Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nitrofurans”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1991

Mechanism of nitrofuran resistance in Salmonella enteritidis phage type 4 and interpretation of nitrofuran susceptibility tests.

The mechanism of nitrofuran resistance in Salmonella enteritidis phage type 4 was studied. Nitrofuran reductase activity was inversely related to the furazolidone MIC for the organism. Strains with low-level nitrofuran resistance, typically found in almost all isolates of S. enteritidis PT4, had intermediate nitrofuran reductase activity. Disc diffusion tests with furazolidone, 15 or 50 micrograms discs, and nitrofurantoin, 50 or 300 micrograms discs, failed to distinguish reliably between susceptible populations and those with low-level resistance. In order to detect low-level resistance to nitrofurans a dilution method should be used with a furazolidone breakpoint of 1 mg/l or a nitrofurantoin breakpoint of 16 mg/l.

Drug Resistance, Microbial↗
PubMed1985

Inhibitors of nitrofuran reduction in Escherichia coli: evidence for their existence, partial purification, binding of nitrofurantoin in vitro, and implications for nitrofuran resistance.

Nitrofurantoin (NF)-resistant mutants of Escherichia coli were isolated as described previously (18). One of the mutants (SSJ-2) was found to possess NF reductase activity equal to that of its parent (E. coli KL16). Two NF-resistant transductional derivatives, SSJ-2A and SSJ-2B, were isolated using SSJ-2 as the donor. SSJ-2 was found to be a double mutant carrying two mutations, nfnA and nfnB, while SSJ-2A (nfnA) and SSJ-2B (nfnB) carried these mutations individually. Heated extracts from SSJ-2A and SSJ-2B were found to inhibit the reduction of NF by unheated extracts of the NF-sensitive strain E. coli KL16 in vitro. Unheated extracts of these mutants reduced NF poorly relative to E. coli KL16. The poor reduction of NF by unheated extracts of SSJ-2A and SSJ-2B was greatly stimulated by heated extracts of SSJ-2B and SSJ-2A, respectively, and also by heated extracts of E. coli KL16. When heated extracts of SSJ-2A and SSJ-2B were mixed in a particular ratio and added to unheated extracts of E. coli KL16 they lost their inhibitory activity. Two proteins, designated inhibitor A and inhibitor B, have been partially purified from heated extracts of SSJ-2B and SSJ-2A, respectively. Their respective molecular weights, as determined by gel chromatography, were 37,000 and 20,500. The two inhibitors bound nitrofurantoin in vitro, and the NF-binding ability was lost when mixed in the molar ration of 3/1 (B/A). These observations were rationalized in terms of a hypothesis which explains (i) maximal NF reduction in wild-type cells, (ii) maximal NF reduction of nfnA-nfnB- double mutant, and (iii) poor NF reduction in nfnA- or nfnB- single mutants. The possible role of these inhibitors in nitrofurantoin resistance is also discussed.

Drug Resistance, Microbial↗
PubMed1984

Distinct reduction of nitrofurans and metronidazole to free radical metabolites by Tritrichomonas foetus hydrogenosomal and cytosolic enzymes.

Anaerobic Tritrichomonas foetus hydrogenosomes supplemented with pyruvate and CoA effectively reduce nitrofurans and metronidazole to their respective anion free radicals. Addition of purified ferredoxins from Clostridium pasteurianum or Spinacia oleracea to these preparations causes a great stimulation of metronidazole reduction, but does not affect nitrofuran reduction. A similar stimulatory effect of ferredoxin on metronidazole reduction, but not on nitrofuran reduction, is observed in incubations containing purified NADPH:ferredoxin oxidoreductase from S. oleracea. NADH is less effective than pyruvate as a reducing cofactor for metronidazole and nitrofuran reduction by the hydrogenosomes, and these activities are not modified by the addition of ferredoxins. In contrast to the results observed with hydrogenosomes, the T. foetus soluble fraction supplemented with NADH or NADPH is able to reduce nitrofurans, but not metronidazole. Under aerobic conditions, the anion free radical metabolites generated from metronidazole and nitrofurans are oxidized, resulting in catalytic superoxide anion formation as detected by spin-trapping experiments. Oxygen consumption and H2O2 formation by T. foetus hydrogenosomes and NADPH:ferredoxin oxidoreductase are also stimulated by nitrofurans and high concentrations of metronidazole. Addition of ferredoxin enhances metronidazole-stimulated, but not nitrofuran-stimulated, oxygen consumption and H2O2 formation in both systems. These results support the role of air oxidation as a detoxification reaction of the metronidazole anion radical and the involvement of ferredoxin in its formation. On the other hand, redox cycling of nitrofurans with formation of high steady state concentrations of oxygen-derived radicals might be of toxicological significance.

