Flumequine Research Articles

Transcriptional and biochemical changes in mouse liver following exposure to a metal/drug cocktail. Attenuating effect of a selenium-enriched diet

Real-life pollution usually involves simultaneous co-exposure to different chemicals. Metals and drugs are frequently and abundantly released into the environment, where they interact and bioaccumulate. Few studies analyze potential interactions between metals and pharmaceuticals in these mixtures, although their joint effects cannot be inferred from their individual properties. We have previously demonstrated that the mixture (PC) of the metals Cd and Hg, the metalloid As and the pharmaceuticals diclofenac (DCF) and flumequine (FLQ) impairs hepatic proteostasis. To gain a deeper vision of how PC affects mouse liver homeostasis, we evaluated here the effects of PC exposure upon some biochemical and morphometric parameters, and on the transcriptional profiles of selected group of genes. We found that exposure to PC caused oxidative damage that exceeded the antioxidant capacity of cells. The excessive oxidative stress response resulted in an overabundance of reducing equivalents, which hindered the metabolism and transport of metabolites, including cholesterol and bile acids, between organs. These processes have been linked to metabolic and inflammatory disorders, cancer, and neurodegenerative diseases. Therefore, our findings suggest that unintended exposure to mixtures of environmental pollutants may underlie the etiology of many human diseases. Fortunately, we also found that a diet enriched with selenium mitigated the harmful effects of this combination of toxicants.

Residue depletion of enrofloxacin and flumequine in feathers of broilers based on quantitative UHPLC-MS/MS detection

To explore potential factors contributing to high fluoroquinolone resistance levels, it is essential to develop analytical methods capable of detecting residues and trace amounts of antibiotic use in broilers. The aim of the present study was to develop and in-house validate a sensitive UHPLC-MS/MS method capable of determining enrofloxacin (ENR) and flumequine (FLU) residues at slaughter age (day 45) when the animals were treated with these antimicrobials one day after hatching. Residue depletion of ENR and FLU in feathers was also assessed. Two experimental trials were performed, both consisting of 5 different treatment groups. In the first trial animals were treated with ENR and in the second one with FLU. The developed method was successfully validated and was found to be sensitive enough to detect residues of fluoroquinolones in the feathers up until slaughter age in all treatment groups. Average ENR concentration on day 45 was 10 ng g−1 feather after drinking water treatment, with all concentrations above the limit of quantification (LOQ) of 5 ng g−1 feather. For FLU average concentration on day 45 after drinking water administration was 4 ng g−1 feather, with an LOQ of 1 ng g−1 feather. Therefore, the method is suited for application to monitor fluoroquinolone use in broilers.

Development of a new synchronous fluorescence spectrometry combined with Al3+ sensitized for simultaneous and rapid determination of trace flumequine, ciprofloxacin and doxycycline hydrochloride residues in wastewater

Antibiotics are a new type of environmental pollutants. Due to its wide application in many fields, antibiotic residues are ubiquitous in the wastewater environments. Given their potential threat on water ecosystem functioning and public health, the detection of antibiotic residues in wastewater environments has become very necessary. Based on the complexation of Al3+ with flumequine (FLU), ciprofloxacin (CIP) and doxycycline hydrochloride (DOX), their molecular conjugated area were increased and fluorescence intensity were enhanced, combined with synchronous fluorescence spectrometry (SFS) had good selectivity and high sensitivity, a novel method of Al3+ sensitized synchronous fluorescence spectrometry for the determination of FLU, CIP and DOX residues in wastewater was established. When the wavelength difference (Δλ) was selected 115.0 nm, synchronous fluorescence spectra of the three antibiotics could be well separated and the interference of wastewater matrix were eliminated primely. The new SFS made good use of spectral separation instead of conventional chemical separation, and the actual wastewater sample could be directly determined after simple filtration. The experiment results showed that the concentrations of FLU, CIP and DOX in the range of 0.5000–800.0 ng·mL-1, 0.5000–640.0 ng·mL-1 and 10.00–3500 ng·mL-1 had a good linear relationship with fluorescence intensity. The detection limits of three antibiotics were 0.02054 ng·mL-1, 0.03956 ng·mL-1 and 0.8524 ng·mL-1, respectively. Recovery rates of three antibiotics in wastewater samples were 90.72%-98.23%, 88.68%-95.08% and 85.94%-96.70%. The new SFS established in this experiment had the advantages of simple, rapid, sensitive, accurate and good selectivity. Simultaneous and rapid detection of FLU, CIP and DOX residues in wastewater was successfully realized. It had good application prospects in real-time water quality monitoring.

