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Introduction: Macranthoidin B (MB) is a primary active component of Flos Lonicerae. In Chinese veterinary clinics, Flos Lonicerae is frequently used in combination with florfenicol to prevent and treat infections in livestock and poultry. However, potential interactions between Flos Lonicerae and florfenicol remain unclear. To systematically study these interactions, it is crucial to investigate the individual phytochemicals within Flos Lonicerae. Therefore, MB was selected for this study to assess its effect on the pharmacokinetics of florfenicol in vivo and to explore the underlying mechanisms involved. Methods: Male Sprague-Dawley rats were administered MB (60 mg/kg BW) or sterile water orally for 7 consecutive days. On the 8th day, a single oral dose of florfenicol (25 mg/kg BW) was given. Florfenicol pharmacokinetics were analyzed using ultra-high performance liquid chromatography. The hepatic expression levels of cytochrome P450 (CYP1A2, CYP2C11, CYP3A1), UDPglucuronosyltransferase (UGT1A1), P-glycoprotein (P-gp), and nuclear receptors, including constitutive androstane receptor (CAR), pregnane X receptor (PXR), and retinoid X receptor alpha (RXRa), were quantified via reverse transcription-quantitative polymerase chain reaction and Western blotting (WB). Hepatic CYP1A2 and CYP2C11 activities were measured using a cocktail method. Additionally, the subcellular expression and localization of CAR, PXR, and RXRain hepatocytes was assessed using WB and immunofluorescence staining. Results: MB significantly reduces the AUC(0-8) and MRT(0-8) of florfenicol. MB also markedly upregulates the mRNA and protein expression of hepatic CYP1A2 and CYP2C11, along with their catalytic activities. Substantial upregulation of CAR and PXR proteins occurs in the hepatocyte nucleus, along with significant nuclear colocalization of the transcriptionally active CAR/RXRa and PXR/RXRaheterodimers, indicating MB-induced nuclear translocation of both CAR and PXR. Discussion: These findings suggest that MB-induced alterations in florfenicol pharmacokinetics, particularly its accelerated elimination, may be due to increased expression and activities of CYP1A2 and CYP2C11, with CAR and PXR potentially involved in these regulatory effects. Further investigation is yet needed to fully elucidate the clinical implications of these interactions concerning the efficacy of florfenicol in veterinary medicine. [ABSTRACT FROM AUTHOR]

Salmonid rickettsial septicemia (SRS), caused by Piscirickettsia salmonis, has been the most severe health concern for the Chilean salmon industry. The efforts to control P. salmonis infections have focused on using antibiotics and vaccines. However, infected salmonids exhibit limited responses to the treatments. Here, we developed a poly (D, L-lactide-glycolic acid) (PLGA)-nanosystem functionalized with Atlantic salmon IgM (PLGA-IgM) to specifically deliver florfenicol into infected cells. Polymeric nanoparticles (NPs) were prepared via the double emulsion solvent-evaporation method in the presence of florfenicol. Later, the PLGA-NPs were functionalized with Atlantic salmon IgM through carbodiimide chemistry. The nanosystem showed an average size of ~380–410 nm and a negative surface charge. Further, florfenicol encapsulation efficiency was close to 10%. We evaluated the internalization of the nanosystem and its impact on bacterial load in SHK-1 cells by using confocal microscopy and qPCR. The results suggest that stimulation with the nanosystem elicits a decrease in the bacterial load of P. salmonis when it infects Atlantic salmon macrophages. Overall, the IgM-functionalized PLGA-based nanosystem represents an alternative to the administration of antibiotics in salmon farming, complementing the delivery of antibiotics with the stimulation of the immune response of infected macrophages. [ABSTRACT FROM AUTHOR]

Florfenicol (FF) is a new antibiotic commonly used in sericulture. This study aimed to examine the effects of low (LC: 0.06 g/L), medium (MC: 0.12 g/L), and high (HC: 1.2 g/L) concentrations of FF on the midgut physiological functions of the silkworm, Bombyx mori (L.) (Lepidoptera: Bombycidae). The results showed that the body weight and the whole cocoon weight of silkworms decreased and the development duration of the fifth instar was prolonged in the HC group. The structure of intestinal microbiota of silkworm larvae was changed by high FF exposure. Specifically, the abundance of conditional pathogens (Curtobacterium, Sanguibater, etc.) was significantly increased, whereas the abundance of Pseudomonas and Pedobacter was decreased significantly. Additionally, the intestinal reactive oxygen species level at 72 h was significantly elevated, and the muscle layer had become loose, together with the appearance of gut goblet cell atrophy. We observed that the increase in Lactobacillus abundance led to a reduction in intestinal fluid pH, resulting in decreased α‐amylase and protease activities, whereas lipase activity exhibited an elevation. The results demonstrated that the accumulation of peroxides induced by exposure to 1.2 g/L FF caused intestinal damage, and the decrease in pH resulting from alterations in microbial composition and structure affected digestive enzyme activity, collectively leading to physiological impairment of the silkworm midgut. These findings provide a valuable reference for the safe use of FF in sericulture. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this study was to determine pharmacokinetics of florfenicol and its metabolite florfenicol amine after a single (30 mg/kg) intravenous (IV) and oral administration of florfenicol in chukar partridges. It also aimed to investigate tissue residue and withdrawal time of florfenicol after multiple‐dose (30 mg/kg, every 24 h for 5 days) oral administration. The research was carried out in two stages: pharmacokinetics and residue. Plasma and tissue concentrations of florfenicol and florfenicol amine were determined by HPLC. The elimination half‐life of florfenicol was 5.25 h for IV and 5.44 h for oral. The volume of distribution at a steady state and total body clearance of florfenicol were 0.38 L/kg and 0.07 L/h/kg, respectively, after IV administration. The peak plasma concentration and bioavailability for oral administration were 45.26 ± 4.06 and 51.55%, respectively. After multiple‐dose oral administration, the highest concentration was detected in the liver (9.21 μg/g) for florfenicol and in the kidney (0.67 μg/g) for florfeniol amine. The calculated withdrawal period of florfenicol was determined as 6, 3, 4, and 5 days for muscle, liver, kidney, and skin + fat, respectively. These data indicate that a 6‐day WT after multiple‐dose administration of florfenicol in chukar partridges can be considered safe for human consumption. [ABSTRACT FROM AUTHOR]

This study compares the effect of two colibacillosis induction methods including intratracheal and subcutaneous routes and treatment with florfenicol on serum parameters of broilers. One hundred and twenty five 35-day-old broilers were divided into 3 control groups (healthy, intratracheal induction control, subcutaneous induction control) and 4 experimental groups (intratracheal induction, intratracheal induction and antibiotic treated, subcutaneous induction, subcutaneous induction and antibiotic treated). Three days after treatment, blood sampling from all groups was performed. CPK activity in the four experimental groups showed a significant increase compared to the control groups. Uric acid in two groups of subcutaneous induction and subcutaneous induction with antibiotic treatment had a significant increase compared to the control groups. Sodium showed a significant increase in the intratracheal induction with antibiotic treatment group compared to the control groups. Potassium, phosphorus, AST, LDH and GGT in the treatment groups did not change significantly compared to the control groups (p<0.05). Taken together, kidney damage in birds inoculated by subcutaneous method is higher than intratracheal method according to the level of uric acid as a serum parameter of kidney function. Both challenge methods do not result in liver damage according to liver parameters, while a strong increase in CPK activity is present in both challenge methods. Florfenicol does not significantly change the serum parameters of birds with colibacillosis (except the amount of sodium in the intratracheal method). [ABSTRACT FROM AUTHOR]

Abstract Background Colibacillosis in broiler chickens is associated with economic loss and localized or systemic infection. Usually, the last resort is antibacterial therapy. Insight into the disease pathogenesis, host responses and plausible immunomodulatory effects of the antibacterials is important in choosing antibacterial agent and optimization of the treatment. Selected responses of broiler chickens experimentally infected with Escherichia coli (E. coli) and also those treated with florfenicol are evaluated in this study. Chickens (n = 70, 5 weeks old) were randomly assigned to four groups. The control groups included normal control (NC) and intratracheal infection control (ITC) (received sterile bacterial medium). The experimental groups consisted of intratracheal infection (IT) that received bacterial suspension and intratracheal infection with florfenicol administration (ITF) group. Results Florfenicol reversed the decreased albumin/globulin ratio to the level of control groups (p > 0.05). Serum interleukin 10 (IL-10) and interferon‐gamma (IFN-γ) concentrations decreased in IT birds as compared to NC group. Florfenicol decreased the serum interleukin 6 (IL-6) concentration as compared to IT group. Milder signs of inflammation, septicemia, and left shift were observed in the leukogram of the ITF group. Florfenicol decreased the severity of histopathological lesions in lungs and liver. Depletion of lymphoid tissue was detected in spleen, thymus and bursa of IT group but was absent in ITF birds. The number of colony forming units of E. coli in liver samples of ITF group was only slightly lower than IT birds. Conclusions Experimental E. coli infection of chickens by intratracheal route is associated with remarkable inflammatory responses as shown by changes in biochemical and hematological parameters. Histopathological lesions in lymphoid organs (especially in the spleen) were also prominent. Florfenicol has positive immunomodulatory effects and improves many of the lesions before the full manifestation of its antibacterial effects. These effects of florfenicol should be considered in pharmacotherapy decision-making process.

