Concentrations Of Furazolidone Research Articles

The Comparison of the Clinical Efficacy and Drug Tissue Distribution of Furazolidone and Tetracycline-quadruple Therapy in Helicobacter pylori Eradication: A Randomized Controlled Trial.

Helicobacter pylori (H. Pylori) is considered a main causative organism of gastric ulcers, gastric cancer and duodenal ulcers. The current treatment relies on a combination of antimicrobial agents and acid suppressant agents, but the eradication effect is not satisfactory. To clarify the concentration of antibiotics at the lesion site, we investigate the clinical efficacy and drug tissue distribution of the combination therapy of furazolidone and tetracycline in eradicating H. Pylori. Patients with H. pylori infection (n = 60) were randomized to either group A or B. Bismuth potassium citrate capsules 220mg, omeprazole enteric-coated capsules 20mg, amoxicillin capsules 1000mg, each twice per day, and furazolidone tablets 500mg were administered to group A. Group B was treated with bismuth potassium citrate capsules 220mg, omeprazole enteric-coated capsules 20mg, amoxicillin capsules 1000mg, and tetracycline tablets 500mg each twice per day for 2 weeks. The serum and gastric juice, gastric antrum, gastric horn, and gastric body samples were taken under a gastroscope on the 14th day. The antimicrobial concentrations in serum and tissue samples were determined by high-performance liquid chromatography. In the negative group of furazolidone, the concentrations of gastric antrum, gastric body, and gastric angle were significantly higher than those in the positive group (P = 0.017, 0.015, and 0.028). The concentrations of furazolidone in gastric fluid, gastric antrum, gastric angle, and gastric body were ∼421 times, 82 times, 17 times, and 51 times higher than those in serum, respectively. The concentrations of tetracycline in the serum and gastric angle of the tetracycline negative group were significantly higher than those in the positive group (P = 0.036 and 0.042), and the tetracycline concentrations in the gastric horn and gastric body were about 4 and 6 times higher than those in the serum, respectively. The concentration of amoxicillin in group B was higher than that in group A, especially in serum, gastric juice, gastric angle, and gastric body (P < 0.05). Furazolidone is mainly concentrated and sequentially distributed in gastric juice, gastric antrum, and gastric body tissue, and tetracycline is mainly distributed in serum, gastric angle, and gastric body, whereas amoxicillin is mainly distributed in serum, gastric juice, gastric angle, and gastric body. Improving the concentration and tissue distribution of antibacterial drugs in the human gastric mucosa is the key to ensuring the ideal eradication rate of quadruple therapy.

S and N co-doped graphene quantum dots as an effective fluorescence probe for sensing of furazolidone after magnetic solid-phase microextraction using magnetic multiwalled carbon nanotubes

Sulfur and nitrogen-doped graphene quantum dots (S, N-GQDs) was synthesized and a selective measurement method was designed for the quantification of furazolidone based on fluorescence quenching of synthesized quantum dots. Furazolidone was first separated and preconcentrated from samples with complex matrices by magnetic solid-phase microextraction using magnetic multiwalled carbon nanotubes (MMWCNTs) as the sorbent. The effective parameters on the extraction of furazolidone were investigated and optimized by one variable at a time and central composite design methods. Under the optimized conditions, the fluorescence quenched linearly with the furazolidone concentration in the range of 8.0–250.0 µg L−1 with a limit of detection (LOD) 2.1 µg L−1. The relative standard deviation (RSD) for intra-day and inter-day analysis (at 40.0 μg L−1 of furazolidone, n = 6) was 3.6 and 5.6%, respectively. The developed method was successfully applied to the quantification of trace amounts of furazolidone in chicken liver, biological fluids, and poultry effluent.