Trophic transfer of antibiotics in the benthic-pelagic coupling foodweb in a macrophyte-dominated shallow lake: The importance of pelagic-benthic coupling strength and baseline organism

In lake ecosystems, pelagic-benthic coupling strength (PBCS) is closely related to foodweb structure and pollutant transport. However, the trophic transfer of antibiotics in a benthic-pelagic coupling foodweb (BPCFW) and the manner in which PBCS influences the trophic magnification factor (TMFs) of antibiotics is still not well understood in the whole lake. Herein, the trophic transfer behavior of 12 quinolone antibiotics (QNs) in the BPCFW of Baiyangdian Lake were studied during the period of 2018–2019. It was revealed that 24 dominant species were contained in the BPCFW, and the trophic level was 0.42–2.94. Seven QNs were detected in organisms, the detection frequencies of ofloxacin (OFL), flumequine (FLU), norfloxacin (NOR), and enrofloxacin (ENR) were higher than other QNs. The ∑QN concentration in all species was 11.3–321 ng/g dw. The TMFs for ENR and NOR were trophic magnification, while for FLU/OFL it was trophic dilution. The PBCS showed spatial-temporal variation, with a range of 0.6977–0.7910. The TMFs of ENR, FLU, and OFL were significantly positively correlated with PBCS. Phytoplankton and macrophyte biomasses showed indirect impact on the TMFs of QNs by directly influencing the PBCS. Therefore, the PBCS was the direct influencing factor for the TMFs of chemicals.

Role of bipyridyl in enhancing ferrate oxidation toward micropollutants

Enhancing Fe(VI) oxidation ability by generating high-valent iron-oxo species (Fe(IV)/Fe(V)) has attracted continuous interest. This work for the first time reports the efficient activation of Fe(VI) by a well-known aza-aromatic chelating agent 2,2′-bipyridyl (BPY) for micropollutant degradation. The presence of BPY increased the degradation constants of six model compounds (i.e., sulfamethoxazole (SMX), diclofenac (DCF), atenolol (ATL), flumequine (FLU), 4-chlorophenol (4-CP), carbamazepine (CBZ)) with Fe(VI) by 2 – 6 folds compared to those by Fe(VI) alone at pH 8.0. Lines of evidence indicated the dominant role of Fe(IV)/Fe(V) intermediates. Density functional theory calculations suggested that the binding of Fe(III) to one or two BPY molecules initiated the oxidation of Fe(III) to Fe(IV) by Fe(VI), while Fe(VI) was reduced to Fe(V). The increased exposures of Fe(IV)/Fe(V) were experimentally verified by the pre-generated Fe(III) complex with BPY and using methyl phenyl sulfoxide as the probe compound. The presence of chloride and bicarbonate slightly affected model compound degradation by Fe(VI) in the presence of BPY, while a negative effect of humic acid was obtained under the same conditions. This work demonstrates the potential of N-donor heterocyclic ligand to activate Fe(VI) for micropollutant degradation, which is instructive for the Fe(VI)-based oxidation processes.

Characteristics of antibiotic resistance genes and microbial community distribution in Wanfeng Lake, upper Pearl River, China.

