 aerosols were conducted in the urbanized coastal zone of the southern Baltic Sea. The main aim of the research was to assess and determine annual, seasonal (heating and non-heating), and daily concentration variability of benzo(a)pyrene in aerosols, these being the most dangerous constituents to human health. The average annual concentration of benzo(a)pyrene (B(a)P) was equal to 2.6 ng·m -3 in PM 1 and 4.6 ng·m -3 in PM 2.5 , and both values were several times higher than the level of 1 ng·m -3 which was set out in the CAFE Directive. High mean daily concentrations of B(a)P persisted for 50 and 65% of the study period in PM1 and PM2.5, respectively. In order to determine the sources of B(a)P in both aerosol fractions, organic (OC) and elemental (EC) carbon concentrations were examined. The highest concentrations of all carbon species were reported during the heating season under local or regional land advection and at low air temperatures. The origin of pollutants was the same and was primarily related to the combustion of fossil fuels in the communal-utility sector. During the non-heating period, the role of transportation, both land and marine, increased and may have been significant in creating higher concentrations of carbon compounds in PM 1 and PM 2.5 . Regardless of the size of the aerosol fractions, B(a)P loads introduced into the Baltic coastal zone were several times higher during the heating period compared to the non-heating season. Graphical abstract ᅟ.

Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intraindividual variance in the urinary metabolite excretion profiles caused by intervention with {beta}-naphthoflavone induction in the rat

Energy Technology Data Exchange (ETDEWEB)

Elovaara, Eivor; Mikkola, Jouni [Laboratory of Toxicokinetics and Metabolism, Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, 00250, Helsinki (Finland); Vaeaenaenen, Virpi [Chemistry Laboratory, Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, 00250, Helsinki (Finland)

2003-04-01

Two fluorimetric HPLC methods are described for the quantification of naphthols, phenanthrols and 1-hydroxypyrene (1-OHP) in urine specimens obtained from male Wistar rats exposed to naphthalene, phenanthrene and pyrene. The polycyclic aromatic hydrocarbons (PAHs) were given intraperitoneally, either alone (1.0 mmol/kg body weight) or as an equimolar mixture (0.33 mmol/kg), using the same dosages for repeated treatments on week 1 and week 2. Between these treatments, PAH-metabolizing activities encoded by aryl hydrocarbon (Ah) receptor-controlled genes were induced in the rats with {beta}-naphthoflavone ({beta}NF). Chromatographic separation of five phenanthrols (1-, 2-, 3-, 4-, and 9-isomers) was accomplished using two different RP C-18 columns. Despite selective detection (programmable wavelengths), the quantification limits in the urine ranged widely: 1-OHP (0.18 {mu}g/l) 1.5 {mu}g/l) <1-naphthol (4 {mu}g/l). The relative standard deviation of the methods was good, as also was the reproducibility. The molar fraction of the dose excreted in 24-h urine as naphthols ({<=}4.0%), phenanthrols ({<=}1.1%), and 1-OHP ({<=}2.4%) was low. Urinary disposition increased differentially in {beta}NF-induced rats: naphthols, 9-phenanthrol (1- to-2-fold); 2-, 3-, and 4-phenanthrols (4- to 5-fold); 1-phenanthrol and 1-OHP (over 11-fold). The OH-metabolites were analyzed before and after enzymatic hydrolysis ({beta}-glucuronidase/arylsulfatase). The percentage excreted as a free phenol in urine varied for 1-OHP (2-11%), 1-naphthol (36-51%), 2-naphthol (59-65%), and the phenanthrols (29-94%). 1-Naphthyl- and 1-pyrenyl {beta}-d-glucuronide served as measures for the completeness of enzymatic hydrolysis. Characteristic differences observed in the urinary disposition of naphthalene, phenanthrene, and pyrene are described, as well as important factors (dose, metabolic capacity, relative urinary output) associated with biomarker validation

Transfer of benzo[a]pyrene from microplastics to Artemia nauplii and further to zebrafish via a trophic food web experiment: CYP1A induction and visual tracking of persistent organic pollutants.

Science.gov (United States)

Batel, Annika; Linti, Frederic; Scherer, Martina; Erdinger, Lothar; Braunbeck, Thomas

2016-07-01

The uptake of microplastic particles and the transfer of potential harmful substances along with microplastics has been studied in a variety of organisms, especially invertebrates. However, the potential accumulation of very small microplastic particles along food webs ending with vertebrate models has not been investigated so far. Therefore, a simple artificial food chain with Artemia sp. nauplii and zebrafish (Danio rerio) was established to analyze the transfer of microplastic particles and associated persistent organic pollutants (POPs) between different trophic levels. Very small (1-20 μm) microplastic particles accumulated in Artemia nauplii and were subsequently transferred to fish. Virgin particles not loaded with POPs did not cause any observable physical harm in the intestinal tracts of zebrafish, although parts of the particles were retained within the mucus of intestinal villi and might even have been taken up by epithelial cells. The transfer of associated POPs was tested with the polycyclic aromatic hydrocarbon benzo[a]pyrene and an ethoxyresorufin-O-deethylase (EROD) assay for CYP1A induction in zebrafish liver as well as via fluorescence analyses. Whereas a significant induction in the EROD assay could not be shown, because of high individual variation and low sensitivity regarding substance concentration, the fluorescence tracking of benzo[a]pyrene indicates that food-borne microplastic-associated POPs may actually desorb in the intestine of fish and are thus transferred to the intestinal epithelium and liver. Environ Toxicol Chem 2016;35:1656-1666. © 2016 SETAC. © 2016 SETAC.

Rapid, efficient and selective preconcentration of benzo[a]pyrene (BaP) by molecularly imprinted composite cartridge and HPLC

Energy Technology Data Exchange (ETDEWEB)

Çorman, Mehmet Emin, E-mail: mecorman@sinop.edu.tr [Hacettepe University, Department of Chemistry, Ankara (Turkey); Sinop University, Department of Bioengineering, Sinop (Turkey); Armutcu, Canan [Hacettepe University, Department of Chemistry, Ankara (Turkey); Uzun, Lokman, E-mail: lokman@hacettepe.edu.tr [Hacettepe University, Department of Chemistry, Ankara (Turkey); Denizli, Adil [Hacettepe University, Department of Chemistry, Ankara (Turkey)

2017-01-01

In this study, cryogel-based molecularly imprinted composite cartridges were designed for the rapid, efficient, and selective preconcentration of benzo[a]pyrene (BaP) from water samples. First, a BaP-imprinted poly(2-hydroxyethyl methacrylate-N-methacryloyl-(L)-phenylalanine) composite cartridge was synthesized under semi-frozen conditions and characterized by scanning electron microscopy, elemental analysis, Fourier transform infrared spectroscopy, and swelling tests. After the optimization of preconcentration parameters, i.e., pH and initial BaP concentration, the selectivity and preconcentration efficiency, and reusability of these cartridges were also evaluated. In selectivity experiments, BaP imprinted composite cartridge exhibited binding capacities 3.09, 9.52, 8.87, and 8.77-fold higher than that of the non-imprinted composite cartridge in the presence of competitors, such as benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), indeno[1,2,3-cd]pyrene (IcdP), and 1-naphthol, respectively. The method detection limit (MDL), relative standard deviation (RSD) and preconcentration efficiency (PE) of the synthesized composite cartridge were calculated as 24.86 μg/L, 1.60%, and 349.6%, respectively. - Highlights: • Cryogel based molecularly imprinted composite cartridges as solid-phase extraction sorbents • Combination unique structural features of cryogels with MIP • An excellent ability to recognize the BaP molecule even if single-run contact • Rapid, efficient, selective and cost-friendly PAH preconcentration • Hydrophobic interactions via N-methacryloyl-(L)-phenylalanine.

pH-Sensitive polymer assisted self-aggregation of bis(pyrene) in living cells in situ with turn-on fluorescence

International Nuclear Information System (INIS)

Duan, Zhongyu; Gao, Yu-Juan; Wang, Yongmei; Hou, Chunyuan; Qiao, Zeng-Ying; Qiao, Shenglin; Wang, Lei; Wang, Hao

2015-01-01

Supramolecular self-assemblies with various nanostructures in organic and aqueous solutions have been prepared with desired functions. However, in situ construction of self-assembled superstructures in physiological conditions to achieve expected biological functions remains a challenge. Here, we report a supramolecular system to realize the in situ formation of nanoaggregates in living cells. The bis(pyrene) monomers were dispersed inside of hydrophobic domains of pH-sensitive polymeric micelles and delivered to the lysosomes of cells. In the acidic lysosomes, the bis(pyrene) monomers were released and self-aggregated with turn-on fluorescence. We envision this strategy for in situ construction of supramolecular nanostructures in living cells will pave the way for molecular diagnostics in the future. (paper)

Morphine-6-glucuronide: analgesic effects and receptor binding profile in rats

Energy Technology Data Exchange (ETDEWEB)

Abbott, F.V.; Palmour, R.M.

1988-01-01

The antinociceptive effects of morphine-6-glucuronide (M6G) were examined in two animal models of pain, the tail immersion test (reflex withdrawal to noxious heat) and the formalin test (behavioral response to minor tissue injury). In the tail immersion test, M6G produced and increase in withdrawal latency that rose rapidly between 0.01 and 0.025 ug ICV or 1 and 2 mg/kg SC. A further increase occurred at doses greater than 0.2 ug ICV or 4 mg/kg SC and was associated with marked catelepsy and cyanosis. Naloxone, 0.1 mg/kg SC, shifted the lower component of the dose-effect relation by a factor of 24. In the formalin test, 0.01 ug M6G ICV produced hyperalgesia, while between 0.05 and 0.2 ug ICV, antinociception increased rapidly without toxicity. The dose effect relations for hyperalgesia and antinociception were shifted to the right by factors of 20- and 3-fold, respectively. By comparison, ICV morphine was 60 (formalin test) to 145-200 (tail immersion test) times less potent than M6G. At sub-nanomolar concentrations, M6G enhanced the binding of (/sup 3/H)-etorphine, (/sup 3/H)-dihydromorphine and (/sup 3/H)-naloxone to rat brain membrane receptors by 20-40%. At higher concentrations, M6G displaced each ligand from binding sites, with K/sub i/ values of about 30 nM, as compared to morphine K/sub i/ values of about 3 nM.

Inhibition of HIV-1 reverse transcriptase-catalyzed synthesis by intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide adducts.

Directory of Open Access Journals (Sweden)

Parvathi Chary

Full Text Available To aid in the characterization of the relationship of structure and function for human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT, this investigation utilized DNAs containing benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE-modified primers and templates as a probe of the architecture of this complex. BPDE lesions that differed in their stereochemistry around the C10 position were covalently linked to N (6-adenine and positioned in either the primer or template strand of a duplex template-primer. HIV-1 RT exhibited a stereoisomer-specific and strand-specific difference in replication when the BPDE-lesion was placed in the template versus the primer strand. When the C10 R-BPDE adduct was positioned in the primer strand in duplex DNA, 5 nucleotides from the 3΄ end of the primer terminus, HIV-1 RT could not fully replicate the template, producing truncated products; this block to further synthesis did not affect rates of dissociation or DNA binding affinity. Additionally, when the adducts were in the same relative position, but located in the template strand, similar truncated products were observed with both the C10 R and C10 S BPDE adducts. These data suggest that the presence of covalently-linked intercalative DNA adducts distant from the active site can lead to termination of DNA synthesis catalyzed by HIV-1 RT.

Magnetic modulation of exciplex fluorescence of pyrene solutions with azacrown-ether excess in the presence of ions of alkali and alkaline earth metals

International Nuclear Information System (INIS)

Borisenko, V.N.; Petrov, N.Kh.; Gromov, S.P.; Alfimov, M.V.

1997-01-01

Photoexcitation of polar pyrene solutions with excess of phenylaza-15-crown-5 as a donor results to intermolecular electron transfer with formation of ion-radical pairs, recombination of which produces fluorescent exciplex. Charge exchange between molecules of crown ether and its cation-radicals is practically absent at that. Magnetic effect, observed for fluorescence, decreases, when adding diamagnetic lithium and calcium ions to exiplex pyrene/crown-ether system. This can be explained by formation of paramagnetic complexes. 15 refs., 5 figs

Synthesis of block copolymers derived from N-trityl-(S)-serine and pyrene end-labeled poly(methyl methacrylate) or poly(N-isopropylacrylamide) via ATRP

International Nuclear Information System (INIS)

Buruiana, Emil C.; Podasca, Viorica; Buruiana, Tinca

2012-01-01

A new monomer bearing N-trityl-L-serine methyl ester in structure, methacryloyloxyethyl carbamoyloxy–N-trityl methyl serine (MTS), was prepared to be further polymerized by atom transfer radical polymerization (ATRP) with pyrene-endcapped poly(methyl methacrylate) (Py–PMMA–Br) or poly(N-isopropylacrylamide) (Py–PNIPA–Br). The resulting block copolymers, poly(methyl methacrylate–block–methacryloyloxyethyl carbamoyloxy–N-trityl methyl serine) (Py–PMMA–b–PMTS) and poly(N-isopropylacrylamide–block–methacryloyloxyethyl carbamoyloxy–N-trityl methyl serine (Py–PNIPA–b–PMTS) were characterized by 1 H ( 13 C) NMR, ultraviolet, FTIR and fluorescence spectroscopy, thermal analysis, differential scanning calorimetry (DSC), atomic force microscopy (AFM), scanning electron microscopy (SEM), and gel permeation chromatography (GPC) measurements. The chemical composition in Py–PMMA–b–PMTS was estimated from the 1 H NMR analysis that indicated a ratio of the repeating units of 46:19 (MMA:MTS). For the Py–PNIPA–b–PMTS the composition rate in the copolymer was 61:25 (NIPA:MTS). Quenching of the pyrene species with N,N-diethylaniline, nitrobenzene, nitrophenol, potassium iodide, p-nitrotoluene and tetracyanoquinodimethane (TCNQ) in DMF solution excited at 348 nm was evidenced, more efficiently being nitrophenol and TCNQ. In this case, the monomer emission at 388–409 nm underwent a significant decrease caused of an electron transfer from the electron-reach photoexcited pyrene molecule to the electron-deficient quenchers. - Highlights: ► Diblock copolymers combine the fluorescence of pyrene–PMMA (PNIPA) with the characteristics of PMTS. ► Such copolymers could be used for nitroderivatives detecting. ► UV/vis and fluorescence measurements give a good correlation for LCST of Py–PNIPA–Br.

Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI.

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Lawrence Soon-U Lee

Full Text Available Irinotecan toxicity correlates with UGT1A1 activity. We explored whether phenotyping UGT1A1 using a probe approach works better than current genotyping methods.Twenty-four Asian cancer patients received irinotecan as part of the FOLFIRI regimen. Subjects took raltegravir 400 mg orally and intravenous midazolam 1 mg. Pharmacokinetic analyses were performed using WinNonLin and NONMEM. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1 and CYP3A4/5.SN-38G/SN-38 AUC ratio correlated well with Raltegravir glucuronide/ Raltegravir AUC ratio (r = 0.784 p<0.01. Midazolam clearance correlated well with irinotecan clearance (r = 0.563 p<0.01. SN-38 AUC correlated well with Log10Nadir Absolute Neutrophil Count (ANC (r = -0.397 p<0.05. Significant correlation was found between nadir ANC and formation rate constant of raltegravir glucuronide (r = 0.598, P<0.005, but not UGT1A1 genotype.Raltegravir glucuronide formation is a good predictor of nadir ANC, and can predict neutropenia in East Asian patients. Prospective studies with dose adjustments should be done to develop raltegravir as a probe to optimize irinotecan therapy.Clinicaltrials.gov NCT00808184.

The use of mrp1-deficient (Danio rerio) zebrafish embryos to investigate the role of Mrp1 in the toxicity of cadmium chloride and benzo[a]pyrene

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Tian, Jingjing [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China); Hu, Jia [School of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, Jiangsu (China); Chen, Mingli [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China); Yin, Huancai [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Miao, Peng; Bai, Pengli [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China); Yin, Jian, E-mail: yinj@sibet.ac.cn [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China)

2017-05-15

Previous studies in our lab have revealed that both P-glycoprotein (Pgp) and multi-resistance associated protein (Mrp) 1 played important roles in the detoxification of heavy metals and polycyclic aromatic hydrocarbon (PAH) in zebrafish embryos. This paper aims to extend this research by using mrp1-deficient model to illustrate the individual function of Mrp1. In this respect, CRISPR/Cas9 system was employed to generate a frameshift mutation in zebrafish mrp1 causing premature translational stops in Mrp1. Significant reduction on the efflux function of Mrps was found in mutant zebrafish embryos, which correlated well with the significantly enhanced accumulation and toxicity of cadmium chloride (CdCl{sub 2}) and benzo[a]pyrene (BαP), indicating the protective role of the corresponding protein. The different alteration on the accumulation and toxicity of Cd{sup 2+} and BαP could be attributed to the fact that Cd{sup 2+} and its metabolites were mainly excreted by Mrp1, while BαP was primarily pumped out by Pgp. More importantly, the compensation mechanism for the absence of Mrp1, including elevated glutathione (GSH) level and up-regulated expression of pgp and mrp2 were also found. Thus, mrp1-deficient zebrafish embryo could be a useful tool in the investigation of Mrp1 functions in the early life stages of aquatic organisms. However, compensation mechanism should be taken into consideration in the interpretation of results obtained with mrp1-deficient fish.