Development of Effervescent Granules with Solid Dispersion of Furazolidone

Introduction. Treatment of infectious and inflammatory diseases demands active substances (AS), characterized by low resistance of microorganisms, high specificity of the mechanism of action and a wide range of antimicrobial activity. Though furazolidone (FZ) – AS meets these criteria, however, practically insolubility in water significantly limits its use. Use of the solid dispersion method (SD) could increase the solubility and dissolution rate of AS with low water solubility. revious studies indicate an increase in the solubility and dissolution rate of FZ in water from SD with polyvinylpyrrolidone-24 000 (PVP-24 000) in a ratio with AS &gt; 6 : 1 by weight. As a result, it becomes possible to introduce SD FZ into the composition of rapidly dissolving effervescent dosage forms, for example, granules for obtaining solutions for external use for the treatment of infectious and inflammatory diseases.Aim. Development of the composition and technology for producing effervescent granules based on solid dispersions of FZ for obtaining a solution for external use.Materials and methods. FZ substance, polyvinylpyrrolidone-24 000 ± 2000 (PVP-24 000 ± 2000), tartaric acid, malic acid, sodium carbonate anhydrous, ethyl alcohol 96 %, purified water. We provided the granules through fluidized bed granulation. The analysis of the obtained granules included the following parameters: description, granule size, loss in mass on drying, disintegration, uniformity of dosage according to GPМ 1.4.1.0004.15 "Granules". Then followed a qualitative and quantitative determination of AS and analysis of the pH of the aqueous solution of the granules. To study the stability and shelf life of the samples of granules, we laid them to the storage in accordance with GPМ 1.10009.15 "Stability and shelf life of drugs".Results and discussion. We developed he composition and technology of FZ effervescent granules for obtaining a solution for external use. Granules are obtained by separate granulation of the main (containing a SD AS) and acid components, followed by mixing in ratios that provide a solution of FZ with a concentration of 0.004 % in water at room temperature. Later we assessed the quality of the obtained compositions and determined, the shelf life (2 years) and storage conditions (in a dry, dark place at a temperature of 25 °C) of the developed compositions of granules.Conclusion. As a result of technological and chemical-pharmaceutical research using the SD method, we developed a new FZ dosage form – effervescent granules, which makes it possible to obtain an aqueous solution with a concentration of FZ 0.004 % in less than 5 minutes without heating. Based on the results of the work, an application was filed with Rospatent No. 2021105988 dated 10.03.2021, "Fast-dissolving dosage form of furazolidone and a method for its production".

Porous-coral-like cerium doped tungsten oxide/graphene oxide micro balls: A robust electrochemical sensing platform for the detection of antibiotic residue

Metal oxides decorated carbon nanomaterials, as an electrode material have been well explored in the field of electrochemical sensor. However, instead of using the high concentration of graphene oxide (GO), we try to explore the influence of minimum quantity of GO in material synthesis. Here we demonstrate the hydrothermal synthesis of low-cost cerium (Ce)-doped tungsten oxide/graphene oxide (CeW/GO) composite for the precise electrochemical detection of antibiotic drug furazolidone (FUZ). For the synthesis of composite, 40 μg/mL concentration of GO has been utilized. Then, several physicochemical and electrochemical techniques were used to examine the morphological, structural, and electrochemical characteristics of the CeW/GO composite. Interestingly, the composite material has a porous-coral-like structure, which is being described here for the first time. The GO nanosheets cover the CeW and make the smooth surface and lead to the porous structure. Then we looked into the analytical behavior of CeW/GO composite modified glassy carbon electrode for the application towards the electrochemical detection of the FUZ using the voltammetric technique. The effect of experimental conditions, including loading concentration of active material, pH, scan rate, accumulation time, and concentration of FUZ, were analyzed with respect to the reduction peak current response of FUZ. At the optimum conditions, the fabricated sensor has a low detection limit (0.054 μM), appreciable sensitivity (2.5 μA μM −1 cm −2 ) with a wide linear range (1–260 μM), and the decent anti-interference ability for FUZ detection. Furthermore, the developed sensor was successfully used to assess the FUZ concentration in the human urine samples, yielding satisfactory results. • porous-coral-like CeW/GO micro balls composite material was designed for the first time. • The CeW/GO composite was employed as a novel electrocatalyst to detect the furazolidone (antibiotic drug). • A detailed study was made on electrochemical performance of the developed sensor. • The performance of CeW/GO/GCE was comparable with the noble metals (Pt, Re, and Au) based modified electrodes.

