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PubMed2002

Nitrofurazone induces non-regenerative hepatocyte proliferation in rats.

The antibiotic nitrofurazone (NF) has been known for its testicular toxicity; in contrast, much less is known about its effect on the liver. NF was given to male rats for up to 7 consecutive days to evaluate NF-induced effects on the liver. NF increased hepatocyte DNA synthesis and liver weight in a dose-dependent manner, with no apparent histological or biochemical evidence of cell damage or loss. The hepatocyte proliferation ceased after a few days despite the continuation of treatment. The absence of cell damage indicates that NF-induced hepatocyte proliferation is different from regenerative proliferation that is seen after partial hepatectomy or cell necrosis.

Administration, Oral↗
PubMed2003

Antioxidants suppress nitrofurazone-induced proliferation of hepatocytes.

On administration to rats at a subtoxic dose, the antibiotic nitrofurazone (NF) has been shown to increase hepatocyte DNA synthesis and liver weight in a dose-dependent manner, with no histological or biochemical evidence of cell damage or necrosis. Free radicals are implicated in NF metabolism, as well as in the DNA synthesis or cell proliferation induced by a number of other chemicals. In the present study, NF was given alone or concomitantly with the antioxidants N-acetylcysteine or cyanidanol. Antioxidants prevent the effects of free radicals. Co-administration decreased hepatocyte proliferation to the same level as the control. This suppression of NF-induced hepatocyte proliferation by antioxidants therefore strongly suggests that free radical production is involved in this process.

Acetylcysteine↗
PubMed2004

Implications of the use of semicarbazide as a metabolic target of nitrofurazone contamination in coated products.

Data from the Brazilian Agricultural Ministry show that before the implementation of the Brazilian programme of nitrofuran control in February 2003, the cases of contamination of Brazilian chicken by nitrofurans were almost exclusively due to furaltadone. After May 2003, such cases decreased until no more reports of Brazilian chicken contamination with this nitrofuran were reported. Curiously, after April 2003, an increase was observed in the numbers of contaminated samples by semicarbazide, the target metabolite of nitrofurazone. Most Brazilian chicken found to be contaminated with semicarbazide has been covered with flour, salt and spices. For this reason, the authors' laboratory initialized a programme for tracing possible sources of food contamination by semicarbazide. After several semicarbazide positives in flour of controlled origin (results varying between 2.2 and 5.2 microg kg(-1)), the different additives used in the cereal industry as flour improvement agents were studied. The results indicate that the compound azodicarbonamide was responsible for the source of the contaminant semicarbazide.

Animals↗
PubMed1989

Antimutagenic specificity against spontaneous and nitrofurazone-induced mutations in Escherichia coli K12ND160.

Escherichia coli K12ND-160 possesses characteristics which make it highly suitable for studies on mutagenic/antimutagenic specificity and has been used to investigate such effects for several agents. Nitrofurazone (NFZ) was used as a mutagen at non-lethal concentrations; it causes mutation from fucose sensitivity to resistance (FucS----FucR) and from inability to utilize melibiose to melibiose utilization (Mel(-)----Mel+), but does not induce mutations from deoxygalactose sensitivity to resistance (DGAS----DGAR). Caffeine is mutagenic for reversions from lactose non-utilization to utilization (Lac(-)----Lac+) and mutations from FucS----FucR, but it is antimutagenic for mutations from 6-azauracil sensitivity to resistance (AzaUS----AzaUR) and Mel(-)----Mel+ reversions and produces no effect on spontaneous DGAS----DGAR mutations. Added guanosine and cytidine (G + C at 100 micrograms/ml each) exert antimutagenic activity against spontaneous Lac(-)----Lac+ reversion, but not against caffeine-induced Lac(-)----Lac+ reversions; a strong antimutagenic effect on spontaneous Mel(-)----Mel+ reversion is also observed. The addition of G + C does not result in either mutagenic or antimutagenic effects against spontaneous or NFZ-induced FucS----FucR or DGAS----DGAR mutations; it is, however, strongly mutagenic for AzaUS----AzaUR mutations. The 'natural antimutagen', chlorophyllin, is antimutagenic for DGAS----DGAR mutations, but fails to demonstrate such activity against spontaneous or caffeine-induced Lac(-)----Lac+ reversion, spontaneous or NFZ-induced Mel(-)----Mel+ reversion, or spontaneous or NFZ-induced FucS----FucR mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

Caffeine↗
PubMed1988

Effect of furazolidone and nitrofurazone on brain gamma-amino butyric acid and glutamate concentrations in chickens.