The use of mrp1-deficient (Danio rerio) zebrafish embryos to investigate the role of Mrp1 in the toxicity of cadmium chloride and benzo[a]pyrene

International Nuclear Information System (INIS)

Tian, Jingjing; Hu, Jia; Chen, Mingli; Yin, Huancai; Miao, Peng; Bai, Pengli; Yin, Jian

2017-01-01

Previous studies in our lab have revealed that both P-glycoprotein (Pgp) and multi-resistance associated protein (Mrp) 1 played important roles in the detoxification of heavy metals and polycyclic aromatic hydrocarbon (PAH) in zebrafish embryos. This paper aims to extend this research by using mrp1-deficient model to illustrate the individual function of Mrp1. In this respect, CRISPR/Cas9 system was employed to generate a frameshift mutation in zebrafish mrp1 causing premature translational stops in Mrp1. Significant reduction on the efflux function of Mrps was found in mutant zebrafish embryos, which correlated well with the significantly enhanced accumulation and toxicity of cadmium chloride (CdCl_2) and benzo[a]pyrene (BαP), indicating the protective role of the corresponding protein. The different alteration on the accumulation and toxicity of Cd"2"+ and BαP could be attributed to the fact that Cd"2"+ and its metabolites were mainly excreted by Mrp1, while BαP was primarily pumped out by Pgp. More importantly, the compensation mechanism for the absence of Mrp1, including elevated glutathione (GSH) level and up-regulated expression of pgp and mrp2 were also found. Thus, mrp1-deficient zebrafish embryo could be a useful tool in the investigation of Mrp1 functions in the early life stages of aquatic organisms. However, compensation mechanism should be taken into consideration in the interpretation of results obtained with mrp1-deficient fish.

Mutagenic activation and detoxification of benzo[a]pyrene in vitro by hepatic cytochrome P450 1A1 and phase II enzymes in three meat-producing animals.

Science.gov (United States)

Darwish, W; Ikenaka, Y; Eldaly, E; Ishizuka, M

2010-01-01

The mutagenic activation activity of hepatic microsomes from three meat-producing animals (cattle, deer and horses) was compared with those of rats as a reference species. In the Ames Salmonella typhimurium TA98 assay, the liver microsomes of all examined animals mutagenically activated benzo[a]pyrene, an ideal promutagens, in terms of production of histidine-independent revertant colonies. The microsomes of horses had the highest ability to produce revertant colonies of the examined animals under both low and high substrate concentrations. Inhibition of this mutagenic activity using alpha-naphthoflavone, anti-rat CYP1A1, CYP3A2 and CYP2E1 antibodies suggests that this activity was mainly because of CYP1A1 in these animals as well as in rats. The addition of co-factors for two phase II enzymes, microsomal UDP glucoronosyl transferase and cytosolic glutathione-S-transferase, reduced the production of the revertant colonies in a concentration-dependent manner. Interestingly, horses had the highest reduction rate among the examined animals, suggesting that phase II enzymes play a great role in producing a state of balance between the bioactivation and detoxification of xenobiotics in these meat-producing animals. This report is the first to investigate the mutagenic activation activity of the hepatic microsomes and the role of phase II enzymes against this activity in meat-producing animals. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Development of an on-line solid phase extraction ultra-high-performance liquid chromatography technique coupled to tandem mass spectrometry for quantification of bisphenol S and bisphenol S glucuronide: Applicability to toxicokinetic investigations.

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Grandin, Flore; Picard-Hagen, Nicole; Gayrard, Véronique; Puel, Sylvie; Viguié, Catherine; Toutain, Pierre-Louis; Debrauwer, Laurent; Lacroix, Marlène Z

2017-12-01

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as Bisphenol S (BPS), in consumer products. At present, no toxicokinetic investigations have been conducted to assess the factors determining human internal exposure to BPS for subsequent risk assessment. Toxicokinetic studies require reliable analytical methods to measure the plasma concentrations of BPS and its main conjugated metabolite, BPS-glucuronide (BPS-G). An efficient on-line SPE-UPLC-MS/MS method for the simultaneous quantification of BPS and BPS-G in ovine plasma was therefore developed and validated in accordance with the European Medicines Agency guidelines for bioanalytical method validation. This method has a limit of quantification of 3ngmL -1 for BPS and 10ngmL -1 for BPS-G, an analytical capacity of 200 samples per day, and is particularly well suited to toxicokinetic studies. Use of this method in toxicokinetic studies in sheep showed that BPS, like BPA, is efficiently metabolized into its glucuronide form. However, the clearances and distributions of BPS and BPS-G were lower than those of the corresponding unconjugated and glucuroconjugated forms of BPA. Copyright © 2017 Elsevier B.V. All rights reserved.

Menadione Suppresses Benzo(αpyrene-Induced Activation of Cytochromes P450 1A: Insights into a Possible Molecular Mechanism.

Directory of Open Access Journals (Sweden)

Yulia A Sidorova

Full Text Available Oxidative reactions that are catalyzed by cytochromes P450 1A (CYP1A lead to formation of carcinogenic derivatives of arylamines and polycyclic aromatic hydrocarbons (PAHs, such as the widespread environmental pollutant benzo(αpyrene (BP. These compounds upregulate CYP1A at the transcriptional level via an arylhydrocarbon receptor (AhR-dependent signaling pathway. Because of the involvement of AhR-dependent genes in chemically induced carcinogenesis, suppression of this signaling pathway could prevent tumor formation and/or progression. Here we show that menadione (a water-soluble analog of vitamin K3 inhibits BP-induced expression and enzymatic activity of both CYP1A1 and CYP1A2 in vivo (in the rat liver and BP-induced activity of CYP1A1 in vitro. Coadministration of BP and menadione reduced DNA-binding activity of AhR and increased DNA-binding activity of transcription factors Oct-1 and CCAAT/enhancer binding protein (C/EBP, which are known to be involved in negative regulation of AhR-dependent genes, in vivo. Expression of another factor involved in downregulation of CYP1A-pAhR repressor (AhRR-was lower in the liver of the rats treated with BP and menadione, indicating that the inhibitory effect of menadione on CYP1A is not mediated by this protein. Furthermore, menadione was well tolerated by the animals: no signs of acute toxicity were detected by visual examination or by assessment of weight gain dynamics or liver function. Taken together, our results suggest that menadione can be used in further studies on animal models of chemically induced carcinogenesis because menadione may suppress tumor formation and possibly progression.

Multimedia transport of particle-bound organics: benzo(a)pyrene test case

Energy Technology Data Exchange (ETDEWEB)

Ryan, P A; Cohen, Y

1986-01-01

A screening multimedia-compartmental (MCM) modeling approach is presented for predicting the distribution of particle-bound pollutants within an environment consisting of the atmosphere, surface water, and surface soil compartments. An MCM model was used to simulate the dynamic distribution of Benzo(a)Pyrene (B(a)P) for a study region located in southeast Ohio. The model incorporates theoretical estimates of the dry deposition velocity and a new semi-empirical model for rain scavenging of B(a)P. The predicted concentrations of B(a)P compared favorably with available field data.

Peptide-Driven Charge-Transfer Organogels Built from Synergetic Hydrogen Bonding and Pyrene-Naphthalenediimide Donor-Acceptor Interactions.

Science.gov (United States)

Bartocci, Silvia; Berrocal, José Augusto; Guarracino, Paola; Grillaud, Maxime; Franco, Lorenzo; Mba, Miriam

2018-02-26

The peptide-driven formation of charge transfer (CT) supramolecular gels featuring both directional hydrogen-bonding and donor-acceptor (D-A) complexation is reported. Our design consists of the coassembly of two dipeptide-chromophore conjugates, namely diphenylalanine (FF) dipeptide conveniently functionalized at the N-terminus with either a pyrene (Py-1, donor) or naphthalene diimide (NDI-1, acceptor). UV/Vis spectroscopy confirmed the formation of CT complexes. FTIR and 1 H NMR spectroscopy studies underlined the pivotal role of hydrogen bonding in the gelation process, and electronic paramagnetic resonance (EPR) measurements unraveled the advantage of preorganized CT supramolecular architectures for charge transport over solutions containing non-coassembled D and A molecular systems. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Endogenous morphine-6-glucuronide (M6G) is present in the plasma of patients: validation of a specific anti-M6G antibody for clinical and basic research.

Science.gov (United States)

Laux-Biehlmann, Alexis; Chung, Hélène; Mouheiche, Jinane; Vérièpe, Julie; Delalande, François; Lamshöft, Marc; Welters, Ingeborg D; Soldevila, Stéphanie; Bazin, Hervé; Lamarque, Laurent; Van Dorsselaer, Alain; Poisbeau, Pierrick; Schneider, Francis; Goumon, Yannick; Garnero, Patrick

2014-01-01

Endogenous morphine and its derivatives (morphine-6-glucuronide [M6G]; morphine-3-glucuronide [M3G]) are formed by mammalian cells from dopamine. Changes in the concentrations of endogenous morphine have been demonstrated in several pathologies (sepsis, Parkinson's disease, etc.), and they might be relevant as pathological markers. While endogenous morphine levels are detectable using enzyme-linked immunosorbant assay (ELISA), mass spectrometry (MS) analysis was, so far, the only approach to detect and quantify M6G. This study describes the preparation of a specific anti-M6G rabbit polyclonal antibody and its validation. The specificity of this antibody was assessed against 30 morphine-related compounds. Then, a M6G-specific ELISA-assay was tested to quantify M6G in the plasma of healthy donors, morphine-treated, and critically ill patients. The antibody raised against M6G displays a strong affinity for M6G, codeine-6-glucuronide, and morphine-3-6-glucuronide, whereas only weak cross-reactivities were observed for the other compounds. Both M6G-ELISA and LC-MS/MS approaches revealed the absence of M6G in the plasma of healthy donors (controls, n = 8). In all positive donors treated with morphine-patch (n = 5), M6G was detected using both M6G-ELISA and LC-MS/MS analysis. Finally, in a study on critically ill patients with circulating endogenous morphine (n = 26), LC-MS/MS analysis revealed that 73% of the positive-patients (19 of 26), corresponding to high M6G-levels in M6G-ELISA, contained M6G. In conclusion, we show that endogenous M6G can be found at higher levels than morphine in the blood of morphine-naive patients. With respect to the interest of measuring endogenous M6G in pathologies, we provide evidences that our ELISA procedure represents a powerful tool as it can easily and specifically detect endogenous M6G levels. © 2013 International Union of Biochemistry and Molecular Biology.

Investigations performed on the compost worm Eisenia fetida and selected species of earthworms concerning the intake of HCB and pyrene with the goal of deriving a bioaccumulation test; Untersuchungen zur Aufnahme von HCB und Pyren durch den Kompostwurm Eisenia fetida und ausgewaehlte Regenwurmwildarten. Ableitung eines Bioakkumulationstests

Energy Technology Data Exchange (ETDEWEB)

Vespermann, A.; Riepert, F.; Pflugmacher, J. [Biologische Bundesanstalt fuer Land- und Forstwirtschaft, Inst. fuer Oekotoxikologie im Pflanzenschutz, Berlin (Germany)

2003-07-01

The man issues of the studies described were the validation of a test design for the assessment of the bioaccumulation potential of environmental pollutants and the applicability of Eisenia fetida as a model-organism and artificial soil (OECD) as a standard test substrate. The test organisms used were E. fetida of our own breeding stock and Allolobophora caliginosa, Allolobophora chlorotica, Allolobophora longa and Lumbricus rubellus sampled from a field site. Test soils used were the artificial soil (OECD) and a BBA field soil. Soils were each contaminated with 10 mg HCB and Pyrene per soil dry-weight. Within the test period of 4 weeks, samples were taken weekly for residue analysis in the worms and soils. Bioaccumulation factors (AF) calculated for E. fetida and the free-living species were in the range of 10-17 (HCB) and 0.9-1.7 (Pyrene) depending on the soil used. By re-calculation of the concentrations in soil to concentrations in soil water, the resulting bioconcentration factors are compared with published BCF values determined from QSAR's of other worm species and fresh water fish. It could be concluded that the existing earthworm tests (OECD 1984, ISO 1998) represent an appropriate design for testing the bioconcentration potential of chemicals in soil. (orig.) [German] Ziel der beschriebenen Untersuchungen war die praktische Ueberpruefung eines Methodenentwurfs zur Erfassung der Bioakkumulation von Umweltchemikalien mit Eisenia fetida, der Eignung von E. fetida als Modellorganismus und des OECD-Kunstbodens als Standardsubstrat. Als Testorganismen wurden aus eigener Zucht der Kompostwurm Eisenia fetida und nach Feldentnahme Allolobophora caliginosa, Allolobophora chlorotica, Allolobophora longa und Lumbricus rubellus eingesetzt. Testboeden waren der OECD-Kunstboden und ein Boden vom Versuchsfeld der BBA in Berlin-Dahlem. Beiden Boeden wurden die Testsubstanzen Hexachlorbenzol und Pyren in einer Konzentration von 10 mg/kg Bodentrockengewicht zugemischt

Hasse diagram as a green analytical metrics tool: ranking of methods for benzo[a]pyrene determination in sediments.

Science.gov (United States)

Bigus, Paulina; Tsakovski, Stefan; Simeonov, Vasil; Namieśnik, Jacek; Tobiszewski, Marek

2016-05-01

This study presents an application of the Hasse diagram technique (HDT) as the assessment tool to select the most appropriate analytical procedures according to their greenness or the best analytical performance. The dataset consists of analytical procedures for benzo[a]pyrene determination in sediment samples, which were described by 11 variables concerning their greenness and analytical performance. Two analyses with the HDT were performed-the first one with metrological variables and the second one with "green" variables as input data. Both HDT analyses ranked different analytical procedures as the most valuable, suggesting that green analytical chemistry is not in accordance with metrology when benzo[a]pyrene in sediment samples is determined. The HDT can be used as a good decision support tool to choose the proper analytical procedure concerning green analytical chemistry principles and analytical performance merits.

Benzo[a]pyrene-induced immunotoxicity in Japanese medaka (Oryzias latipes): relationship between lymphoid CYP1A activity and humoral immune suppression

International Nuclear Information System (INIS)

Carlson, E.A.; Li, Y.; Zelikoff, J.T.

2004-01-01

Exposure to the environmental contaminant benzo[a]pyrene (BaP) results in suppression of immune function in both mammalian and fish species. This laboratory has previously demonstrated that a single intraperitoneal (IP) injection of BaP reduced lymphocyte proliferation, phagocyte-mediated superoxide generation, and antibody-forming cell (AFC) numbers in Japanese medaka (Oryzias latipes). The objective of the current study was to determine the role of BaP metabolism in the observed immunosuppression. Results from rodent studies have suggested that BaP elicits its immunotoxic effects via upregulation of cytochrome P4501A1 (CYP1A1) and the subsequent production of immunosuppressive BaP metabolites. In this study, exposure of medaka to 200 μg BaP/g BW significantly induced CYP1A expression or activity within lymphoid tissue 48 h post-IP injection; induction was observed specifically within distinct subpopulations of kidney mononuclear cells. Concurrent injection of fish with BaP and the CYP1A1 inhibitors α-naphthoflavone (ANF) or dehydroepiandrosterone (DHEA) resulted in inhibition of renal EROD activity and amelioration of BaP-induced suppression of medaka AFC numbers. Results of this study suggest that (1) BaP-induced suppression of medaka humoral immunity relies upon the CYP1A-catalyzed production of immunotoxic BaP metabolites and (2) BaP metabolites may be created in situ, directly by specific cells within kidney lymphoid tissue. Thus, apparently, mechanisms involved in BaP-induced immunosuppression have been phylogenetically conserved from fish to mammals

Further characterization of benzo[a]pyrene diol-epoxide (BPDE)-induced comet assay effects.

Science.gov (United States)

Bausinger, Julia; Schütz, Petra; Piberger, Ann Liza; Speit, Günter

2016-03-01

The present study aims to further characterize benzo[a]pyrene diol-epoxide (BPDE)-induced comet assay effects. Therefore, we measured DNA effects by the comet assay and adduct levels by high-performance liquid chromatography (HPLC) in human lymphocytes and A549 cells exposed to (±)-anti-benzo[a]pyrene-7,8-diol 9,10-epoxide [(±)-anti-BPDE] or (+)-anti-benzo[a]pyrene-7,8-diol 9,10-epoxide [(+)-anti-BPDE]. Both, the racemic form and (+)-anti-BPDE, which is the most relevant metabolite with regard to mutagenicity and carcinogenicity, induced DNA migration in cultured lymphocytes in the same range of concentrations to a similar extent in the alkaline comet assay after exposure for 2h. Nevertheless, (+)-anti-BPDE induced significantly enhanced DNA migration after 16 and 18h post-cultivation which was not seen in response to (±)-anti-BPDE. Combination of the comet assay with the Fpg (formamidopyrimidine-DNA glycosylase) protein did not enhance BPDE-induced effects and thus indicated the absence of Fpg-sensitive sites (oxidized purines, N7-guanine adducts, AP-sites). The aphidicolin (APC)-modified comet assay suggested significant excision repair activity of cultured lymphocytes during the first 18h of culture after a 2 h-exposure to BPDE. In contrast to these repair-related effects measured by the comet assay, HPLC analysis of stable adducts did not reveal any significant removal of (+)-anti-BPDE-induced adducts from lymphocytes during the first 22h of culture. On the other hand, HPLC measurements indicated that A549 cells repaired about 70% of (+)-anti-BPDE-induced DNA-adducts within 22h of release. However, various experiments with the APC-modified comet assay did not indicate significant repair activity during this period in A549 cells. The conflicting results obtained with the comet assay and the HPLC-based adduct analysis question the real cause for BPDE-induced DNA migration in the comet assay and the reliability of the APC-modified comet assay for the

Dose-dependent stimulation of hepatic retinoic acid hydroxylation/oxidation and glucuronidation in brook trout, Salvelinus fontinalis, after exposure to 3,3{prime}, 4,4{prime}-tetrachlorobiphenyl

Energy Technology Data Exchange (ETDEWEB)

Boyer, P.M.; Ndayibagira, A.; Spear, P.A.