Blue-emitting glutathione-capped copper nanoclusters as fluorescent probes for the highly specific biosensing of furazolidone

Herein, a facile, straightforward and green method was developed to prepare copper nanoclusters by using glutathione (GSH) as the protecting agent and ascorbic acid as the reducing agent. The glutathione-templated copper nanoclusters (GSH-Cu NCs) were characterized through fluorescence spectroscopy, UV–vis absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and fluorescence lifetime analysis. The as-synthesized Cu NCs showed blue fluorescence with a peak centered at 426 nm. The Cu NCs had excellent water solubility, stability and dispersibility. Based on the inner filter effect and static quenching mechanism, Cu NCs were employed to detect furazolidone in bovine serum samples. Under optimal detection conditions, a good linear relationship was observed between F0/F and the furazolidone concentration from 0.05 to 60 μM. The detection limit (LOD) was 0.012 μM. Furthermore, the fluorescence probe was successfully used in the quantification of furazolidone in bovine serum samples. In addition, this analytical method provides a rapid, easy and ultrasensitive fluorescence platform for the detection of furazolidone.

Study of the Antibacterial Activity of Phenylacetic Acid Derivative Against the Causative Agent of Cholera

The in vitro and in vivo activity of a phenylacetic acid derivative, diclofenac, was studied against V.cholerae O1 El Tor strains and biofilms formed by them. In the presence of a subinhibitory concentration of diclofenac (250 mg/l), a 4-fold decrease in the values of the minimum inhibitory concentrations of furazolidone and chloramphenicol was found in 30% and 100% of the strains resistant to these drugs, and a significant increase in the diameters of growth inhibition zones around discs with chloramphenicol. furazolidone, streptomycin (for all strains) and doxycycline (for two strains) in comparison with the control. Furazolidone, nalidixic acid, chloramphenicol, streptomycin, to which the infecting strain was resistant, were used in in vivo experiments in combination with diclofenac for the treatment of white mice; in the experimental group the number of surviving animals increased to 80% in comparison with monotherapy with these drugs (50% or less). The subinhibitory concentration of diclofenac did not have a pronounced effect on the antibiotic sensitivity of biofilms. The study using transmission electron microscopy method on the biofilm of the V.cholerae O1 El Tor 19667 strain after exposing it to diclofenac (250 mg/l) for 120 h revealed signs of destruction of the exopolysaccharide matrix. These results indicate the prospects for studying this group of drugs, as well as others in order to develop new ways to overcome bacterial resistance.

Depicting the binding of furazolidone/furacilin with DNA by multiple spectroscopies, voltammetric as well as molecular docking.

The interaction between DNA and furazolidone/furacillin was investigated using various analytical techniques including spectroscopy and electroanalysis and molecular modelling. With the aid of acridine orange (AO), the fluorescence lifetimes of DNA-AO, DNA-furazolidone/furacillin-AO remained almost the same, which proved that the ground state complex was formed due to furazolidone/furacillin binding with DNA. Circular dichroism spectra and Fourier transform infrared spectroscopy showed that the second structure of DNA changed. Viscosity experiments presented that relative viscosity of DNA was increased with the increasing concentrations of furazolidone and almost unchanged for furacilin. In addition, the results of melting temperature (Tm ), ionic strength, site competition experiments, cyclic voltammetry, and molecular docking all proved the intercalation binding mode for furazolidone and groove binding mode for furacilin. The binding constants (Ka ) obtained from Wolfe-Shimmer equation were calculated as 3.66 × 104 L mol-1 and 3.95 × 104 L mol-1 for furazolidone-DNA and furacilin-DNA, respectively.