Wanfeng Lake, a highland lake in the upper part of the Pearl River Basin, China, has long been disturbed by aquaculture and human activities, resulting in the accumulation of antibiotics and antibiotic resistance genes (ARGs), which pose a major threat to humans and animals. In this study, 20 antibiotics, 9 ARGs, 2 mobile genetic elements (intl1 and intl2), and microbial community structure were investigated in Wanfeng Lake. The results of the study showed that the total concentration of antibiotics in surface water was 372.72ng/L, with ofloxacin (OFX) having the highest concentration (169.48ng/L), posing a high ecological risk to aquatic organisms. The total concentration of antibiotics in sediments was 235.86ng/g, with flumequine (FLU) having the highest concentration (122.54ng/g). This indicates that the main type of antibiotics in Wanfeng Lake are quinolones. QPCR analysis results of the relative abundance of ARGs in both surface water and sediments showed that sulfonamide resistance genes > macrolide resistance genes > tetracycline resistance genes > quinolone resistance genes, indicating that sulfonamide resistance genes were the dominant type. The metagenomic results showed that the predominant microorganisms in the sediment under the phylum level were Planctomycetes, Proteobacteria, Euryarchaeota, and Chloroflexi. Pearson's correlation analysis showed a significantly positive correlation between antibiotics and environmental factors with ARGs in Wanfeng Lake and a significant positive correlation between antibiotics and ARGs with microorganisms in sediments. This suggests that there is a potential pressure of antibiotics on ARGs, while microorganisms provide the driving force for the evolution and spread of ARGs. This study provides a basis for further research on the occurrence and spread of antibiotics and ARGs in Wanfeng Lake. A total of 14 antibiotics were detected in surface water and sediments. OFX poses a high ecological risk in all points of surface water. Antibiotics and ARGs were significantly positively correlated in Wanfeng Lake. Antibiotics and ARGs in sediments were positively correlated with microorganisms.

Efficient removal of veterinary drugs from aqueous solutions using magnetically separable carbonaceous materials derived from cobalt and iron metal-organic frameworks.

Rapid synthesis of carbon-based magnetic materials derived from cobalt and iron metal-organic frameworks (MOFs), ZIF-67, and MIL-100(Fe), by microwave-assisted method, followed by carbonization under a N2 atmosphere is described in this study. The carbon-derived MOFs (CDMs) were evaluated for the removal of theemerging pollutants sulfadiazine (SDZ) and flumequine (FLU)used asveterinary drugs. The study aimed to link the adsorption behavior with their surface properties and elemental composition. C-ZIF-67 and C-MIL-100(Fe) showed hierarchical porous structures with specific surface areas of 295.6 and 163.4 m2 g-1, respectively. The Raman spectra of the CDMs show the characteristic D and G bands associated with defect-rich carbon and sp2 graphitic carbon, respectively. The CDMs exhibit cobalt species (Co3O4, CoO, and Co) in C-ZIF-67 and iron species (Fe2O3, Fe3O4, and Fe) in C-MIL-100 (Fe) which are related to the magnetic behavior of CDMs. C-ZIF-67 and C-MIL-100 (Fe) had saturation magnetization values of 22.9 and 53.7 emu g-1, respectively, allowing easy solid-liquid separation using a magnet. SDZ and FLU removal rates on CDMs follow pseudo-second-order kinetics, and adsorption isotherms fit the Langmuir model based on regression coefficient values. Adsorption thermodynamics calculations showed that the adsorption of SDZ and FLU by CDMs was a thermodynamically favorable process. Therefore, these properties of C-ZIF-67 and C-MIL-100 (Fe) and their regeneration ability facilitate their use as adsorbents for emerging pollutants.

An In Vivo Whole-Transcriptomic Approach to Assess Developmental and Reproductive Impairments Caused by Flumequine in Daphnia magna.

