Nitrofuran drugs beyond redox cycling: Evidence of Nitroreduction-independent cytotoxicity mechanism.

Nitrofurans (5-nitro-2-hydrazonylfuran as pharmacophore) are a group of widely used antimicrobial drugs but also associated to a variety of side effects. The molecular mechanisms that underlie the cytotoxic effects of nitrofuran drugs are not yet clearly understood. One-electron reduction of 5-nitro group by host enzymes and ROS production via redox cycling have been attributed as mechanisms of cell toxicity. However, the current evidence suggests that nitrofuran ROS generation by itself is uncapable to explain the whole toxic effects associated to nitrofuran consumption, proposing a nitro-reduction independent mechanism of toxicity. In the present work, a series of nitrated and non-nitrated derivatives of nitrofuran drugs were synthesized and evaluated in vitro for their cytotoxicity, ROS-producing capacity, effect on GSH-S-transferase and antibacterial activity. Our studies showed that in human cells non-nitrated derivatives were less toxic than parental drugs but, unexpectedly preserved the ability to generate intracellular ROS in similar amounts to nitrofurans despite not entering into a redox cycle mechanism. In addition, some non-nitrated derivatives although being uncapable to generate ROS exhibited the highest cell toxicity among all derivatives. Inhibition of cytosolic glutathione-S-transferase activity by some derivatives was also observed. Finally, only nitrofuran derivatives displayed antibacterial effect. Results suggest that the combined 2-hydrazonylfuran moiety, redox cycling of 5-nitrofuran, and inhibitory effects on antioxidant enzymes, would be finally responsible for the toxic effects of the studied nitrofurans on mammalian cells.

An update on derivatisation and repurposing of clinical nitrofuran drugs.

5-nitrofurans (NFs) have been in clinical use for over 60 years. These affordable drugs are used for the treatment of a broad spectrum of diseases ranging from urinary tract infections to cancer. The anti-pathogenic effect of clinical NFs occurs following a step-wise process involving activation by azoreduction, followed by nitroreduction catalysed by azoreductases and nitroreductases (NTRs), respectively. Azoreduction yields stable metabolites that have the ability to covalently bind to cellular proteins. Nitroreduction, on the other hand, occurs by type I or II reduction of the nitro group in the presence of parasitic NADPH-cytochrome P450 reductases. Type I NTRs catalyse, under anaerobic conditions, the reduction of NFs to produce anti-pathogenic hydroxylamine. Under aerobic conditions, nitroreduction catalysed by type II NTRs produces reactive oxygen and nitrogen species (ROS/RNS), causing oxidative stress to pathogens and ultimate death. This multi-activity nature of NFs thus allows the repurposing of these drugs from agricultural chemicals and basic antibiotics to efficient therapies against human life-threatening diseases. Cases of NF resistance in pathogens are also limited likely due to this multi-activity, as well as effectivity under both aerobic and anaerobic conditions. However, multi-activity of these drugs can also infer toxicity. Molecular derivatisation is an effective strategy to improve efficacy, lower toxicity, diversify activity and address pathogen resistance associated with the use of these drugs.

Attachment of a 5-nitrofuroyl moiety to spirocyclic piperidines produces non-toxic nitrofurans that are efficacious in vitro against multidrug-resistant Mycobacterium tuberculosis.

A selectively antimycobacterial compound belonging to the nitrofuran class of antimicrobials has been developed via conjugation of the nitrofuran moiety to a series of spirocyclic piperidines through an amide linkage. It proved to have comparable activity against drug-sensitive (H37Rv) strain as well as multidrug-resistant, patient-derived strains of Mycobacterium tuberculosis. The compound is druglike, showed no appreciable cytotoxicity toward human retinal pigment epithelial cell line ARPE-19 in concentrations up to 100 µM and displayed low toxicity when evaluated in mice.

Hazardous ecotoxicological impact of two commonly used nitrofuran-derived antibacterial drugs: Furazolidone and nitrofurantoin.