Nickel-Ferrite Oxide Decorated on Reduced Graphene Oxide, an Efficient and Selective Electrochemical Sensor for Detection of Furazolidone

Here, in this paper, magnetic nickel–ferrite oxide nanoparticles decorated reduced graphene oxide (NiFe2O4/rGO) was successfully prepared to employ as an efficient electrocatalyst for the electrochemical detection of furazolidone, an antibiotic and antibacterial drug. The NiFe2O4/rGO was characterized by different analytical methods, including FT–IR spectroscopy, X-ray diffraction spectroscopy, energy–dispersive X-ray spectroscopy, and electrochemical methods. In addition, the morphology of NiFe2O4/rGO was monitored using microscopic images of TEM and FE–SEM. NiFe2O4/rGO was used to modify a glassy carbon electrode (GCE). The differential pulse voltammetric studies represented that the NiFe2O4/rGO–GCE was more sensitive compared to rGO–GCE and unmodified GCE towards furazolidone detection. This electrochemical sensor was linearly related to furazolidone concentration in two linear ranges of 0.1– $10.0~\mu $ mol $L^{-1}$ and 10.0– $150.0~\mu $ mol $L^{-1}$ . However, the performance of this furazolidone sensor was quantitatively limited by the detection limit of $0.05~\mu $ mol $L^{-1}$ . To evaluate its selectivity, some common ions and other relevant species can interfere in the result of furazolidone sensor was investigated. This study, in addition to real sample analysis, represented that the suggested electrochemical sensor was practically selective and sensitive towards furazoldone. The determined value by the suggested sensor was in the related confidence interval accepted for the definite one.

Selective and sensitive furazolidone biosensor based on DNA-modified TiO2-reduced graphene oxide

In this study, a new methodology was used to develop a novel and sensitive electrochemical DNA biosensor for determination of furazolidone. This biosensor was fabricated from TiO2-reduced graphene oxide (rGO) modified-carbon paste electrode (CPE) decorated with ds-DNA. The oxidation signals of guanine and adenine were used as probes to study the interactions, using differential pulse voltammetry. By interaction of furazolidone with the ds-DNA, the oxidation peaks current of guanine and adenine were decreased at the modified-CPE. A linear dependence of the guanine and adenine oxidation signals with furazolidone concentration were observed in the range of 1.0–150.0pmolL−1 with a detection limit of 0.55 and 0.43pmolL−1 based on guanine and adenine signals, respectively. The relative standard deviation for five replicate measurements of 10.0pmolL−1 furazolidone was 4.3%. The influence of potential interfering compounds on the selectivity was studied. This biosensor was successfully applied for determination of trace amounts of furazolidone in real samples.

Development and analysis of furazolidone-resistant Escherichia coli mutants.

Furazolidone-resistant mutants were obtained from four clinical isolates of diarrhoeagenic Escherichia coli. The stability of the resistance and the frequency of mutation were established. The minimal inhibitory concentration of furazolidone, nitrofurantoin, nalidixic acid, ampicillin, chloramphenicol and tetracycline was established both in the presence and absence of the efflux pump inhibitor Phe-Arg-β-Naphtylamyde. The presence of mutations in the nitroreductase genes nfsA and nfsB was analysed by PCR; sequencing and their enzymatic activity was assessed by a spectrophotometric assay. Alterations in outer membrane proteins were studied by SDS-PAGE. The frequency of mutation ranged from <9.6×10(-10) to 9.59×10(-7) . Neither an effect on efflux pumps inhibited by Phe-Arg-β-Naphtylamyde nor cross-resistance with the antibiotics studied was observed. Nineteen mutants (52.94%) presented mutations in the nitroreductase-encoding genes: 17 in the nfsA gene (15 mutants with an internal stop codon, 2 with amino acid changes), 2 in the nfsB (all amino acid changes). Alterations in the outer membrane proteins OmpA and OmpW were also observed. Although more studies are necessary to find other resistance mechanisms, present data showed the low potential of selecting furazolidone-resistant mutants, together with the lack of cross-resistance with unrelated antimicrobial agents.

