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PubMed1986

Oxygen depletion in irradiated aqueous solutions containing electron affinic hypoxic cell radiosensitizers.

The oxygen concentration in stirred aqueous solutions contained in sealed glass vessels was continuously monitored during irradiation with a sensitive Clark-type oxygen probe. The yield of radiolytic oxygen depletion, g(-O2), in alpha medium was determined to be about 0.44 microM/Gy (equivalent to 3.6 ppm/rad) over a range of oxygen from about 1,000 to 209,000 ppm. Over this same range of oxygen concentration, it was observed that oxygen is depleted in the presence of misonidazole, and that g(-O2) is slightly reduced at low oxygen and at high misonidazole concentrations. Oxygen depletion was observed in solutions of other nitroaromatic sensitizers of widely varying electron affinities: metronidazole, paranitroacetophenone, nitrofurazone, and nifurpipone. Significant protection of oxygen from radiolytic depletion was observed in concentrated solutions of nifurpipone, the most electron affinic drug studied (E17 = -214 mV). No such effect was observed for the least electron affinic compound, metronidazole (E17 = -486 mV).

Acetophenones↗
PubMed1975

The nitrofurans as sperm immobilizing agents.

In certain critical concentrations nitrofurantoin sodium and nitrofurazone cause sperm immobilization. Intraoperative was irrigation with these solutions in 16 patients produced sterility in the immediate postoperative period. This procedure minimizes time-consuming postoperative sperm analyses. Moreover, in underdeveloped countries where postoperative followup is difficult to obtain, this procedure would provide an additional positive factor in an attempt to ensure sterility.

Animals↗
PubMed1997

Wound healing activity of Leucas lavandulaefolia Rees.

Leucas lavandulaefolia Rees (Labiatae), commonly known as Halkusha, is a well-known plant in Indian traditional medicine. On the basis of its traditional use and literature references, this plant was selected for evaluation of its wound healing potential. A methanol extract of L. lavandulaefolia was examined for its wound healing activity both in the form of an ointment as well as an injection in two types of wound model in rats: (i) the excision wound model and (ii) the incision wound model. Both the injection and the ointment of the methanol extract of the plant material produced a significant response in both of the wound types tested. The results were also comparable to those of a standard drug, nitrofurazone, in terms of wound contracting ability, wound closure time, tensile strength and regeneration of tissues at the wound site.

Animals↗
PubMed1998

Electronic spin resonance detection of superoxide and hydroxyl radicals during the reductive metabolism of drugs by rat brain preparations and isolated cerebral microvessels.

A spin trapping technique was used to analyze by electron spin resonance (ESR) the formation of oxygen-derived free radicals during the cerebral reductive metabolism of xenobiotics able to undergo a single electron reduction, i.e. quinones, pyridinium compounds and nitroheterocyclics. Paraquat, menadione and nitrofurazone were used as model compounds of these three classes of molecules. ESR spectra indicative of superoxide and hydroxyl radical formation were obtained by incubation of brain homogenates directly within the ESR cavity at 37 degrees C for each of the three molecules tested. These signals were dependent on nucleotide cofactors, and increased in a time-dependent manner. The NADPH and NADH dependent free radical production was further characterized in brain microsomal and mitochondrial fractions, respectively. By using various combinations of reactive species inactivating enzymes (superoxide dismutase, catalase), a metal chelator (deferoxamine), and an hydroxyl trapping agent (dimethylsulfoxide), it was shown that (1) the primary radical generated was the superoxide anion; and (2) a significant production of the hydroxyl radical also occurred, that was secondary to the superoxide anion production. Consistent signals indicative of the production of both oxygen-derived free radicals were obtained when isolated cerebral microvessels which constitute the blood-brain barrier were incubated with the model molecules. This is of particular toxicological relevance, because this barrier represents a key element in the protection of the brain, and is in close contact with blood-born exogenous molecules.

Animals↗
PubMed1999

Transendothelial permeability changes induced by free radicals in an in vitro model of the blood-brain barrier.

