The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
H C Widjaja-greefkes - One of the best experts on this subject based on the ideXlab platform.
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Differential effects of Nitrofurans on the production/release of steroid hormones by porcine adrenocortical cells in vitro.
European journal of pharmacology, 1997Co-Authors: L P Jager, G J De Graaf, H C Widjaja-greefkesAbstract:Changes in the biogenesis of corticosteroids caused by Nitrofurans were studied. The three Nitrofurans used: furazolidone, furaltadone and Nitrofurantoin, altered the steroid production/release by porcine adrenocortical cells in vitro during 1 h incubations. With pregnenolone as a substrate the Nitrofurans inhibited aldosterone production/release. Although the Nitrofurans differed in potency (Nitrofurantoin > furazolidone > furaltadone) maximum inhibition occurred at 100 microM. In this concentration the Nitrofurans changed also the release/production of other corticosteroids. The output of corticosterone and cortisol decreased by 50%. The production/release of deoxycortisol stayed the same. In contrast the output of progesterone and 17alpha-hydroxyprogesterone increased to more than 200% of control. The Nitrofurans slightly reduced the output of androstenedione. No significant increases of the production/release of other steroids (testosterone, dehydroepiandrosterone, estradiol-17beta and estrone) by the cell suspension could be observed. The profile of the Nitrofuran-induced changes lead to the conclusion that Nitrofurans interfere with mitochondrial enzymes. These enzymes, presumably cytochrome P450(11,18) mediate the hydroxylation and the oxidation at C11 and C18, the final steps in the biogenesis of aldosterone, corticosterone and cortisol. The rapid and reversible fall in the output of these steroids occurs in vitro at concentrations which are below therapeutic blood concentrations seen in vivo. At higher concentrations the Nitrofurans hinder the biogenesis of androgens. Thus Nitrofurans can also affect steps in the steroid biogenesis located in the endoplasmatic reticulum.
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Differential effects of Nitrofurans on the production/release of steroid hormones by porcine adrenocortical cells in vitro.
European Journal of Pharmacology, 1997Co-Authors: L P Jager, G J De Graaf, H C Widjaja-greefkesAbstract:Abstract Changes in the biogenesis of corticosteroids caused by Nitrofurans were studied. The three Nitrofurans used: furazolidone, furaltadone and Nitrofurantoin, altered the steroid production/release by porcine adrenocortical cells in vitro during 1 h incubations. With pregnenolone as a substrate the Nitrofurans inhibited aldosterone production/release. Although the Nitrofurans differed in potency (Nitrofurantoin>furazolidone>furaltadone) maximum inhibition occurred at 100 μM. In this concentration the Nitrofurans changed also the release/production of other corticosteroids. The output of corticosterone and cortisol decreased by 50%. The production/release of deoxycortisol stayed the same. In contrast the output of progesterone and 17α-hydroxyprogesterone increased to more than 200% of control. The Nitrofurans slightly reduced the output of androstenedione. No significant increases of the production/release of other steroids (testosterone, dehydroepiandrosterone, estradiol-17β and estrone) by the cell suspension could be observed. The profile of the Nitrofuran-induced changes lead to the conclusion that Nitrofurans interfere with mitochondrial enzymes. These enzymes, presumably cytochrome P45011,18 mediate the hydroxylation and the oxidation at C11 and C18, the final steps in the biogenesis of aldosterone, corticosterone and cortisol. The rapid and reversible fall in the output of these steroids occurs in vitro at concentrations which are below therapeutic blood concentrations seen in vivo. At higher concentrations the Nitrofurans hinder the biogenesis of androgens. Thus Nitrofurans can also affect steps in the steroid biogenesis located in the endoplasmatic reticulum.
Wan Chan - One of the best experts on this subject based on the ideXlab platform.