Calreticulin-STAT3 Signaling Pathway Modulates Mitochondrial Function in a Rat Model of Furazolidone-Induced Dilated Cardiomyopathy

BackgroundCalreticulin is a Ca2+-binding chaperone of the endoplasmic reticulum which regulates the signal transducer and activator of transcription 3 (STAT3). The effects of the calreticulin-STAT3 signaling pathway on cardiac mitochondria and on the progress of dilated cardiomyopathy (DCM) are still unclear.Methods and ResultsThe DCM model was generated in rats by the daily oral administration of furazolidone. Echocardiographic and hemodynamic studies demonstrated enlarged LV dimensions and reduced systolic and diastolic functions at thirty weeks after the first furazolidone administration. Morphometric analysis showed significant myocardial degeneration, interstitial fibrosis, and mitochondrial swelling with fractured or dissolved cristae in the model group. Compared with the control group, the mitochondrial membrane potential (MMP) level of the freshly isolated cardiac mitochondria and the enzyme activities of cytochrome c oxidase and succinate dehydrogenase in the model group were significantly decreased (P<0.05). Real-time PCR and western-blot revealed the increased expression of calreticulin associated with decreased activity of STAT3 in the model group. When cultured neonatal rat cardiomyocytes were exposed to furazolidone, a dose-dependent decrease in cell viability and MMP, and the increase of apoptosis rate were observed. The mRNA and protein expression of CRT gradually increased with the increase of furazolidone concentration, associated with a gradual decrease of the STAT3 phosphorylation level both in the whole cell and mitochondrial fraction. When calreticulin was knocked down with siRNA in cardiomyocytes, these changes of cardiomyocytes and mitochondria induced by furazolidone were significantly attenuated.ConclusionsA rat model of DCM induced by furazolidone is successfully established. The calreticulin-STAT3 signaling pathway is involved in cardiac mitochondrial injury and the progress of furazolidone induced DCM.

Helicobacter pylori antibiotic resistance in Brazil: clarithromycin is still a good option

The antibiotic susceptibility is the cornerstone for the eradication therapies of Helicobacter pylori. To evaluate the prevalence of primary resistance of H. pylori was evaluated in an urban Brazilian population. H. pylori isolates were obtained from patients submitted to an upper gastrointestinal endoscopy for the evaluation of dyspeptic symptoms. Biopsies from antrum, corpus and fundus were taken to determine the antibiotic susceptibility of H. pylori isolates. The minimal inhibitory concentration of furazolidone and bismuth were routinely determined by agar dilution method and the minimal inhibitory for amoxicillin, clarithromycin, tetracycline, levofloxacin, and metronidazole were routinely determined with the E-test. Fifty-four patients were included. In vitro antimicrobial susceptibility of H. pylori strains were obtained from 39 patients. Resistance to metronidazole was detected in 20 patients (51%), to clarithromycin in 3 patients (8%), to levofloxacin in 9 patients (23%) and to bismuth in 2 patients (5%). There was no observed resistance to amoxicillin, tetracycline or furazolidone. Due to the low amoxicillin and clarithromycin resistance observed in this study, therapies using these antimicrobials remain appropriated first-line H. pylori therapy.

Determination of furazolidone in urine by square-wave voltammetric method

A fast, simple and sensitive square-wave voltammetric (SWV) method for the determination of trace amounts of furazolidone (FZ) in urine is reported. A three-electrode system containing stationary mercury dropping (SMDE) working electrode, Pt auxiliary electrode and Ag/AgCl reference electrode was used throughout. Briton-Rabinson buffer solution is used as both pH adjusting agent and supporting electrolyte. The calibration graph showed good linearity in the concentration range of 20–900 ng ml−1 of furazolidone with a regression coefficient of 0.9996. The equation Δ(i) = 0.0095CFZ + 0.234 was used for calculation of furazolidone concentration in the sample solution, where CFZ is the concentration of furazolidone in ng ml−1 and Δ(i) is the difference between voltammogram peak currents of sample and blank solution. The RSD for 8 replicate measurements of a 60 ng ml−1 solution and LOD of the proposed method were found to be 2.2% and 5.2 ng ml−1, respectively. The procedure was successfully applied to the determination of furazolidone in urine samples.