2000-03-01

Extremely low stores of vitamin A have been reported in fish and birds inhabiting regions contaminated by coplanar polychlorinated biphenyls (PCBs) and other organochlorines, suggesting many possible effects on retinoid biochemical pathways. Metabolic imbalances associated with biologically active retinoids (e.g., retinoic acid) could be associated with tetratogenesis, edema, growth inhibition, reproductive impairment, immunosuppression, and susceptibility to cancer. Sexually mature brook trout were injected imtraperitoneally with the coplanar PCB 3,3{prime}, 4,4{prime}-tetrachlorobiphenyl (TCBP) and again 4 weeks later. At 8 weeks, retinoic acid metabolism was measured in liver microsomes. To the authors' knowledge, retinoic acid conjugation by UDP-glucuronyltransferase is described here for the first time in fish. A substantial rate of glucuronidation was detected in the microsomes from control brook trout, which tended to increase over the dose range of TCBP. Glucuronidation was significantly greater in fish receiving the 10 {micro}g/g body weight dose level. Metabolism through the cytochrome P450 system was also dose-dependent, resulting in significantly greater production of 4-hydroxyretinoic acid at the 10 {micro}g/g dose level. In contrast, subsequent oxidation to 4-oxo-retinoic acid was greatest at the 1 {micro}g/g dose level and did not increase further at higher doses. Liver stores of dehydroretinyl palmitate/oleate were significantly decreased at the 5 and 10 {micro}g/g dose levels.

Benzo(a)pyrene activation and detoxification by human pulmonary alveolar macrophages and lymphocytes

International Nuclear Information System (INIS)

Marshall, M.V.; McLemore, T.L.; Martin, R.R.; Marshall, M.H.; Wray, N.P.; Busbee, D.L.; Cantrell, E.T.; Arnott, M.S.; Griffin, A.C.

1980-01-01

Comparisons of pulmonary alveolar macrophages and circulating lymphocytes from five smokers and five nonsmokers for their ability to metabolize benzo(a)pyrene as determined by high pressure liquid chromatography were carried out. Utilizing this approach, further investigation of activation and detoxification by several human cell types could provide the basis for more precise and comprehensive studies of carcinogen and drug metabolism in the human lung, and for a better assessment of cancer risk in selected populations

Determination of Benzo(a)pyrene in Malaysian commercialized coffee powder using solid phase extraction and gas chromatography

International Nuclear Information System (INIS)

Noraini Kasim; Rozita Osman; Norashikin Saim; Licaberth Ismail

2012-01-01

Roasting is a critical process in coffee production as it enables the development of flavor and aroma. Benzo[a]pyrene (BaP) is a non desirable product of incomplete combustion at temperatures between 300 and 600 degree Celsius and may be produced during roasting step. In this study, selected samples of roasted coffee powder were analysed for BaP. Extraction of BaP was achieved using C 18 solid phase extraction (SPE) prior to analysis by gas chromatography. Calibration curve prepared with concentrations ranged between 3 - 50 ppm showed good linearity with r = 0.999. The limit of detection (LOD) was 0.25 ppm and the limit of quantification (LOQ) was 0.85 ppm. Recovery of BaP obtained from spiked sample (3 ppm) was 88.7 % with RSD (n=3) of 5.4 %. Benzo[a]pyrene was detected in all samples, at level ranging from 0.14 to 0.62 ppb. (author)

Can Coronene and/or Benzo(a)pyrene/Coronene ratio act as unique markers for vehicle emission?

International Nuclear Information System (INIS)

Shen, Guofeng; Chen, Yuanchen; Wei, Siye; Fu, Xiaofang; Ding, Aijun; Wu, Haisuo; Tao, Shu

2014-01-01

Coronene is a high molecular weight polycyclic aromatic hydrocarbon with seven aromatic rings. It, more specifically a lower ratio of Benzo[a]pyrene to Coronone (BaP/COR), is suggested as a marker for vehicle emission. In the present study, emissions of Coronene were measured from residential combustions of wood, crop straw, and pellets. The detection of COR in non-vehicle emission sources, and comparable BaP/COR ratios between the solid fuel combustion and vehicle emissions indicated that the generality of COR or the BaP/COR ratio as markers for the vehicle emission would be questionable, especially for the area where solid fuel combustion dominated the PAHs emission. Highlights: • Coronene alone is not a unique marker for vehicle emission. • The specific ratio, BaP/Coronene, could be very high for gasoline emission. • The use of a specific ratio, BaP/Coronene, as a marker is debatable. -- Coronene alone is not a unique tracer for vehicle emission and the use of specific Benzo[a]pyrene to Coronene ratio needs more evaluation studies

Distribution of sorbed phenanthrene and pyrene in different humic fractions of soils and importance of humin

International Nuclear Information System (INIS)

Pan, B.; Xing, B.S.; Liu, W.X.; Tao, S.; Lin, X.M.; Zhang, X.M.; Zhang, Y.X.; Xiao, Y.; Dai, H.C.; Yuan, H.S.

2006-01-01

Contributions of fulvic-humic acids (FA/HA) and humin (HM) to sorption of phenanthrene (PHE) and pyrene (PYR) in a soil were differentiated using a humic separation procedure after multi-concentration sorption experiments. It was found that the amount of solutes in FA/HA did not change significantly after 48 h, while that in HM increased continuously and slowly up to the end of the experimental period (720 h), indicating that HM was the main region for slow sorption. Based on the fitting results using Freundlich equation, it was found that nonlinearity of both solutes was greater in HM than in FA/HA, consistent with the sorption characteristics of individually extracted HA and HM in a separate experiment. The observed nonlinearity of the solute distribution was confirmed by using three other soil samples with organic carbon contents ranging from 0.7 to 7.9%. Distribution dynamics of PHE and PYR among various fractions were also discussed. - Humic fractionation after sorption experiment revealed that humin fraction is the main region for slow and nonlinear sorption of phenanthrene and pyrene

Effects of clofibric acid on the biliary excretion of benoxaprofen glucuronide and taurine conjugate in rats.

Science.gov (United States)

Okada, K; Kanoh, H; Mohri, K

2011-10-01

Benoxaprofen (BOP) is a 2-methyl propionic acid derivative with anti-inflammatory activity. BOP has an asymmetric carbon, and receives chiral inversion from R to S in vivo. BOP is metabolized to glucuronide (BOP-G) and taurine conjugate (BOP-T). The configuration of BOP-G is mainly S, and that of BOP-T is R. Chiral inversion of R to S of the propionic acid moiety and amino acid conjugation of carboxyl compounds proceed via an acyl CoA intermediate. It is known that fibrates, used in hyperlipidemia, induce acyl CoA synthetase and increase CoA concentration. We administered racemic BOP (10 mg/kg body weight) to rats (CFA+) pre-administered clofibric acid (CFA, 280 mg/kg/day), and studied BOP, BOP-G, and BOP-T enantiomer concentrations in plasma and bile up to 12 h after administration. The findings were compared with those in rats (CFA-) that had not received CFA. Furthermore, we studied the amounts of BOP-G enantiomer produced by glucuronidation in vitro using microsomes pretreated with CFA. The amounts of (S)-BOP-G in CFA+ rats were 2.7-fold larger than that in CFA- rats. Although (R)-BOP-T was excreted in CFA- rats, BOP-T could not be detected in CFA+ rats. Plasma clearance values of racemic BOP and (S)-BOP in CFA+ rats were 5-fold and 6-fold larger than those in CFA- rats, respectively. (S)-BOP-G formation activities were higher than (R)-BOP-G formation activities in both CFA+and CFA- microsomes. These findings suggest that CFA increases biliary excretion of (S)-BOP-G and facilitates plasma elimination of BOP, and further suggests that CFA predominantly induces chiral inversion to S rather than metabolic reaction to (R)-BOP-T, resulting in an increase of (S)-BOP-G.

ABSORPTIONS IN THE VISIBLE OF PROTONATED PYRENE COLLISIONALLY COOLED TO 15 K

Energy Technology Data Exchange (ETDEWEB)

Hardy, F.-X.; Gause, O.; Rice, C. A.; Maier, J. P., E-mail: j.p.maier@unibas.ch [Department of Chemistry, University of Basel, Klingelbergstr. 80, 4056-CH Basel (Switzerland)

2013-12-01

Protonated polycyclic hydrocarbons have been added to the list of suggested carriers of diffuse interstellar absorptions. To test this proposition requires laboratory spectra measured under interstellar conditions, in particular with the rotational and vibrational degrees of freedom equilibrated to low temperatures. This has been achieved for protonated pyrene with absorption bands in the visible, using an ion trap and collisional cooling to ≈15 K. A two-photon excitation-dissociation scheme was employed to record the (1) {sup 1} A' ← X {sup 1} A' electronic spectrum on around 10{sup 5} ions per duty cycle. The origin band of the absorption spectrum of this relatively large polycyclic aromatic species with 27 atoms is located at 4858.86 Å. Two further comparably intense spectral features are present at 4834.48 and 4809.32 Å. This is one of the largest protonated aromatics studied in the gas phase and compared to astronomical observations; however, it is not a carrier of known diffuse interstellar bands.

Gene expression of heat shock protein 70, interleukin-1β and tumor necrosis factor α as tools to identify immunotoxic effects on Xenopus laevis: A dose–response study with benzo[a]pyrene and its degradation products

International Nuclear Information System (INIS)

Martini, Federica; Fernández, Carlos; Tarazona, José V.; Pablos, M. Victoria

2012-01-01

The exposure to benzo[a]pyrene (B[a]P) results in an alteration of immune function in mammals and fish, and the analysis of cytokine mRNA levels has been suggested for predicting the immunomodulatory potential of chemicals. To obtain evidence of the innate immune responses to B[a]P in Xenopus laevis, the present study monitored the mRNA expression of interleukin 1-β (IL-1β), tumor necrosis factor α (TNF-α) and heat shock protein 70 (HSP70) in a laboratorial exposure. Tadpoles exposed to 8.36, 14.64, 89.06 and 309.47 μg/L of B[a]P,were used for detecting hsp70, IL-1β and TNF-α mRNA induction. A dose–response increase in the expression of hsp70 and IL-1β mRNA was found. The results of this study confirmed the use of hsp70 and IL-1β, but not TNF-α, as sensitive indicators of immunotoxic effect of B[a]P in X. laevis. Further research would be required for the validation of these endpoints. - Highlights: ► We study innate immune responses to benzo[a]pyrene in Xenopus laevis. ► mRNA expression of three typical proinflammatory proteins was monitored. ► Heat shock protein 70 mRNA induction showed a concentration/response/time relationship. ► Interleukin 1-β also showed a clear concentration/response relationship. ► Interleukin 1-β and heat shock protein 70 are useful indicators of immunotoxic effects. - The present study analyzed the use of cytokine mRNA levels as an earlier tool for predicting immunotoxicological risks to Xenopus laevis in a dose–response pattern.

Branched DNA nanostructures efficiently stabilised and monitored by novel pyrene-perylene 2'-α-l-amino-LNA FRET pairs

DEFF Research Database (Denmark)

Astakhova, I Kira; Santhosh Kumar, T; Campbell, Meghan A

2013-01-01

Novel pyrene-perylene α-l-LNA FRET pairs described herein effectively detect assembly of 2- and 3-way branched DNA nanostructures prepared by postsynthetic microwave-assisted CuAAC click chemistry. The fluorescent signalling of assembly by internally positioned FRET pairs is achieved with low...

Metabolism of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene in cultured human bronchus and pancreatic duct

DEFF Research Database (Denmark)

Harris, Curtis C.; Autrup, Herman; Stoner, Gary

1977-01-01

The metabolism of two carcinogenic polynuclear aro matic hydrocarbons, benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene, was studied in expiants of human pancreatic duct and bronchus cultured in a chemically defined medium. In cultured human bronchial mucosa, activity of aryl hydrocarbon hy...

Photochemical products causing fluorescence enhancement for 6H-benzo[cd]pyren-6-one in de-aerated and pre-irradiated solutions

Energy Technology Data Exchange (ETDEWEB)

Yagishita, M., E-mail: yagishita.mayuko@nies.go.jp [Department of Environmental Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510 (Japan); National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba-City, Ibaraki 305-8506 (Japan); Nakajima, D. [National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba-City, Ibaraki 305-8506 (Japan); Ohshima, S. [Department of Environmental Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510 (Japan)

2016-11-15

Polycyclic aromatic ketones emit very weak fluorescence, but their fluorescence is significantly enhanced by about one hundred times after preliminary irradiation of their degassed solution. To investigate the mechanism of such fluorescence enhancement, liquid chromatography/time-of-flight mass spectrometry measurements were performed for degassed methanol, ethanol, and acetonitrile solutions of 6H-benzo[cd]pyren-6-one (naphthanthrone), in which fluorescence enhancement had been induced. As a result, two kinds of photochemical products were identified as the substance causing fluorescence enhancement: they were produced by dehydrogenation and dehydration of adducts of a solvent molecule to naphthanthrone. On the basis of the findings, the mechanism of the fluorescence enhancement of naphthanthrone was discussed. Fluorescence enhancement; 6H-benzo[cd]pyren-6-one; Polycyclic aromatic ketones; Liquid chromatography-mass spectrometry; Photochemical reaction.

Photochemical products causing fluorescence enhancement for 6H-benzo[cd]pyren-6-one in de-aerated and pre-irradiated solutions

International Nuclear Information System (INIS)

Yagishita, M.; Nakajima, D.; Ohshima, S.

2016-01-01

Polycyclic aromatic ketones emit very weak fluorescence, but their fluorescence is significantly enhanced by about one hundred times after preliminary irradiation of their degassed solution. To investigate the mechanism of such fluorescence enhancement, liquid chromatography/time-of-flight mass spectrometry measurements were performed for degassed methanol, ethanol, and acetonitrile solutions of 6H-benzo[cd]pyren-6-one (naphthanthrone), in which fluorescence enhancement had been induced. As a result, two kinds of photochemical products were identified as the substance causing fluorescence enhancement: they were produced by dehydrogenation and dehydration of adducts of a solvent molecule to naphthanthrone. On the basis of the findings, the mechanism of the fluorescence enhancement of naphthanthrone was discussed. Fluorescence enhancement; 6H-benzo[cd]pyren-6-one; Polycyclic aromatic ketones; Liquid chromatography-mass spectrometry; Photochemical reaction

Induction of micronuclei by X radiation and various chemical agents in red blood cells of Pleurodeles waltl. Uptake, release and excretion of one of them: benzo(a)pyrene

International Nuclear Information System (INIS)

Grinfeld, S.

1983-11-01

The first part of the study is concerned with the effects of X radiation and of various substances dissolved in the breeding water (carbaryl, N-nitrosocarbaryl, benzo(a)pyrene, formol, cafeine, colchicine...) on the formation of micronuclei in red blood cells of Pleurodele larvae. The curves of the dose-effect relationships and of the kinetics of micronuclei formation are established for X radiation and benzo(a)pyrene. In the second part, a scintigraphic study concerning benzo(a)pyrene uptake, release and excretion by larvae, is presented. This study enables the dose-effect curve and the kinetics of micronuclei formation for this substance, to be interpreted. This study must allow the development of a cytogenetic test for the detection of radiomimetic substances in aqueous medium. Pleurodele is proposed as a new animal for the study of genetic toxicology [fr

Introduction of sample tubes with sodium azide as a preservative for ethyl glucuronide in urine.

Science.gov (United States)

Luginbühl, Marc; Weinmann, Wolfgang; Al-Ahmad, Ali

2017-09-01

Ethyl glucuronide (EtG) is a direct alcohol marker, which is widely used for clinical and forensic applications, mainly for abstinence control. However, the instability of EtG in urine against bacterial degradation or the post-collectional synthesis of EtG in contaminated samples may cause false interpretation of EtG results in urine samples. This study evaluates the potential of sodium azide in tubes used for urine collection to hinder degradation of ethyl glucuronide by bacterial metabolism taking place during growth of bacterial colonies. The tubes are part of a commercial oral fluid collection device. The sampling system was tested with different gram-positive and gram-negative bacterial species previously observed in urinary tract infections, such as Escherichia coli, Staphylococcus aureus, Enterecoccus faecalis, Staphylococcus epidermidis, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa. Inhibition of bacterial growth by sodium azide, resulting in lower numbers of colony forming units compared to control samples, was observed for all tested bacterial species. To test the prevention of EtG degradation by the predominant pathogen in urinary tract infection, sterile-filtered urine and deficient medium were spiked with EtG, and inoculated with E. coli prior to incubation for 4 days at 37 °C in tubes with and without sodium azide. Samples were collected every 24 hours, during four consecutive days, whereby the colony forming units (CFU) were counted on Columbia blood agar plates, and EtG was analyzed by LC-MS/MS. As expected, EtG degradation was observed when standard polypropylene tubes were used for the storage of contaminated samples. However, urine specimens collected in sodium azide tubes showed no or very limited bacterial growth and no EtG degradation. As a conclusion, sodium azide is useful to reduce bacterial growth of gram-negative and gram-positive bacteria. It inhibits the degradation of EtG by E. coli and can be used for

Hydrodynamic and Thermophoretic Effects on the Supramolecular Chirality of Pyrene-Derived Nanosheets.