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Plant Uptake and Metabolism of Nitrofuran Antibiotics in Spring Onion Grown in Nitrofuran-Contaminated Soil
Journal of agricultural and food chemistry, 2017Co-Authors: Yinan Wang, K. K. Jason Chan, Wan ChanAbstract:Environmental pollution caused by the discharge of mutagenic and carcinogenic Nitrofurans to the aquatic and soil environment is an emerging public health concern because of the potential in producing drug-resistant microbes and being uptaken by food crops. Using liquid chromatography–tandem mass spectrometry analysis and with spring onion (Allium wakegi Araki) as the plant model, we investigated in this study the plant uptake and accumulation of Nitrofuran from a contaminated environment. Our study revealed for the first time high uptake and accumulation rates of Nitrofuran in the edible parts of the food crop. Furthermore, results indicated highly efficient plant metabolism of the absorbed Nitrofuran within the plant, leading to the formation of genotoxic hydrazine-containing metabolites. The results from this study may disclose a previously unidentified human exposure pathway through contaminated food crops.
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Plant Uptake and Metabolism of Nitrofuran Antibiotics in Spring Onion Grown in Nitrofuran-Contaminated Soil
2017Co-Authors: Yinan Wang, K. Jason K. Chan, Wan ChanAbstract:Environmental pollution caused by the discharge of mutagenic and carcinogenic Nitrofurans to the aquatic and soil environment is an emerging public health concern because of the potential in producing drug-resistant microbes and being uptaken by food crops. Using liquid chromatography–tandem mass spectrometry analysis and with spring onion (Allium wakegi Araki) as the plant model, we investigated in this study the plant uptake and accumulation of Nitrofuran from a contaminated environment. Our study revealed for the first time high uptake and accumulation rates of Nitrofuran in the edible parts of the food crop. Furthermore, results indicated highly efficient plant metabolism of the absorbed Nitrofuran within the plant, leading to the formation of genotoxic hydrazine-containing metabolites. The results from this study may disclose a previously unidentified human exposure pathway through contaminated food crops
L P Jager - One of the best experts on this subject based on the ideXlab platform.
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Differential effects of Nitrofurans on the production/release of steroid hormones by porcine adrenocortical cells in vitro.
European journal of pharmacology, 1997Co-Authors: L P Jager, G J De Graaf, H C Widjaja-greefkesAbstract:Changes in the biogenesis of corticosteroids caused by Nitrofurans were studied. The three Nitrofurans used: furazolidone, furaltadone and Nitrofurantoin, altered the steroid production/release by porcine adrenocortical cells in vitro during 1 h incubations. With pregnenolone as a substrate the Nitrofurans inhibited aldosterone production/release. Although the Nitrofurans differed in potency (Nitrofurantoin > furazolidone > furaltadone) maximum inhibition occurred at 100 microM. In this concentration the Nitrofurans changed also the release/production of other corticosteroids. The output of corticosterone and cortisol decreased by 50%. The production/release of deoxycortisol stayed the same. In contrast the output of progesterone and 17alpha-hydroxyprogesterone increased to more than 200% of control. The Nitrofurans slightly reduced the output of androstenedione. No significant increases of the production/release of other steroids (testosterone, dehydroepiandrosterone, estradiol-17beta and estrone) by the cell suspension could be observed. The profile of the Nitrofuran-induced changes lead to the conclusion that Nitrofurans interfere with mitochondrial enzymes. These enzymes, presumably cytochrome P450(11,18) mediate the hydroxylation and the oxidation at C11 and C18, the final steps in the biogenesis of aldosterone, corticosterone and cortisol. The rapid and reversible fall in the output of these steroids occurs in vitro at concentrations which are below therapeutic blood concentrations seen in vivo. At higher concentrations the Nitrofurans hinder the biogenesis of androgens. Thus Nitrofurans can also affect steps in the steroid biogenesis located in the endoplasmatic reticulum.
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Differential effects of Nitrofurans on the production/release of steroid hormones by porcine adrenocortical cells in vitro.