Determination of the depletion of furazolidone residues in chicken tissues using a Bacillus stearothermophilus test

This study assessed the applicability of a Bacillus stearothermophilus test for detection of the depletion of furazolidone anticoccidial drug residues in chicken tissues. Thirty-three Ross breed chicken were dosed orally with furazolidone (2 mg/kg body weight) daily for 5 days. After the last treatment the birds were sacrificed in groups of three at intervals of 1, 3, 6, 10, 24, 48, 144, 240, 360 and 480 h. Liver, kidney and breast muscle samples were collected and immediately analysed at each interval for furazolidone residues. Serum was separated from the blood collected from jugular veins into bottles containing glass beads and analysed. Supernatant from the homogenates was analysed for the presence or absence of furazolidone residues using the B. stearothermophilus test. Semi quantification of furazolidone residues was done by comparing the obtained zones of inhibition on a Bacillus subtilis test plates and the zones from calibrated standard curves. Qualitatively the B. stearothermophilus test was positive for furazolidone residues up to 480 h post treatment in serum samples, 360 h in liver samples, 480 h in kidney samples and 360 h in muscle samples. Semi quantitatively from the B. subtilis test plates, serum samples were observed to have the highest furazolidone concentration of 3.2 μg/ml. The lowest furazolidone concentration was recorded in kidney tissues at 0.21 μg/ml. Kidney and serum tissues appear to be good tissues for testing of furazolidone tissues. The Kidney samples would appear best for post-mortem screening of furazolidone residues while serum could be used antemortem screening of depletion in chicken.

Residues of enrofloxacin, furazolidone and their metabolites in Nile tilapia ( Oreochromis niloticus)

The residues of enrofloxacin and its metabolite in Nile tilapia ( Oreochromis niloticus) were studied after oral dose of 50 mg/kg for 7 days. To find the differences between Nile tilapia and Chinese shrimp ( Penaeus chinensis), the residues of enrofloxacin in P. chinensis were also studied under the same conditions. The results showed that enrofloxacin metabolized into ciprofloxacin in both Nile tilapia and P. chinensis, the maximal concentration of enrofloxacin in muscle, liver and plasma of Nile tilapia were 3.61 μg/g, 5.96 μg/g, 1.25 μg/ml respectively, and ciprofloxacin in muscle was 0.22 μg/g. The maximal concentration of enrofloxacin and ciprofloxacin in P. chinensis were 1.68 μg/g and 0.07 μg/g respectively. The predicted withdrawal time for Nile tilapia was 22 days, and P. chinensis was 12 days under our experiment conditions. The residues of furazolidone [3-(5-nitrofurfurylidenamino)-2-oxazolidinone] and its main metabolite 3-amina-2-oxazolidinone (AOZ) in Nile tilapia were first determined by HPLC/MS. Results showed that after oral dose of 30 mg/kg for 7 days, the maximum concentration of furazolidone in Nile tilapia was 413 μg/kg after 6 h, whereas AOZ residue reached its maximum (31 μg/kg) right after stopping treatment. In contrast to the high metabolic rate of furazolidone, AOZ was very difficult to eliminate in vivo, thus the withdrawal time of furazolidone in Nile tilapia was 22 days at least.

Effects of furazolidone pretreatment of Salmonella enteritidis PT4 at sub- and suprainhibitory concentrations on phagocytosis and intracellular survival in chicken macrophages.