Science.gov (United States)

Micali, Norberto; Vybornyi, Mykhailo; Mineo, Placido; Khorev, Oleg; Häner, Robert; Villari, Valentina

2015-06-22

Chiroptical properties of two-dimensional (2D) supramolecular assemblies (nanosheets) of achiral, charged pyrene trimers (Py3 ) are rendered chiral by asymmetric physical perturbations. Chiral stimuli in a cuvette can originate either from controlled temperature gradients or by very gentle stirring. The chiroptical activity strongly depends on the degree of supramolecular order of the nanosheets, which is easily controlled by the method of preparation. The high degree of structural order ensures strong cooperative effects within the aggregates, rendering them more susceptible to external stimuli. The samples prepared by using slow thermal annealing protocols are both CD and LD active (in stagnant and stirred solutions), whereas for isothermally aged samples chiroptical activity was in all cases undetectable. In the case of temperature gradients, the optical activity of 2D assemblies could be recorded for a stagnant solution due to migration of the aggregates from the hottest to the coldest regions of the system. However, a considerably stronger exciton coupling, coinciding with the J-band of the interacting pyrenes, is developed upon subtle vortexing (0.5 Hz, 30 rpm) of the aqueous solution of the nanosheets. The sign of the exciton coupling is inverted upon switching between clockwise and counter-clockwise rotation. The supramolecular chirality is evidenced by the appearance of CD activity. To exclude artefacts from proper CD spectra, the contribution from LD to the observed CD was determined. The data suggest that the aggregates experience asymmetrical deformation and alignment effects because of the presence of chiral flows. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

BENZO[A]PYRENE AND ITS K-REGION DIOL INDUCE DNA DAMAGE IN C3H10T1/2C18 CELLS AS MEASURED BY THE ALKALINE SINGLE CELL GEL (COMET) ASSAY

Science.gov (United States)

160. Benzo[a]pyrene and its K-region diol induce DNA damage in C3HlOTl/2Cl8 cells as measured by the alkaline single cell gel (Comet) assay In a continuing series of studies on the genotoxicity ofK-region dihydrodiols of polycyclic aromatic hydrocarbons, we have repo...

A Fluorescent Thermometer Based on a Pyrene-Labeled Thermoresponsive Polymer

Directory of Open Access Journals (Sweden)

Ulrich S. Schubert

2010-08-01

Full Text Available Thermoresponsive polymers that undergo a solubility transition by variation of the temperature are important materials for the development of ‘smart’ materials. In this contribution we exploit the solubility phase transition of poly(methoxy diethylene glycol methacrylate, which is accompanied by a transition from hydrophilic to hydrophobic, for the development of a fluorescent thermometer. To translate the polymer phase transition into a fluorescent response, the polymer was functionalized with pyrene resulting in a change of the emission based on the microenvironment. This approach led to a soluble polymeric fluorescent thermometer with a temperature range from 11 °C to 21 °C. The polymer phase transition that occurs during sensing is studied in detail by dynamic light scattering.

Main metabolites of 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea and 1-(2-chloroethyl)-3-(2',3', 4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea in rats

International Nuclear Information System (INIS)

Madelmont, J.C.; Moreau, M.F.; Godeneche, D.; Duprat, J.; Plagne, R.; Meyniel, G.

1982-01-01

The metabolism of two glycosylnitrosoureas, 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea (RFCNU) and 1-(2-chloroethyl)-3-(2',3',4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea (RPCNU), has been investigated in the rat. With the label on the carboxyl moiety of RFCNU, we have shown that hydrolysis of the 4-nitrobenzoyl ester occurred to a large extent in vivo; 4-nitrobenzoic acid and its glucuronide were the major urinary metabolites. Two other minor metabolites and their glucuronides were identified as 4-aminobenzoic acid and 4-acetamidobenzoic acid. With the label on the chloroethyl moieties of RFCNU and RPCNU, we have shown that chloroethanol was a major degradation product of this alkylating part of the molecule. The concentration of chloroethanol in plasma vs. time has been determined. In urine, four metabolites derived from alkylated glutathione, namely thiodiacetic acid and its sulfoxide, N-acetylcarboxymethylcysteine, and N-acetylhydroxyethylcysteine, have been identified

Interdependence of pyrene interactions and tetramolecular G4-DNA assembly.

Science.gov (United States)

Doluca, Osman; Withers, Jamie M; Loo, Trevor S; Edwards, Patrick J B; González, Carlos; Filichev, Vyacheslav V

2015-03-28

Controlling the arrangement of organic chromophores in supramolecular architectures is of primary importance for the development of novel functional molecules. Insertion of a twisted intercalating nucleic acid (TINA) moiety, containing phenylethynylpyren-1-yl derivatives, into a G-rich DNA sequence alters G-quadruplex folding, resulting in supramolecular structures with defined pyrene arrangements. Based on CD, NMR and ESI-mass-spectra, as well as TINA excited dimer (excimer) fluorescence emission we propose that insertion of the TINA monomer in the middle of a dTG4T sequence (i.e. dTGGXGGT, where X is TINA) converts a parallel tetramolecular G-quadruplex into an assembly composed of two identical antiparallel G-quadruplex subunits stacked via TINA-TINA interface. Kinetic analysis showed that TINA-TINA association controls complex formation in the presence of Na(+) but barely competes with guanine-mediated association in K(+) or in the sequence with the longer G-run (dTGGGXGGGT). These results demonstrate new perspectives in the design of molecular entities that can kinetically control G-quadruplex formation and show how tetramolecular G-quadruplexes can be used as a tuneable scaffold to control the arrangement of organic chromophores.

Design of experiments, a powerful tool for method development in forensic toxicology: application to the optimization of urinary morphine 3-glucuronide acid hydrolysis.

Science.gov (United States)

Costa, S; Barroso, M; Castañera, A; Dias, M

2010-04-01

The application of the design of experiments to optimize method development in the field of forensic toxicology using the urinary morphine 3-glucuronide acid hydrolysis as an example is described. Morphine and its trideuterated analogue (used as an internal standard) were extracted from urine samples by liquid-liquid extraction (ToxiTubes A) and derivatized by silylation. Chromatographic analysis was done by gas chromatography-mass spectrometry in the selected ion monitoring mode. Using the peak area ratio (morphine-to-internal standard) as the response, we investigated the independent variables that could influence the acid hydrolysis, including temperature (range 70-130 degrees C), acid volume (range 500-1,000 microL) and time (range 15-90 min). A 2(3) full factorial design for the screening and a response surface methodology, including a central composite design for optimization, were applied. The factors which influenced the response to a greater extent were temperature and its interaction both with time and acid volume. By application of a multiple regression analysis to the experimental data, a second-order polynomial equation was obtained. The optimal predicted conditions for morphine 3-glucuronide acid hydrolysis were 115 degrees C, 38 min and 500 microL for temperature, time and acid volume, respectively. Using design of experiments, instead of the one factor at a time approach, we achieved the optimum combination of all factor values, and this allowed the best results to be obtained, simultaneously optimizing resources. In addition, time and money can be saved, since other approaches are in general more time-consuming and laborious, and do not take into account the interactions between factors.

Validated LC-MS/MS method for the determination of 3-hydroxflavone and its glucuronide in blood and bioequivalent buffers: application to pharmacokinetic, absorption, and metabolism studies.

Science.gov (United States)

Xu, Beibei; Yang, Guanyi; Ge, Shufan; Yin, Taijun; Hu, Ming; Gao, Song

2013-11-01

The purpose of this study is to develop an UPLC-MS/MS method to quantify 3-hydroxyflavone (3-HF) and its metabolite, 3-hydroxyflavone-glucuronide (3-HFG) from biological samples. A Waters BEH C8 column was used with acetonitrile/0.1% formic acid in water as mobile phases. The mass analysis was performed in an API 5500 Qtrap mass spectrometer via multiple reaction monitoring (MRM) with positive scan mood. The one-step protein precipitation by acetonitrile was used to extract the analytes from blood. The results showed that the linear response range was 0.61-2500.00 nM for 3-HF and 0.31-2500.00 nM for 3-HFG. The intra-day variance is less than 16.5% and accuracy is in 77.7-90.6% for 3-HF and variance less than 15.9%, accuracy in 85.1-114.7% for 3-HFG. The inter-day variance is less than 20.2%, accuracy is in 110.6-114.2% for 3-HF and variance less than 15.6%, accuracy in 83.0-89.4% for 3-HFG. The analysis was done within 4.0 min. Only 10 μl of blood is needed due to the high sensitivity of this method. The validated method was successfully used to pharmacokinetic study in A/J mouse, transport study in the Caco-2 cell culture model, and glucuronidation study using mice liver and intestine microsomes. The applications revealed that this method can be used for 3-HF and 3-HFG analysis in blood as well as in bioequivalent buffers such HBSS and KPI. Copyright © 2013 Elsevier B.V. All rights reserved.

Bioavailability of {sup 99m}Tc-paclitaxel-glucuronide ({sup 99m}Tc-PAC-G)

Energy Technology Data Exchange (ETDEWEB)

Biber Muftuler, F.Z.; Demir, I.; Uenack, P.; Ichedef, C.; Yurt Kilcar, A. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

2011-07-01

An antitumor agent paclitaxel (PAC) has been proved to be efficient in the treatment of breast and ovarian cancer. Glucuronic acid-derived paclitaxel compound (paclitaxel-glucuronide (PAC-G)) was enzymatically synthesized using microsome preparate separated from rat livers. The biodistribution mechanism of PAC-G in healthy female Albino Wistar rats has been investigated. The expected structure is confirmed according to LC/MS results, and the possible attachment is to C2-hydroxyl group. PAC-G was labeled with {sup 99m}Tc and the radiochemical yield of radiolabeled compound ({sup 99m}Tc-PAC-G) was 98.0 {+-} 02.74% (n=9). The range of the breast/blood and breast/muscle ratios is approximately between 3 and 35 in 240 min. All these experimental studies indicate that {sup 99m}Tc-PAC-G may potentially be used in breast tissue as an imaging agent. (orig.)

Species-related exposure of phase II metabolite gemfibrozil 1-O-β-glucuronide between human and mice: A net induction of mouse P450 activity was revealed.

Science.gov (United States)

Luo, Min; Dai, Manyun; Lin, Hante; Xie, Minzhu; Lin, Jiao; Liu, Aiming; Yang, Julin

2017-12-01

Gemfibrozil is a fibrate drug used widely for dyslipidemia associated with atherosclerosis. Clinically, both gemfibrozil and its phase II metabolite gemfibrozil 1-O-β-glucuronide (gem-glu) are involved in drug-drug interaction (DDI). But the DDI risk caused by gem-glu between human and mice has not been compared. In this study, six volunteers were recruited and took a therapeutic dose of gemfibrozil for 3 days for examination of the gemfibrozil and gem-glu level in human. Male mice were fed a gemfibrozil diet (0.75%) for 7 days, following which a cocktail-based inhibitory DDI experiment was performed. Plasma samples and liver tissues from mice were collected for determination of gemfibrozil, gem-glu concentration and cytochrome p450 enzyme (P450) induction analysis. In human, the molar ratio of gem-glu/gemfibrozil was 15% and 10% at the trough concentration and the concentration at 1.5 h after the 6th dose. In contrast, this molar ratio at steady state in mice was 91%, demonstrating a 6- to 9-fold difference compared with that in human. Interestingly, a net induction of P450 activity and in vivo inductive DDI potential in mice was revealed. The P450 activity was not inhibited although the gem-glu concentration was high. These data suggested species difference of relative gem-glu exposure between human and mice, as well as a net inductive DDI potential of gemfibrozil in mouse model. Copyright © 2017 John Wiley & Sons, Ltd.

Repair of DNA damage induced by ionizing radiation and benzo[a]pyrene in mammalian cells

International Nuclear Information System (INIS)

Cerutti, P.; Shinohara, K.; Remsen, J.

1977-01-01

The biological effects of DNA-damaging agents are codetermined by the structural characteristics of the lesions, the quality and extent of the local distortion of DNA and chromatin structure, and the mode(s) of damage processing used by a given type of cell. Persistent damage (i.e., damage that is not removed before it is reached by DNA replication) may be mostly responsible for mutagenesis and carcinogenesis. To understand the effects of environmental physical and chemical DNA-damaging agents on human health, the mechanisms of damage processing used by human cells have to be elucidated. We report our studies of the excision of gamma-ray products of the 5,6-dihydroxydihydrothymine type (t 0 /sub 2//sup γ/) in normal human fibroblasts and in fibroblasts from patients with the hereditary diseases Fanconi's anemia (FA) and ataxia telangiectasia (AT). Both diseases are characterized by chromosomal instability and increased susceptibility for the development of cancer. Formation and repair of DNA-benzo[a]pyrene adducts were studied in baby hamster kidney cells, secondary mouse embryo cells, and human lymphoma. The relative persistence of DNA-B[a]P may explain the high mutagenicity of the 7,8-dihydroxy-9,10-epoxy-tetrahydrobenzo[a]pyrene metabolites in rodent cells that has been observed by several investigators

Estimation of AOT and SDS CMC in a methanol using conductometry, viscometry and pyrene fluorescence spectroscopy methods

Science.gov (United States)

Mitsionis, Anastasios I.; Vaimakis, Tiverios C.

2012-09-01

Critical micelle concentration (CMC) of two anionic surfactants in methanol was estimated using conductometry, viscometry and pyrene fluorescence spectroscopy methods. The surfactants used, were sodium bis(2-ethylhexyl) sulfosuccinate (Aerosol-OT, AOT) and sodium dodecyl sulfate (SDS) dispersed in pure methanol. The CMC determination was evaluated in room temperature. The results have shown nearly similar concentrations.

Analysis of Benzo[a]pyrene in Vegetable Oils Using Molecularly Imprinted Solid Phase Extraction (MISPE Coupled with Enzyme-Linked Immunosorbent Assay (ELISA

Directory of Open Access Journals (Sweden)

Michael Pschenitza

2014-05-01

Full Text Available This paper describes the development of a molecularly imprinted polymer-based solid phase extraction (MISPE method coupled with enzyme-linked immunosorbent assay (ELISA for determination of the PAH benzo[a]pyrene (B[a]P in vegetable oils. Different molecularly imprinted polymers (MIPs were prepared using non-covalent 4-vinylpyridine/divinylbenzene co-polymerization at different ratios and dichloromethane as porogen. Imprinting was done with a template mixture of phenanthrene and pyrene yielding a broad-specific polymer for PAHs with a maximum binding capacity (Q of ~32 μg B[a]P per 50 mg of polymer. The vegetable oil/n-hexane mixture (1:1, (v/v was pre-extracted with acetonitrile, the solvent evaporated, the residue reconstituted in n-hexane and subjected to MISPE. The successive washing with n-hexane and isopropanol revealed most suitable to remove lipid matrix constituents. After elution of bound PAHs from MISPE column with dichloromethane, the solvent was evaporated, the residue reconstituted with dimethyl sulfoxide and diluted 100-fold with methanol/water (10:90, (v/v for analysis of B[a]P equivalents with an ELISA. The B[a]P recovery rates in spiked vegetable oil samples of different fatty acid composition were determined between 63% and 114%. The presence of multiple PAHs in the oil sample, because of MIP selectivity and cross-reactivity of the ELISA, could yield overestimated B[a]P values.

Benz(a)pyrene levels in medicinal plants and the possibility of contamination of drugs of plant origin

Energy Technology Data Exchange (ETDEWEB)

Kalinina, I A; Dikun, P P

1983-01-01

Benz(a)pyrene (BP) levels in extracts and solvent cake obtained by alcoholic and aqueous extraction of specimens of 20 different medicinal plants were measured to explore into the possibility of its passage from these plants to drugs. Seventy percent alcoholic extracts were found to contain 40-60% of BP passed from raw material, while aqueous extracts--2-3% (in some cases 10-14%). Maximal concentrations of BP in alcoholic extracts were 0.6-0.7 micrograms/1 and 0.03-0.04 micrograms/1--in aqueous ones. A significant correlation between BP level in extracts and its content in plants was established. BP pathways in the course of solasodine manufacturing from nightshade (Solanum lacinatum) were studied. As little as 1% of BP passed to extract after primary extraction in 2%--sulfuric acid. Solasodine contained about 3 micrograms/kg of BP.

Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

International Nuclear Information System (INIS)

Crowell, Susan Ritger; Amin, Shantu G.; Anderson, Kim A.; Krishnegowda, Gowdahalli; Sharma, Arun K.; Soelberg, Jolen J.; Williams, David E.; Corley, Richard A.

2011-01-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated as byproducts of natural and anthropogenic combustion processes. Despite significant public health concern, physiologically based pharmacokinetic (PBPK) modeling efforts for PAHs have so far been limited to naphthalene, plus simpler PK models for pyrene, nitropyrene, and benzo[a]pyrene (B[a]P). The dearth of published models is due in part to the high lipophilicity, low volatility, and myriad metabolic pathways for PAHs, all of which present analytical and experimental challenges. Our research efforts have focused upon experimental approaches and initial development of PBPK models for the prototypic PAH, B[a]P, and the more potent, albeit less studied transplacental carcinogen, dibenzo[def,p]chrysene (DBC). For both compounds, model compartments included arterial and venous blood, flow limited lung, liver, richly perfused and poorly perfused tissues, diffusion limited fat, and a two compartment theoretical gut (for oral exposures). Hepatic and pulmonary metabolism was described for both compounds, as were fractional binding in blood and fecal clearance. Partition coefficients for parent PAH along with their diol and tetraol metabolites were estimated using published algorithms and verified experimentally for the hydroxylated metabolites. The preliminary PBPK models were able to describe many, but not all, of the available data sets, comprising multiple routes of exposure (oral, intravenous) and nominal doses spanning several orders of magnitude. Supported by Award Number P42 ES016465 from the National Institute of Environmental Health Sciences. -- Highlights: ► We present PBPK models for benzo[a]pyrene (B[a]P) and dibenzo[def,p]chrysene (DBC). ► B[a]P model accurately predicts data from multiple sources over a wide dose range. ► DBC model was based on the B[a]P model as less chemical specific data is available. ► DBC model accurately predicted preliminary

Urinary pregnandiol-3-glucuronide and estrone conjugates to creatinine ratios in early pregnancies complicated by vaginal bleeding.