This paper discusses the impact of two nitrofuran-derived drugs, namely furazolidone and nitrofurantoin on growth of oat and common radish as well as their impact on bacteria Allivibrio fischeri and crustaceans Heterocypris incongruens. Results indicated that both compounds were highly phytotoxic for radish (R. sativus) being simultaneously nearly not harmful for oat (A. sativa). Growing inhibition of shoots, roots, fresh matter and photosynthetic pigments is correlated with growing concentration of drugs in soil. Ecotoxicological impact of both compounds on model luminescence bacteria Aliivibrio fischeri and freshwater crustaceans Heterocypris incongruens as a representative organisms of two different level of food chain, is also reported herein, and the obtained data show significant toxicity against these two organisms. Basing on obtained results, it was concluded that both nitrofuran drugs in case of distribution through environment, by improper utilisation after use or unplanned environmental intoxication with unused drugs may cause serious environmental problems and therefore both should be handled with a reasonable care at any step of their production or utilisation.

Physicochemical, pharmacokinetic, efficacy and toxicity profiling of a potential nitrofuranyl methyl piperazine derivative IIIM-MCD-211 for oral tuberculosis therapy via in-silico-in-vitro-in-vivo approach.

Recent tuberculosis (TB) drug discovery programme involve continuous pursuit for new chemical entity (NCE) which can be not only effective against both susceptible and resistant strains of Mycobacterium tuberculosis (Mtb) but also safe and faster acting with the target, thereby shortening the prolonged TB treatments. We have identified a potential nitrofuranyl methyl piperazine derivative, IIIM-MCD-211 as new antitubercular agent with minimum inhibitory concentration (MIC) value of 0.0072 µM against H37Rv strain. Objective of the present study is to investigate physicochemical, pharmacokinetic, efficacy and toxicity profile using in-silico, in-vitro and in-vivo model in comprehensive manner to assess the likelihood of developing IIIM-MCD-211 as a clinical candidate. Results of computational prediction reveal that compound does not violate Lipinski's, Veber's and Jorgensen's rule linked with drug like properties and oral bioavailability. Experimentally, IIIM-MCD-211 exhibits excellent lipophilicity that is optimal for oral administration. IIIM-MCD-211 displays evidence of P-glycoprotein (P-gp) induction but no inhibition ability in rhodamine cell exclusion assay. IIIM-MCD-211 shows high permeability and plasma protein binding based on parallel artificial membrane permeability assay (PAMPA) and rapid equilibrium dialysis (RED) assay model, respectively. IIIM-MCD-211 has adequate metabolic stability in rat liver microsomes (RLM) and favourable pharmacokinetics with admirable correlation during dose escalation study in Swiss mice. IIIM-MCD-211 has capability to appear into highly perfusable tissues. IIIM-MCD-211 is able to actively prevent progression of TB infection in chronic infection mice model. IIIM-MCD-211 shows no substantial cytotoxicity in HepG2 cell line. In acute toxicity study, significant increase of total white blood cell (WBC) count in treatment group as compared to control group is observed. Overall, amenable preclinical data make IIIM-MCD-211 ideal candidate for further development of oral anti-TB agent.

Pentacyclic nitrofurans that rapidly kill nifurtimox-resistant trypanosomes.

OBJECTIVES: In response to reports of Trypanosoma brucei resistance to the nitroaromatic drug nifurtimox, we evaluated the potential of antituberculosis nitrofuran isoxazolines as inhibitors of trypanosome growth. METHODS: The susceptibility of T. brucei brucei was assessed in vitro. The lowest effective concentration to inhibit growth (EC90) against drug-susceptible and -resistant parasites, time-kill kinetics, reversibility of inhibition and propensity for P-glycoprotein-mediated exclusion from the blood-brain barrier were determined. RESULTS: Nitrofuran isoxazolines were potent inhibitors of T. brucei brucei proliferation at nanomolar concentrations, with pentacyclic nitrofurans being 100-fold more potent than nifurtimox. Activity was sustained against nifurtimox-resistant parasites, suggesting the possibility of a unique mechanism of activation and potential for use in the treatment of drug-resistant infections. Exposure of parasites to the maximum concentrations of Compound 15 achieved in vivo with oral dosing yielded >2 logs of irreversible killing in <4 h, indicating rapid trypanocidal activity. CONCLUSIONS: Pentacyclic nitrofuran isoxazolines warrant further development for the treatment of drug-susceptible and nifurtimox-resistant trypanosome infections.

Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53.