Antibiotics are widely used to prevent and treat bacterial infections, increasing aquaculture productivity. However, their imprudent use can lead to unintended consequences, including pathological alterations in vital organs of aquatic organisms. The safety of florfenicol following in-feed administration at 10 times the recommended dose and three times the recommended period in Pangasianodon hypophthalmus was studied. Florfenicol induced significant histoarchitectural anomalies as observed from the photomicrographs of double-stained sections of various tissues, including gills, liver, and kidneys of P. hypophthalmus, following in-feed administration at graded doses, viz., 0mg, 10mg, 30mg, 50mg and 100 mg/kg biomass–1 day–1 for 30 days, i.e., three times the recommended therapeutic duration. Gills exhibited lamellar fusion, epithelial lifting, and hyperplasia indicative of respiratory distress. There were hepatocellular vacuolation, degeneration, and congestion, suggesting impaired hepatic integrity. The kidney sections demonstrated tubular degeneration, necrosis, and interstitial inflammation implying renal dysfunction. These changes were prominent at higher doses, mostly in 50 mg and 100 mg groups, and in the extended duration of the treatment, underscoring the potential adverse effects of florfenicol on the histological integrity and physiological homeostasis of P. hypophthalmus. As the catfish species holds significant economic value in Asian aquaculture, understanding the impacts of antibiotic exposure is crucial for sustainable fish farming practices. Implementing appropriate antibiotic usage protocols and monitoring strategies can mitigate the risks associated with antibiotic-induced pathological alterations in commercially important aquatic species.

Background: Colibacillosis in broiler chickens is associated with economic loss and localized or systemic infection. Usually, the last resort is antibacterial therapy. Insight into the disease pathogenesis, host responses and plausible immunomodulatory effects of the antibacterials is important in choosing antibacterial agent and optimization of the treatment. Selected responses of broiler chickens experimentally infected with Escherichia coli (E. coli) and also those treated with florfenicol are evaluated in this study. Chickens (n = 70, 5 weeks old) were randomly assigned to four groups. The control groups included normal control (NC) and intratracheal infection control (ITC) (received sterile bacterial medium). The experimental groups consisted of intratracheal infection (IT) that received bacterial suspension and intratracheal infection with florfenicol administration (ITF) group. Results: Florfenicol reversed the decreased albumin/globulin ratio to the level of control groups (p > 0.05). Serum interleukin 10 (IL-10) and interferon‐gamma (IFN-γ) concentrations decreased in IT birds as compared to NC group. Florfenicol decreased the serum interleukin 6 (IL-6) concentration as compared to IT group. Milder signs of inflammation, septicemia, and left shift were observed in the leukogram of the ITF group. Florfenicol decreased the severity of histopathological lesions in lungs and liver. Depletion of lymphoid tissue was detected in spleen, thymus and bursa of IT group but was absent in ITF birds. The number of colony forming units of E. coli in liver samples of ITF group was only slightly lower than IT birds. Conclusions: Experimental E. coli infection of chickens by intratracheal route is associated with remarkable inflammatory responses as shown by changes in biochemical and hematological parameters. Histopathological lesions in lymphoid organs (especially in the spleen) were also prominent. Florfenicol has positive immunomodulatory effects and improves many of the lesions before the full manifestation of its antibacterial effects. These effects of florfenicol should be considered in pharmacotherapy decision-making process. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine antibiotic levels in plasma and interstitial fluid (ISF) after SC placement of compounded florfenicol (FF) calcium sulfate beads (CSBs) in New Zealand White rabbits (Oryctolagus cuniculus). ANIMALS 6 juvenile female rabbits (n = 5 treatment and 1 control). METHODS An ultrafiltration probe and CSBs were placed SC in 6 rabbits (n = 5 for FF CSBs and 1 for control CSBs). Plasma (3, 6, 12, 24, and 48 hours and 7, 14, and 21 days) and ISF (daily for 21 days) samples were collected, and FF was measured by HPLC for pharmacokinetic analysis. Hematology, biochemistry, and histopathology were assessed. RESULTS Means ± SD for the area under the curve, maximum concentration, time of maximum concentration, terminal halflife, and mean residence time to the last data point for plasma and ISF were 16.63 ± 8.16 and 17,902 ± 7,564 h·μg/mL, 0.79 ± 0.38 and 245 ± 223 μg/mL, 2.90 ± 0.3 and 59 ± 40 hours, 30.81 ± 16.9 and 27.3 ± 9.39 hours, 23.4 ± 10 and 73.7 ± 13 hours, respectively. Plasma FF was < 2 μg/mL at all time points. The ISF FF remained > 8 μg/mL for 109.98 to 231.58 hours. One rabbit death occurred during treatment, but the cause of death was undetermined. Local tissue inflammation was present, but no clinically significant systemic adverse effects were found on hematology, biochemistry, or histopathology in the remaining rabbits. CLINICAL RELEVANCE Florfenicol CSBs maintained antibiotic concentrations in ISF at levels likely to be effective against bacteria sensitive to > 8 μg/mL for 5 to 10 days while maintaining low (< 2 μg/mL) plasma levels. Florfenicol CSBs may be effective for local antibiotic treatment in rabbit abscesses. [ABSTRACT FROM AUTHOR]

Catalytic dechlorination of organic chlorides by palladium (Pd) with HCOOH represents one of the most effective and promising techniques for environmental remediation. In this study, we adopted alkaline-modified porous natural sponge as support of a Pd nanocatalyst (Pd@M-Sponge) and HCOOH as a hydrogen source for the hydrodechlorination of florfenicol (FF), o-chlorophenol (o-CP), and p-chlorophenol (p-CP). Favorable conversion efficiency of FF, o-CP, and p-CP was achieved at 25 °C and atmospheric pressure attributed to the small diameter and high catalytic reactivity of the prepared Pd NPs, in addition to the slight internal mass transfer limitation of the prepared Pd@M-Sponge. High reaction rate constants were obtained even in the conditions of a low molar ratio of HCOOH to p-CP (10:1) and a high concentration of p-CP (500 mg/L). The prepared catalyst also demonstrated superior recyclability without any obvious decrease in catalytic reactivity in 20 successive p-CP dechlorination cycles. This work provides an ideal recyclable and cost-effective catalyst based on renewable and biocompatible natural material for the catalytic hydrodechlorination of chlorinated organic pollutants with formic acid and a new view for the exploration and designing of highly reactive and stable catalysts for hydrodechlorination. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of florfenicol (FFC) in green sea and hawksbill sea turtles were evaluated following intramuscular (i.m.) administration at two different dosages of 20 or 30 mg/kg body weight (b.w.). This study (longitudinal design) used 5 green sea and 5 hawksbill sea turtles for the two dosages. Blood samples were collected at assigned times up to 168 h. FFC plasma samples were analyzed using validated high‐performance liquid chromatography equipped with diode array detection. The pharmacokinetic analysis was performed using a non‐compartment approach. The FFC plasma concentrations increased with the dosage. The elimination half‐life was similar between the treatment groups (range 19–25 h), as well as the plasma protein binding (range 18.59%–20.65%). According to the surrogate PK/PD parameter (T > MIC, 2 μg/mL), the 20 and 30 mg/kg dosing rates should be effective doses for susceptible bacterial infections in green sea and hawksbill sea turtles. [ABSTRACT FROM AUTHOR]

To investigate the impact of florfenicol on soil microbial community structure and diversity, an indoor florfenicol exposure model was established. Soil samples were collected at different concentrations of florfenicol (0, 0.05, 0.5, 5, and 50 mg/kg) on days 0, 7, 30, and 60. High-throughput sequencing was employed to examine the changes in soil microbial community structure, diversity, and abundance. The analysis revealed a total of 31874 operational taxonomic units (OTUs) in the soil samples, averaging 9524 OTUs per sample. The number of soil microbial community OTUs declined with increasing florfenicol concentration. The microbial species richness and diversity showed a decreasing trend at day 7, while the treatment group with 50 mg/kg florfenicol at 60 days exhibited the lowest richness index. Examination of the soil microbial community structure identified 50 phyla and 1303 genera. At the phylum level, the abundance of Actinobacteria and Bacteroides decreased with increasing florfenicol concentration. Similarly, at the genus level, some of the dominant genera displayed a decline in abundance with the rise of florfenicol concentration. Cluster analysis demonstrated significant temporal and concentration variability. The results indicate differences in the composition, diversity, dominance, abundance, and evenness of soil bacterial communities among different groups. Florfenicol has a significant negative impact on the structure and diversity of soil microbial communities. The findings of this study provide a scientific basis for the rational use of florfenicol in livestock farming to maintain a healthy and stable soil microecological environment. [ABSTRACT FROM AUTHOR]