Science.gov (United States)

Davidson, B J

1986-10-01

There is no simple and rapid test available to predict the outcome of an early pregnancy complicated by vaginal bleeding. In this prospective study, 15 women with normal pregnancies collected a weekly urine sample between 6 and 13 weeks' gestation. A single random urine sample was obtained from 15 women with bleeding who continued to carry their child and 50 women who proceeded to have a spontaneous abortion (SAB). Pregnandiol-3-glucuronide (PDG) was determined with the use of enzyme-multiplied immunoassay technique (EMIT) and estrone conjugates (E1C) were measured by radioimmunoassay (RIA). The ratios of these metabolites to creatinine (C) were calculated. PDG/C ratios in normal women rose gradually from 6 weeks on. All women with bleeding during a normal pregnancy had ratios in the normal range, but 94% of women with a SAB had ratios below the normal range. The E1C/C ratio remained unchanged from 6 to 11 weeks and then rose rapidly. Until 11 weeks, there was no clear separation between the E1C/C ratios of the women with a SAB and the women with bleeding who continued their pregnancies. The prognosis of threatened abortion can be made by a urinary PDG/C ratio but not by an E1C/C ratio. EMIT is simple and quick and uses technology present in many laboratories.

Reaction of a chemotherapeutic agent, 6-mercaptopurine, with a direct-acting, electrophilic carcinogen, benzo[a]pyrene-7,8-diol 9,10-epoxide.

Science.gov (United States)

MacLeod, M C; Stewart, E; Daylong, A; Lew, L K; Evans, F E

1991-01-01

The chemotherapeutic agent 6-mercaptopurine (6-MP) has been shown to react covalently with the ultimate carcinogenic metabolite of benzo[a]pyrene, 7-r,8-t-dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), in aqueous solution, forming a single adduct. NMR studies of the HPLC-purified product were consistent with its identification as 10(S)-(6'-mercaptopurinyl)-7,8,9-trihydroxy-7,8,9,10- tetrahydrobenzo[a]pyrene. Reaction kinetics were analyzed by using both HPLC separation of the products formed and a spectrophotometric assay for adduct formation. A simple model in which direct reaction between 6-MP and BPDE takes place without formation of a physical complex was found to adequately predict the dependence of product ratios on 6-MP concentration. Variations in the observed rate constant for this reaction with changes in temperature, pH, and buffer concentration were determined and compared to the effects of these variables on the observed rate constant for BPDE hydrolysis. In each case, the processes were affected quite differently, suggesting that different rate-determining steps are involved. The data suggest that the reaction mechanism involves SN2 attack of the anion of 6-MP, formed by ionization of the sulfhydryl group, on carbon 10 of BPDE, resulting in a trans-9,10 reaction product.

In vitro investigations of α-amylase mediated hydrolysis of cyclodextrins in the presence of ibuprofen, flurbiprofen, or benzo[a]pyrene

DEFF Research Database (Denmark)

Riisager, Ludmilla Lumholdt; Holm, R.; Jørgensen, E. B.

2012-01-01

-γ-cyclodextrins have different biopharmaceutical behaviours than the other evaluated cyclodextrins. The rate of degradation was affected by the addition of the inclusion complex forming additives flurbiprofen, ibuprofen and benzo[a]pyrene. This effect between the degradation dynamics and the included additives...

Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia.

Science.gov (United States)

Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H

2015-11-15

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel (Phenylethynyl)pyrene-LNA Constructs for Fluorescence SNP Sensing in Polymorphic Nucleic Acid Targets

DEFF Research Database (Denmark)

Astakhova, Irina Kira; Samokhina, Evgeniya; Babu, B Ravindra

2012-01-01

We describe fluorescent oligonucleotide probes labeled with novel (phenylethynyl)pyrene dyes attached to locked nucleic acids. Furthermore, we prove the utility of these probes for the effective detection of single-nucleotide polymorphisms in natural nucleic acids. High-affinity hybridization......DNA and RNA gene fragments. Target sequences were obtained by analysis of 200 clinical samples from patients currently receiving anti-HIV/AIDS combination therapy at the Russian Federal AIDS Center. Using these fluorescent oligonucleotides, we were able to detect the target mutation despite all the challenges...

Pyrene conjugation and spectroscopic analysis of hydroxypropyl methylcellulose compounds successfully demonstrated a local dielectric difference associated with in vivo anti-prion activity.

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Kenta Teruya

Full Text Available Our previous study on prion-infected rodents revealed that hydroxypropyl methylcellulose compounds (HPMCs with different molecular weights but similar composition and degree of substitution have different levels of long-lasting anti-prion activity. In this study, we searched these HPMCs for a parameter specifically associated with in vivo anti-prion activity by analyzing in vitro chemical properties and in vivo tissue distributions. Infrared spectroscopic and thermal analyses revealed no differences among HPMCs, whereas pyrene conjugation and spectroscopic analysis revealed that the fluorescence intensity ratio of peak III/peak I correlated with anti-prion activity. This correlation was more clearly demonstrated in the anti-prion activity of the 1-year pre-infection treatment than that of the immediate post-infection treatment. In addition, the intensity ratio of peak III/peak I negatively correlated with the macrophage uptake level of HPMCs in our previous study. However, the in vivo distribution pattern was apparently not associated with anti-prion activity and was different in the representative tissues. These findings suggest that pyrene conjugation and spectroscopic analysis are powerful methods to successfully demonstrate local dielectric differences in HPMCs and provide a feasible parameter denoting the long-lasting anti-prion activity of HPMCs in vivo.

Pyrene-Containing ortho-Oligo(phenylene)ethynylene Foldamer as a Ratiometric Probe Based on Circularly Polarized Luminescence.

Science.gov (United States)

Reiné, Pablo; Justicia, Jose; Morcillo, Sara P; Abbate, Sergio; Vaz, Belen; Ribagorda, María; Orte, Ángel; Álvarez de Cienfuegos, Luis; Longhi, Giovanna; Campaña, Araceli G; Miguel, Delia; Cuerva, Juan M

2018-04-20

In this manuscript, we report the first synthesis of an organic monomolecular emitter, which behaves as a circularly polarized luminescence (CPL)-based ratiometric probe. The enantiopure helical ortho-oligo(phenylene)ethynylene ( o-OPE) core has been prepared by a new and efficient macrocyclization reaction. The combination of such o-OPE helical skeleton and a pyrene couple leads to two different CPL emission features in a single structure whose ratio linearly responds to silver(I) concentration.

The preparation of highly water-soluble multi-walled carbon nanotubes by irreversible noncovalent functionalization with a pyrene-carrying polymer

International Nuclear Information System (INIS)

Xue Chaohua; Zhou Renjia; Shi Minmin; Gao Yan; Wu Gang; Chen Hongzheng; Wang Mang; Zhang Xiaobin

2008-01-01

Multi-walled carbon nanotubes (MWNTs) have been solubilized in water via a noncovalent method of exfoliation and centrifugation cycles with the assistance of hydrolyzed poly(styrene-co-maleic anhydride) carrying pyrene (HPSMAP). After the obtained solution was micro-filtered and dried, a water-soluble complex of HPSMAP-MWNTs was obtained. The solubility of HPSMAP-MWNTs was measured to be 46.2 mg ml -1 with a net MWNT concentration of 7.4 mg ml -1 in water. Thermal gravimetric analyses showed that there was a large amount of polymer remaining on the surface of MWNTs irreversibly after thoroughly removing the free polymer. Other characterizations using transmission electron microscopy, Fourier transform infrared (FTIR) spectroscopy, fluorescence spectra, and fluorescence decay were conducted

Nasal metabolism of benzo[a]pyrene and dihydrosafrole in Beagle dogs and nonhuman primates

International Nuclear Information System (INIS)

Fischer, J.P.; Whaley, S.L.; Dahl, A.R.

1986-01-01

The purpose of this study was to determine the extent of nasal metabolism of 3 H-dihydrosafrole and 14 C-benzo[a]pyrene ( 14 C-BaP) by Beagle dogs and cynomolgus monkeys in two regions of the nasal cavity, the ethmoid (olfactory), and maxillary (respiratory) turbinates. Clearance of these two compounds from the nose was studied by collection of nasopharyngeal mucus, blood, urine, and feces during nasal instillation and up to 48 h afterwards. Analysis of the nasopharyngeal mucus showed that either turbinate region in both species metabolized 14 C-Bap to dihydrodiols, quinones, phenols, and tetrols. 3 H-Dihydrosafrole instilled in either turbinate region was extensively metabolized to 2-methyoxy-4-propylphenol. Other major metabolites were 2-methoxy-4-[2-propenyl]-phenol, and 3,4-methylenedioxy-1-(1-hydroxypropyl)benzene. The present study demonstrated a relatively noninvasive technique for studying regional nasal metabolic capabilities in xenobiotic in vivo. The results show that nasal cavities of dogs and monkeys are capable of metabolizing BaP into biologically significant compounds after instillation at both ethmoid and maxillary turbinates. 6 references, 4 tables

Compartmental analysis of benzo[a]pyrene toxicokinetics

International Nuclear Information System (INIS)

Bevan, D.R.; Weyand, E.H.

1986-01-01

A multicompartmental model to describe quantitatively the toxicokinetics of benzo[a]pyrene (B[a]P) was developed using SAAM (Simulation, Analysis and Modeling). [ 3 H]-B[a]P dissolved in triethylene glycol was administered intratracheally to male Sprague-Dawley rats, and amounts of [ 3 H] were quantified in various tissues at selected times up to 6 hr after administration. Elimination of [ 3 H]-B[a]P and/or metabolites from lungs was biphasic, with half-times of 5.3 min. and 116 min. [ 3 H]-B[a]P and/or metabolites were subsequently distributed primarily to liver and carcass (muscle, bones, fat, skin and associated blood). Carcass contained about 20% of administered [ 3 H] at 6 hr after administration, and agreement between the model and experimental data required that the carcass be modeled as two compartments, one with rapid and one with slow exchange. Approximately 50% of the administered dose was excreted in feces in 6 hr and only 2% appeared in urine. Enterohepatic circulation was accounted for in the model. The model was then used to predict amounts of [ 3 H]-B[a]P and/or metabolites which would be excreted into bile in animals with bile duct cannulas, and good agreement between the model and data was observed

Determination of lead, zinc and benzo(a)pyrene in incineration flue gas

International Nuclear Information System (INIS)

Han Baohua; Gao Zhuqin; Guo Qian

2003-01-01

An analitical method was developed for the determination of lead(Pb), zinc(Zn) and benzo(a)pyrene (BaP) in flue gas of radwaste pyroysis incinerator, respectively using Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) and High Performance Liquid Chromatography (HPLC). The sample preparation and the influence of major components in back-ground were researched. Interference correction coefficient for Pb and Zn are given in this article. The recovery of Pb, Zn and BaP are all above 84.0% and the relative standard deviation (RSD) were 3.51% for Pb, 7.28% for Zn and 4.50% for BaP, respectively. It shows that this analytical method can meet the incineration processes. (authors)

Benzo[a]pyrene, Aflatoxine B1 and Acetaldehyde Mutational Patterns in TP53 Gene Using a Functional Assay: Relevance to Human Cancer Aetiology

Science.gov (United States)

Paget, Vincent; Lechevrel, Mathilde; André, Véronique; Le Goff, Jérémie; Pottier, Didier; Billet, Sylvain; Garçon, Guillaume; Shirali, Pirouz; Sichel, François

2012-01-01

Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B1 exposure. Likewise G>T transversions in codons 157 and 158 have been related to tobacco exposure in human lung cancers. However, controversies remain about the interpretation of TP53 mutational pattern in tumours as the fingerprint of genotoxin exposure. By using a functional assay, the Functional Analysis of Separated Alleles in Yeast (FASAY), the present study depicts the mutational pattern of TP53 in normal human fibroblasts after in vitro exposure to well-known carcinogens: benzo[a]pyrene, aflatoxin B1 and acetaldehyde. These in vitro patterns of mutations were then compared to those found in human tumours by using the IARC database of TP53 mutations. The results show that the TP53 mutational patterns found in human tumours can be only partly ascribed to genotoxin exposure. A complex interplay between the functional impact of the mutations on p53 phenotype and the cancer natural history may affect these patterns. However, our results strongly support that genotoxins exposure plays a major role in the aetiology of the considered cancers. PMID:22319594

Evaluation of sewage sludge and slow pyrolyzed sewage sludge-derived biochar for adsorption of phenanthrene and pyrene.

Science.gov (United States)

Zielińska, Anna; Oleszczuk, Patryk

2015-09-01

The present study investigated the sorption of phenanthrene (PHE) and pyrene (PYR) by sewage sludges and sewage sludge-derived biochars. The organic carbon normalized distribution coefficient (log K(OC) for C(w) = 0.01 S(w)) for the sewage sludges ranged from 5.62 L kg(-1) to 5.64 L kg(-1) for PHE and from 5.72 L kg(-1) to 5.75 L kg(-1) for PYR. The conversion of sewage sludges into biochar significantly increased their sorption capacity. The value of log K(OC) for the biochars ranged from 5.54 L kg(-1) to 6.23 L kg(-1) for PHE and from 5.95 L kg(-1) to 6.52 L kg(-1) for PYR depending on temperature of pyrolysis. The dominant process was monolayer adsorption in the micropores and/or multilayer surface adsorption (in the mesopores), which was indicated by the significant correlations between log K(OC) and surface properties of biochars. PYR was sorbed better on the tested materials than PHE. Copyright © 2015 Elsevier Ltd. All rights reserved.

A rat organo-typic model for identifying and characterizing Ρ53 mutations induced by benzo(a)pyrene treatment

International Nuclear Information System (INIS)

Le Rhun, Y.; Duthu, A.; May, E.; Paris, F.; Martin, M.

1997-01-01

A p53 wild-type cell line was established from embryo rat lung treated by the benzo(a)pyrene. Two different p53 mutant cell lines were derived from this parental cell line and showed different characteristics including tumor induction, radiosensitivity and chemo-sensitivity. This system is a useful tools for analysing the effect of various p53 mutants in neoplastic development. (authors)

Determination of benzo[a]pyrene in edible oils using phase-transfer-catalyst-assisted saponification and supramolecular solvent microextraction coupled to HPLC with fluorescence detection.

Science.gov (United States)

Wang, Jin; Liu, Laping; Shi, Ludi; Yi, Tingquan; Wen, Yuxia; Wang, Juanli; Liu, Shuhui

2017-01-01

For the analysis of edible oils, saponification is well known as a useful method for eliminating oil matrices. The conventional approach is conducted with alcoholic alkali; it consumes a large volume of organic solvents and impedes the retrieval of analytes by microextraction. In this study, a low-organic-solvent-consuming method has been developed for the analysis of benzo[a]pyrene in edible oils by high-performance liquid chromatography with fluorescence detection. Sample treatment involves aqueous alkaline saponification, assisted by a phase-transfer catalyst, and selective in situ extraction of the analyte with a supramolecular solvent. Comparison of the chromatograms of the oil extracts obtained by different microextraction methods showed that the supramolecular solvent has a better clean-up effect for the unsaponifiable matter from oil matrices. The method offered excellent linearity over a range of 0.03- 5.0 ng mL -1 (r > 0.999). Recovery rates varied from 94 to 102% (RSDs <5.0%). The detection limit and quantification limit were 0.06 and 0.19 μg kg -1 , respectively. The proposed method was applied for the analysis of 52 edible oils collected online in China; the analyte contents of 23 tested oil samples exceeded the maximum limit of 2 μg kg -1 for benzo[a]pyrene set by the Commission Regulation of the European Union. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ancient plant remains with special reference to buckthorn, Frangula alnus Mill., pyrenes from Dascyleum, Balıkesir, NW Turkey

Directory of Open Access Journals (Sweden)

Emel Oybak Dönmez

2016-12-01

Full Text Available Carbonized plant remains recovered from the ancient city Dascyleum (Daskyleion in the province of Balıkesir in northwestern Turkey provide an outline of several phases of plant use in archaic, Hellenistic, and medieval times. At the study site, various crop plant remains of Near Eastern agriculture, including cereals (barley, Hordeum vulgare L. and bread/durum/rivet wheat, Triticum aestivum L. / T. durum Desf. / T. turgidum L. and pulses [bitter vetch, Vicia ervilia (L. Willd.; grass pea, Lathyrus sativus L. / L. cicera L.; fava bean, V. faba L.; and chickpea, Cicer arietinum L.] were found. Drupaceous fruits and pyrenes of buckthorn (Frangula alnus Mill. were also found, probably representing dyes and/or medicines used by the inhabitants of the mound. Archaeometrical analyses of the ancient buckthorn pyrenes by high performance liquid chromatography with photodiode array detector (HPLC-PDA provide chemical evidence for traces of ancient mordants remaining until the present day. Some of the pulse seed remains retrieved from the medieval layers at the study site were found to have been infested by bruchid beetles (Bruchidae.

Estimating the Biodegradation Kinetics by Mixed Culture Degrading Pyrene (Pyr

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B. S. U. Ibn Abubakar

2017-02-01

Full Text Available Biodegradation and kinetics of Pyrene (Pyr degradation by a mixed culture previously isolated from hydrocarbon-polluted soil were conducted. Preliminary investigation on environmental factors affecting the degradation of Pyr such as temperature, pH and concentrations of Pyr was performed. These factors were optimised and established in aqueous experiments. In order to develop kinetics of Pyr degradation, an optimum temperature of 30oC and pH of 7.0 was used. Biodegradation kinetics was carried out, at first, using higher concentration between (100-700 ppm as sole source of carbon in mineral salt medium (MSM supplemented with 0.1% yeast extract. The result indicated that a range of concentration between (100-700 ppm inhibits the performance of the mixed culture. A concentration range between (10-100 ppm did not inhibit the growth of the mixed culture. A First-order rate constant, k was higher (0.0487 mg/lh with a substrate concentration of 20 ppm than other concentrations. The average degradation rate constant is 0.0029 mg/Lh for all the concentrations tested. This indicated that the mixed culture could degrade over 0.0696 ppm of Pyr per day. It also confirmed that kinetics of microbial degradation was partially fitted into Monod model. The data can be used to estimate biodegradation of Pyr by a mixed culture and preliminarily estimation of degradation rates.