The tumor-suppressor p53 prevents cancer development via initiating cell-cycle arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its tumor-suppressor function, but also endow mutant p53 with a gain of function (GOF), creating a proto-oncogene that contributes to tumorigenesis, tumor progression, and chemo- or radiotherapy resistance. Thus, targeting mutant p53 to restore a wild-type p53 signaling pathway provides an attractive strategy for cancer therapy. We demonstrate that small-molecule NSC59984 not only restores wild-type p53 signaling, but also depletes mutant p53 GOF. NSC59984 induces mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway. NSC59984 restores wild-type p53 signaling via p73 activation, specifically in mutant p53-expressing colorectal cancer cells. At therapeutic doses, NSC59984 induces p73-dependent cell death in cancer cells with minimal genotoxicity and without evident toxicity toward normal cells. NSC59984 synergizes with CPT11 to induce cell death in mutant p53-expressing colorectal cancer cells and inhibits mutant p53-associated colon tumor xenograft growth in a p73-dependent manner in vivo. We hypothesize that specific targeting of mutant p53 may be essential for anticancer strategies that involve the stimulation of p73 in order to efficiently restore tumor suppression. Taken together, our data identify NSC59984 as a promising lead compound for anticancer therapy that acts by targeting GOF-mutant p53 and stimulates p73 to restore the p53 pathway signaling.

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA).

It is important to determine the toxicity of compounds and co-solvents that are used in cell monolayer permeability studies to increase confidence in the results obtained from these in vitro experiments. This study was designed to evaluate the cytotoxicity of new nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA) in Caco-2 cells to select analogues for further in vitro permeability analyses. In this study, nitrofurantoin and nifuroxazide, in addition to 6 furanic and 6 thiophenic nifuroxazide derivatives were tested at 2, 4, 6, 8 and 10 µg/mL. In vitro cytotoxicity assays were performed according to the MTT (methyl tetrazolium) assay protocol described in ISO 10993-5. The viability of treated Caco-2 cells was greater than 83% for all tested nitrofurantoin concentrations, while those treated with nifuroxazide at 2, 4 and 6 µg/mL had viabilities greater than 70%. Treatment with the nifuroxazide analogues resulted in viability values greater than 70% at 2 and 4 µg/mL with the exception of the thiophenic methyl-substituted derivative, which resulted in cell viabilities below 70% at all tested concentrations. Caco-2 cells demonstrated reasonable viability for all nifuroxazide derivatives, except the thiophenic methyl-substituted compound. The former were selected for further permeability studies using Caco-2 cells.

The effects of the nitrofuran furaltadone on Ulva lactuca.

The use of pharmaceuticals in the food production industry as prophylatic and therapeutic agents is necessary to promote animal health, but may entail significant consequences to natural ecosystems, especially in the cases of overdosing and use of banned pharmaceuticals. The vast effects that antibiotics released into the environment have on non-target organisms are already under the scope of researchers but little attention has been given to primary producers such as macroalgae. The present study assessed furaltadone's, an antibacterial agent illegally used for veterinary purposes, uptake capacity by Ulva lactuca and its effect in the growth of this cosmopolitan macroalgae. Differences in macroalgal growth were shown when submitted to prophylactic and therapeutic concentrations of furaltadone in the water (16 and 32 µg mL⁻¹, respectively). The therapeutic concentration caused higher growth impairment than the prophylactic treatment did, with 87.5% and 58% reductions respectively. Furthermore, together with data collected from the accumulation assays, with values of internal concentrations as high as 18.84 µg g⁻¹ WW, suggest that the macroalgae U. lactuca should be included in field surveys as a biomonitor for the detection of nitrofurans.

Assessment of isorhamnetin 3-O-neohesperidoside from Acacia salicina: protective effects toward oxidation damage and genotoxicity induced by aflatoxin B1 and nifuroxazide.

Antioxidant activity of isorhamnetin 3-O-neohesperidoside, isolated from the leaves of Acacia salicina, was determined by the ability of this compound to inhibit xanthine oxidase activity and to scavenge the free radical 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(.-)) diammonium salt. Antigenotoxic activity was assessed using the SOS chromotest assay. This compound has the ability to scavenge the ABTS(.+) radical by a hydrogen donating mechanism. We also envisaged the study of the antioxidant effect of this compound by the enzymatic xanthine/xanthine oxidase (X/XOD) assay. Results indicated that isorhamnetin 3-O-neohesperidoside was a potent inhibitor of xanthine oxidase and superoxide anion scavengers. Moreover, this compound induced an inhibitory activity against nifuroxazide and aflatoxine B1 (AFB1) induced genotoxicity. Taken together, these observations provide evidence that isorhamnetin 3-O-neohesperidoside isolated from the leaves of A. salicina is able to protect cells against the consequences of oxidative stress.