Antibiotics are widely used to prevent and treat bacterial infections, increasing aquaculture productivity. However, their imprudent use can lead to unintended consequences, including pathological alterations in vital organs of aquatic organisms. The safety of florfenicol following in-feed administration at 10 times the recommended dose and three times the recommended period in Pangasianodon hypophthalmus was studied. Florfenicol induced significant histoarchitectural anomalies as observed from the photomicrographs of double-stained sections of various tissues, including gills, liver, and kidneys of P. hypophthalmus, following in-feed administration at graded doses, viz., 0mg, 10mg, 30mg, 50mg and 100 mg/kg biomass-1 day-1 for 30 days, i.e., three times the recommended therapeutic duration. Gills exhibited lamellar fusion, epithelial lifting, and hyperplasia indicative of respiratory distress. There were hepatocellular vacuolation, degeneration, and congestion, suggesting impaired hepatic integrity. The kidney sections demonstrated tubular degeneration, necrosis, and interstitial inflammation implying renal dysfunction. These changes were prominent at higher doses, mostly in 50 mg and 100 mg groups, and in the extended duration of the treatment, underscoring the potential adverse effects of florfenicol on the histological integrity and physiological homeostasis of P. hypophthalmus. As the catfish species holds significant economic value in Asian aquaculture, understanding the impacts of antibiotic exposure is crucial for sustainable fish farming practices. Implementing appropriate antibiotic usage protocols and monitoring strategies can mitigate the risks associated with antibiotic-induced pathological alterations in commercially important aquatic species. [ABSTRACT FROM AUTHOR]

Objective: Florfenicol (FFC) is a broad‐spectrum antibiotic approved by the U.S. Food and Drug Administration to treat both systemic and external bacterial infections in food fish. The objective of this study was to evaluate the effect of FFC‐medicated feed on the gut microbiota of Zebrafish Danio danio to determine (1) if the therapeutic dose of FFC‐medicated feed induces dysbiosis and (2) if fish with altered gut microbiota were more susceptible to subsequent infection by the common opportunistic fish pathogen Aeromonas hydrophila. Methods: Zebrafish that were treated with regular and FFC‐medicated feeds were artificially challenged with A. hydrophila at the end of the recommended 15‐day antibiotic withdrawal period. The gut microbiota of the Zebrafish at different stages was analyzed using 16S ribosomal RNA gene sequencing. Result: Our results found that FFC‐medicated feed induced disruption of the gut microbiota. Dysbiosis was observed in all treated groups, with a significant increase in bacterial diversity, and was characterized by a remarkable bloom of Proteobacteria and a drastic decline of Mycoplasma and Cetobacterium in treated animals but without noticeable clinical signs or mortalities. In addition, the increase of Proteobacteria was not significantly reduced after the recommended 15‐day withdrawal period, and the Zebrafish treated with FFC‐medicated feed exhibited a significantly higher mortality rate when they were subsequently challenged with A. hydrophila compared to the control (regular feed) groups. Interestingly, the most dramatic changes in the gut microbiome composition occurred at the transition time between the late stage of the medicated treatment and the beginning of the withdrawal period instead of the time during the Aeromonas infection. Conclusion: The administration of FFC‐medicated feed at the recommended dose induced gut dysbiosis in Zebrafish, and fish did not recover to the baseline after the recommended withdrawal period. Our findings suggest that the use of antibiotics in fish elicits a response similar to those previously described in mammals and possibly makes the host more susceptible to subsequent infections of opportunistic pathogens. This study using a controlled model system suggests that antibiotics in aquaculture may have long‐term effects on the general well‐being of the fish. Impact statementOur results suggested that bacterial community in the gut of healthy Zebrafish could be readily disturbed as a result of antibiotic administration. In addition, after medicated feed, Zebrafish were more susceptible to bacterial secondary infection (e.g., Aeromonas hydrophila). [ABSTRACT FROM AUTHOR]

Using a hydrothermal technique, a highly sensitive metal-organic Cu-MOFs sensor has been created to detect florfenicol (FFC) fluorescent in chicken meat. The sensor has demonstrated the ability to respond to the presence of FFC in an aqueous solution with accuracy and selectivity, as evidenced by an increase in fluorescence intensity. The interactions and adsorption mechanism based on hydrogen bonding, π- π, and n-π interactions demonstrate the high sensitivity and specificity of Cu-MOFs towards. FFC was detected quantitatively with a recovery of 96.48–98.79% in chicken meat samples. Within a broad linear range of 1–50 μM, the Cu-MOFs nanosensor exhibits a fast response time of 1 min, a low limit of detection (LOD) of 2.93 μM, and a limit of quantification (LOQ) of 8.80 μM. The potential applicability of the Cu-MOFs nanosensor for the detection of FFC in food matrices is confirmed by the results obtained with high-performance liquid chromatography (HPLC). Chemical compounds: Copper (II) nitrate (PubChem CID: 18616); Terephthalic acid (PubChem CID: 7489); Polyvinyl pyrrolidone (PubChem CID: 486422059); N, N-dimethylformamide (PubChem CID: 6228); Ethyl alcohol (PubChem CID: 702); Hydrochloric acid (PubChem CID: 313); Sodium hydroxide (PubChem CID: 14798); Acetic acid (PubChem CID: 176); Trichloroacetic acid (PubChem CID: 6421); Florfenicol (PubChem CID: 114811).

SUMMARY: The administration of drugs via the oral route is challenging due to the presence of physiologic barrier. BCRP, which can actively transport substrates from intra- to extracellular environment, has an important functional role in the composition of physiologic barrier. Therefore, overcoming BCRP efflux is a strategy to improve the absorption of substrate drugs. Curcumin is a natural feed additive for poultry health and production. However, it is unknown whether curcumin affects the expression of BCRP. The purpose of this study was to investigate the role of curcumin in the regulation of BCRP and its influences on pharmacokinetics of BCRP substrate florfenicol. Results showed that curcumin (60 μM) inhibited the expression of BCRP mRNA by 58% and BCRP protein by 52% in primary chicken hepatocytes. Moreover, intracellular mitoxantrone (a selective BCRP substrate) fluorescence was 1.58-fold higher in cells pretreated with 60 μM curcumin than in untreated cells, indicating that curcumin inhibited the transport function of BCRP. In vivo experiments showed that curcumin reduced BCRP expression in the liver, kidney, duodenum, jejunum and ileum of chicken. Coadministration of curcumin (150 mg/kg) significantly changed the pharmacokinetic behavior of orally administered florfenicol (substrate of chicken BCRP), with a higher area under the curve (35.51 vs. 25.81 h·ug/L) and a higher Cmax values (9.94 vs. 7.61 μg/mL). The bioavailability of orally administered florfenicol was increased from 51.6 to 72.8% by curcumin. Together, our results indicate that curcumin inhibited the expression and efflux function of BCRP in chicken and improved the bioavailability of BCRP substrate florfenicol.

ABSTRACT: Objectives: The emergence of the florfenicol resistance gene fexA in Campylobacter poses a serious threat to public health, but the extent of the spread of fexA in Campylobacter from various hosts has not been well understood. This study aimed to investigate the fexA in Campylobacter isolates from different hosts. Methods: PCR was used to identify fexA-positive Campylobacter from different hosts during 2008–2019 in China, and the fexA-positive isolates were characterized by susceptibility tests, whole-genome sequencing, and natural transformation. Results: A total of 69 (2.54%, 69/2721) fexA-positive Campylobacter were identified, and the fexA-positive isolates increased remarkably (0.42%–16.90%) since it was first detected in 2010. By source, the 69 isolates were obtained from chickens (3.57%, 57/1595), geese (3.43%, 7/204), ducks (1.02%, 2/197), and environments (2.86%, 3/105); the fexA-positive isolates were not isolated in humans and pigs. In addition to fexA, these isolates also carried other antimicrobial resistance genes and exhibited multidrug resistance. Whole-genome sequencing analysis showed the fexA gene can disseminate clonally or horizontally via either multidrug resistance genomic islands or insertion sequences among the Campylobacter. The genetic structure IS1216-∆ISEfa11-hp-fexA-NAD(P)H-∆ISEfa11-IS1216 was conserved and widespread in the Campylobacter of various origins, and the IS1216 can form fexA-carrying circular intermediates, emphasizing that IS1216 plays an important role in the spread of fexA in Campylobacter. Conclusions: This study indicates the wide spread of fexA-positive Campylobacter in poultry and environments. Because multidrug resistance genomic islands and IS1216 can facilitate the transmission of fexA, systematic surveillance should be implemented to prevent the spread of fexA to humans.