Association to HeLa cells and surface behavior of exogenous gangliosides studied with a fluorescent derivative of GM1

International Nuclear Information System (INIS)

Masserini, M.; Giuliani, A.; Palestini, P.; Acquotti, D.; Pitto, M.; Chigorno, V.; Tettamanti, G.

1990-01-01

Cultured HeLa cells were incubated with pyrene-GM1/ 3 H-radiolabeled GM1 ganglioside (1:4 M/M) mixtures for various times. The process of association of pyrene-GM1 with cells was qualitatively and quantitatively the same as that of 3 H-GM1. The pyrene-GM1 and 3 H-GM1 proportions in the various forms of association with cells were similar to that of the starting ganglioside mixture. After 2-h incubation, the association of ganglioside with cells was well established whereas almost no metabolic processing had occurred. During a 24-h incubation, pyrene- and 3 H-GM1 underwent similar metabolic processing and gave rise to catabolic (GM2 and GM3) and anabolic (GDla) derivatives. Fluorescence spectroscopy experiments carried out with the excimer formation technique on subcellular fractions containing plasma membranes showed that exogenous ganglioside was, in part, associated with the cells in a micellar form removable by trypsin treatment, and in part inserted in a seemingly molecular dispersion. Addition of Ca 2+ salts caused aggregation of the ganglioside, as indicated by the increase of the excimer:monomer fluorescence ratio. The phenomenon was Ca 2+ concentration dependent (maximum at 10 mM), and subsequent addition of EDTA has no effect. The saccharide portion of exogenously incorporated pyrene-GM1 was available to interact with external ligands, as shown by its ability to bind cholera toxin whose addition reduced the collision rate among the ganglioside lipid moieties

Metabolism of benzo(a)pyrene, N-nitrosomethylamine, and N-nitrosopyrrolidine and identification of the major carcinogen-DNA adducts formed in cultured human esophagus

DEFF Research Database (Denmark)

Harris, Curtis C.; Autrup, Herman; Stoner, Gary D.

1979-01-01

The wide variation in the world-wide incidence of esophageal carcinoma suggests that environmental agents including chemicals cause this cancer. Since the interaction between chemical procarcinogens and human esophagus has not been studied previously, we examined the metabolic fate of benzo......(a)pyrene (BP), N-nitrosodimethylamine (DMN), and A/-nitrosopyrrolidine in cultured nontumorous esophagus from two patients with and six patients without esophageal carcinoma. Esophageal explants were cultured in a chemically defined medium for 7 days prior to adding [3H]BP (1.5 JUM),[14C]DMN (100 /IM), or [14C...

Cytochrome b5 and epoxide hydrolase contribute to benzo[a]pyrene-DNA adduct formation catalyzed by cytochrome P450 1A1 under low NADPH:P450 oxidoreductase conditions

International Nuclear Information System (INIS)

Stiborová, Marie; Moserová, Michaela; Černá, Věra; Indra, Radek; Dračínský, Martin; Šulc, Miroslav; Henderson, Colin J.; Wolf, C. Roland; Schmeiser, Heinz H.; Phillips, David H.; Frei, Eva; Arlt, Volker M.

2014-01-01

In previous studies we had administered benzo[a]pyrene (BaP) to genetically engineered mice (HRN) which do not express NADPH:cytochrome P450 oxidoreductase (POR) in hepatocytes and observed higher DNA adduct levels in livers of these mice than in wild-type mice. To elucidate the reason for this unexpected finding we have used two different settings for in vitro incubations; hepatic microsomes from control and BaP-pretreated HRN mice and reconstituted systems with cytochrome P450 1A1 (CYP1A1), POR, cytochrome b 5 , and epoxide hydrolase (mEH) in different ratios. In microsomes from BaP-pretreated mice, in which Cyp1a1 was induced, higher levels of BaP metabolites were formed, mainly of BaP-7,8-dihydrodiol. At a low POR:CYP1A1 ratio of 0.05:1 in the reconstituted system, the amounts of BaP diones and BaP-9-ol formed were essentially the same as at an equimolar ratio, but formation of BaP-3-ol was ∼1.6-fold higher. Only after addition of mEH were BaP dihydrodiols found. Two BaP-DNA adducts were formed in the presence of mEH, but only one when CYP1A1 and POR were present alone. At a ratio of POR:CYP1A1 of 0.05:1, addition of cytochrome b 5 increased CYP1A1-mediated BaP oxidation to most of its metabolites indicating that cytochrome b 5 participates in the electron transfer from NADPH to CYP1A1 required for enzyme activity of this CYP. BaP-9-ol was formed even by CYP1A1 reconstituted with cytochrome b 5 without POR. Our results suggest that in livers of HRN mice Cyp1a1, cytochrome b 5 and mEH can effectively activate BaP to DNA binding species, even in the presence of very low amounts of POR

Laboratory determination of the infrared band strengths of pyrene frozen in water ice: Implications for the composition of interstellar ices

Energy Technology Data Exchange (ETDEWEB)

Hardegree-Ullman, E. E. [New York Center for Astrobiology and Department of Physics, Applied Physics, and Astronomy, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180 (United States); Gudipati, M. S.; Werner, M. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Boogert, A. C. A. [Infrared Processing and Analysis Center, Mail Code 100-22, California Institute of Technology, Pasadena, CA 91125 (United States); Lignell, H. [Department of Chemistry, University of California Irvine, Irvine, CA 92697-2025 (United States); Allamandola, L. J. [Space Science Division, Mail Stop 245-6, NASA Ames Research Center, Moffett Field, CA 94035 (United States); Stapelfeldt, K. R., E-mail: hardee@rpi.edu, E-mail: gudipati@jpl.nasa.gov [NASA Goddard Space Flight Center, Exoplanets and Stellar Astrophysics Laboratory, Code 667, Greenbelt, MD 20771 (United States)

2014-04-01

Broad infrared emission features (e.g., at 3.3, 6.2, 7.7, 8.6, and 11.3 μm) from the gas phase interstellar medium have long been attributed to polycyclic aromatic hydrocarbons (PAHs). A significant portion (10%-20%) of the Milky Way's carbon reservoir is locked in PAH molecules, which makes their characterization integral to our understanding of astrochemistry. In molecular clouds and the dense envelopes and disks of young stellar objects (YSOs), PAHs are expected to be frozen in the icy mantles of dust grains where they should reveal themselves through infrared absorption. To facilitate the search for frozen interstellar PAHs, laboratory experiments were conducted to determine the positions and strengths of the bands of pyrene mixed with H{sub 2}O and D{sub 2}O ices. The D{sub 2}O mixtures are used to measure pyrene bands that are masked by the strong bands of H{sub 2}O, leading to the first laboratory determination of the band strength for the CH stretching mode of pyrene in water ice near 3.25 μm. Our infrared band strengths were normalized to experimentally determined ultraviolet band strengths, and we find that they are generally ∼50% larger than those reported by Bouwman et al. based on theoretical strengths. These improved band strengths were used to reexamine YSO spectra published by Boogert et al. to estimate the contribution of frozen PAHs to absorption in the 5-8 μm spectral region, taking into account the strength of the 3.25 μm CH stretching mode. It is found that frozen neutral PAHs contain 5%-9% of the cosmic carbon budget and account for 2%-9% of the unidentified absorption in the 5-8 μm region.

Urinary steroid hormone analysis of ovarian cycles and pregnancy in mandrills (Mandrillus sphinx) indicate that menses, copulatory behavior, sexual swellings and reproductive condition are associated with changing estrone conjugates (E(1)C) and pregnanediol-3-glucuronide (PdG).

Science.gov (United States)

Phillips, Rebecca Sellin; Wheaton, Catharine J

2008-07-01

The objective of this study was to determine if sexual swellings in mandrills (Mandrillus sphinx) are a reflection of reproductive endocrine state. Urine samples were assayed using an enzyme immunoassay measuring pregnanediol-3-glucuronide (PdG) and estrone conjugates (E(1)C). Hormone patterns of ovarian cycles, pregnancy and lactation were characterized and compared with sexual swellings and copulations relative to menses and peak E(1)C. Cycle lengths averaging 28.7 days and pregnancy length of 181 days determined by hormonal and sexual swelling measures were similar to those reported in other Old World primate species. First day of copulation was observed during rising E(1)C concentrations and preceded observations of peak swelling by 1-2 days. Observations of peak sexual swellings occurred at or on the day after peak E(1)C and decreased following the ovulatory increase in PdG. Observations of menses and sexual swellings are a useful method to track mandrill ovarian cycles and can assist zoos in determining the reproductive state of females in their collections. Zoo Biol 27:320-330, 2008. (c) 2008 Wiley-Liss, Inc.

Effects of benzo[a]pyrene on growth, the antioxidant system, and DNA damage in earthworms (Eisenia fetida) in 2 different soil types under laboratory conditions.

Science.gov (United States)

Duan, Xiaochen; Xu, Li; Song, Jing; Jiao, Jiaguo; Liu, Manqiang; Hu, Feng; Li, Huixin

2015-02-01

The aims of the present study were to compare the toxic effects of benzo[a]pyrene (BaP) and to screen for rapid and sensitive biomarkers that can be used to assess the environmental risks of BaP in earthworms in different natural soil types. The authors exposed Eisenia fetida to 2 types of soil (red soil and fluvo-aquic soil) spiked with different concentrations (0 mg kg(-1), 1 mg kg(-1), 10 mg kg(-1), 100 mg kg(-1), and 500 mg kg(-1)) of BaP for 7 d or 14 d. Benzo[a]pyrene-induced weight variation altered the activities of antioxidant enzymes (superoxide dismutase [SOD]; catalase [CAT]; and guaiacol peroxidase [POD]) and changed the content of malondialdehyde (MDA). In addition, using the comet assay, the authors determined the DNA damage in earthworms. The results revealed that the comet assay was suitable for evaluating the genotoxicity of BaP in the soil, even at the lowest examined concentration. The MDA content was the least sensitive indicator of BaP toxicity. A 3-way analysis of variance (ANOVA) was used to determine whether the soil type, exposure concentration, and duration affected the BaP toxicity. The antioxidant enzyme activities and the MDA content were shown to be significantly correlated with the exposure concentration. The percentage of weight variation (p earthworms is a simple and efficient means of assessing BaP genotoxicity in a terrestrial environment, and the effects of the soil type and exposure time on the other parameters that were investigated in E. fetida, which were used as responsive biomarkers, should be considered. © 2014 SETAC.

Monitoring of radiolytic degradation of benzo(a)pyrene using γ-rays in aqueous media by HPLC

International Nuclear Information System (INIS)

Butt, S. Bilal; Qureshi, Rashid N.; Ahmed, Shafaat

2005-01-01

Poly nuclear aromatic hydrocarbons (PAHs) are generated in the environment by various industrial processes and anthropogenic activities. These compounds are quite stable and persist in the environment due to the aromatic bonding within the rings. Benzo(a)pyrene (B(a)P) is a potential carcinogenic and conditions for its degradation have been optimized by investigating γ-ray dose intensity, its concentration effect and the influence of surfactant presence. HPLC has been used to monitor the degree of degradation of B(a)P under the optimum conditions

Spectroscopic and TD-DFT studies on the dual mode fluorescent chemosensors based on pyrene thiosemicarbazones, and its application as molecular-scale logic devices

Energy Technology Data Exchange (ETDEWEB)

Basheer, Sabeel M. [Department of Chemistry, National Institute of Technology, Tiruchirappalli 620 015 (India); Willis, Anthony C. [Research School of Chemistry, The Australian National University, Canberra, ACT 2601 (Australia); Sreekanth, Anandaram, E-mail: sreekanth@nitt.edu [Department of Chemistry, National Institute of Technology, Tiruchirappalli 620 015 (India)

2017-03-15

Two newly synthesised pyrene based molecules are hereby reported as molecular switches. The absorption and emission response for receptors with and without F{sup −}, CN{sup −} and Cu{sup 2+} ions can mimic multiple logic gate such as AND, NOR, XNOR, OR, XOR, INHIBITION and TRANSFER gates. The fluorescence reversibility was checked with the alternative addition of fluoride and calcium ions, which can be explained by the “Read-Erase-Read-Write” logic loop. The calculated binding constant value show PyBTSC is better chemosensor than PyCTSC, and the binding affinity is in the order of Cu{sup 2+}Г‹Ж’F{sup -}Г‹Ж’CN{sup −.} The detailed mechanism was investigated using DFT and TD-DFT calculations. The fluorescence quenching behaviour of receptor-F complex can be explained by PET mechanism along with ESPT process. The proton attached to the nitrogen which is adjacent to pyrene moiety is first make the hydrogen bond with fluoride ion at the excited state, which has confirmed by natural bond orbital (NBO) and potential energy surface (PES) analysis. - Graphical abstract: The newly synthesised thiocarbazone derivates used as an effective and selective colourimetric and “turn on” fluorescence sensor for copper ion and ‘turn off’ for fluoride and cyanide anion. The presence and absence of ions were considered as input signals and the corresponding absorption and emission responses were consired as output. The proton transfer from the nitrogen adjacent to pyrene moiety, and which takes place at the excited state (ESPT).

Novel poly(triphenylamine-alt-fluorene) with asymmetric hexaphenylbenzene and pyrene moieties: synthesis, fluorescence, flexible near-infrared electrochromic devices and theoretical investigation

KAUST Repository

Wang, Po-I.

2016-01-13

© The Royal Society of Chemistry 2016. In this study, a new triphenylamine-alt-fluorene conjugated copolymer, HPBPYFL6, with hexaphenylbenzene (HPB) and pyrene as asymmetrical pendant groups was synthesized via Suzuki coupling polymerization. The conjugated polymer had a weight-average molecular weight of 5.8 × 104 g mol-1 with a polydispersity index of 2.5 characterized by gel permeation chromatography (GPC). HPBPYFL6 showed good solubility in common organic solvents such as NMP, THF, toluene and dichloromethane at 25°C. In addition, HPBPYFL6 possessed a high glass transition temperature of 260°C and a 10% weight-loss temperature of 503°C in nitrogen. HPBPYFL6 bearing a pyrene moiety had a solvatochromic fluorescence shift from a green to an orange emission as the polarity of the solvent increased. Cyclic voltammetry of HPBPYFL6 films cast onto indium-tin oxide-coated glass (ITO-glass) exhibited two oxidation redox couples at an E1/2 value of 0.82 and 1.17 V versus Ag/Ag+ in an acetonitrile solution. The HPBPYFL6 film on graphene-coated PET had an E1/2 value of 0.24 and 1.12 V. Conjugated polymer films exhibited reversible electrochromic behaviour with a colour change from pale yellow to deep blue upon electrochemical oxidation and high absorbance in the near-infrared (NIR) region. The switching and bleaching times were 5.16 s and 3.12 s for 1231 nm and were 3.30 s and 3.74 s for 1030 nm of HPBPYFL6 on ITO-glass. The strong NIR electrochromic absorbance of HPBPYFL6 was attributed to intervalence charge transfer by the incorporation of the HPB moiety. This phenomenon was confirmed by chemical oxidation as the oxidant contents increased in the solution state. Furthermore, the electrochromic mechanism was interpreted by DFT calculation and the simulated NIR electrochromic spectra of model compound HPBPYFL are in good agreement with the experimental data.

Benzo(a)pyrene-7,8-dihydrodiol 9,10-oxide adenosine and deoxyadenosine adducts: structure and stereochemistry.

Science.gov (United States)

Jeffrey, A M; Grzeskowiak, K; Weinstein, I B; Nakanishi, K; Roller, P; Harvey, R G

1979-12-14

The structure and absolute stereoconfigurations of four adenosine adducts with (+/-)-7 alpha,8 beta-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) and their deoxyadenosine analogs have been determined. They result from both cis and trans addition of the N6 amino group of ademine to the 10 position of both enantiomers of BDPE. This was determined from studies of the nuclear magnetic resonance spectra, mass spectra, and circular dichroism spectra, as well as from their pKa values and chemical reactivities.

Effects of Andrographis paniculata and Orthosiphon stamineus extracts on the glucuronidation of 4-methylumbelliferone in human UGT isoforms.

Science.gov (United States)

Ismail, Sabariah; Hanapi, Nur Aziah; Ab Halim, Mohd Rohaimi; Uchaipichat, Verawan; Mackenzie, Peter I

2010-05-14

The effects of Andrographis paniculata and Orthosiphon stamineus extracts on the in vitro glucuronidation of 4-methylumbelliferone (4MU) by recombinant human UGTs, UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A10, UGT2B7 and UGT2B15 were determined. The potential inhibitory effects of both of the extracts on the activity of each of the UGT isoforms were investigated using 4MU as the substrate. Incubations contained UDP-glucuronic acid (UDPGA) as the cofactor, MgCl(2), cell lysate of respective isoform, and 4MU at the approximate apparent K(m) or S(50) value of each isoform. Final concentrations of Andrographis paniculata and Orthosiphon stamineus extracts used were 0.025, 0.25, 2.5, 25 and 50 microg/mL and 0.01, 0.10, 1.0, 10 and 50 microg/mL respectively. Both extracts variably inhibited the activity of most of the isoforms in a concentration dependent manner. Andrographis paniculata extract was the better inhibitor of all the isoforms studied (IC(50) 1.70 microg/mL for UGT1A3, 2.57 microg/mL for UGT1A8, 2.82 microg/mL for UGT2B7, 5.00 micorg/mL for UGT1A1, 5.66 microg/mL for UGT1A6, 9.88 microg/mL for UGT1A7 and 15.66 microg/mL for UGT1A10). Both extracts showed less than 70% inhibition of UGT2B15, so the IC(50) values were >50 microg/mL. The inhibition of human UGTs by Andrographis paniculata and Orthosiphon stamineus extracts in vitro suggests a potential for drug-herbal extract interactions in the therapeutic setting.