5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene.

Chagas disease represents a serious public health problem in South America. The first line of treatment is Nifurtimox and Benznidazole which generate toxic effects in treated patients. We have recently shown that a number of 5-nitrofuranes possess activity against Trypanosoma cruzi through oxidative stress and inhibition of parasite ergosterol biosynthesis, specifically at the level of squalene epoxidase. Here, we identify new 5-nitrofuranes and the thia-analogues with excellent effects on the viability of T. cruzi and adequate parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated, during 120h, with the compounds showed that some of them accumulated squalene suggesting the squalene epoxidase activity inhibition of the parasite. Nifurtimox was able to accumulate squalene only at lower incubation times. Due to this fact some derivatives were also tested as antifungal agents. Quantitative structure-activity relationship studies were also performed showing relevant features for further new derivatives design. Taken together, the results obtained in the present work point to a more general effect of 5-nitrofuranes and 5-nitrothiophenes in trypanosomatids, opening potential therapeutic possibilities of them for these infectious diseases.

5-Nitro-2-furyl derivative actives against Trypanosoma cruzi: preliminary in vivo studies.

Ten 5-nitro-2-furyl derivatives, with good to excellent in vitro anti-Trypanosoma cruzi activity, and nifurtimox were tested oral and intraperitoneally on healthy animals for its acute toxicity on murine models. According to animals' survival percentage, organ histological results, biochemical and haematological findings, three new derivatives, with toxicity like nifurtimox, were selected to test in vivo as antichagasic agents. Clearly, dependences between chemical structure and both acute toxicity and in vivo anti-T. cruzi activity were observed. 4-Hexyl-1-[3-(5-nitro-2-furyl)-2-propenylidene]semicarbazide displayed good profile as anti-T. cruzi agent and better acute toxicity profile than nifurtimox.

Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions.

Several nitrofurans and nitroimidazoles have been widely used in veterinary medicine. Some of these compounds are breast carcinogens in rodents and their mechanism of action is hypothesized to be related to reactive metabolites generated by nitroreduction and/or via oxygen-dependent redox cycling. The present work describes the nitroreductive metabolism of nitrofurazone, nitrofurantoin, furazolidone, and metronidazole by the cytosolic and microsomal fractions of mammary tissue from female Sprague-Dawley rats. The data obtained were compared with those obtained with nifurtimox and benznidazole, two well-known rodent carcinogen/mutagens nitroheterocycles. The nitroreductase activity of pure milk xanthine-oxidoreductase (XOR) was evaluated for screening purposes. All the nitrofurans were nitroreduced either by the pure XOR or the cytosolic fraction in the presence of hypoxanthine, and these activities were inhibited by allopurinol. Furthermore, they were nitroreduced by the microsomal fraction in the presence of NADPH, except for the nitrofurazone, suggesting the participation of cytochrome P450 reductase. Nitrofurans metabolism was significantly more intense than that of NFX. No equivalent nitroreductase activity was observed in either subcellular fraction using nitroimidazolic compounds as substrates. These results suggest that the nitroreductive metabolism of nitrofurans and the subsequent redox cycling might be involved in the associated mammary tissue carcinogenic effects.

Antioxidant activity and inhibition of aflatoxin B1-, nifuroxazide-, and sodium azide-induced mutagenicity by extracts from Rhamnus alaternus L.

The effect of extracts obtained from Rhamnus alaternus L. leaves on genotoxicity and SOS response induced by aflatoxin B(1) (10 microg/assay) as well as nifuroxazide (20 microg/assay) was investigated in a bacterial assay system, i.e., the SOS chromotest with Escherichia coli PQ37. The evaluation of the mutagenic and antimutagenic actions of the same extracts against the sodium azide (1.5 microg/plate)-induced mutagenicity was assayed using the Salmonella typhimurium assay system. The R. alaternus tested extracts exhibited no genotoxicity either with or without the external S9 activation mixture. However, all the extracts, particularly aqueous extract (A) and its chloroformic fraction (A(2)) significantly decreased the genotoxicity induced by aflatoxin B(1) and nifuroxazide. Moreover, the different extracts showed no mutagenicity when tested with Salmonella typhimurium strains TA1535 and TA1538 either with or without the S9 mix. Aqueous extract as well as its A(2) fraction exhibited the highest level of protection towards the direct mutagen, sodium azide-induced response in TA1535 strain with mutagenicity inhibition percentages of 83.6% and 91.4%, respectively, at a dose of 250 microg/plate. The results obtained by the Ames test assay confirm those of SOS chromotest. These same active extracts exhibited high xanthine oxidase (XOD) inhibiting with respective IC(50) values of 208 and 137 microg/ml, and superoxide anion-scavenging effects (IC(50) values of 132 and 117 microg/ml) when tested in the XOD enzymatic assay system. Our findings emphasize the potential of R. alaternus to prevent mutations and also its antioxidant effect.