The canine urinary excretion of florfenicol was evaluated to explore its potential for treating urinary tract infections. Nine healthy male intact purpose‐bred Beagles and four healthy client‐owned dogs each received a single oral dose of florfenicol 20 mg/kg (300 mg/mL parenteral solution) with food. All voluntary urinations were collected for 12 h. Although florfenicol is reportedly bitter tasting, 7/9 Beagles and 4/4 client‐owned dogs completely ingested the florfenicol and were enrolled; salivation (n = 1) and headshaking (n = 3) were observed. The last measured urine florfenicol concentrations were variable: Beagles (0.23–3.19 mcg/mL), Pug (3.01 mcg/mL) English Setter (21.29 mcg/mL), Greyhound (32.68 mcg/mL), and Standard Poodle (13.00 mcg/mL). Urine half‐life was similar for the Beagles and the Pug, 0.75–1.39 h, whereas the half‐life was 1.70–1.82 h for the English Setter, Greyhound, and Standard Poodle. Larger breed dogs exceeded 8 mcg/mL florfenicol (wild‐type cutoff) in their urine at 12 h, whereas the Beagles and Pug had <8 mcg/mL; it is unclear if this is an individual, breed, or size difference. These data suggest oral florfenicol may need to be administered q6‐12h for canine urinary tract infections, but further data are needed (more enrolled dogs, multiple‐dose regimens) before considering clinical trials or breed‐specific differences. [ABSTRACT FROM AUTHOR]

The objectives of this study were to compare the serum and seminal plasma pharmacokinetic profiles of florfenicol (FLO) and florfenicol amine (FLA) after the administration of FLO either by IM or SC routes in beef bulls. Four clinically healthy Hereford bulls underwent a comprehensive physical exam, including breeding soundness examination, CBC, and chemistry profile panel. Bulls were healthy and classified satisfactory potential breeders. In one group (n = 2), a single dose of FLO was administered SC in the middle of the neck at a dose of 40 mg/kg of body weight. In the second group (n = 2), a single dose was administered IM in the muscles of the neck at a dose of 20 mg/kg. Concentrations of FLO and FLA in serum and seminal plasma were determined by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Blood and semen samples were collected before the administration of FLO and at 12, 24, 36, 48, 72, 96, 120, 144, and 168 h after injection. The blood was collected from the coccygeal vessels, and semen was collected by electroejaculation. All samples were immediately refrigerated, processed within the first hour after collection, and finally stored at −80 °C. The mean level of total FLO in serum was higher when administered by the SC route (1,415.5 ng/mL) than by the IM route (752.4 ng/mL; P = 0.001). Differences were observed between the percentage of FLA in serum (1.8%; ranging from 1.3 to 2.9) and in seminal plasma (27.5%; ranging from 15.9 to 34.2; P = 0.0001). The mean level (±SD) of FLA was higher in seminal plasma compared to serum (467 ± 466 ng/mL and 18 ± 16 ng/mL, respectively; P = 0.001). The mean level of total FLO in seminal plasma was 1,454.8 ng/mL for the SC route and 1,872.9 ng/mL for the IM route without differences between the two routes (P = 0.51). Differences in the mean level of total FLO between serum and seminal plasma were detected (1,187 ± 2,069 ng/mL and 1,748 ± 1,906 ng/mL, respectively; P = 0.04). From the present investigation, it was concluded that FLO is a suitable antibiotic based on its pharmacokinetic attributes and may be employed for the treatment of bull genital infections when its use is indicated. To study the pharmacokinetics of FLO in seminal plasma, the analysis of FLA should be incorporated. [ABSTRACT FROM AUTHOR]

Florfenicol (FF) is a broad-spectrum antibiotic used to treat gastrointestinal and respiratory infections in domestic animals. Considering FF's rapid elimination via urine after drug treatment, its use increases concerns about environmental contamination. The objective of the study was to establish a sustainable chromatographic method for simple analysis of FF in pig urine to investigate the urinary excretion of FF after a single intramuscular administration of 20 mg FF/kg body weight. The urine sample was prepared using a centrifuge and regenerated cellulose filter, and the diluted sample was analyzed. The method was validated in terms of linearity, the limit of detection (0.005 µg/mL) and quantitation (0.016 µg/mL), repeatability and matrix effect (%RSD ranged up to 2.5), accuracy (varied between 98% and 102%), and stability. The concentration-time profile of pig urine samples collected within 48 h post-drug administration showed that 63% of FF's dose was excreted. The developed method and previously published methods used to qualify FF in the urine of animal origin were evaluated by the National Environmental Method Index (NEMI), Green Analytical Procedure Index (GAPI) and Analytical GREENness Metric Approach (AGREE). The greenness profiles of published methods revealed problems with high solvents and energy consumption, while the established method was shown to be more environmentally friendly. [ABSTRACT FROM AUTHOR]

The growing interest in employing nano-sized pharmaceutical formulations in veterinary medicine has prompted the exploration of the novel nanocarriers' ability to augment the therapeutic outcome. In this study, we harnessed niosomes, spherical nanocarriers formed through non-ionic surfactant self-assembly, to enhance the therapeutic efficacy of the broad-spectrum antibiotic florfenicol. Pre-formulation studies were conducted to identify the optimal parameters for preparing florfenicol-loaded niosomes (FLNs). These studies revealed that the formulation that consisted of Span 60, cholesterol, and dihexadecyl phosphate (DDP) at a molar ratio of 1:1:0.1 exhibited the highest entrapment efficiency (%EE) and uniform size distribution. In vitro antibacterial testing demonstrated the niosomal capacity to significantly reduce florfenicol minimum inhibitory concentration (MIC) against E. coli and S. aureus. Pharmacokinetic profiles of free florfenicol and FLN were assessed following oral administration of 30 mg florfenicol/kg body weight to healthy or E. coli–infected chickens. FLN exhibited a substantially higher maximum plasma concentration (Cmax) of florfenicol compared to free florfenicol. Furthermore, FLN showed significantly higher area under the curve (AUC0–t) than free florfenicol as revealed from the relative bioavailability studies. Lethal dose (LD) 50 values for both free florfenicol and FLN exceeded 5 g/kg of body weight, indicating high safety profile. Assessment of mortality protection in mice against lethal E. coli infections showed the significantly higher capability of FLN to improve the survival rate (75%) than free florfenicol (25%). Collectively, these findings demonstrate the niosomal ability to improve the oral bioavailability as well as the antibacterial activity of the incorporated veterinary antibiotic florfenicol. [ABSTRACT FROM AUTHOR]

[Display omitted] In this work, a series of BiOCl x Br 1-x (BCB) solid solutions are facilely designed for visible-light-driven photocatalytic ozonation (PCO) degradation of florfenicol (FF) in water environments, which could add to the library of efficient, cost-effective and robust nanocatalysts for water purification. BCB solid solutions in the structure of 2D nanosheets are achieved involving the etching of BiOBr "micro-flowers" with HCl at different concentrations, allowing a removal ratio of FF up to 97.3 % within 1 h, superior to bare BiOBr and bare BiOCl. A strengthened synergistic effect between photocatalysis and ozonation is substantiated, where the separation of photo-induced charge transfer is accelerated, the band gap is tuned and the utilization efficiency of ozone is enhanced. This facilitates the production of reactive oxygen species identified as •OH, •O 2 –, and 1O 2 that will attack the FF molecule for degradation based on three pathways. [ABSTRACT FROM AUTHOR]

Thioflavin T (ThT) can bind to G-quadruplex through non-covalent interaction to form G-quadruplex/ThT complex, showing strong fluorescence intensity, while free ThT fluorescence is very weak. In the presence of florfenicol (FF), the high affinity of the aptamer (Apt) with a G-quadruplex structure to the target enables the formation of the Apt/FF complex and the release of ThT, resulting in a decrease in fluorescence intensity. Based on this feature, this study designed a sensitive and rapid on- site detection system for the detection of florfenicol, a label-free fluorescent aptasensor based on G-quadruplex/thioflavin T. The detection range of this aptamer sensor was 0.0128-200 ng/mL, the actual detection limit was 0.0128 ng/mL, and the total detection time was 10 min. At the same time, the recovery rate of the actual spiked samples (milk and eggs) was calculated, and the spiked recovery rate was between 91.2% and 117.1%. The established label -free fluorescent aptasensor has the advantages of high specificity, low cost, and short time - consuming, and can be used for on-site detection of actual samples. [ABSTRACT FROM AUTHOR]

Two rapid, simple, sensitive and selective derivative spectrofluorimetric methods (first and second derivative synchronous spectrofluorimetric (FDSFS and SDSFS) procedures) have been developed for the analysis of florfenicol in the presence of its various degradation products. FDSFS was applied to assay the drug in the presence of its alkaline, oxidative and photolytic degradation products while SDSFS was used to quantify it in the presence of its acidic degradation product. These methods permitted quantification of florfenicol at corresponding λ Em of 288, 287, 279 and 284 nm without interferences from any of its degradation products. Full validation procedures were applied to the suggested method according to International Conference of Harmonization guidelines. Moreover, different degradation kinetic parameters were calculated such as half-life (t 1/2), degradation rate constant (K) and activation energy (E a). Using the analytical eco-scale, green analytical procedure index and analytical greenness metric approach AGREE as greenness assessment tools, the proposed method was found to be environmentally friendly.