The antimicrobial effect of the nitrofuran derivative furazolidone at sub- and suprainhibitory concentrations on Salmonella enteritidis PT4 and the influence with regard to interaction with avian macrophages was investigated in this study. Phagocytosis of furazolidone-sensitive (FzS) S. enteritidis with chicken macrophages in the presence of furazolidone at concentrations of 1/8, 1/4, 1/2 and 8x MIC resulted in an increase in the rate of phagocytic killing of approximately 3-, 6-, 6.5- and 9-fold, respectively, with 1/2 and 8x MIC concentrations producing statistically significant (P<0.05) increases in phagocytosis. Treatment of the FzS Salmonella with furazolidone at concentrations of 4x and 10x MIC, for 15 min prior to phagocytosis, also significantly (P<0.005) increased phagocytic uptake when compared with untreated bacteria. The rate of phagocytosis monitored over 90 min was highest between 30 and 60 min with the furazolidone pretreated salmonella, compared with the delayed rate of the control between 60 and 90 min. Exposure of FzS and FzR strains with suprainhibitory concentrations of furazolidone at 4x, 8x and 10x MIC for 30 min prior to phagocytosis demonstrated an increase in bacterial killing. Exposure of strains to sub-inhibitory concentrations of furazolidone led to an increase in chemiluminescence during phagocytosis with macrophages, suggesting an increase in oxidative metabolism in the macrophages as a result of an increase in activation and phagocytosis. Pretreatment of the strains with suprainhibitory concentrations of furazolidone for 30 min prior to phagocytosis demonstrated a similar increase in oxidative metabolism in the macrophages. Measurement of the amount of 14C-furazolidone associated with chicken macrophages was determined over 20 h incubation. The level of radioactivity of 14C-furazolidone alone was used to estimate the amount of cell-associated nitrofuran when incubated with the macrophages by means of regression analysis. Incubation with concentrations of 16, 32 and 64 microg/ml for 20 h resulted in the cell association of >or=1 microg/ml of furazolidone, which is the concentration required for the agent to exhibit bactericidal activity on furazolidone-sensitive Salmonella strains. Furazolidone was able to reduce intracellular salmonella viability at all concentrations, but total killing was achieved only with concentrations of >or=8 microg/ml, which supports the results for furazolidone association with the macrophages. This substantiates that the bioactivity of the nitrofuran was not inhibited or diminished in the intracellular environment of the macrophage and that exposure of salmonella to nitrofurans enhances phagocytosis.

Serum profiles of luteinizing hormone, oestradiol and cholesterol and ovarian functions in layer poultry birds (Gallus domesticus) fed diets containing furazolidone.

This study was carried out to assess the serum profiles of luteinizing hormone (LH), oestradiol, cholesterol and ovarian functions in layer poultry birds (Rhode Island Red: Gallus domesticus) fed a diet containing various concentrations of furazolidone (FZ). A total of 40 birds were randomly assigned to receive FZ 0, 200, 400 or 800 mg/kg feed (ppm) daily during the pre-laying age, i.e. 13-18 weeks (for 5 weeks). Blood samples were collected at weekly intervals. Concentrations of LH and oestradiol in serum were estimated at alternate weeks using radioimmunoassays. Serum cholesterol levels were analysed by an enzymatic calorimetric method. Furazolidone administration was terminated at the 18th week of age. The birds were sacrificed at 22nd week of age and ovarian tissues were processed for morphometric studies. Serum LH, oestradiol and cholesterol levels were affected by age (p < 0.001) and FZ dose (p < 0.001). Serum LH and oestradiol levels were lower (p < 0.05) in birds receiving FZ 800 mg/kg feed daily compared with the controls, whereas serum cholesterol profiles were lower (p < 0.05) in all FZ-administered groups than in the control group. The mean weight of ovaries having no yolky follicles observed in the group receiving FZ 400 or 800 mg/kg feed per day was reduced (p < 0.05) compared with the control group. Dosing FZ at 800 mg/kg feed per day reduced (p < 0.05) the mean volume of ovaries having no yolky follicles compared with the control group. In birds receiving FZ 800 mg/kg feed per day, the mean length of the oviduct was reduced (p < 0.05) as compared with the control group. Morphometric studies revealed that the mean number of oocytes with diameter in the range 401-800 microm decreased (p < 0.05) in birds fed FZ 400 or 800 mg/kg feed per day. Initial egg production was affected by age (p < 0.001) and dose (p < 0.001) of FZ. The mean number of eggs laid by different groups revealed that egg production was reduced (p < 0.05) in birds receiving FZ 800 mg/kg feed per day as compared with the controls. The present data suggest that FZ causes suppression in serum profiles of LH, oestradiol, cholesterol and ovarian functions in Rhode Island Red layer poultry birds. Therefore, great care must be taken with use of FZ in layer poultry birds (Gallius domesticus) with regard to dosage and duration of administration.