Among veterinary antibiotics, flumequine (FLU) is still widely used in aquaculture due to its efficacy and cost-effectiveness. Although it was synthesized more than 50 years ago, a complete toxicological framework of possible side effects on non-target species is still far from being achieved. The aim of this research was to investigate the FLU molecular mechanisms in Daphnia magna, a planktonic crustacean recognized as a model species for ecotoxicological studies. Two different FLU concentrations (2.0 mg L-1 and 0.2 mg L-1) were assayed in general accordance with OECD Guideline 211, with some proper adaptations. Exposure to FLU (2.0 mg L-1) caused alteration of phenotypic traits, with a significant reduction in survival rate, body growth, and reproduction. The lower concentration (0.2 mg L-1) did not affect phenotypic traits but modulated gene expression, an effect which was even more evident under the higher exposure level. Indeed, in daphnids exposed to 2.0 mg L-1 FLU, several genes related with growth, development, structural components, and antioxidant response were significantly modulated. To the best of our knowledge, this is the first work showing the impact of FLU on the transcriptome of D. magna.

Use of Fluorescence Spectroscopy and Chemometrics to Visualise Fluoroquinolones Photodegradation Major Trends: A Confirmation Study with Mass Spectrometry.

In this work, we employed EEM-PARAFAC (fluorescence excitation-emission matrices-parallel factor analysis) as a low-cost tool to study the oxidation pathways of (fluoro)quinolones. Amounts of 12.5 μM of enrofloxacin (ENR), ciprofloxacin (CIP), ofloxacin (OFL), oxolinic acid (OA), and flumequine (FLU), as individual solutions, were irradiated under UVA light. A 5-component PARAFAC model was obtained, four of them related to the parent pollutants, named as ENR-like (including CIP), OFL-like, OA-like, and FLU-like, and an additional one related to photoproducts, called ENRox-like (with an emission red-shift with respect to the ENR-like component). Mass spectrometry was employed to correlate the five PARAFAC components with their plausible molecular structures. Results indicated that photoproducts presenting: (i) hydroxylation or alkyl cleavages exhibited fingerprints analogous to those of the parent pollutants; (ii) defluorination and hydroxylation emitted within the ENRox-like region; (iii) the aforementioned changes plus piperazine ring cleavage emitted within the OA-like region. Afterwards, the five antibiotics were mixed in a single solution (each at a concentration of 0.25 μM) in seawater, PARAFAC being also able to deconvolute the fingerprint of humic-like substances. This approach could be a potential game changer in the analysis of (fluorescent) contaminants of emerging concern removals in complex matrices, giving rapid visual insights into the degradation pathways.

Facile synthesis of triazine-based microporous organic network for high-efficient adsorption of flumequine and nadifloxacin: A comprehensive study on adsorption mechanisms and practical application potentials

Flumequine (FLU) and nadifloxacin (NAD), as emerging contaminants, have received extensive attention recently. In this study, a triazine-based microporous organic network (TMON) was synthetized and developed as an excellent adsorbent for FLU and NAD. The adsorption behavior and influence factors were investigated in both single and binary systems. Insight into the adsorption mechanisms were conducted through experiments, models, and computational studies, from macro and micro perspectives including functional groups, adsorption sites, adsorption energy and frontier molecular orbital. The results showed that the maximum adsorption capacities of TMON for FLU and NAD are 325.27 and 302.28 mg/g under 30 °C higher than records reported before. TMON exhibits the better adaptability and anti-interference ability for influence factors, leading to the preferable application effect in kinds of real water samples. TMON also shows the application potentials for the adsorption of other quinolone antibiotics and CO2 capture. Hydrogen-bonding interaction played the most critical role compared to π-π stacking effect, π-π electron-donor-acceptor interaction, CH-π interaction, and hydrophobic interaction during the adsorption. TMON could be regarded as a promising environmental adsorbent for its large surface area, stable physical and chemical properties, excellent recyclability, and wide range of applications.