The widespread use and subsequent accumulation of florfenicol (FFC), a common antibiotic, through the food chain poses significant risks to aquatic ecosystems and human health, necessitating effective strategies for its removal from water bodies. To solve the challenge, herein, we developed a novel aluminum-based metal–organic framework CAU-1, engineered for the efficient adsorption of FFC. CAU-1 contains the plentiful –NH2 and μ-OH groups with the positively charged on the surface. In the adsorption process, CAU-1 perform hydrogen bonding interactions with FFC’s functional groups (−F, –OH, −Cl, –NH–, and −SO2–). Furthermore, the positively charged surface of CAU-1 enhances FFC adsorption via electrostatic attraction together. FFC adsorption equilibrium on CAU-1 is attained within 180 min with a monolayer adsorption capacity of 386 mg/g at 303 K, surpassing most of the reported adsorbents. The exothermic FFC adsorption process on CAU-1 remains largely unaffected by coexisting ions. Additionally, CAU-1 can be efficiently regenerated using a mixed solution of 0.1 M HCl and ethanol–water as an eluent. This work highlights CAU-1’s potential as an effective adsorbent for FFC removal, emphasizing the importance of tuning or designing surface functional groups on adsorbents to boost their adsorption capabilities.

ABSTRACT: Objectives: The aim of this study was to characterize the floR-carrying plasmids originating from Glaesserella parasuis and Actinobacillus indolicus isolated from pigs with respiratory disease in China. Methods: A total of 125 G. parasuis and 28 A. indolicus strains collected between 2009 and 2022 were screened for florfenicol resistance. Characterization of floR-positive isolates and plasmids were determined by antimicrobial susceptibility testing, serotyping, multilocus sequence typing (MLST), conjugation and transformation assays, whole-genome sequencing (WGS), and phylogenetic analysis. Results: One A. indolicus and six G. parasuis were identified as positive for floR. The six G. parasuis were assigned to four different serovars, including serovars 6, 7, 9, and unknown. In addition to strain XP11, six floR genes were located on plasmids. The six floR-bearing plasmids could be transformed into Pasteurella multocida and divided into two different types, including ∼5000 bp and ∼6000 bp plasmids. The ∼5000 bp plasmids consisting of rep, lysR, mobB, and floR genes, exhibited high similarity among Pasteurellaceae bacteria. Furthermore, the ∼6000 bp plasmids, consisting of rep, lysR, mobC, mobA/L, and floR genes, showed high similarity between G. parasuis and Actinobacillus Spp. Notably, WGS results showed that the floR modules of the two types of plasmids could be transferred and integrated into the diverse Pasteurellaceae- origined plasmids. Conclusion: This study firstly reported the characterization of floR-carrying plasmids from A. indolicus and a non-virulent serovar of G. parasuis in pigs in China and elucidated the transmission mechanism of the floR resistance gene among the Pasteurellaceae family.

Salmonid rickettsial septicemia (SRS), caused by Piscirickettsia salmonis, has been the most severe health concern for the Chilean salmon industry. The efforts to control P. salmonis infections have focused on using antibiotics and vaccines. However, infected salmonids exhibit limited responses to the treatments. Here, we developed a poly (D, L-lactide-glycolic acid) (PLGA)-nanosystem functionalized with Atlantic salmon IgM (PLGA-IgM) to specifically deliver florfenicol into infected cells. Polymeric nanoparticles (NPs) were prepared via the double emulsion solvent-evaporation method in the presence of florfenicol. Later, the PLGA-NPs were functionalized with Atlantic salmon IgM through carbodiimide chemistry. The nanosystem showed an average size of ~380–410 nm and a negative surface charge. Further, florfenicol encapsulation efficiency was close to 10%. We evaluated the internalization of the nanosystem and its impact on bacterial load in SHK-1 cells by using confocal microscopy and qPCR. The results suggest that stimulation with the nanosystem elicits a decrease in the bacterial load of P. salmonis when it infects Atlantic salmon macrophages. Overall, the IgM-functionalized PLGA-based nanosystem represents an alternative to the administration of antibiotics in salmon farming, complementing the delivery of antibiotics with the stimulation of the immune response of infected macrophages.

Simple Summary: Florfenicol is a synthetic analog of chloramphenicol, which is used mostly in livestock animals. Its potential as an alternative agent in companion animals is strong because of its beneficial properties, such as its extensive wide spectrum and relatively increased, compared to chloramphenicol, safety during administration. However, the emergence of resistant strains can overcome this potential. The distribution of florfenicol-resistant bacteria was investigated among multidrug-resistant (MDR) Enterobacterales isolated from diagnostic samples of companion animals in Greece, which were collected throughout the country. Data regarding sample origin, type of infection, bacterial species, and resistance profiles were assembled and compared. The presence of specific florfenicol-associated antibiotic resistance genes (ARGs) was examined, and the results were interpreted in comparison with those of antibiotic susceptibility testing (AST). The results of this study indicate that the distribution of florfenicol-resistant MDR Enterobacterales in pets throughout the country is considerable (17.9%) and mainly attributed to the plasmid-mediated floR gene. Thus, there is an increased risk of co-acquisition of florfenicol-specific ARGs through horizontal transfer, along with several other resistance genes. Even though the potential of florfenicol to constitute an alternative antibiotic in companion animals seems high, continuous monitoring of antibiotic resistance profiles is needed. Florfenicol is a promising antibiotic for use in companion animals, especially as an alternative agent for infections caused by MDR bacteria. However, the emergence of resistant strains could hinder this potential. In this study, florfenicol resistance was investigated in a total of 246 MDR Enterobacterales obtained from canine and feline clinical samples in Greece over a two-year period (October 2020 to December 2022); a total of 44 (17,9%) florfenicol-resistant strains were recognized and further investigated. Most of these isolates originated from urine (41.9%) and soft tissue (37.2%) samples; E. coli (n = 14) and Enterobacter cloacae (n = 12) were the predominant species. The strains were examined for the presence of specific florfenicol-related resistance genes floR and cfr. In the majority of the isolates (31/44, 70.5%), the floR gene was detected, whereas none carried cfr. This finding creates concerns of co-acquisition of plasmid-mediated florfenicol-specific ARGs through horizontal transfer, along with several other resistance genes. The florfenicol resistance rates in MDR isolates seem relatively low but considerable for a second-line antibiotic; thus, in order to evaluate the potential of florfenicol to constitute an alternative antibiotic in companion animals, continuous monitoring of antibiotic resistance profiles is needed in order to investigate the distribution of florfenicol resistance under pressure of administration of commonly used agents. [ABSTRACT FROM AUTHOR]

As is the case with other veterinary antibiotics, florfenicol (FFC) faces certain limitations, such as low solubility in water, or the fact that it is reported to interfere with the immune response after some immunoprofilactic actions in livestock. Aiming to improve its efficacy and overall performance, FFC was loaded into a polymeric nanobased delivery system by succesfully using the emulsion-evaporation technique. The poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with FFC were characterized in terms of size (101 ± 0.52 nm), zeta potential (26.80 ± 1.30 mV) and poly-dispersity index (0.061 ± 0.019). The achieved loading was 2.24 μg FFC/mg of NPs, with an entrapment efficiency of 7.9%. The antimicrobial effect, the anti-biofilm formation and the cytotoxicity properties of the NPs were evaluated. The results indicated a MIC decreased by ~97.13% for S. aureus, 99.33% for E.coli and 64.1% for P. aeruginosa when compared to free FFC. The minimum inhibitory concentration (MIC) obtained indicated the potential for using a significantly lower dose of florfenicol. The delivery system produced biofilm inhibition while showing no cytotoxic effects when tested on porcine primary fibroblasts and horse mesenchymal stem cells. These findings suggest that florfenicol can be improved and formulations optimized for use in veterinary medicine through its incorporation into a nanobased delivery system designed to release in a controlled manner over time. [ABSTRACT FROM AUTHOR]