1. The concentrations of gamma-amino butyric acid (GABA) and glutamate were measured in the brains of chickens which were treated with furazolidone (FZ) or nitrofurazone (NF) at oral doses of 12.5, 25 or 50 mg/kg for 5 days. 2. At the end of the treatment, birds on the small dose of FZ or NF lost about 9% of their bodyweight, and those on the high doses lost about 18%. 3. Both drugs produced dose-dependent increases in the concentrations of GAA and glutamate which were statistically significant at doses of 25 and 50 mg/kg of NF and 50 mg/kg of FZ.

Animals↗
PubMed1989

Effect of furazolidone and nitrofurazone on brain gamma-amino butyric acid and glutamate concentrations in chickens.

1. The concentrations of gamma-amino butyric acid (GABA) and glutamate were measured in the brains of chickens which were treated with furazolidone (FZ) or nitrofurazone (NF) at oral doses of 12.5, 25 or 50 mg/kg for 5 days. 2. At the end of the treatment, the birds lost about 9% of their bodyweight when on the small dose of FZ or NF and about 18% when on the high doses. 3. Both drugs produced dose-dependent increases in the concentrations of GABA and glutamate which were statistically significant at doses of 25 and 50 mg/kg of NF, and 50 mg/kg of FZ.

Animals↗
PubMed1999

Activities of a nitrofurazone-containing urinary catheter and a silver hydrogel catheter against multidrug-resistant bacteria characteristic of catheter-associated urinary tract infection.

The in vitro inhibitory activity of a nitrofurazone-coated urinary catheter (NFC) against 86 recently obtained susceptible and multidrug-resistant (MDR) clinical isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus faecium, which are species implicated in catheter-associated urinary tract infection and which traditionally have been susceptible to nitrofuran derivatives, was determined using an agar diffusion assay. In a subset of these strains, the activity of the NFC was compared with that of a silver hydrogel urinary catheter (SHC), and the durability of each catheter's inhibitory activity was assessed during serial daily transfers of catheter segments to fresh culture plates. Except for vancomycin-resistant E. faecium, the NFC was active against all isolates tested and showed comparable inhibition zones with susceptible and MDR strains of each species. In contrast, the SHC inhibited only certain staphylococci (P < 0.01 versus the NFC), and among these strains, the SHC produced smaller inhibition zones than did the NFC (P < 0.01). Inhibition was evident for up to 5 days with the NFC, but for only 1 day (if at all) with the SHC (P < 0.01). These data document that, for most genera which traditionally have been susceptible to nitrofuran derivatives, the NFC remains active against contemporary MDR isolates. They also demonstrate that the in vitro antibacterial activity of the NFC is markedly superior to that of the SHC in several respects. Thus, the NFC shows promise for clinical use in the current era of MDR bacteria.

Anti-Infective Agents, Local↗
PubMed1978

Genetics of nitrofurazone resistance in Escherichia coli.

Wild-type Escherichia coli cells are sensitive to nitrofurazone (NF) and many other nitrofuran derivatives. A variety of evidence indicated that these compounds are converted to toxic "active" metabolites by reductases present in the bacteria. Sensitive E. coli K-12 acquired threefold-greater resistance to NF in one mutational step. These partially resistant mutants could undergo a second mutation that made them 10 times as resistant as the wild type. Mutation of wild-type strain K-12 to the higher level of resistance in a single step was not observed. The first mutational step was associated with partial loss of reduced nicotinamide adenine dinucleotide phosphate-linked, O(2)-insensitive NF reductase activity, and the second step was associated with loss of the remaining activity. The two-step mutants did, however, contain other NF reductases that were inhibited by O(2) and reduced NF only under anaerobic conditions. We designated the genes that control reductase activity "nitrofuran sensitivity genes" (nfsA and nfsB). Thus, wild-type strains are nfsA(+)nfsB(+), and the resistant double mutants are nfsA nfsB. A variety of crosses established that these genes are both located close to gal, that the most probable sequence is lac nfsB gal nfsA, and that the single-step mutants with an intermediate level of resistance are nfsA nfsB(+). The nfsA(+)nfsB strains contained about 70 to 80% of the wild-type reductase I activity-apparently enough to confer wild-type sensitivity. This reductase activity was resistant to 2 M urea. The nfsA nfsB(+) strains had only 20 to 30% of the wild-type activity, and this residual activity was sensitive to 2 M urea.

Crosses, Genetic↗
PubMedDate not supplied

A mechanistic study of ovarian carcinogenesis induced by nitrofurazone using rasH2 mice.