Experimental Design Assisted HPLC/UV and LC-MS/MS for Simultaneous Determination of Selected Veterinary Antibiotics in Broiler Chicken

Antibiotics are used in the poultry industry to treat and prevent diseases. Their frequent use resulted in the appearance of antibiotic residuals in poultry meat, which is considered a serious public health issue. Among frequently used antibiotics are cefotaxime (CTX), ciprofloxacin (CIP), colistin (CST), doxycycline (DOX), flumequine (FLU), sulfamethoxazole (SMZ), trimethoprim (TMP) and tylosin (TYL). This study aimed to develop an optimized and validated method for concurrent estimation of the eight antibiotics in broiler chicken samples based on an easy extraction method followed by HPLC-UV and LC/MS/MS analysis. An experimental design was used for the optimization of the extraction procedure. Optimal conditions for separation were determined by using a central composite design after studying (1) mobile phase initial concentration, (2) column temperature, and (3) flow rate. The method was validated on the bases of ICH guidelines. The detection limits ranged from 3 to 5 µg kg−1 for HPLC- UV and ranged from 0.01 to 0.05 µg kg−1 for LC/MS/MS, while quantification limits ranged from 10 to 16 µg kg−1 for HPLC- UV and ranged from 0.01 to 0.11 µg kg−1 for LC/MS/MS. The chromatographic techniques were utilized for the analysis of spiked broiler chicken samples at a concentration range from 30 to 300 µg kg−1) for HPLC-UV and 0.01–20 µg kg−1 for LC/MS/MS. The proposed methods were used for quantification of the residues of the studied antibiotics in real broiler samples obtained from local supermarkets in Ismailia governorate, Egypt. The detected levels of residual antibiotics were within the permissible limits.

Enantioselective Behavior of Flumequine Enantiomers and Metabolites' Identification in Sediment.

The enantioselective adsorption, degradation, and transformation of flumequine (FLU) enantiomers in sediment were investigated to elucidate the enantioselective environmental behaviors. The results of adsorption test showed that stereoselective differences of FLU enantiomers in sediment samples and the adsorbing capacity of S-(-)-FLU and R-(+)-FLU are higher than the racemate, and the pH values of the sediment determined the adsorption capacity. Enantioselective degradation behaviors were found under nonsterilized conditions and followed pseudo-first-order kinetic. The R-(+)-FLU was preferentially degraded, and there was significant enantioselectivity of the degradation of FLU. It can be concluded that the microorganism was the main reason for the stereoselective degradation in sediments. The physicochemical property of sediments, such as pH value and organic matter content, can affect the degradation rate of FLU. In addition, the process of transformation of FLU enantiomers in water-sediment system had enantioselective behavior, and R-(+)-FLU was preferential transformed. Meanwhile, the main metabolites of FLU in the sediment were decarboxylate and dihydroxylation products. This study contributes the evidence of comprehensively assessing the fate and risk of chiral FLU antibiotic and enantioselective behavior in the environment.

Ecological Risk Assessment of Quinolones Antibiotics and the Correlation Analysis Between QNs and Physical-Chemical Parameters in Groundwater, Shijiazhuang City

Most studies on antibiotics in groundwater have focused on pollution characteristics, whereas less attention has been paid to the ecological risks of antibiotics and the correlation to environmental parameters. In this study, the groundwater in Shijiazhuang City was selected as the research area. Through high performance liquid chromatography-tandem mass spectrometry (HPLC-MS), the concentration of quinolones (QNs) in the groundwater was analyzed. Correlation analysis was conducted between QNs concentrations and physical-chemical parameters. The results showed that:① the detection frequency of flumequine (FLU) was the highest (100%), followed by enoxacin (ENO) (80.0%) and ciprofloxacin (CIP) (75.0%). ② The concentration of QNs ranged from 3.02 to 98.5 ng·L-1; in terms of spatial distribution, the highest concentration of QNs appeared at S4 (98.5 ng·L-1), whereas the lowest concentration was exhibited at S19 (3.02 ng·L-1). ③ Temperature (T), chemical oxygen demand (COD), total dissolved solids (TDS), total number of colonies (BCTC), and pH were significantly correlated with QNs (P<0.01 or P<0.05) based on correlation analysis. ④ For the spatial distribution of ecological risk, the results showed that the ecological risk at S4 was high, whereas the risks for other sites were low. For the type of QNs, ciprofloxacin (CIP) was at a medium-high risk level, whereas the other QNs were at a low-risk level. Thus, in order to guarantee the ecological safety of groundwater in Shijiazhuang City, more attention should be paid to the risk management and control of antibiotics in groundwater in the future.