The misuse of antibiotics enhances the development of resistant microorganisms and decreases the efficacy of treatments. Florfenicol (FF) is one of the antibiotics approved for use in aquaculture in Egypt. Because of its extensive usage, potential negative impacts on aquatic creatures are a major concern. This motivates us to search for an appropriate neoadjuvant to work synergistically with FF and reduce adverse effects. Results from this study will contribute towards improving the understanding of the impacts of FF on Oreochromis niloticus and the possible amelioratory effects of Spirulina platensis algae (SP). O. niloticus (n = 240; 40 ± 2.5 g) were fed on two diets supplemented with or without SP for 4 weeks, then divided into four treatments each in three replicates (n = 60/treatment). G1; was fed a control diet, and the other groups were fed diets supplemented with FF (10 mg /kg of BW, G2), SP (2 g/kg of diet, G3), or FF + SP (G4) for 10 days. Among the four groups, the SP group (G3) had the best immunostimulatory effects as observed by a significant (p < 0.05) elevation in phagocytic activity, phagocytic index, IL6, and TNF-α. The treatment with FF had significantly impacted hepatic and renal tissues, as the values of liver enzymes and creatinine demonstrated tissue deterioration and also resulted in oxidative stress, which was expressed by an increase of GPx, CAT, and SOD in (G2). Additionally, the combined FF + SP improved the hematological parameters and decreased the oxidative damage induced by FF (G4). Thus, it was clear that FF has harmful effects on O. niloticus and that SP can modulate such impacts. These data recommend the use of SP as an effective immunostimulant and a probable adjuvant to FF in O. niloticus diets to attain maximum disease resistance. [ABSTRACT FROM AUTHOR]

Florfenicol (FLO) is a widely used antibacterial drug, which is often detected in the environment. In this paper, the photolysis mechanism of FLO in water was investigated using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The focus of the study is to elucidate the direct photolysis mechanism of FLO in the water environment and the indirect photolysis of free radicals (·OH, ·NO3, and ·SO4−) as active species. The effect of metal ions Ca2+/Mg2+/Zn2+ on the indirect photolysis was also investigated. The results show that the direct photolysis of FLO involves C–C/C–N/C–S bond cleavage, the C5–S7 bond cleavage is most likely to occur, and the C17–C18 cleavage reaction is not easy to occur during the direct photodegradation of FLO. The indirect photolysis of FLO is more likely to occur in the environment than direct photolysis. The main indirect photolysis involves OH-addition, NO3-addition, and SO4-addition on benzene ring. The order of difficulty in the indirect photolysis with ·OH is C2 > C3 > C4 > C5 > C6 > C1, Ca2+ can promote the indirect photolysis with ·OH, and Mg2+/Zn2+ has a dual effect on the indirect photolysis with ·OH. In other words, Mg2+ and Zn2+ can inhibit or promote the indirect photolysis with ·OH. These studies provide important information for theoretical research on the environmental behavior and degradation mechanism of drug molecules. [ABSTRACT FROM AUTHOR]

Florfenicol (FF) is a commonly used antibacterial agent in animals. We investigated the pharmacokinetics of FF and its metabolite florfenicol amine (FFA) in donkeys. Donkeys were administered FF (30 mg/kg bodyweight, p.o.). Pharmacokinetic parameters were calculated using a non-compartmental model. The FF (FFA) pharmacokinetics parameters were characterized by along elimination half-life (t1/2 kz) of 5.92 h (15.95 h), plasma peak concentration (Cmax) of 0.13 μg/mL (0.08 μg/mL), and the time taken to reach Cmax (Tmax) of 0.68 h (0.72 h). The area under plasma concentration-time curve and mean residence time of FF (FFA) in plasma were 1.31 μg·mL-1·h (0.47 μg·mL-1·h) and 10.37 h (18.40 h), respectively. The t1/2 kz of FF and FFA in urine was 21.93 and 40.26 h, and the maximum excretion rate was 10.56 and 4.03 μg/h reached at 25.60 and 32.20 h, respectively. The respective values in feces were 0.02 and 0.01 μg·h-1 reached at 33.40 h. The amount of FF and FFA recovered in feces was 0.52 and 0.22 μg, respectively. In conclusion, FF (FFA) is rapidly absorbed and slowly eliminated after a single oral administration to donkeys. Compared to FF, FFA was more slowly eliminated. FF (FFA) is mostly excreted through urine. [ABSTRACT FROM AUTHOR]

UV photolysis has been recommended as an alternative pretreatment method for the elimination of antibacterial activity of antibiotics against the indicator strain, but the pretreated antibiotic intermediates might not lose their potential to induce antibiotic resistance genes (ARGs) proliferation during subsequent biotreatment processes. The presence of florfenicol (FLO) in wastewater seriously inhibits the metabolic performance of anaerobic sludge microorganisms, especially the positive correlation between UV irradiation doses and ATP content, while it did not significantly affect the organics utilization ability and protein biosynthetic process of aerobic microorganisms. After sufficient UV pretreatment, the relative abundances of floR from genomic or plasmid DNA in subsequent aerobic and anaerobic biotreatment processes both decreased by two orders of magnitude, maintained at the level of the groups without FLO selective pressure. Meanwhile, the abundances of floR under anaerobic condition were always lower than that under aerobic condition, suggesting that anaerobic biotreatment systems might be more suitable for the effective control of target ARGs. The higher abundance of floR in plasmid DNA than in genome also indicated that the potential transmission risk of mobile ARGs should not be ignored. In addition, the relative abundance of intI1 was positively correlated with floR in its corresponding genomic or plasmid DNA (p < 0.05), which also increased the potential horizontal transfer risk of target ARGs. This study provides new insights into the effect of preferential UV photolysis as a pretreatment method for the enhancement of metabolic performance and source control of target ARGs in subsequent biotreatment processes. Key points: • Sufficient UV photolytic pretreatment efficiently controlled the abundance of floR • A synchronous decrease in abundance of intI1 reduced the risk of horizontal transfer • An appreciable abundance of floR in plasmid DNA was a potential source of total ARGs [ABSTRACT FROM AUTHOR]

Background: Pollution with heavy metals (HMs) is time- and concentration-dependent. Lead and zinc pollute the aquatic environment, causing severe health issues in aquatic animals. Materials and methods: Nile tilapia, the predominant cultured fish in Egypt, were experimentally exposed to 10% of LC50 of lead nitrate (PbNO3) and zinc sulfate (ZnSO4). Samples were collected in three different periods, 4, 6, and 8 weeks, in addition to a trial to treat the experimental fish infected with Aeromonas hydrophila, with an antibiotic (florfenicol). Results: Liver enzymes were linearly upsurged in a time-dependent manner in response to HMs exposure. ALT was 92.1 IU/l and AST was 82.53 IU/l after eight weeks. In the eighth week of the HMs exposure, in the hepatic tissue, the levels of glutathione peroxidase (GPx), catalase (CAT), and metallothionein (MT) were increased to 117.8 U/mg prot, 72.2 U/mg prot, and 154.5 U/mg prot, respectively. On exposure to HMs, gene expressions of some cytokines were linearly downregulated in a time-dependent manner compared to the control. After four weeks of exposure to the HMs, the oxidative burst activity (OBA) of immune cells was decreased compared to the control 9.33 and 10.3 cells, respectively. Meanwhile, the serum bactericidal activity (SBA) significantly declined to 18.5% compared to the control 32.6% after eight weeks of exposure. Clinical signs of A. hydrophila infection were exaggerated in polluted fish, with a mortality rate (MR) of 100%. The re-isolation rate of A. hydrophila was decreased in fish treated with florfenicol regardless of the pollution impacts after eight weeks of HMs exposure. Conclusion: It could be concluded that the immune suppression and oxidative stress resulting from exposure to HMs are time-dependent. Clinical signs and post-mortem lesions in polluted fish infected with A. hydrophila were prominent. Infected-Nile tilapia had weak responses to florfenicol treatment due to HMs exposure. [ABSTRACT FROM AUTHOR]