In order to clarify whether the ovarian tumors induced in a long-term carcinogenicity study of nitrofurazone (NF) in mice can be also produced in a short-term model using transgenic (Tg) mice carrying the human c-Ha-ras gene (rasH2 mice), the following 3 experiments were performed. In experiment 1, both rasH2 mice and their wild CB6F1 littermates carrying no c-Ha-ras gene (non-Tg mice) that were fed a diet containing 500 to 1,000 ppm NF for 7 weeks demonstrated ovarian atrophy characterized by decreased labeling indices (LIs) for proliferating cell nuclear antigen (PCNA) in granulosa cells. In experiment 2, increased numbers of atretic follicles and decreased PCNA LIs in granulosa cells were recognized in rasH2 mice given diets containing 250 or 500 ppm NF for 26 weeks, but no tumor induction was grossly observed. In experiment 3, similar ovarian atrophy was observed in association with increased serum luteinizing hormone (LH) levels in both rasH2 and non-Tg mice given diet containing 1,000 ppm NF for 11 days. These results indicate that long-term NF treatment induces ovarian tumors in mice, possibly by continuous stimulation with gonadotropins such as LH via a negative-feedback phenomenon secondary to ovarian atrophy (as the tumor-induction mechanism), although we could not completely rule out a genotoxic mechanism.

Animals↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 20). Testicular toxicity of nitrofurazone after 2 and 4 weeks.

Nitrofurazone (NF) has been previously demonstrated to induce testicular toxicity with 4 weeks of oral administration in rats. In the present study, rats were administered NF to assess whether testicular toxicity becomes evident with a 2-week administration period. Male Sprague-Dawley rats were administered oral doses of NF at 50 mg/kg for 2 or 4 weeks. Another group was administered NF at 100 mg/kg for 2 weeks. The control animals received the vehicle (0.5% methylcellulose) for 4 weeks. Organ weights of the testis and epididymis were significantly decreased in all NF-administered animals, and seminiferous tubules were severely atrophied, due to a total absence of spermatids and degeneration and desquamation of spermatocytes. In the epididymis, decreased numbers of spermatozoa were evident in the ducts. In rats that were administered NF at 50 mg/kg, the changes in the epididymis in the 2-week group were less prominent than those in the 4-week group. In the testis, however, the changes were similar in both groups. Thus it was demonstrated that NF-induced testicular toxicity comparable to that observed after 4 weeks of administration is also detectable after 2 weeks.

Administration, Oral↗
PubMed2001

High-performance liquid chromatographic determination of carbadox, olaquindox, furazolidone, nitrofurazone, and nitrovin in feed.

A high-performance liquid chromatography with gradient programming method was developed to determine the amount of carbadox (CBX), olaquindox (OLQ), furazolidone (FZ), nitrofurazone (NF), and nitrovin (NTV) in feed simultaneously. Complete separation of the drugs was obtained using a C8 silica gel column with gradients of acetonitrile as mobile phase. The mobile phase used an acetonitrile gradient with an initial hold time of 1 min at 0% acetonitrile, followed by an increase to 50% acetonitrile over 10 min. The correlation coefficients (r) for calibration curves of the five feed additives were greater than 0.999. The relative standard deviations (RSDs) of peak areas from four injections for these drugs at three concentrations were less than 3.0%, although the RSD for NTV at 5 ppm was somewhat large (6.7%). The medicated feeds were extracted by pretreating with water, extracted with 95% dimethylformamide overnight at room temperature, and cleaned up on a column of alumina oxide. Recoveries of CBX, OLQ, FZ, NF, and NTV from low level spiked feed were 102.0, 94.6, 97.4, 110.6, and 66.0%, respectively, and from high level spiked feed, they were 114.09, 99.1, 97.3, 109.9, and 62.7%, respectively.

Animal Feed↗
PubMed1979

High pressure liquid chromatographic detection and estimation of furazolidone and nitrofurazone in animal feeds.

The feed sample is extracted with acetone or dimethylformamide-acetone (1 + 1) and the filtered extracts are evaporated to dryness. The residue is dissolved in chloroform and transferred to a silica gel column. The nitrofurans are eluted with methanol-chloroform (50 + 50). A portion of the eluate is evaporated to dryness and the residue is redissolved in a small volume of methanol. Aliquots of the methanolic solution are injected into a liquid chromatograph with a muBondapak C18 column, using 30% acetonitrile as the eluting solvent and ultraviolet detection at 365 nm. Several samples spiked with 0.5--50 ppm furazolidone or nitrofurazone and 2 commercial samples were analyzed by the proposed method.

Animal Feed↗
PubMed1979

High pressure liquid chromatographic determination of nitrofurazone in milk.