EEM-PARAFAC as a convenient methodology to study fluorescent emerging pollutants degradation: (fluoro)quinolones oxidation in different water matrices

Commercial (fluoro)quinolones ((F)Qs), ciprofloxacin (CIP), enrofloxacin (ENR), ofloxacin (OFL), oxolinic acid (OA) and flumequine (FLU) (3 μM each), were degraded with solar-photo-Fenton in a compound parabolic concentrator photoreactor (total volume 5 L) in ultra-pure water at pH = 5.0, salty water at pH = 5.0, and simulated wastewater at pH = 5.0 and 7.5. Iron speciation (its hydrolysis and the complexation with (F)Qs 15 μM and/or chlorides 0.5 M) was calculated at pH 5.0, observing, negligible formation of Fe(III)-chloride complexes, and that >99 % of the total (F)Qs are forming complexes stoichiometry 1:1 with Fe(III) (which also increases the percentage of Fe(OH)2+), being minoritarian the free antibiotic form. On the other hand, EEM-PARAFAC (fluorescence excitation-emission matrices-parallel factor analysis) was employed to simultaneously study the behaviour of: i) 4 structure-related groups corresponding to parent pollutants and slightly oxidised by-products, ENR-like (including CIP), OFL-like, OA-like, FLU-like; ii) intermediates still showing (F)Q characteristics (exhibiting analogous fluorescent fingerprint to ENR-like one, but shifted to shorter wavelengths); iii) humic-like substances. The scores from the 4 PARAFAC components corresponding to the parent pollutants were plotted vs. accumulated energy, exhibiting slower decay than their individual removals (measured with HPLC-UV/vis) due to the contribution of the aforementioned by-products to the overall fluorescence. Moreover, thiabendazole (TBZ) 3 μM was added as fluorescence interference. The presence of (F)Qs greatly enhanced TBZ degradation due to (F)Q-Fe(III) complex formation, keeping iron active at pH = 5.0 for Fenton process. The EEM-PARAFAC model was able to recognise the former six components plus an additional one attributable to TBZ-like.

Effects of veterinary drugs on rearing and safety of black soldier fly (Hermetia illucens) larvae

Insect proteins are expected to be increasingly used for food and feed. Black soldier fly larvae (BSF, Hermetia illucens) can convert low quality organic substrates, such as manure, into protein-rich ingredients for food and feed. However, pig and chicken manure can contain residues from antibiotics and anti-parasitic drugs, resulting from treatments of the animals for diseases. This study aimed to evaluate the possible effects of veterinary drugs on black soldier fly larvae rearing, including growth and survival, as well as on the presence of residues in the larvae. The study focused on regularly found veterinary drugs in manure. Five-days old larvae were exposed to either 0.05 and 0.5 mg/kg flubendazole (FLUB), 0.05 and 0.5 mg/kg ivermectin (IVM), 0.5 and 5 mg/kg doxycycline (DOX), 0.5 and 5 mg/kg flumequine (FLUM) or 0.5 and 5 mg/kg sulfadiazine (SULF) for one week. The growth of larvae reared on substrate with IVM (0.5 mg/kg) was significantly lower than the control, while the survival of the larvae was not affected. The growth and survival of the larvae was not affected by the other treatments. Chemical analyses showed that concentrations of the veterinary drugs in the larvae, after exposure, were generally low. Only DOX concentrations in the larvae were high; these levels would exceed the European Commission maximum limit for DOX in meat products. Mass-balance calculations showed possible degradation or metabolism of veterinary drugs by the larvae, except for SULF. In conclusion, when using manure as substrate for BSF rearing, the possible presence of veterinary drugs in manure should be carefully controlled to ensure optimal insect growth and safety of the insect products.