A method utilizing high-performance liquid chromatography-fluorescence detection (HPLC–FLD) has been developed and refined for the simultaneous detection of florfenicol (FF) and its metabolite florfenicol amine (FFA) along with three fluoroquinolone (ciprofloxacin (CIP), enrofloxacin (ENR), and sarafloxacin (SAR)) residues in different parts of eggs (whole egg, egg yolk, and egg albumen). The QuEChERS ("Quick, easy, cheap, effective, rugged, and safe") procedure utilized 0.1 M disodium EDTA solution, water, and acetonitrile as extractants; sodium sulfate, sodium chloride, and trisodium citrate as dehydrating salts; and N-propylethylenediamine and C18 as adsorbents. A dual-channel FLD method was utilized to analyze the target compounds using an XBridge BEH C18 chromatographic column (4.6 mm × 150 mm, 5 μm). The mobile phase was employed isocratically using a solution of 0.01 M sodium dihydrogen phosphate, 0.005 M sodium dodecyl sulfate, and 0.1% triethylamine (pH 4.8) in combination with acetonitrile at a ratio of 65:35 (V/V). The limits of detection (LOD) and quantification (LOQ) of the analytes ranged from 0.03 to 1.5 µg/kg and from 0.1 to 5.0 µg/kg, respectively. The recoveries of the analytes in the blank egg samples ranged from 71.9% to 94.8% when reference standard concentrations of the LOQ, half of the maximum residual limit (MRL), MRL, and twice the MRL were added. The parameters of the presented protocol were validated and subsequently applied to the analysis of real samples, demonstrating the applicability and reliability of the method. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is an important analytical technique because of its use for the quantification of different antibiotics used for the treatment of different diseases. Florfenicol is considered a broad-spectrum antibiotic drug that is used for bacterial infection and livestock species, including porcine, bovine, and chicken. In the current study, the qualitative and quantitative evolution of different concentrations of florfenicol drug along with a number of excipients has been done by using Raman spectroscopy. Some major Raman peaks such as 379 cm−1, 478 cm−1, 878 cm−1, 918 cm−1, 1341 cm−1 and 1457 cm−1 are related to the excipient and 630 cm−1, 769 cm−1, 973 cm−1, 1142 cm−1 and 1681 cm−1 are related to the API concentrations and their intensities are increased and decreased with different concentration of excipient and API. The determination of Raman spectral data set of different concentrations of florfenicol drug has been done by using principal component analysis and partial least square regression model. The results of this study can lead to establishing an effective and reliable method to verify florfenicol contents in pharmaceutical samples which may be employed on an industrial scale. [ABSTRACT FROM AUTHOR]

Piscirickettsiosis is the most prevalent bacterial disease affecting seawater salmon in Chilean salmon industry. Antibiotic therapy is the first alternative to counteract infections caused by Piscirickettsia salmonis. The presence of bacterial biofilms on materials commonly used in salmon farming may be critical for understanding the bacterial persistence in the environment. In the present study, the CDC Biofilm Reactor® was used to investigate the effect of sub‐ and over‐MIC of florfenicol on both the pre‐formed biofilm and the biofilm formation by P. salmonis under the antibiotic stimuli on Nylon and high‐density polyethylene (HDPE) surfaces. This study demonstrated that FLO, at sub‐ and over‐MIC doses, decreases biofilm‐embedded live bacteria in the P. salmonis isolates evaluated. However, it was shown that in the P. salmonis Ps007 strain the presence of sub‐MIC of FLO reduced its biofilm formation on HDPE surfaces; however, biofilm persists on Nylon surfaces. These results demonstrated that P. salmonis isolates behave differently against FLO and also, depending on the surface materials. Therefore, it remains a challenge to find an effective strategy to control the biofilm formation of P. salmonis, and certainly other marine pathogens that affect the sustainability of the Chilean salmon industry. [ABSTRACT FROM AUTHOR]

Florfenicol(FF) is an excellent veterinary antibiotic, limited by poor solubility and poor bioavailability. Here in, we aimed to explore the applicability of fast disintegrating tablets compressed from Florfenicol-loaded solid dispersions (FF-SD-FDTs) to improve the dissolution rate and oral bioavailability of Florfenicol. Utilizing selecting appropriate preparation methods and carriers, the solid dispersions of Florfenicol (FF-SDs) were prepared by solvent evaporation and the fast disintegrating tablets (FF-SD-FDTs) were prepared by the direct compression (DC) method. The tablet properties including hardness, friability, disintegration time, weight variation, etc. all met the specifications of Chinese Veterinary Pharmacopeia(CVP). FF-SD-FDTs significantly improved drug dissolution and dispersion of FF in vitro compared to florfenicol conventional tablets (FF-CTs). A pharmacokinetics study in German shepherd dogs proved the AUC0-∞ and Cmax values of FF-SD-FDTs are 1.38 and 1.38 times more than FF-CTs, respectively. Overall, it can be concluded that FF-SD-FDTs with excellent disintegration and dissolution properties were successfully produced, which greatly improved the oral bioavailability of the poorly soluble drug FF, and the study provided a new idea for a broader role of FF in pet clinics. [ABSTRACT FROM AUTHOR]

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Antibiotics have been widely used in the aquatic industry. Enrofloxacin, florfenicol and sulfamethoxazole are three typical antibiotic types of fluoroquinolone, chloramphenicol and sulfamethoxazole. Their safety reference values in aqua-culture and ecological risks in natural waters have not been clear. In this study, species sensitivity distribution (SSD) was used to determine the biological reference value of typical antibiotics for freshwater aquaculture, and SSD forward method and risk entropy value were used to evaluate the ecological risk of three antibiotics in natural rivers. The results showed that the safety reference values of enrofloxacin, florfenicol and sulfamethoxazole were 58 μg/L, 267 μg/L and 42 μg/L. Potentially affected fraction and risk entropy indicate that there is no ecological risk for the three antibiotics in natural waters. This study provides scientific basis and theoretical guidance for the scientific use of antibiotics in aquatic industry and systematic evaluation of ecological risk of antibiotics in waters. [ABSTRACT FROM AUTHOR]

The issue of antimicrobial resistance is becoming an increasingly serious challenge in both human and veterinary medicine. Prudent antimicrobial use in veterinary medicine is warranted and supported by international guidelines, with the Antimicrobial Advice Ad Hoc Expert Group (AMEG) placing particular emphasis on the critically important group B antimicrobials. These antimicrobials are commonly employed, especially in the poultry and swine industry. The impact of florfenicol, a veterinary antibiotic, was studied on the resistance development of Escherichia coli. The aim of the study was to investigate the effect of the use of florfenicol on the development of phenotypic and genomic resistances, not only to the drug itself but also to other drugs. The minimum inhibitory concentrations (MICs) of the antibiotics were investigated at 1×, 10×, 100× and 1000× concentrations using the adapted Microbial Evolution and Growth Arena (MEGA-plate) method. The results demonstrate that florfenicol can select for resistance to fluoroquinolone antibiotics (167× MIC value increase) and cephalosporins (67× MIC value increase). A total of 44 antimicrobial resistance genes were identified, the majority of which were consistent across the samples. Chromosomal point mutations, including alterations in resistance-associated and regulatory genes (acrB, acrR, emrR and robA), are thought to trigger multiple drug efflux pump activations, leading to phenotypically increased resistance. The study underscores the impact of florfenicol and its role in the development of antimicrobial resistance, particularly concerning fluoroquinolone antibiotics and cephalosporins. This study is the first to report florfenicol's dose-dependent enhancement of other antibiotics' MICs, linked to mutations in SOS-box genes (mdtABC-tolC, emrAB-tolC and acrAB-tolC) and increased multidrug efflux pump genes. Mutations in the regulatory genes acrR, emrR and rpbA support the possibility of increased gene expression. The results are crucial for understanding antimicrobial resistance and its development, highlighting the promising potential of in vitro evolutionary and coselection studies for future research. [ABSTRACT FROM AUTHOR]

Florfenicol (FLO) has been shown to elicit diverse toxic effects in plants, insects, and mammals. Previously, our investigations revealed that FLO induced abnormal cardiac development and early embryonic mortality in chicken embryos. However, the effect of FLO on mitochondrial responses in stem cells remains unclear. In this study, we show that FLO significantly diminishes proliferation viability and obstructs the directed differentiation of P19 stem cells (P19SCs) into cardiomyocytes. Proteomic analysis revealed 148 differentially expressed proteins in response to FLO. Functional analysis has pinpointed FLO interference with biological processes associated with oxidative phosphorylation within the mitochondria. In alignment with the results of proteomic analysis, we confirmed that FLO inhibits the expression of both nuclear DNA-encoded and mitochondrial DNA-encoded subunits of the electron transport chain. Subsequent experiments demonstrated that FLO disrupts mitochondrial dynamics and induces the mitochondrial unfolded protein response to maintain mitochondrial homeostasis. These findings collectively highlight the significance of mitochondrial dynamics and the mitochondrial unfolded protein response to mediate the decreased proliferation viability and directed differentiation potential in P19SCs treated with FLO. In conclusion, this study provides a comprehensive overview of mitochondrial responses to FLO-induced cytotoxicity and enhances our understandings of the molecular mechanisms underlying FLO-induced embryonic toxicity. [ABSTRACT FROM AUTHOR]