Toxicidade de fármacos nitrofurânicos / Toxicity of nitrofuran drugs

Durante o planejamento estrutural de novos fármacos, é possível prever a influência de grupamentos específicos na atividade farmacológica. Entre estes, encontra-se o grupo nitro, que possui potencial atividade antimicrobiana, estando presente em diversos fármacos como o metronidazol, nitrofural, furazolidona, oxamniquina, cloranfenicol, entre outros. Também, a introdução do grupo nitro na molécula pode alterar as propriedades físico-químicas e eletrônicas da substância, estando presente em fármacos de outras classes terapêuticas como anti-úlcera, ansiolítico, antiinflamatório. Entretanto, restrições têm sido apontadas para o planejamento de novos fármacos contendo este grupo, devido à toxicidade relacionada. Este estudo trata-se da revisão sobre a toxicidadede compostos nitrofurânicos, bem como os possíveis mecanismos e a utilização do método de latenciação na diminuição desta toxicidade.

Antigenotoxic activities of crude extracts from Acacia salicina leaves.

For centuries, plants have been used in traditional medicines and there has been recent interest in the chemopreventive properties of compounds derived from plants. In the present study, we investigated the effects of extracts of Acacia salicina leaves on the genotoxicity of benzo[a]pyrene (B(a)P) and nifuroxazide in the SOS Chromotest. Aqueous, total oligomers flavonoids (TOF)-enriched, petroleum ether, chloroform, ethyl acetate, and methanol extracts were prepared from powdered Acacia leaves, and characterized qualitatively for the presence of tannins, flavonoids, and sterols. All the extracts significantly decreased the genotoxicity induced by 1 microg B(a)P (+S9) and 10 microg nifuroxazide (-S9). The TOF-enriched and methanol extracts decreased the SOS response induced by B(a)P to a greater extent, whereas the TOF-enriched and the ethyl acetate extracts exhibited increased activity against the SOS response produced by nifuroxazide. In addition, the aqueous, ethyl acetate, and methanol extracts showed increased activity in scavenging the 1,1-diphenyl- 2-picrylhydrazyl (DPPH) free radical, while 100-300 microg/ml of all the test extracts were active in inhibiting O2-production in a xanthine/xanthine oxidase system. In contrast, only the petroleum ether extract was effective at inhibiting nitroblue tetrazolium reduction by the superoxide radical in a nonenzymatic O2- -generating system. The present study indicates that extracts of A. salicina leaves are a significant source of compounds with antigenotoxic and antioxidant activity (most likely phenolic compounds and sterols), and thus may be useful for chemoprevention.

Organ-targeted mutagenicity of nitrofurantoin in Big Blue transgenic mice.

Nitrofurans are widely used in human medicine, as nitrofurantoin and nifuroxazide, still prescribed for long-term antimicrobial prophylaxis of urinary tract and gastrointestinal infection in humans respectively. Recent experiments in mammals, as well as reports mentioning toxic effects in humans associated with a long-term use, specially in the case of nitrofurantoin, raised the need for reevaluating their genotoxicity. The objective of this study was to determine whether these two compounds induce a mutagenic effect in the Big Blue transgenic mouse mutation assay. Mice were orally treated either with nitrofurantoin or nifuroxazide for five consecutive days and sacrificed 3 weeks later. In order to optimize the genotoxic response, the doses used for each compound were 25-fold higher as the posology in humans. They corresponded to 50% of the highest doses tolerated by mice. The mutant frequency was determined from kidney, lung, bladder, caecum, colon, small intestine, spleen and stomach. A weak mutagenic response of nitrofurantoin-treated mice specifically in the kidney was observed. As in the case of other nitrofuran compounds, the mutation spectra determined from treated samples exhibited slightly more GC-->TA transversions as compared with untreated conditions. These data are relevant to the targeted action of nitrofurantoin as a urinary antimicrobial agent. No significant increase of mutants was detected in the case of nifuroxazide-treated mice whatever the organs analysed.