Evaluation of the residues of furazolidone and its metabolite, 3-amino-2-oxazolidinone (AOZ), in eggs

The use of furazolidone in food-producing animals is banned within the EU. Detection of the protein-bound side-chain metabolite, 3-amino-2-oxazolidinone (AOZ), in animal tissues is the most effective method of enforcing the ban. The study was undertaken to find out if the same applies to eggs. The concentrations of furazolidone and AOZ in eggs reached a plateau of ≈360–380 μg kg-1 by the fourth day of treating birds with 400mgkg -1 furazolidone. After a 4-day withdrawal from treatment, intact furazolidone could not be detected. AOZ residues could still be detected up to 21 days following withdrawal from treatment. During treatment, most intact furazolidone residues occur in the albumen. For AOZ, there is a more even distribution of residues between albumen and the yolk. The concentration of furazolidone in egg homogenates stored at -20°C decreases by 44% after 55 days. AOZ residues are stable during this period. From these results, it is clear that AOZ is a more suitable marker residue than the parent compound for monitoring concentrations of the drug in eggs.

Furazolidone disposition after intravascular and oral dosing in the channel catfish.

1. The pharmacokinetics, tissue distribution and excretion of the nitrofuran drug furazolidone have been examined in the channel catfish. [14C]Furazolidone was administered by intravascular or oral routes in a single dosage of 1 mg/kg body weight. 2. A two-compartment pharmacokinetic model best described parent furazolidone concentrations in the plasma after intravascular dosing. Elimination of parent compound was extremely rapid, with a terminal half-life of 0.27h and total body clearance of 1901 ml/h/kg. 3. After oral dosing, furazolidone concentrations in the plasma were highest at 1 h and were below the limit of determination (< 20 ng/ml) at 5 h. The oral bioavailability of parent furazolidone administered in solution was 58%, compared with 28% in a feed mixture. 4. Concentrations of furazolidone and its metabolites were highest in the excretory tissues and lowest in the muscle after oral dosing. Parent furazolidone comprised 10% of the total 14C in the muscle at 8 h and was not detectable (< 1 ng/g) at 24 h; total 14C concentrations declined from 274 to 59 ng furazolidone equiv./g between 8 and 168 h. Non-extractable (bound) residues comprised 18% of total 14C in muscle at 8 h and 33% at 168h. 5. Renal excretion was the primary route of elimination of 14C residues and accounted for nearly 55% of the oral dose.

Matrix Solid Phase Dispersion (MSPD) Isolation and Liquid Chromatographic Determination of Furazolidone in Pork Muscle Tissue

A method for the isolation and liquid chromatographic (LC) determination of furazolidone in pork muscle tissue is presented. Blank or furazolidone-fortified pork muscle tissue samples (0.5 g) were blended with octadecylsilyl (C18, 18% load, endcapped, 2 g) derivatized silica. A column made from C18/pork matrix was first washed with hexane (8 mL), followed by elution of furazolidone with ethyl acetate. The ethyl acetate extract was then passed through an activated alumina column. The eluate contained furazolidone that was free from interfering compounds when analyzed by LC with UV detection (photodiode array, 365 nm). Detector response with increasing concentrations of furazolidone isolated from fortified samples was linear (r = 0.998 +/- 0.002) with an average percentage recovery of 89.5 +/- 8.1% for the concentration range (7.8-250 ng/g) examined and resulted in a minimum detectable limit of 390 pg on column, and a detector response of more than 5 times baseline noise. The inter-assay variability was 9.9 +/- 5.4% with an intra-assay variability of 1.5%.