A rapid high pressure liquid chromatographic (HPLC) screening method for the quantitative determination of nitrofurazone in milk has been developed. The drug is extracted with ethyl acetate from a 2.0 ml milk serum sample, the organic layer is evaporated to dryness, and the residue is dissolved in the mobile phase and injected into the liquid chromatogarph. A reverse phase muBondapak C18 column is used with monitoring at 365 nm. The detection limit is 5 ppb and recoveries are 57--67%. Mass spectroscopic confirmation of the HPLC nitrofuran peak is described.

Animals↗
PubMed1978

Nitrofurazone: vas irrigation as an adjunct in vasectomy.

Intraoperative vas irrigation with nitrofurazone utilized in a 1-mg/ml concentration can cause immediate sterility postoperatively. This irrigation procedure adds little time to the standard vasectomy and can easily be performed as an outpatient office procedure, minimizing time-consuming postoperative semen analyses. Moreover, in developing countries where postoperative vasectomy follow-up may be more difficult to obtain and may even be nonexistent, this procedure would provide an additional positive factor in an attempt to ensure sterility.

Cell Count↗
PubMedDate not supplied

[Use of the combination of a nitrofurazone derivative with polyethylene glycols in the prevention of the formation of peritoneal adhesions - experimental study].

The authors studied the effectiveness of the association of Nitrofurazone derivates with Polyethylene glycol (NPG) on peritoneal adhesions prevention. Despite the fact of constitutional characteristics may elicit or not the formation of adhesions and bands, they concluded that, although the drugs have not demonstrated the capacity of avoiding such phenomena, they could block this process at a fibrinous stage, which is relatively safe concerning the possibility of intestinal obstruction.

Animals↗
PubMedDate not supplied

Simultaneous determination of nitrofurazone, nitrofurantoin, and furazolidone in channel catfish (Ictalurus punctatus) muscle tissue by liquid chromatography.

A liquid chromatographic (LC) method was developed for the simultaneous determination of nitrofurazone (NFZ), nitrofurantoin (NFT), and furazolidone (FZD) in catfish muscle tissue. The drugs were extracted from the tissue with acetonitrile, and the lipids were removed from the extract with hexane. The acetonitrile extract was evaporated by rotary evaporation, and the resultant drug residues were dissolved with LC mobile phase. The mixture was sonicated, centrifuged, and filtered. The drugs were determined by using LC with a C18 reversed-phase (ODS Hypersil) column, a mobile phase of acetonitrile-1% aqueous acetic acid (25 + 75), and a photodiode array ultraviolet detector at 375 nm. NFZ, NFT, and FZD were each determined in catfish tissue at 5 fortification levels (80, 40, 20, 10, and 5 ng drug/g tissue). Average recoveries of each of the 3 drugs at each level ranged from 70.7 to 101.5%, and relative standard deviations ranged from 2.2 to 18.6%. The limit of detection of each drug was approximately 1 ng drug/g tissue, and the limit of quantitation was 5 ng drug/g tissue. In the second part of the study, the method was used to determine nitrofuran residues incurred in catfish tissue. Live channel catfish were intravascularly doses (10 mg/kg body wt) with NFZ to generate drug-incurred fish muscle tissue. Incurred NFZ levels exceeded 400 ng drug/g tissue at 2 h after dosing but decreased rapidly to approximately 1 ng drug/g tissue by 8 h after dosing, as determined by this method.

Animals↗
PubMedDate not supplied

Simultaneous determination of nitrofurazone and furazolidone in shrimp (Penaeus vannamei) muscle tissue by liquid chromatography with UV detection.

A liquid chromatographic (LC) method was developed for the simultaneous determination of nitrofurazone (NFZ) and furazolidone (FZD) in shrimp muscle tissue. The drugs are extracted from the tissue with acetonitrile, and the lipids and lipophilic pigments are removed from the extract with hexane. The remaining acetonitrile extract is evaporated by rotary evaporation, and the resultant residues are dissolved with LC-grade water, applied to a preconditioned C18 solid-phase extraction column, and eluted with acetonitrile. The acetonitrile eluant is then dried under nitrogen, and the resultant drug residues are dissolved with mobile phase and filtered. The drugs are determined by LC by using a C18 reversed-phase (octyldecylsilyl Hypersil) column, a mobile phase of acetonitrile--1% aqueous acetic acid (25 + 75, v/v), and a photodiode array UV detector at 375 nm. NFZ and FZD were determined in shrimp tissue at each of 5 spiking levels (64, 32, 16, 8, and 4 ng drug/g tissue). Absolute recoveries ranged from 70.6 to 78.4%, and relative standard deviations ranged from 4.0 to 13.6%. The limit of detection of pure standard of each drug was approximately the equivalent of 1 ng drug/g tissue, and the limit of determination in a sample was 4 ng drug/g tissue.

Animals↗