European Journal of Pharmacology, 1997Co-Authors: L P Jager, G J De Graaf, H C Widjaja-greefkesAbstract:Abstract Changes in the biogenesis of corticosteroids caused by Nitrofurans were studied. The three Nitrofurans used: furazolidone, furaltadone and Nitrofurantoin, altered the steroid production/release by porcine adrenocortical cells in vitro during 1 h incubations. With pregnenolone as a substrate the Nitrofurans inhibited aldosterone production/release. Although the Nitrofurans differed in potency (Nitrofurantoin>furazolidone>furaltadone) maximum inhibition occurred at 100 μM. In this concentration the Nitrofurans changed also the release/production of other corticosteroids. The output of corticosterone and cortisol decreased by 50%. The production/release of deoxycortisol stayed the same. In contrast the output of progesterone and 17α-hydroxyprogesterone increased to more than 200% of control. The Nitrofurans slightly reduced the output of androstenedione. No significant increases of the production/release of other steroids (testosterone, dehydroepiandrosterone, estradiol-17β and estrone) by the cell suspension could be observed. The profile of the Nitrofuran-induced changes lead to the conclusion that Nitrofurans interfere with mitochondrial enzymes. These enzymes, presumably cytochrome P45011,18 mediate the hydroxylation and the oxidation at C11 and C18, the final steps in the biogenesis of aldosterone, corticosterone and cortisol. The rapid and reversible fall in the output of these steroids occurs in vitro at concentrations which are below therapeutic blood concentrations seen in vivo. At higher concentrations the Nitrofurans hinder the biogenesis of androgens. Thus Nitrofurans can also affect steps in the steroid biogenesis located in the endoplasmatic reticulum.
Magnus W. P. Bebbington - One of the best experts on this subject based on the ideXlab platform.
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intramolecular Nitrofuran diels alder reactions extremely substituent tolerant cycloadditions via asynchronous transition states
Journal of Organic Chemistry, 2017Co-Authors: Thomas Y Cowie, Marcos Veguillas, Robert L. Rae, Andrew W. Prentice, Martin J. Paterson, Mathilde Rouge, Justyna M żurek, Magnus W. P. BebbingtonAbstract:Nitrofurans undergo intramolecular Diels–Alder reactions with tethered electron-poor dienophiles more rapidly and in higher yield than non-nitrated furans. Computational studies indicate that increased stabilization of a partial positive charge on the nitro-substituted carbon in both transition state and product is the driving force for these reactions. Frontier molecular orbital energy differences indicate a switch from normal to inverse electron demand upon nitration. There does not appear to be a contribution from any differences in aromatic stabilization energy between furans and Nitrofurans. Calculations show that the Nitrofuran reactions proceed via a highly asynchronous transition state allowing easier bond formation between two sterically hindered carbons.
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Intramolecular Nitrofuran Diels–Alder Reactions: Extremely Substituent-Tolerant Cycloadditions via Asynchronous Transition States
2017Co-Authors: Thomas Y. Cowie, Marcos Veguillas, Robert L. Rae, Mathilde Rougé, Justyna M. Żurek, Andrew W. Prentice, Martin J. Paterson, Magnus W. P. BebbingtonAbstract:Nitrofurans undergo intramolecular Diels–Alder reactions with tethered electron-poor dienophiles more rapidly and in higher yield than non-nitrated furans. Computational studies indicate that increased stabilization of a partial positive charge on the nitro-substituted carbon in both transition state and product is the driving force for these reactions. Frontier molecular orbital energy differences indicate a switch from normal to inverse electron demand upon nitration. There does not appear to be a contribution from any differences in aromatic stabilization energy between furans and Nitrofurans. Calculations show that the Nitrofuran reactions proceed via a highly asynchronous transition state allowing easier bond formation between two sterically hindered carbons
Jasna Rakonjac - One of the best experts on this subject based on the ideXlab platform.