Aerobiosis↗
PubMed1992

Reduction of nitrofuran compounds by heart lipoamide dehydrogenase: role of flavin and the reactive disulfide groups.

In order to elucidate the mechanism of the biological activation of nitrofurans, the interaction of these compounds with lipoamide dehydrogenase (LipDH)** was investigated. LipDH catalysed one-electron reduction of several nitrofuran derivatives. The reaction could be demonstrated spectroscopically and was enhanced by cadmium, arsenite and anaerobiosis. The role of flavin in the nitroreductase activity was supported by (a) the nitrofuran effect on the spectral properties of anaerobic, arsenite-inhibited, NADH-reduced LipDH; (b) FAD catalytic activity in a NADH-nitrofuran model system; and (c) the nitroreductase activity of LipDH monomer. Two-electron nitrofuran reduction to less oxidized products was inhibited by cadmium, arsenite and NAD+. The possible role of reactive nitrosofuran derivatives as intermediates of the nitrofuran reduction sequence was supported by the LipDH capability for catalysing 2-nitroso-1-naphthol redox-cycling. The nitroso naphthol reduction was inhibited by cadmium and arsenite, like the two-electron nitrofuran reduction.

Anaerobiosis↗
PubMed1991

Inhibition of T cell mitogenesis by nitrofurans.

A group of nitrofurans (5-nitro-2-furaldehyde, nifuroxime, nitrofurazone, nitrofurantoin, 5-nitro-2-furoic acid and 2-nitrofuran) were evaluated for inhibition of mitogenesis (DNA synthesis) in human peripheral blood T cells. T cells, either triggered by phorbol myristate acetate (PMA) or in the presence of accessory cells, were activated with a specified mitogen [phytohemagglutin (PHA), concanavalin A (ConA), or anti-CD3] and the amount of tritiated thymidine incorporated into DNA was determined. The results obtained indicate that nitrofurans inhibit mitogenesis irrespective of activator. 5-Nitro-2-furaldehyde was much more inhibitory than the other compounds, while 2-nitrofuran was less inhibitory. When the aldehyde group (5-nitro-2-furaldehyde) was replaced by a carboxyl group (5-nitro-2-furoic acid), the inhibitory activity was also reduced greatly. These results show that while the nitro group alone confers inhibitory activity to the furan ring, the group at the 2 position is crucial. In general, the mitogenic response of purified T cells (lacking accessory cells) triggered by PMA (phorbol ester) was inhibited less than that of the T cell-accessory cell system. With the latter, 50% inhibition of T cell mitogenesis was achieved by nifuroxime, nitrofurazone, and nitrofurantoin at 45-51 and 34-39 microM with PHA and ConA respectively. When purified T cells were used, the values were 71-85 and 55-60 microM respectively. For a given drug concentration, mitogenesis was more inhibited when induced by ConA or anti-CD3 than by PHA. The importance of using a single cell system (purified T cells) was emphasized by the interesting finding that only this system showed enhancement of mitogenesis, up to 35-40% at low drug levels. With the exception of the nitrofuraldehyde, the nitrofurans at strongly inhibitory levels were only moderately cytotoxic, exhibiting 62-85% cell survival after exposure to drug for 68 hr. Our results suggest that nitrofurans inhibit T cell mitogenesis by a relatively non-toxic mechanism; these results are comparable to those obtained for mammalian cells under aerobic conditions.

Adult↗
PubMed1969

Effect of nitrofurans and chlortetracycline on microorganisms associated with shrimp.