Benzo[a]pyrene and Benzo[k]fluoranthene in Some Processed Fish and Fish Products

Directory of Open Access Journals (Sweden)

Olatunde S. Olatunji

2015-01-01

Full Text Available In this study, the concentration levels of the probable carcinogenic PAH fractions, benzo[a]pyrene (BaP and benzo[k]fluoranthrene (BkF in fillets of some processed fish species were investigated. Fish species comprising Merluccius poli (hake, Tyrsites atun (snoek, Seriola lalandi (yellow-tail and Brama brama (angel fish were bought in fish shops at Gordon’s Bay, Western Cape, South Africa. The fish were gutted, filleted and prepared for edibility by frying, grilling and boiling. Polycyclic aromatic hydrocarbons were extracted from each homogenized fish sample, cleaned-up using solid phase extraction (SPE, and analysed for the PAH fractions, BaP and BkF using a Gas Chromatograph coupled with a Flame Ionization Detector (GC-FID. The sum of the two PAHs (∑2PAH i.e., BaP and BkF ranged between 0.56 and 1.46 µg/kg, in all boiled, grilled and fried fish species. The fried fish extracts showed significantly higher (p < 0.05 abundance of ∑2PAH, than grilled and boiled fish. Dietary safety and PAHs toxicity was also discussed.

Benzo(a)pyrene-induced cytochrome p4501A expression of four freshwater fishes (Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus).

Science.gov (United States)

Lee, Jin Wuk; Yoon, Hong-Gil; Lee, Sung Kyu

2015-05-01

Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus are useful indicator species for CYP1A biomarker studies; however, comparative studies have not been performed. To compare susceptibility, dose- and time-dependent CYP1A induction at the mRNA and protein levels in response to benzo(a)pyrene (BaP) exposure was analyzed. At the mRNA level, a statistically significant difference was found among the four species; however, such was not observed at the protein level. C. carpio showed the highest CYP1A induction level and the steepest slope in the dose-response curve. To assess susceptibility, the difference in CYP1A mRNA induction among species must be considered, and C. carpio was the most sensitive species of the four evaluated in terms of CYP1A expression. Copyright © 2015 Elsevier B.V. All rights reserved.

Membrane remodeling, an early event in benzo[α]pyrene-induced apoptosis

International Nuclear Information System (INIS)

Tekpli, Xavier; Rissel, Mary; Huc, Laurence; Catheline, Daniel; Sergent, Odile; Rioux, Vincent; Legrand, Philippe; Holme, Jorn A.; Dimanche-Boitrel, Marie-Therese; Lagadic-Gossmann, Dominique

2010-01-01

Benzo[α]pyrene (B[α]P) often serves as a model for mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Our previous work suggested a role of membrane fluidity in B[α]P-induced apoptotic process. In this study, we report that B[α]P modifies the composition of cholesterol-rich microdomains (lipid rafts) in rat liver F258 epithelial cells. The cellular distribution of the ganglioside-GM1 was markedly changed following B[α]P exposure. B[α]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[α]P-induced depletion of cholesterol in lipid rafts was linked to a reduced expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). Aryl hydrocarbon receptor (AhR) and B[α]P-related H 2 O 2 formation were involved in the reduced expression of HMG-CoA reductase and in the remodeling of membrane microdomains. The B[α]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[α]P altered the composition of plasma membrane microstructures through AhR and H 2 O 2 dependent-regulation of lipid biosynthesis. In F258 cells, the B[α]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization.

Effect of ageing on benzo[a]pyrene extractability in contrasting soils

Energy Technology Data Exchange (ETDEWEB)

Duan, Luchun [CERAR-Centre for Environmental Risk Assessment and Remediation and Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); Naidu, Ravi, E-mail: Ravi.Naidu@newcastle.edu.au [CERAR-Centre for Environmental Risk Assessment and Remediation and Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); Liu, Yanju; Palanisami, Thavamani; Dong, Zhaomin; Mallavarapu, Megharaj [CERAR-Centre for Environmental Risk Assessment and Remediation and Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); Semple, Kirk T. [Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ (United Kingdom)

2015-10-15

Highlights: • In vitro assessment of B[a]P in contaminated soils using 4 different methods. • An exponential kinetic model fits well with the extractability data. • Fitting parameter and {sup 14}C residue correlates with key soil properties. • Fractionation of B[a]P was obtained based on extractability by extractants. - Abstract: Changes in benzo[a]pyrene (B[a]P) extractability over 160 days ageing in four contrasting soils varying in organic matter content and clay mineralogy were investigated using dichloromethane: acetone 1:1 (DCM/Ace), 60 mM hydroxypropyl-β-cyclodextrin (HPCD) solution, 1-butanol (BuOH) and Milli-Q water. The B[a]P extractability by the four methods decreased with ageing and a first-order exponential model could be used to describe the kinetics of release. Correlation of the kinetic rate constant with major soil properties showed a significant effect of clay and sand contents and pore volume fraction (<6 nm) on sequestration of the desorbable fraction (by HPCD) and the water-extractable fraction. Analysis of {sup 14}C-B[a]P in soils after ageing showed a limited loss of B[a]P via degradation. Fractionation of B[a]P pools associated with the soil matrix was analysed according to extractability of B[a]P by the different extraction methods. A summary of the different fractions is proposed for the illustration of the effect of ageing on different B[a]P-bound fractions in soils. This study provides a better understanding of the B[a]P ageing process associated with different fractions and also emphasises the extraction capacity of the different methods employed.

Effect of ageing on benzo[a]pyrene extractability in contrasting soils

International Nuclear Information System (INIS)

Duan, Luchun; Naidu, Ravi; Liu, Yanju; Palanisami, Thavamani; Dong, Zhaomin; Mallavarapu, Megharaj; Semple, Kirk T.

2015-01-01

Highlights: • In vitro assessment of B[a]P in contaminated soils using 4 different methods. • An exponential kinetic model fits well with the extractability data. • Fitting parameter and 14 C residue correlates with key soil properties. • Fractionation of B[a]P was obtained based on extractability by extractants. - Abstract: Changes in benzo[a]pyrene (B[a]P) extractability over 160 days ageing in four contrasting soils varying in organic matter content and clay mineralogy were investigated using dichloromethane: acetone 1:1 (DCM/Ace), 60 mM hydroxypropyl-β-cyclodextrin (HPCD) solution, 1-butanol (BuOH) and Milli-Q water. The B[a]P extractability by the four methods decreased with ageing and a first-order exponential model could be used to describe the kinetics of release. Correlation of the kinetic rate constant with major soil properties showed a significant effect of clay and sand contents and pore volume fraction (<6 nm) on sequestration of the desorbable fraction (by HPCD) and the water-extractable fraction. Analysis of 14 C-B[a]P in soils after ageing showed a limited loss of B[a]P via degradation. Fractionation of B[a]P pools associated with the soil matrix was analysed according to extractability of B[a]P by the different extraction methods. A summary of the different fractions is proposed for the illustration of the effect of ageing on different B[a]P-bound fractions in soils. This study provides a better understanding of the B[a]P ageing process associated with different fractions and also emphasises the extraction capacity of the different methods employed

Complex metabolic interactions between benzo(a)pyrene and tributyltin in presence of dichlorodiphenyltrichloroethane in South American catfish Rhamdia quelen.

Science.gov (United States)

Oliveira, Heloísa H P; Babin, Mathieu; Garcia, Juan Ramon Esquivel; Filipak Neto, Francisco; Randi, Marco A F; Oliveira Ribeiro, Ciro A; Pelletier, Émilien

2013-10-01

In an attempt to explore complex metabolic interactions between toxicants present in polluted freshwater, hepatic metabolism of benzo(a)pyrene (BaP) and tributyltin (TBT) in fish was investigated when these compounds were administrated alone, mixed together and along with dichlorodiphenyltrichloroethane (DDT). Ten Rhamdia quelen per group were treated with a single intra-peritoneal (IP) dose (5-day experiment) or three successive doses (15-day experiment) either containing BaP (0.3; 3 or 30mgkg(-1)) or TBT (0.03; 0.3 or 3mgkg(-1)) or a combination of BaP+TBT, BaP+DDT, TBT+DDT and BaP+TBT+DDT under their respective lower doses, with DDT dose kept at 0.03mgkg(-1). Tetrahydroxy-benzo(a)pyrene (BaP-tetrol-I), and dibutyltin (DBT) and monobutyltin (MBT) were analyzed to assess BaP and TBT hepatic metabolism, respectively. A significant difference in BaP-tetrol-I concentration was observed in liver and bile between the lowest and the highest doses of BaP in both 5 and 15-day experiments. In the 15-day experiment, the presence of TBT with BaP reduced the amount of BaP-tetrol-I in bile compared to the BaP alone. The time of exposure and the number of doses affected BaP-tetrol-I concentration in the bile of fish exposed to BaP 0.3mgkg(-1) and BaP+DDT. TBT and its metabolites concentrations showed a dose-dependent increase in the liver in both experiments and in the bile in the 5-day experiment. TBT at its lowest dose was completely metabolized into DBT and MBT in the liver in the 15-day experiment. No TBT metabolites were detected in the bile of fish exposed to the mixtures in the 5-day experiment, except for a small MBT amount found in BaP+TBT+DDT. This study strengthens the hypothesis of a metabolic interaction between BaP and TBT in fish and suggests DDT as an important third player when present in the mixture. Copyright © 2013 Elsevier Inc. All rights reserved.

Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS

Science.gov (United States)

Yang, Le-Le; Xiao, Na; Li, Xiao-Wei; Fan, Yong; Alolga, Raphael N.; Sun, Xiao-Yue; Wang, Shi-Lei; Li, Ping; Qi, Lian-Wen

2016-10-01

Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G. Our results showed that the plasma concentration-time curves of quercetin and Q3G show two maxima (Tmax1 ≈ 0.75 h, Tmax2 ≈ 5 h). After oral administration of 100 mg/kg quercetin or 100 mg/kg Q3G in rats, predominantly Q3G was detected in plasma with AUC at 39529.2 ± 6108.2 mg·h·L-1 or 24625.1 ± 1563.8 mg·h·L-1, 18-fold higher than quercetin with AUC at 1583.9 ± 583.3 mg·h·L-1 or 1394.6 ± 868.1 mg·h·L-1, respectively. After intravenous injection of 10 mg/kg in rats, Q3G showed extensive tissue uptake in kidney (409.2 ± 118.4 ng/g), liver (166.1 ± 52.9 ng/g), heart (97.7 ± 22.6 ng/g), and brain (5.8 ± 1.2 ng/g). In conclusion, we have shown that Q3G is a major active component in plasma and tissue for oral administration of quercetin or Q3G.

Overexpression of Catalase Enhances Benzo(a)pyrene Detoxification in Endothelial Microsomes.

Science.gov (United States)

Yang, Fang; Yang, Hong; Ramesh, Aramandla; Goodwin, J Shawn; Okoro, Emmanuel U; Guo, ZhongMao

2016-01-01

We previously reported that overexpression of catalase upregulated xenobiotic- metabolizing enzyme (XME) expression and diminished benzo(a)pyrene (BaP) intermediate accumulation in mouse aortic endothelial cells (MAECs). Endoplasmic reticulum (ER) is the most active organelle involved in BaP metabolism. To examine the involvement of ER in catalase-induced BaP detoxification, we compared the level and distribution of XMEs, and the profile of BaP intermediates in the microsomes of wild-type and catalase transgenic endothelial cells. Our data showed that endothelial microsomes were enriched in cytochrome P450 (CYP) 1A1, CYP1B1 and epoxide hydrolase 1 (EH1), and contained considerable levels of quinone oxidoreductase-1 (NQO1) and glutathione S-transferase-pi (GSTP). Treatment of wild-type MAECs with 1μM BaP for 2 h increased the expression of microsomal CYP1A1, 1B1 and NQO1 by ~300, 64 and 116%, respectively. However, the same treatment did not significantly alter the expression of EH1 and GSTP. Overexpression of catalase did not significantly increase EH1, but upregulated BaP-induced expression of microsomal CYP1A1, 1B1, NQO1 and GSTP in the following order: 1A1>NQO1>GSTP>1B1. Overexpression of catalase did not alter the distribution of each of these enzymes in the microsomes. In contrast to our previous report showing lower level of BaP phenols versus BaP diols/diones in the whole-cell, this report demonstrated that the sum of microsomal BaP phenolic metabolites were ~60% greater than that of the BaP diols/diones after exposure of microsomes to BaP. Overexpression of catalase reduced the concentrations of microsomal BaP phenols and diols/diones by ~45 and 95%, respectively. This process enhanced the ratio of BaP phenol versus diol/dione metabolites in a potent manner. Taken together, upregulation of phase II XMEs and CYP1 proteins, but not EH1 in the ER might be the mechanism by which overexpression of catalase reduces the levels of all the BaP metabolites, and

Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water

Science.gov (United States)

Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F. Y.; Luan, Tiangang

2015-01-01

Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment. PMID:26239357

Explant culture of human peripheral lung. I. Metabolism of benzo[alpha]pyrene

DEFF Research Database (Denmark)

Stoner, G.D.; Harris, C.C.; Autrup, Herman

1978-01-01

the predominant alveolar epithelial cell type. Lamellar inclusion bodies were released from the type 2 cells and accumulated in the alveolar spaces. The metabolism of benzo[alpha]pyrene (BP) in human lung explants cultured for up to 7 days was investigated. Human lung explants had measurable aryl hydrocarbon......Human lung explants have been maintained in vitro for a period of 25 days. Autoradiographic studies indicated that the broncholar epithelial cells, type 2 alveolar epithelial cells, and stromal fibroblasts incorporated 3H-thymidine during the culture. After 7 to 10 days, type 2 cells were...... hydroxylase activity and could metabolize BP into forms that were bound to cellular DNA and protein. Peripheral lung had significantly lower aryl hydrocarbon hydroxylase activity than cultured bronchus but both tissues had similar binding levels of BP to DNA. Radioautographic studies indicated that all cell...

Destruction of acenaphthene, fluorene, anthracene and pyrene by a dc gliding arc plasma reactor

International Nuclear Information System (INIS)

Yu Liang; Tu Xin; Li Xiaodong; Wang Yu; Chi Yong; Yan Jianhua

2010-01-01

In this study, four kinds of PAHs (polycyclic aromatic hydrocarbons) i.e. acenaphthene, fluorene, anthracene and pyrene are used as targets for investigation of PAHs treatment process assisted by dc gliding arc discharge. The effects of carrier gas and external resistance on the PAHs decomposition process are discussed. The results indicate that the destruction rate can be achieved to the highest with the carrier gas of oxygen and the external resistance of 50 kΩ independent of type of PAHs. Furthermore, experimental results suggest that destruction energy efficiency of gliding arc plasma would be improved by treating higher concentration pollutants. Based on the analysis of experimental results, possible destruction mechanisms in different gas discharge are discussed.

Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia

International Nuclear Information System (INIS)

Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H.

2015-01-01

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. - Highlights: • Breast-feeding can be a factor for the development of neonatal hyperbilirubinemia. • UDP-glucuronosyltransferase (UGT) 1A1 is the sole bilirubin-metabolizing enzyme. • Extrahepatic UGT1A1 plays an important role in bilirubin metabolism. • We discuss the potential mechanism of breast milk-induced neonatal jaundice.

Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia

Energy Technology Data Exchange (ETDEWEB)

Fujiwara, Ryoichi, E-mail: fujiwarar@pharm.kitasato-u.ac.jp [Department of Pharmaceutics, School of Pharmacy, Kitasato University, Tokyo (Japan); Maruo, Yoshihiro [Department of Pediatrics, Shiga University of Medical Science, Shiga (Japan); Chen, Shujuan [Department of Pharmacology, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093 (United States); Tukey, Robert H., E-mail: rtukey@ucsd.edu [Department of Pharmacology, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093 (United States); Department of Chemistry & Biochemistry, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093 (United States)

2015-11-15

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. - Highlights: • Breast-feeding can be a factor for the development of neonatal hyperbilirubinemia. • UDP-glucuronosyltransferase (UGT) 1A1 is the sole bilirubin-metabolizing enzyme. • Extrahepatic UGT1A1 plays an important role in bilirubin metabolism. • We discuss the potential mechanism of breast milk-induced neonatal jaundice.

Phytoremediation for co-contaminated soils of chromium and benzo[a]pyrene using Zea mays L.

Science.gov (United States)

Chigbo, Chibuike; Batty, Lesley

2014-02-01

A greenhouse experiment was carried out to investigate the single effect of benzo[a]pyrene (B[a]P) or chromium (Cr) and the joint effect of Cr-B[a]P on the growth of Zea mays, its uptake and accumulation of Cr, and the dissipation of B[a]P over 60 days. Results showed that single or joint contamination of Cr and B[a]P did not affect the plant growth relative to control treatments. However, the occurrence of B[a]P had an enhancing effect on the accumulation and translocation of Cr. The accumulation of Cr in shoot of plant significantly increased by ≥ 79 % in 50 mg kg(-1) Cr-B[a]P (1, 5, and 10 mg kg(-1)) treatments and by ≥ 86 % in 100 mg kg(-1) Cr-B[a]P (1, 5, and 10 mg kg(-1)) treatments relative to control treatments. The presence of plants did not enhance the dissipation of B[a]P in lower (1and 5 mg kg(-1)) B[a]P contaminated soils; however, over 60 days of planting Z. mays seemed to enhance the dissipation of B[a]P by over 60 % in 10 mg kg(-1) single contaminated soil and by 28 to 41 % in 10 mg kg(-1)B[a]P co-contaminated soil. This suggests that Z. mays might be a useful plant for the remediation of Cr-B[a]P co-contaminated soil.