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In vitro synergy between sodium deoxycholate and furazolidone against enterobacteria
BMC Microbiology, 2020Co-Authors: Catrina Olivera, Julian Spagnuolo, Ieuan G. Davies, Jasna RakonjacAbstract:Background Antimicrobial combinations have been proven as a promising approach in the confrontation with multi-drug resistant bacterial pathogens. In the present study, we identify and characterize a synergistic interaction of broad-spectrum nitroreductase-activated prodrugs 5-Nitrofurans, with a secondary bile salt, s odium d eoxycholate (DOC) in growth inhibition and killing of enterobacteria. Results Using checkerboard assay, we show that combination of Nitrofuran furazolidone (FZ) and DOC generates a profound synergistic effect on growth inhibition in several enterobacterial species including Escherichia coli , Salmonella enterica , Citrobacter gillenii and Klebsiella pneumoniae . The Fractional Inhibitory Concentration Index (FICI) for DOC-FZ synergy ranges from 0.125 to 0.35 that remains unchanged in an ampicillin-resistant E. coli strain containing a β-lactamase-producing plasmid. Findings from the time-kill assay further highlight the synergy with respect to bacterial killing in E. coli and Salmonella . We further characterize the mechanism of synergy in E. coli K12, showing that disruption of the tolC or acrA genes that encode components of multidrug efflux pumps causes, respectively, a complete or partial loss, of the DOC-FZ synergy. This finding indicates the key role of TolC-associated efflux pumps in the DOC-FZ synergy. Overexpression of n itric o xide-detoxifying enzyme Hmp results in a three-fold increase in FICI for DOC-FZ interaction, suggesting a role of nitric oxide in the synergy. We further demonstrate that DOC-FZ synergy is largely independent of NfsA and NfsB, the two major activation enzymes of the Nitrofuran prodrugs. Conclusions This study is to our knowledge the first report of Nitrofuran-deoxycholate synergy against Gram-negative bacteria, offering potential applications in antimicrobial therapeutics. The mechanism of DOC-FZ synergy involves FZ-mediated inhibition of TolC-associated efflux pumps that normally remove DOC from bacterial cells. One possible route contributing to that effect is via FZ-mediated nitric oxide production.
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Novel 5-Nitrofuran-Activating Reductase in Escherichia coli.
Antimicrobial agents and chemotherapy, 2019Co-Authors: Vuong Van Hung Le, Ieuan G. Davies, Christina D. Moon, David A. Wheeler, Patrick J. Biggs, Jasna RakonjacAbstract:The global spread of multidrug-resistant enterobacteria warrants new strategies to combat these pathogens. One possible approach is the reconsideration of "old" antimicrobials, which remain effective after decades of use. Synthetic 5-Nitrofurans such as furazolidone, Nitrofurantoin, and nitrofurazone are such a class of antimicrobial drugs. Recent epidemiological data showed a very low prevalence of resistance to this antimicrobial class among clinical Escherichia coli isolates in various parts of the world, forecasting the increasing importance of its uses to battle antibiotic-resistant enterobacteria. However, although they have had a long history of clinical use, a detailed understanding of the 5-Nitrofurans' mechanisms of action remains limited. Nitrofurans are known as prodrugs that are activated in E. coli by reduction catalyzed by two redundant nitroreductases, NfsA and NfsB. Furazolidone, nevertheless, retains relatively significant antibacterial activity in the nitroreductase-deficient ΔnfsA ΔnfsB E. coli strain, indicating the presence of additional activating enzymes and/or antibacterial activity of the unreduced form. Using genome sequencing, genetic, biochemical, and bioinformatic approaches, we discovered a novel 5-Nitrofuran-activating enzyme, AhpF, in E. coli The discovery of a new Nitrofuran-reducing enzyme opens new avenues for overcoming 5-Nitrofuran resistance, such as designing Nitrofuran analogues with higher affinity for AhpF or screening for adjuvants that enhance AhpF expression.