Nitrofuran AF-2 displayed greater inhibitory effect than did nitrofuran Z when a mixed bacterial culture, including several proteolytic bacteria, isolated from shrimp was subjected to these compounds in vitro. Nitrofuran Z exhibited greater bactericidal properties than did chlortetracycline in all cultures used. Only 10 mug of nitrofuran AF-2 per ml was sufficient to inhibit the growth of mixed bacteria in nutrient broth, whereas 50 mug of nitrofuran Z per ml was necessary to accomplish the same inhibition. A 50-mug amount of chlortetracycline per ml displayed about the same inhibitory effect as either 10 mug of AF-2 per ml or 20 mug of Z per ml. The isolated proteolytic bacteria showed greater suppression of growth when subjected to AF-2 than when subjected to Z; however, both nitrofurans were effective in preventing growth. The addition of either 1 mug of AF-2 per ml or 5 mug of Z per ml to nutrient broth inhibited the growth of Achromobacter aquarmarinus, whereas chlortetracycline was less effective, requiring about 20 mug to suppress growth to the same degree.

Alcaligenes↗
PubMed1985

Mutagenicity studies of a carcinogenic nitrofuran and some analogues.

Earlier studies showed a strong carcinogenicity of the nitrofuran compound 1,2-dihydro-2-(5'nitro-2'furyl)-3-hydroxy-quinazoline-4-one since carcinomas of the urinary bladder in rats and dogs appeared already after six months of treatment. In order to compare possible mutagenic properties of the compound and to get some information on the genotoxic moiety of the molecule, the genotoxicity of four nitrofuran derivatives and of two chemical analogues without the nitrofuran residue was tested in the Ames Test, E. coli WP2 uvrA, and in the rec-assay with Bacillus subtilis. 2-Nitrofuran was also included in this study. Only 2-nitrofuran and the nitrofuran containing derivatives were active in these bacterial test systems. Metabolic activation by liver homogenate was not needed to demonstrate the genotoxic effects. 1,2-dihydro-2-(5'nitro-2'furyl)-3-hydroxy-quinazoline-4-one was more active in the mutagenicity tests in the presence of exogenous metabolic activation. Further studies revealed that this compound was able to induce unscheduled DNA synthesis but was not mutagenic in the micronucleus test.

Animals↗
PubMed1990

Catalysis of nitrofuran redox-cycling and superoxide anion production by heart lipoamide dehydrogenase.

Heart lipoamide dehydrogenase (LADH) catalyzed redox-cycling and O2-. production by (5-nitro-2-furfurylidene)amino derivatives using NADH as electron donor. NADH was a much more effective electron donor than NADPH for the nitroreductase activity. O2-. production was demonstrated by cytochrome c reduction, adrenochrome formation and the effect of superoxide dismutase. Under optimum conditions, nitroreductase activity was about 1% of LADH activity. One electron oxygen reduction and NADH oxidation correlated in 2:1 stoichiometry. The nitroreductase kinetics was in accordance with an ordered bi-bi mechanism. Nitrofuran derivatives bearing unsaturated five- or six-membered nitrogen heterocycles were more effective substrates than those bearing other groups, namely nifurtimox, nitrofurazone, nitrofurantoin and 5-nitro-2-furoic acid. Other nitro compounds (chloramphenicol, benznidazole, 2-nitroimidazole and 5-nitroindole) were ineffective. With the triazole, traizine and imidazole nitrofuran derivatives, the nitroreductase pH curve showed a maximum at pH 8.8, different from the pH optimum for the lipoamide reductase and diaphorase activities. Spectroscopic observations demonstrated pH-dependent structural changes in the triazole(I) and triazine derivatives which would affect their behavior as nitroreductase substrates. The nitroreductase activity was inhibited by p-chloromercuribenzoate and enhanced by cadmium and arsenite, whereas the NADH-induced LADH inactivation failed to affect the nitroreductase activity. In the absence of oxygen. LADH catalyzed nitrofuran reduction to products more reduced than the nitroanion, which were not reoxidized by oxygen. The anaerobic nitrofuran reduction was inhibited by cadmium and arsenite. The assayed nitrofuran compounds did not inhibit LADH lipoamide reductase activity, at variance with their action on glutathione reductase (Grinblat et al., Biochem Pharmacol 38: 767-772, 1989).

Animals↗