Chemical sensing of Benzo[a]pyrene using Corchorus depressus fluorescent flavonoids.

Science.gov (United States)

Ahmad, Wajiha; Rana, Nosheen Fatima; Riaz, Sundus; Ahmad, Nasir Mehmood; Hameed, Maryam; Naeem, Ayesha; Tahir, Rabbiya

2018-04-01

Plant phytochemicals, such as flavonoids are in use for the development of optical biosensor. Benzo[a]pyrene (B[a]P), is a pervasive environmental and dietary carcinogen. A fluorescent assay is developed using plant isolated flavonoid for the detection of B[a]P. High content saponins are excluded from the flavonoid-containing methanolic extract of Corchorus depressus by implying reduction of silver ions by saponins resulting in formation of silver nanoparticles. Isolated plant flavonoids are used to develop a spectrofluorometric assay for the detection of B[a]P. Decrease in the flavonoid fluorescence intensity by B[a]P is found to be based on both static and dynamic quenching. Specificity of the assay for B[a]P was tested for other carcinogens belonging to different classes of compounds. Flavonoids-mediated sensing can be implied for the development of new generation of nanoparticle-based biosensors that can be more sensitive and less susceptible to external factors, such as temperature and humidity.

A wearable biochemical sensor for monitoring alcohol consumption lifestyle through Ethyl glucuronide (EtG) detection in human sweat.

Science.gov (United States)

Selvam, Anjan Panneer; Muthukumar, Sriram; Kamakoti, Vikramshankar; Prasad, Shalini

2016-03-21

We demonstrate for the first time a wearable biochemical sensor for monitoring alcohol consumption through the detection and quantification of a metabolite of ethanol, ethyl glucuronide (EtG). We designed and fabricated two co-planar sensors with gold and zinc oxide as sensing electrodes. We also designed a LED based reporting for the presence of EtG in the human sweat samples. The sensor functions on affinity based immunoassay principles whereby monoclonal antibodies for EtG were immobilized on the electrodes using thiol based chemistry. Detection of EtG from human sweat was achieved through chemiresistive sensing mechanism. In this method, an AC voltage was applied across the two coplanar electrodes and the impedance across the sensor electrodes was measured and calibrated for physiologically relevant doses of EtG in human sweat. EtG detection over a dose concentration of 0.001-100 μg/L was demonstrated on both glass and polyimide substrates. Detection sensitivity was lower at 1 μg/L with gold electrodes as compared to ZnO, which had detection sensitivity of 0.001 μg/L. Based on the detection range the wearable sensor has the ability to detect alcohol consumption of up to 11 standard drinks in the US over a period of 4 to 9 hours.

Effect of green tea catechins and hydrolyzable tannins on benzo[a]pyrene-induced DNA adducts and structure-activity relationship.

Science.gov (United States)

Cao, Pengxiao; Cai, Jian; Gupta, Ramesh C

2010-04-19

Green tea catechins and hydrolyzable tannins are gaining increasing attention as chemopreventive agents. However, their mechanism of action is poorly understood. We investigated the effects of four green tea catechins and two hydrolyzable tannins on microsome-induced benzo[a]pyrene (BP)-DNA adducts and the possible structure-activity relationship. BP (1 microM) was incubated with rat liver microsomes and DNA in the presence of the test compound (1-200 microM) or vehicle. The purified DNA was analyzed by (32)P-postlabeling. The inhibitory activity of the catechins was in the following descending order: epigallocatechin gallate (IC(50) = 16 microM) > epicatechin gallate (24 microM) > epigallocatechin (146 microM) > epicatechin (462 microM), suggesting a correlation between the number of adjacent aromatic hydroxyl groups in the molecular structure and their potencies. Tannic acid (IC(50) = 4 microM) and pentagalloglucose (IC(50) = 26 microM) elicited as much DNA adduct inhibitory activity as the catechins or higher presumably due to the presence of more functional hydroxyl groups. To determine if the activity of these compounds was due to direct interaction of phenolic groups with electrophilic metabolite(s) of BP, DNA was incubated with anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) (0.5 microM) in the presence of test compounds (200 microM) or vehicle. Significant inhibition of DNA adduct formation was found (tannic acid > pentagalloglucose > epigallocatechin gallate > epicatechin gallate). This notion was confirmed by analysis of the reaction products of anti-BPDE with the catechins and pentagalloglucose by electrospray ionization mass spectrometry and liquid chromatography-mass spectrometry. In conclusion, our data demonstrate that green tea catechins and the hydrolyzable tannins are highly effective in inhibiting BP-DNA adduct formation at least, in part, due to direct interaction of adjacent hydroxyl groups in their structures and that the activity is

Effect of Green Tea Catechins and Hydrolyzable Tannins on Benzo[a]pyrene-Induced DNA Adducts and Structure–Activity Relationship

Science.gov (United States)

Cao, Pengxiao; Cai, Jian; Gupta, Ramesh C.

2016-01-01

Green tea catechins and hydrolyzable tannins are gaining increasing attention as chemopreventive agents. However, their mechanism of action is poorly understood. We investigated the effects of four green tea catechins and two hydrolyzable tannins on microsome-induced benzo[a]pyrene (BP)–DNA adducts and the possible structure–activity relationship. BP (1 μM) was incubated with rat liver microsomes and DNA in the presence of the test compound (1–200 μM) or vehicle. The purified DNA was analyzed by 32P-postlabeling. The inhibitory activity of the catechins was in the following descending order: epigallocatechin gallate (IC50 = 16 μM) > epicatechin gallate (24 μM) > epigallocatechin (146 μM) > epicatechin (462 μM), suggesting a correlation between the number of adjacent aromatic hydroxyl groups in the molecular structure and their potencies. Tannic acid (IC50 = 4 μM) and pentagalloglucose (IC50 = 26 μM) elicited as much DNA adduct inhibitory activity as the catechins or higher presumably due to the presence of more functional hydroxyl groups. To determine if the activity of these compounds was due to direct interaction of phenolic groups with electrophilic metabolite(s) of BP, DNA was incubated with anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) (0.5 μM) in the presence of test compounds (200 μM) or vehicle. Significant inhibition of DNA adduct formation was found (tannic acid > pentagalloglucose > epigallocatechin gallate > epicatechin gallate). This notion was confirmed by analysis of the reaction products of anti-BPDE with the catechins and pentagalloglucose by electrospray ionization mass spectrometry and liquid chromatography–mass spectrometry. In conclusion, our data demonstrate that green tea catechins and the hydrolyzable tannins are highly effective in inhibiting BP–DNA adduct formation at least, in part, due to direct interaction of adjacent hydroxyl groups in their structures and that the activity is higher with an increasing

Metabolism of nasally instilled benzo(a)pyrene and dihydrosafrole in dogs and monkeys

International Nuclear Information System (INIS)

Petridou-Fischer, J.; Whaley, S.; Dahl, A.

1987-01-01

Cytochrome P-450 monooxygenases are found in the nasal cavities of a variety of species and could play an important role in the metabolism of inhaled airborne xenobiotics. The object of this study was to examine the metabolism of 14 C-benzo(a)pyrene (BaP) and 3 H-dihydrosafrole (DHS) deposited at the ethmoid and maxillary turbinate regions in Beagle dogs and Cynomolgus monkeys. While the animals were anesthetized, either compound was instilled at 10 minute intervals for 2 hours through catheters positioned at each region. Cotton swab samples of mucus from the nasopharynx were collected at 30 minute intervals during instillation. Metabolites in mucus were identified using high pressure liquid chromatography. Results showed that both regions in both species were capable of metabolizing BaP and DHS. BaP metabolites identified in the mucus were dihydrodiols, quinones, phenols, and tetrols. DHS metabolites were 2-methoxy-4-propyl-phenol, 2-methoxy-4-(2-propenyl)benzene, and 3,4-methylenedioxy-1-(1-hydroxypropyl)benzene. Radioactivity was found in urine and feces of animals treated with either compound, and was detected in the blood of animals treated with DHS. No differences were noted for the nasal metabolism between the two species. This study indicated that not only the nasal tissues, but also the alimentary tract, may be exposed to metabolites of inhaled xenobiotics carried by the mucus

Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

Energy Technology Data Exchange (ETDEWEB)

Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca; Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca; White, Paul A., E-mail: Paul.White@hc-sc.gc.ca; Halappanavar, Sabina, E-mail: Sabina.Halappanavar@hc-sc.gc.ca

2013-12-01

Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

Chemopreventive efficacy of a betel leaf extract against benzo[a]pyrene-induced forestomach tumors in mice.

Science.gov (United States)

Bhide, S V; Zariwala, M B; Amonkar, A J; Azuine, M A

1991-09-01

The effect of betel leaf extract and some of its constituents, eugenol, hydroxychavicol, beta-carotene and alpha-tocopherol, on benzo[a]pyrene-induced forestomach neoplasia in male Swiss mice was examined. Betel leaf and its constituents decreased the number of papillomas per animal with the maximum protection, considering molar dosage, exhibited by beta-carotene and alpha-tocopherol. Except for beta-carotene, eugenol, hydroxychavicol and alpha-tocopherol increased the levels of reduced glutathione in the liver while glutathione S-transferase activity was enhanced by all except eugenol. Of seven sources, Banarasi betel leaves showed the maximum amounts of beta-carotene and alpha-tocopherol.

Potassium cyanate-induced modification of toxic and mutagenic effects of gamma-radiation and benzo(A)-pyrene

International Nuclear Information System (INIS)

Serebryanyj, A.M.; Sal'nikova, L.E.; Bakhitova, L.M.; Pashin, Yu.V.; AN SSSR, Moscow

1989-01-01

In experiments with CHO-AT3-2 cell culture, a study was made of the effect of potassium cyanate (KNCO) on the effect of gamma-radiation and benzo(a)pyrene (BP) by the following tests: cell viability, induction of cells with micronuclei and fragmentated nuclei and mutations by thymidinekinase (TK) and Na + /K + -ATPase loci. Some tests have revealed the increase in the effect of gamma-radiation and BP produced by potassium cyanate. It is suggested that sensitizing effects are related to repair system inhibition and/or changes in the cell chromatin structure produced by KNCO

Efficient small molecule bulk heterojunction solar cells with high fill factors via pyrene-directed molecular self-assembly

KAUST Repository

Lee, Olivia P.; Yiu, Alan T.; Beaujuge, Pierre; Woo, Claire; Holcombe, Thomas W.; Millstone, Jill E.; Douglas, Jessica D.; Chen, Mark S.; Frechet, Jean

2011-01-01

Efficient organic photovoltaic (OPV) materials are constructed by attaching completely planar, symmetric end-groups to donor-acceptor electroactive small molecules. Appending C2-pyrene as the small molecule end-group to a diketopyrrolopyrrole core leads to materials with a tight, aligned crystal packing and favorable morphology dictated by π-π interactions, resulting in high power conversion efficiencies and high fill factors. The use of end-groups to direct molecular self-assembly is an effective strategy for designing high-performance small molecule OPV devices. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficient small molecule bulk heterojunction solar cells with high fill factors via pyrene-directed molecular self-assembly

KAUST Repository

Lee, Olivia P.

2011-10-21

Efficient organic photovoltaic (OPV) materials are constructed by attaching completely planar, symmetric end-groups to donor-acceptor electroactive small molecules. Appending C2-pyrene as the small molecule end-group to a diketopyrrolopyrrole core leads to materials with a tight, aligned crystal packing and favorable morphology dictated by π-π interactions, resulting in high power conversion efficiencies and high fill factors. The use of end-groups to direct molecular self-assembly is an effective strategy for designing high-performance small molecule OPV devices. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Linking embryo toxicity with genotoxic responses in the freshwater snail Physa acuta: single exposure to benzo(a)pyrene, fluoxetine, bisphenol A, vinclozolin and exposure to binary mixtures with benzo(a)pyrene.

Science.gov (United States)

Sánchez-Argüello, Paloma; Aparicio, Natalia; Fernández, Carlos

2012-06-01

Genotoxic effects on fauna after waterborne pollutant exposure have been demonstrated by numerous research programmes. Less effort has been focused on establishing relationship between genotoxicity and long-term responses at higher levels of biological organization. Taking into account that embryos may be more sensitive indicators of reproductive impairment than alterations in fertility, we have developed two assays in multiwell plates to address correlations between embryo toxicity and genotoxicity. The potential teratogenicity was assessed by analyzing abnormal development and mortality of Physa acuta at embryonic stage. Genotoxicity was measured by the micronucleus (MN) test using embryonic cells. Our results showed that linkage between genotoxicity and embryo toxicity depends on mechanisms of action of compounds under study. Embryo toxic responses showed a clear dose-related tendency whereas no clear dose-dependent effect was observed in micronucleus induction. The higher embryo toxicity was produced by benzo(a)pyrene exposure followed by fluoxetine and bisphenol A. Vinclozolin was the lower embryo toxic compound. Binary mixtures with BaP always resulted in higher embryo toxicity than single exposures but antagonistic effects were observed for MN induction. Benzo(a)pyrene produced the higher MN induction at 0.04 mg/L, which also produced clear embryo toxic effects. Fluoxetine did not induce cytogenetic effects but 0.25mg/L altered embryonic development. Bisphenol A significantly reduced hatchability at 0.5mg/L while MN induction appeared with higher treatments than those that start causing teratogenicity. Much higher concentration of vinclozolin (5mg/L) reduced hatchability and induced maximum MN formation. In conclusion, while validating one biomarker of genotoxicity and employing one ecologically relevant effect, we have evaluated the relative sensitivity of a freshwater mollusc for a range of chemicals. The embryo toxicity test is a starting point for the

Role of UDP-Glucuronosyltransferase 1A1 in the Metabolism and Pharmacokinetics of Silymarin Flavonolignans in Patients with HCV and NAFLD

Directory of Open Access Journals (Sweden)

Ying Xie

2017-01-01

Full Text Available Silymarin is the most commonly used herbal medicine by patients with chronic liver disease. Silymarin flavonolignans undergo rapid first-pass metabolism primarily by glucuronidation. The aims of this investigation were: (1 to determine the association of UGT1A1*28 polymorphism with the area under the plasma concentration-time curves (AUCs for silybin A (SA and silybin B (SB; (2 to evaluate the effect of UGT1A1*28 polymorphism on the profile of flavonolignan glucuronide conjugates found in the plasma; and (3 to investigate the role of UGT1A1 enzyme kinetics on the pharmacokinetics of SA and SB. AUCs and metabolic ratios for thirty-three patients with chronic liver disease administered oral doses of silymarin were compared between different UGT1A1*28 genotypes. The AUCs, metabolic ratios, and the profiles of major SA and SB glucuronides did not differ significantly among the three UGT1A1 genotypes. In contrast, an increase in the proportion of sulfated flavonolignan conjugates in plasma was observed in subjects with UGT1A1*28/*28 genotype compared to subjects carrying wild type alleles. Differences in SA and SB in vitro intrinsic clearance estimates for UGTIA1 correlated inversely with SA and SB exposures observed in vivo indicating a major role for UGT1A1 in silymarin metabolism. In addition, a significant difference in the metabolic ratio observed between patients with NAFLD and HCV suggests that any effect of UGT1A1 polymorphism may be obscured by a greater effect of liver disease on the pharmacokinetics of silymarin. Taken together, these results suggest the presence of the UGT1A1*28 allele does not contribute significantly to a large inter-subject variability in the pharmacokinetics of silybin A and silybin B which may obscure the ability to detect beneficial effects of silymarin in patients with liver disease.

Role of extrahepatic UDP-glucuronosyltransferase 1A1: advances in understanding breast milk-induced neonatal hyperbilirubinemia

OpenAIRE

Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H.

2015-01-01

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic ...

An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

Energy Technology Data Exchange (ETDEWEB)

Tian, Shuangmei; Pan, Luqing, E-mail: panlq@ouc.edu.cn; Sun, Xiaohua

2013-11-15

Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

International Nuclear Information System (INIS)

Tian, Shuangmei; Pan, Luqing; Sun, Xiaohua

2013-01-01

Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

Influence of bleaching and coloring on ethyl glucuronide content in human hair.

Science.gov (United States)

Petzel-Witt, Silvana; Pogoda, Werner; Wunder, Cora; Paulke, Alexander; Schubert-Zsilavecz, Manfred; Toennes, Stefan W

2018-01-01

Ethyl glucuronide (EtG) is increasingly used in forensic toxicology as a marker for alcohol use in analyses of hair samples, especially in abstinence control. Some cosmetic treatments are considered to markedly reduce the EtG content. In view of especially many women with coloured hair the present study was performed to further investigate the effect of a variety of colouring procedures (bleaching, tinting, permanent and semi-permanent dyeing, henna) on the EtG content. Untreated hair samples (n = 12, EtG 13.9-64.7 pg/mg) were re-analyzed (gas chromatography- negative chemical ionization mass spectrometry, 0.8 pg/mg quantification limit) after different treatment procedures. A decrease of the EtG content of at least 10% occurred in every case. The reduction in comparison to the untreated hair was expectedly high for permanent dyeing and bleaching with 18.1% of the initial content (median, range 0.0-50.9%) and 18.4% (0.0-46.7%), respectively. For henna this was 38.3% (0.0-83.0%), for tinting 70.4% (29.0-90.8%), for semi-permanent dyeing 41.9% (0.0-77.4%). With permanent hair dye the EtG content was decreased to below 7 pg/mg in 10 of 12 cases, in 3 cases even below the LOD (0.2 pg/mg). Surprisingly henna treatment without oxidative component had a marked influence, EtG was below 2 pg/mg in 2 of 12 samples. The study showed that all tested coloration procedures markedly affected the deposited EtG content. Even temporary or henna coloration may have a marked effect. The present data support the recommendation to exclude hair samples with colour manipulations for analysis on the EtG content as a precaution in alcohol abstinence programs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.