In the present study, we investigated the changes in blood-brain barrier (BBB) permeability following brain endothelial cell exposure to different xenobiotics able to promote free radical generation during their metabolism. Our in vitro BBB model consisted of confluent monolayers of immortalized rat brain capillary endothelial cells (RBE4) grown on collagen-coated filters in the presence of C6 glioma cells grown in the lower compartment. We have recently shown that a range of xenobiotics, including menadione, nitrofurazone, and methylviologen (paraquat) may undergo monoelectronic redox cycling in isolated brain capillaries, giving rise to reactive oxygen species. In this study, addition of 100 microM menadione to the culture medium for 30 min significantly increased the permeability of endothelial cell monolayers to radiolabeled sucrose. The effect on endothelial permeability induced by menadione was dose-dependent and reversible. These permeability changes preceded the onset of cell death, as assessed by the Trypan blue exclusion method. Pre-incubation with superoxide dismutase and catalase blocked changes in sucrose permeability to control levels in a dose-dependent manner, suggesting the involvement of reactive oxygen species in menadione-induced BBB opening.

Animals↗
PubMed1979

Inhibition of DNA synthesis by nitroheterocycles. II. Mechanisms of cytotoxicity.

Nitroheterocycles have been shown to inhibit the incorporation of 3H-TdR by cultured L-929 cells, and the degree of inhibition is related to their electron-affinity. On the basis of their chemical reactivity and potential clinical utility, nitrofurazone, misonidazole and metronidazole were selected for more detailed studies of the mechanism of inhibition of DNA synthesis. Double-isotope labelling in conjunction with hydroxyapatite chromatography allowed the evaluation of drug effects on initiation of DNA replicons, DNA chain elongation and DNA damage (single-strand breaks), and their correlation with eventual cell viability. Partial inhibition of initiation of DNA synthesis generally preceded other measurable effects, and was not reversed by incubation in the absence of drug. In the absence of DNA strand breaks (at low drug doses or after a repair interval) the rate of elongation was similar in both treated and untreated cell populations. Measurable DNA damage (strand breaks) was predictive for cytotoxicity. At lower drug doses, or under aerobic conditions, DNA synthesis was not always associated with a decrease in plating efficiency (cytotoxicity) but was reflected in decreased colony size (growth rate) of the cells. Thus the aerobic "toxicity" previously reported for chronic exposure to these agents may be better described as a "cytostatic" effect. Under anaerobic conditions (where cell killing is much greater) inhibition of initiation plays a less important role, and the nitroheterocycles are metabolically reduced to intermediates which are truly cytotoxic.

Anaerobiosis↗
PubMed2005

Depletion of four nitrofuran antibiotics and their tissue-bound metabolites in porcine tissues and determination using LC-MS/MS and HPLC-UV.

Depletion of the nitrofuran antibiotics furazolidone, furaltadone, nitrofurantoin and nitrofurazone and their tissue-bound metabolites AOZ, AMOZ, AHD and SEM from pig muscle, liver and kidney tissues is described. Groups of pigs were given feed medicated with one of the nitrofuran drugs at a therapeutic concentration (400?mg?kg(-1)) for ten days. Animals were slaughtered at intervals and tissue samples collected for analysis for six weeks following withdrawal of medicated feed. These samples were analysed both for parent nitrofurans (using LC-MS/MS and HPLC-UV), and for tissue-bound metabolites (using LC-MS/MS). The parent drugs were detectable only sporadically and only in pigs subjected to no withdrawal period whatsoever. This confirms the instability of the four major nitrofuran antibiotics in edible tissues. In contrast, the metabolites accumulated to high concentrations in tissues (ppm levels) and had depletion half lives of between 5.5 and 15.5 days. The metabolites of all four drugs were still readily detectable in tissues six weeks after cessation of treatment. This emphasizes the benefits of monitoring for the stable metabolites of the nitrofurans.

Animals↗
PubMed1976

In vitro penetration of topical antiseptics through eschar of burn patients.

The ability of topical antiseptics to penetrate eschar of burn patients was determined by the agar diffusion technique. Gentamicin sulfate, mafenide acetate, nitrofurazone, povidone-iodine, silver nitrate, and silver sulfadiazine were tested against clinical isolates of Candida albicans, Staphylococcus, Streptococcus, and gram-negative bacilli including Pseudomonas aeruginosa. In practically all instances, the diameters of the zones of inhibition observed using eschar were comparable to those obtained with filter-paper discs. This finding showed that the antimicrobial agents could penetrate eschar and retain their effectiveness after penetration.