The difference of trophic magnification factors of Quinolones antibiotics (QNs) between pelagic and benthic foodwebs in a shallow lake: importance of carbon and nitrogen sources

Feeding habitat and carbon source play critical roles in certain the trophic transfer and bioaccumulation ability of chemicals in aquatic ecosystems. However, it remains largely unknown how these factors affect the trophic magnification factors (TMFs) of antibiotics in lake ecosystem. This study compared the differences of TMFs for Quinolones (QNs) antibiotics and carbon/nitrogen sources between pelagic foodweb (PFW, 11 species) and benthic foodweb (BFW, 14 species) in Baiyangdian Lake, Northern China. δ13C showed higher values in BFW, while δ15N appeared higher values in PFW. The mean percentage of pelagic nitrogen source (PNS) was higher than benthic nitrogen source (BNS), while the mean percentages of pelagic carbon source (PCS) and benthic carbon source (BCS) were approximately equal. Relatively high concentrations of enrofloxacin (ENR), flumequine (FLU), norfloxacin (NOR), and ofloxacin (OFL) were detected, and the total concentrations of QNs were 27.73–126.4 ng/g dw in PFW, while 23.49–121.3 ng/g dw in BFW. ENR and NOR appeared trophic magnification, while FLU and OFL exhibited trophic dilution. The TMFs of these QNs in PFW were significantly higher than in BFW. The concentration of QNs in biological samples were significantly positive correlation with δ15N, while negative correlated with δ13C. The TMFs for FLU and OFL were positively correlated with PCS/PNS, while negatively correlated with BCS/BNS. The opposite was true for NOR and ENR. Capsule abstractFirst studied the differences of TMFs for typical QNs and carbon/nitrogen sources between PFW and BFW in a shallow lake.

Flumequine-loaded titanate nanotubes as antibacterial agents for aquaculture farms.

Flumequine (FLUM), a quinolone-derived antibiotic is one of the most prescribed drugs in aquaculture farms. However, its intensive use becomes worrisome because of its environmental risks and the emergence of FLUM-resistant bacteria. To overcome these problems we propose in this study the encapsulation and the delivery of FLUM by titanate nanotubes (TiNTs). Optimal FLUM loading was reached by suspending the dehydrated powder nanomaterials (FLUM : TiNTs ratio = 1 : 5) in ethanol. The drug entrapment efficiency was calculated to be 80% approximately with a sustained release in PBS at 37 °C up to 5 days. Then FLUM@TiNTs was evaluated for both its in vitro drug release and antimicrobial activity against Escherichia coli (E. coli). Spectacularly high antibacterial activity compared to those of free FLUM antibiotic was obtained confirming the efficiency of TiNTs to protect FLUM from rapid degradation and transformation within bacteria improving thereby its antibacterial effect. Indeed FLUM@TiNTs was efficient to decrease gradually the bacterial viability to reach ≈5% after 5 days versus ≈75% with free FLUM. Finally, the ex vivo permeation experiments on sea bass (Dicentrachus labrax) intestine shows that TiNTs act to increase the intestinal permeation of FLUM during the experiment. Indeed the encapsulated FLUM flux increased 12 fold (1.46 μg cm2 h−1) compared to the free antibiotic (0.18 μg cm2 h−1). Thanks to its physical properties (diameter 10 nm, tubular shape…) and its high stability in the simulated intestinal medium, TiNTs are easy internalized by enterocytes, thus involving an endocytosis mechanism, and then improve intestinal permeation of FLUM. Taken together, FLUM@TiNTs hold potential as an effective approach for enhancing the antimicrobial activity of FLUM and pave the way not only for future pharmacokinetic studies in the treatment and targeting of fish infections but also for instating of novel strategies that overcome the challenges associated with the abusive use of antibiotics in fish farming.

Kinetics and mechanisms of flumequine degradation by sulfate radical based AOP in different water samples containing inorganic anions.