Comparative genotoxic evaluation of 2-furylethylenes and 5-nitrofurans by using the comet assay in TK6 cells.

The genotoxicity of three 2-furylethylene derivatives and four 5-nitrofurans was evaluated by using the comet assay in human lymphoblastoid cultured TK6 cells. The 2-furylethylene derivatives were 2-furyl-1-nitroethene, 1-(5-bromofur-2-yl)-2-nitroethene and 1-(5-bromofur-2-yl)-2-bromo-2-nitroethene, while the 5-nitrofurans were nitrofurantoin, nitrofurazone, furazolidone and 5-nitro-2-furanacrolein. The treatments lasted for 3 h in the absence of metabolic activation. No genotoxic effects were observed for two of the 2-furylethylene compounds, while the derivative 1-(5-bromofur-2-yl)-2-nitroethene showed a statistically significant response mainly at the highest concentration tested; this effect was considered biologically relevant and the compound was classified as slightly genotoxic. On the other hand, for the classical 5-nitrofurans tested there is a tendency towards a dose-related increase of the DNA damage in the comet assay and the observed increases for the parameters analysed (Olive tail moment, tail % DNA and tail length) were significant for all compounds. Then, the four 5-nitrofurans tested were considered genotoxic. These results show that the position of the nitro group influences the genotoxicity of the assayed compounds. Thus, in this comet assay, the 2-furylethylene derivatives having the nitro group attached outside the furan ring appear to be much less genotoxic than the 5-nitrofurans.

Hipersensibilidad a los nitrofuranos / Nitrofurane hypersensitivity

Antecedentes y objetivos: La nitrofurantoína y la nitrofurazona son antibacterianos de amplio espectro que se emplean como antinfecciosos urinario y dermatológico, respectivamente. Material y métodos: Presentamos dos casos de hipersensibilidad a los nitrofuranos, uno con una anafilaxia tras la ingestión de nitrofurantoína y otro con una reacción local de dermatitis de contacto tras la aplicación tópica de nitrofurazona. Resultados y conclusiones: El estudio alergológico con pruebas cutáneas y determinación de IgE frente a nitrofurantoína en el caso de la anafilaxia (mecanismo de hipersensibilidad del tipo I) y con pruebas epicutáneas a nitrofurazona en el caso de la dermatitis de contacto (mecanismo de hipersensibilidad del tipo IV) fue positivo; ambos pacientes toleraron otros nitrofuranos no implicados en la reacción. Encontramos pocos casos de alergia a estos fármacos en la literatura revisada. Aunque en el caso de nuestros pacientes no existió reactividad cruzada con otros fármacos que contienen el anillo furano, para poder confirmar esta observación se necesitan más estudios

Introduction: Nitrofurantoin and nitrofurazone are antibacterial agents used in urinary tract and cutaneous infections respectively. Material and methods: Two cases of hypersensitivity are presented, one with anaphylaxis after taking nitrofurantoin and another with a localized reaction of contact dermatitis after using nitrofurazone. Results and conclusions: In both cases the allergic examination including skin tests and IgE determinations with nitrofurantoin in the case of anaphilaxis and with epicutaneous tests for nitrofurazone in the case of contact dermatitis was positive; both tolerated other nitrofurans not involved in the reaction. We found few cases of allergy to these drugs in the revised literature. Although in our cases there was no cross reactivity among nitrofurans, more estudies are necessary in order to confirm that this is a general rule

Genotoxicity of 2-nitro-7-methoxy-naphtho[2,1-b]furan (R7000): a case study with some considerations on nitrofurantoin and nifuroxazide.

Two nitrofurans present broad-spectrum antimicrobial properties and some of them are used in human and veterinary medicine. Most of these molecules are mutagens and some of them were reported as carcinogens. Due to its extreme mutagenic potency in bacteria, the nitronaphtho derivative 2-nitro-7-methoxy-naphtho[2,1-b]furan (R7000) was used as a tool to analyze the mechanism of the genotoxic action of this family of chemicals. In the present paper, we review essential data on the genotoxicity of R7000 and briefly discuss the case of nitrofurantoin and nifuroxazide, two nitrofurans, still in use as urinary and gastrointestinal disinfectants.