Anti-Infective Agents, Local↗
PubMedDate not supplied

Pulsed electromagnetic fields in experimental cutaneous wound healing in rats.

Electromagnetic fields are now being used in many diseases such as osseous, ligamental, cartilaginous, or nervous reparation, diabetes, and myocardial or cerebral ischemia. Although many publications show the usefulness of magneto-therapy, discrepancies exist about the utility of electromagnetic fields in skin wound healing. The objective of this work was to study the effect of pulsed electromagnetic fields on wound healing in rats. Twenty-two male Wistar rats were used; a circular lesion was made in the back of each animal. They were divided into three groups: group C (control) with sham treatment (n = 8), group NF, treated with topical nitrofurazone solution (n = 7), and group PEMF, treated with pulsed electromagnetic fields of 20 mT (n = 7). The treatments were 35 minutes twice a day. The absolute and relative values of the area and perimeter of the wounds showed significantly lower values in the PEMF group at days 7, 14, and 21 compared with those in group C (p < 0.01, analysis of variance), whereas the PEMF group showed significantly lower values at day 21 only compared with the NF group (p < 0.01, analysis of variance). The results suggest a significant beneficial stimulation in the wound healing process in rats treated with PEMF, which could lead to the development of a practical tool for research and clinical use.

Administration, Topical↗
PubMed1987

Control of burn wound sepsis: a comparison of in vitro topical antimicrobial assays.

The Minimal Inhibitory Concentration (MIC) and the Nathan's Agar Well Diffusion (NAWD) tests are bacterial antimicrobial susceptibility predictors. Some suggest that the NAWD is not as reliable as the MIC test. We compared the MIC and NAWD tests as to how well they agree to bacterial sensitivity or resistance and predicted clinical outcome of burn wound infections. Using 65 bacterial isolates from burned patients, the MIC and NAWD tests agreed in 60.0% of the isolates (vs. a perfect agreement of 100%, p less than 0.001), implying that these tests are not interchangeable. From 18 burned patients treated with nitrofurazone or mafenide acetate, 28 infectious isolates were evaluated. The outcome of these infections was correctly predicted by NAWD in 92.8% and the MIC in 72.0% of the cases (p less than 0.05). It seems that for burns treated with topical antimicrobials, the NAWD is a more reliable predictor of bacterial susceptibility.

Bacteria↗
PubMed2000

Assessing overall risk in reproductive experiments.

Toxicologists are often interested in assessing the joint effect of an exposure on multiple reproductive endpoints, including early loss, fetal death, and malformation. Exposures that occur prior to mating or extremely early in development can adversely affect the number of implantation sites or fetuses that form within each dam and may even prevent pregnancy. A simple approach for assessing overall adverse effects in such studies is to consider fetuses or implants that fail to develop due to exposure as missing data. The missing data can be imputed, and standard methods for the analysis of quantal response data can then be used for quantitative risk assessment or testing. In this article, a new bias-corrected imputation procedure is proposed and evaluated. The procedure is straightforward to implement in standard statistical packages and has excellent operating characteristics when used in combination with a marginal model fit with generalized estimating equations. The methods are applied to data from a reproductive toxicity study of Nitrofurazone conducted by the National Toxicology Program.

Abnormalities, Drug-Induced↗
PubMed1986

Contact hypersensitivity to topical antibacterial agents.

Three hundred ninety patients with suspected contact dermatitis to topical medicaments were patch tested with various commercially available antibacterial agents to evaluate the incidence of contact hypersensitivity. The common sensitizers were nitrofurazone, neomycin, oxytetracycline, cetrimide, and framycetin. The least common sensitizers were sodium fusidate, chlorhexidine hydrochloride, and gentian violet. Cross-sensitivity was observed between neomycin, framycetin, and gentamicin.

Anti-Infective Agents↗
PubMed1978

Contact dermatitis in Salvador, Brazil.