Many studies have reported that hydroxyl radical (HO˙) driven advanced oxidation processes (AOPs) could degrade fluoroquinolones (FQs) antibiotics effectively. Compared with HO˙, sulfate radical (SO4˙−) shows a similar oxidation capacity but a longer half-life. SO4˙− could cause chain reactions and resulted in the generation of halogen radicals and carbonate radicals from the main anions in sea water including Cl−, Br− and HCO3−. However, few studies were focused on the degradation of FQs in marine aquaculture water and seawater, as well as the bioaccumulation of transformation products. As a typical member of FQs, flumequine (FLU) was degraded by UV/peroxodisulfate (PDS) AOPs in synthetic fresh water, marine aquaculture water and seawater. The reaction rate constants in the three water samples were 0.0348 min−1, 0.0179 min−1 and 0.0098 min−1, respectively. The reason was attributed to the inhibition of the anions as they could consume SO4˙− and initiate the quenching reaction of free radicals. When the pH value increased from 5 to 9, the reaction rate decreased from 0.0197 min−1 to 0.0066 min−1. The energy difference between HOMO and LUMO of FLU was calculated to be 8.07 eV indicating that FLU was a stable compound. The atoms on quinolone ring of FLU with high negative charge would be more vulnerable to attack by free radicals through electrophilic reactions. Two possible degradation pathways of FLU were inferred according to the degradation products. Preliminary bioaccumulation analysis of transformation products by the EPI suite software proved that the values of log Kow and log BCF of the final product P100 were less than those of FLU and the intermediates.

Antibacterial treatment of lumpfish (Cyclopterus lumpus) experimentally challenged with Vibrio anguillarum, atypical Aeromonas salmonicida and Pasteurella atlantica.

Lumpfish is a novel farmed species used as cleaner fish for the removal of lice from farmed salmon. As often with new, farmed species, there are challenges with bacterial infections. The frequency of prescription of antibiotic agents to lumpfish is increasing, despite the lack of knowledge about appropriate doses, duration of treatment and application protocols for the various antibacterial agents. In the current study, we have tested the effect of medicated feed with florfenicol (FFC), oxolinic acid (OA) and flumequine (FLU) on lumpfish experimentally challenged with Vibrio anguillarum, atypical Aeromonas salmonicida and Pasteurella atlantica. We found that all three antibacterial agents efficiently treated lumpfish with vibriosis using 10 and 20mgkg-1 day-1 of FFC, 25mgkg-1 day-1 of OA and 25mgkg-1 day-1 FLU, whereas only FFC (20mgkg-1 day-1 ) had good effect on lumpfish with pasteurellosis. None of the antibacterial agents were efficient to treat lumpfish with atypical furunculosis. FFC 20mgkg-1 day-1 showed promising results in the beginning of the experiment, but the mortality increased rapidly 14days post-medication. Efficient treatment is important for the welfare of lumpfish and for reducing the risk of development of antibiotic-resistant bacteria. To our knowledge, this is the first study to establish protocols for antibacterial treatment of lumpfish.

Preparation of Ag Loaded WO3 Nano Rod and Its Highly Efficient Degradation of Flumequine under Sunlight Irradiation

The aim of this study was to evaluate the efficiency of Ag/WO3 photocatalytic process for degradation of Flumequine (FL) antibiotic from aqueous solutions. In this study, WO3 and Ag/WO3 particles were synthesized and characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), energy dispersive X-ray spectrometry (EDS)/Map, Brunauer, Emmett, Teller (BET)/Barrett, Joyner, Halenda (BJH) and UV–vis diffuse reflectance spectroscopy (DRS) techniques. The photocatalytic degradation of FL from aqueous solutions was studied by Ag/WO3 photocatalyst under sunlight irradiation. The response surface methodology (RSM) with Central Composite Design (CCD) with 4 variables was used to investigate the relationship between the obtained responses and process variables and optimize with Design Expert software. In this study, the effect of pH, time (min), photocatalyst mass (g) and FL concentration (mg/L) were evaluated at 5 levels. Finally, the software is the best point to achieve the highest degradation efficiency of FL 99.54%, in optimal conditions at pH 3.07, time 101.14 (min), photocatalyst mass 0.13 (g) and FL concentration 41.3 (mg/L).