The mechanism by which Y. ruckeri infection induces enteritis in Chinese sturgeon remains unclear, and the efficacy of drug prevention and control measures is not only poor but also plagued with numerous issues. We conducted transcriptomic and 16 S rRNA sequencing analyses to examine the differences in the intestinal tract of hybrid sturgeon before and after Y. ruckeri infection and florfenicol intervention. Our findings revealed that Y. ruckeri induced the expression of multiple inflammatory factors, including il1β, il6, and various chemokines, as well as casp3, casp8, and multiple tumor necrosis factor family members, resulting in pathological injury to the body. Additionally, at the phylum level, the relative abundance of Firmicutes and Bacteroidota increased, while the abundance of Plesiomonas and Cetobacterium decreased at the genus level, altering the composition of the intestinal flora. Following florfenicol intervention, the expression of multiple apoptosis and inflammation-related genes was down-regulated, promoting tissue repair. However, the flora became further dysregulated, increasing the risk of infection. In conclusion, our analysis of the transcriptome and intestinal microbial composition demonstrated that Y. ruckeri induces intestinal pathological damage by triggering apoptosis and altering the composition of the intestinal microbiota. Florfenicol intervention can repair pathological damage, but it also exacerbates flora imbalance, leading to a higher risk of infection. These findings help elucidate the molecular mechanism of Y. ruckeri-induced enteritis in sturgeon and evaluate the therapeutic effect of drugs on intestinal inflammation in sturgeon.

The intensification of production practices in the aquaculture industry has led to the indiscriminate use of antibiotics to combat diseases and reduce costs, which has resulted in environmental pollution, posing serious threats to aquaculture sustainability and food safety. However, the toxic effect of florfenicol (FF) exposure on the hepatopancreas of crustaceans remains unclear. Herein, by employing Chinese mitten crab (Eriocheir sinensis) as subjects to investigate the toxic effects on histopathology, oxidative stress, apoptosis and microbiota of hepatopancreas under environment-relevant (0.5 and 5 μg/L), and extreme concentrations (50 μg/L) of FF. Our results revealed that the damage of hepatopancreas tissue structure caused by FF exposure in a dose-and time-dependent manner. Combined with the increased expression of apoptosis-related genes (Caspase 3, Caspase 8, p53, Bax and Bcl-2) at mRNA and protein levels, activation of catalase (CAT) and superoxide dismutase (SOD), and malondialdehyde (MDA) accumulation, FF exposure also induced oxidative stress, and apoptosis in hepatopancreas. Interestingly, 7 days exposure triggered more pronounced toxic effect in crabs than 14 days under environment-relevant FF concentration. Integrated biomarker response version 2 (IBRv2) index indicated that 14 days FF exposure under extreme concentration has serious toxicity effect on crabs. Furthermore, 14 days exposure to FF changed the diversity and composition of hepatopancreas microbiota leading remarkable increase of pathogenic microorganism Spirochaetes following exposure to 50 μg/L of FF. Taken together, our study explained potential mechanism of FF toxicity on hepatopancreas of crustaceans, and provided a reference for the concentration of FF to be used in culture of Chinese mitten crab.

ObjectiveTo establish a method for the determination of chloramphenicol drugs in hen eggs by ultra-performance liquid chromatography-tandem mass spectrometry with Captiva EMR-Lipid pretreatment.MethodsSamples were extracted with ammoniated acetonitrile，then purified with Captiva EMR-Lipid，and finally detected by UPLC-MS/MS with electrospray ionization in multiple reaction monitoring mode via positive and negative ions scanning. Compounds were quantified by internal standard method.ResultsThere were good linear relationships for 3 compounds in the range of 0.03-6.0 μg/L with correlation coefficients （r） not less than 0.995. The limits of detection of chloramphenicol （CAP）， florfenicol （FF） and florfenicol amine （FFA） were 0.02， 0.01， 0.04 μg/kg， respectively. And the limits of quantitation were 0.06， 0.03， 0.12 μg/kg， respectively. The method recoveries were between 92.3%-109.6%，with relative standard deviations（n=6） between 1.4%-8.2%.ConclusionWith simple operation and high accuracy， the method was suitable for the determination of CAP， FF and FFA in hen eggs.

Florfenicol is a broad-spectrum antibiotic commonly prescribed in an extra-label manner for treating meat and dairy goats. Scientific data in support of a milk withdrawal interval recommendation is limited to plasma pharmacokinetic data and minimal milk residue data that is limited to cattle. Therefore, a rapid residue detection test (RRDT) could be a useful resource to determine if milk samples are free of drug residues and acceptable for sale. This study compared a commercially available RRDT (Charm® FLT strips) to detect florfenicol residues in fresh milk samples from healthy adult dairy breed goats treated with florfenicol (40 mg/kg subcutaneously twice 4 days apart) with quantitative analysis of florfenicol concentrations using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). In addition, storage claims for testing bovine milk using the RRDT were assessed using stored goat milk samples. Milk samples were collected every 12 h for a minimum of 26 days. Commercial RRDT strips remained positive in individual goats ranging from 528 to 792 h (22-33 days) after the second dose, whereas, UPLC-MS/MS indicated the last detectable florfenicol concentration in milk samples ranged from 504 to 720 h (21-30 days) after the second dose. Results from stored milk samples from treated goats indicate that samples can be stored for up to 5 days in the refrigerator and 60 days in the freezer after milking prior to being tested with a low risk of false-negative test results due to drug degradation. Elevated somatic cell counts and bacterial colony were noted in some of the milk samples in this study, but further study is required to understand the impact of these quality factors on RRDT results.

Catalytic dechlorination of organic chlorides by palladium (Pd) with HCOOH represents one of the most effective and promising techniques for environmental remediation. In this study, we adopted alkaline-modified porous natural sponge as support of a Pd nanocatalyst (Pd@M-Sponge) and HCOOH as a hydrogen source for the hydrodechlorination of florfenicol (FF), o-chlorophenol (o-CP), and p-chlorophenol (p-CP). Favorable conversion efficiency of FF, o-CP, and p-CP was achieved at 25 °C and atmospheric pressure attributed to the small diameter and high catalytic reactivity of the prepared Pd NPs, in addition to the slight internal mass transfer limitation of the prepared Pd@M-Sponge. High reaction rate constants were obtained even in the conditions of a low molar ratio of HCOOH to p-CP (10:1) and a high concentration of p-CP (500 mg/L). The prepared catalyst also demonstrated superior recyclability without any obvious decrease in catalytic reactivity in 20 successive p-CP dechlorination cycles. This work provides an ideal recyclable and cost-effective catalyst based on renewable and biocompatible natural material for the catalytic hydrodechlorination of chlorinated organic pollutants with formic acid and a new view for the exploration and designing of highly reactive and stable catalysts for hydrodechlorination.

The study aimed to examine the chronic toxicity effects of oxytetracycline (OTC) and florfenicol (FLO) antibiotics, commonly used in shrimp farms, on the growth performance, chlorophyll a content, and total protein of Chaetoceros muelleri microalgae. C. muelleri, initially at a density of 4,000 cells per milliliter, underwent exposure to oxytetracycline at doses of 7.43 milligrams per liter and florfenicol at 5.20 milligrams per liter for 12 days. Subsequent assessments focused on growth metrics, chlorophyll a content, and total protein. The findings highlighted a significant reduction in the growth, chlorophyll a content, and protein synthesis of C. muelleri following exposure to both OTC and FLO antibiotics (p < 0.05). Moreover, the study revealed that FLO exhibited higher toxicity toward C. muelleri compared to OTC. The observed decline in growth, chlorophyll a content, and protein synthesis in C. muelleri under OTC and FLO exposure could be attributed to the inhibitory impact of these antibiotics on cellular respiration and protein synthesis pathways.

Abstract The objective of this study was to synthesize and characterize pharmaceutical characteristics of florfenicol sustained-release granules (FSRGs) in vitro and in vivo. FSRGs were synthesized using monostearate, polyethylene glycol 4000 and starch. In vitro dissolution profiles were studied using the rotating basket method in pH 1.2 HCl solution and pH 4.3 acetate buffer. Twenty-four male healthy Landrace×Yorkshire pigs were equally divided into three groups and administered a 20 mg/kg i.v bolus of florfenicol solution and dosed orally with FSRGs in the fasting and fed states. The Higuchi model was the best fit for the drug release profile in pH 1.2 and pH 4.3 media, and the mechanism of drug dissolution was governed by both diffusion and dissolution. We established a level A in vitro - in vivo correlation for FSRGs and the in vivo profile of the FSRGs can be estimated by the in vitro drug release.