In Salvador, Brazil, 536 patients were patch tested with 24 contact allergens. The most common sensitizers included potassium dichromate, thimerosal, hydroquinone, nitrofurazone ointment and nickel sulfate. The results of this South American study are compared with those published by North American and European dermatologists. Low frequencies of positive reactions were encountered in Salvador to some substances, including mercury bichloride and p-phenylenediamine. The influences of climate and life style in determining patterns of contact sensitivity are discussed.

Adult↗
PubMed1972

Cell division and prophage induction in Escherichia coli: effects of pantoyl lactone and various furan derivatives.

Strain T-44 is a thermosensitive mutant of Escherichia coli in which both cell division and prophage repression are altered at elevated temperatures. The effects of various ribosides, pantoyl lactone, and the furfural derivatives nitrofurazone and 5-methyl furfural suggest that some low-molecular-weight compound is important in the control of cell division and prophage repression in this strain. This low-molecular-weight compound may have a five-membered oxygen-containing ring as part of its structure.

Cell Division↗
PubMed1996

Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase.

We identified the nfsA gene, encoding the major oxygen-insensitive nitroreductase in Escherichia coli, and determined its position on the E. coli map to be 19 min. We also purified its gene product, NfsA, to homogeneity. It was suggested that NfsA is a nonglobular protein with a molecular weight of 26,799 and is associated tightly with a flavin mononucleotide. Its amino acid sequence is highly similar to that of Frp, a flavin oxidoreductase from Vibrio harveyi (B. Lei, M. Liu, S. Huang, and S.-C. Tu, J. Bacteriol. 176:3552-3558, 1994), an observation supporting the notion that E. coli nitroreductase and luminescent-bacterium flavin reductase families are intimately related in evolution. Although no appreciable sequence similarity was detected between two E. coli nitroreductases, NfsA and NfsB, NfsA exhibited a low level of the flavin reductase activity and a broad electron acceptor specificity similar to those of NfsB. NfsA reduced nitrofurazone by a ping-pong Bi-Bi mechanism possibly to generate a two-electron transfer product.

Amino Acid Sequence↗
PubMed1988

Oxidative metabolites of 5-nitrofurans.

We synthesized the 4-hydroxy derivatives of nitrofurazone, furazolidone and nitrofurantoin. Then we dosed rats orally with these antibiotics and isolated the intensely yellow, polar metabolites from their urine. A comparison of the ultraviolet and nuclear magnetic resonance spectra of these metabolites with the corresponding synthetic derivatives confirmed that the metabolites are 4-hydroxynitrofurazone, 4-hydroxyfurazolidone and 4-hydroxynitrofurantoin.

Animals↗
PubMed1991

Effect of nitrofurans on duodenal ulceration induced by cysteamine or indometacin.

The present experiments examined the protective effect of the nitrofuran drugs, furazolidone (FZ) and nitrofurazone (NF), on duodenal ulceration induced by cysteamine or indometacin in rats. FZ at oral doses of 25, 50 or 100 mg/kg for 2 consecutive days signficantly reduced, in a dose-dependent manner, the incidence and extent of cysteamine-induced ulceration. However, oral NF (100 mg/kg) given for 2 consecutive days had no significant effect on duodenal ulceration. The duodenal mucus content of rats was not significantly affected by either FZ or cysteamine treatments. FZ at an oral dose of 100 mg/kg for 2 consecutive days significantly reduced the incidence and extent of indometacin-induced ulceration. Smaller doses of 25 or 50 mg/kg had no significant effects.

Animals↗
PubMed1978

Comparative in vitro activity of five nitrofurans.

Five nitrofurans- nitrofurantoin, nifuratel, nitrofurazone, furazolidone and and SQ 18,506--have been tested against 201 microbial strains. Escherichia coli, Streptococcus faecalis, micrococci and Staphylococcus epidermidis were sensitive to all five compounds; furazolidone and SQ 18,506 were the most active against these species. Klebsiella aerogenes was less sensitive, and Proteus spp., Providencia stuartii and Pseudomonas aeruginosa strains were resistant. Nifuratel was inhibitory for some Candida albicans strains, and SQ 18,506 was highly active against this species. Nifuratel was judged overall to have superior in vitro antimicrobial properties to nitrofurantoin.

Bacteria↗