Disposition and Residue Depletion of Metronidazole in Pigs and Broilers.
Ontology highlight
ABSTRACT:
SUBMITTER: Pan Y
PROVIDER: S-EPMC5543052 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP) and Mycoplasam suis (MS) in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3) and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw) and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg) based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t1/2β), Tmax, and area under the curve (AUC) were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 μg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different (p < 0.05) to the 2.5 mg/kg group, but not to the 10 mg/kg group or the positive control group (tiamulin). In conclusion, 10% enrofloxacin enteric-coated granules had significant potential for treating APP and MS, and it provided an alternative enrofloxacin palatability formulation.
| S-EPMC5440587 | biostudies-literature
Project description:Aditoprim (ADP) is a newly developed antibacterial agent in veterinary medicine. The metabolism and disposition of ADP in swine, broilers, carp and rats were investigated by using a radio tracer method combined with a radioactivity detector and a liquid chromatography/ion trap/time-of-flight mass spectrometry. After a single oral administration, more than 94% of the dose was recovered within 14 d in the four species. The urine excretion was dominant in swine and rats, making up 78% of the dose. N-monodesmethyl-ADP, N-didesmethyl-ADP, and 10 new metabolites were characterized. These metabolites were biotransformed from the process of demethylation, ?-hydroxylation, N-oxidation, and NH2-glucuronidation. After an oral dose for 7 d, ADP-derived radioactivity was widely distributed in tissues, and high concentrations were especially observed in bile, liver, kidney, lung, and spleen. The radioactivity in the liver was eliminated much more slowly than in other tissues, with a half-life of 4.26, 3.38, 6.69, and 5.21 d in swine, broilers, carp, and rats, respectively. ADP, N-monodesmethyl-ADP, and N-didesmethyl-ADP were the major metabolites in edible tissues. Notably, ADP was detected with the highest concentration and the longest duration in these tissues. These findings indicated that ADP is the marker residue and the liver is the residue target tissue.
| S-EPMC4738305 | biostudies-literature
Project description:Zearalenone (ZEA) is a secondary fungal metabolite produced mainly by a Fusarium graminearum. To clarify the toxicokinetics, and residues of ZEA and its major metabolites ?-zearalenol (?-ZOL) and ?-zearalenol (?-ZOL) in chickens, ZEA was then administered intravenously (iv) or orally (po) to broiler chickens at a dosage of 1.2 mg/kg body weight. The concentrations of ZEA, ?-ZOL and ?-ZOL in the plasma and various tissues were quantified using LC-MS/MS. The plasma concentrations of ZEA were measurable up to 2 h after iv and po administration, and the concentrations of ?-ZOL and ?-ZOL were detected up to 4 h after both types of administration. A two-compartment model was developed to describe the toxicokinetic of ZEA in broilers. The values of t1/2? and Vd were 1.36 ± 0.29 h and 6.40 ± 0.89 l/kg, respectively. The absolute oral bioavailability was 29.66 ± 5.6%. ZEA, ?-ZOL and ?-ZOL were measurable in the vital organs after po administration. These results suggest that ZEA is absorbed from the gastrointestinal tract and it has ability to penetrate into the various tissues of broiler chickens.
| S-EPMC5598537 | biostudies-literature
Project description:This study aims to search for the effect of 50uM Metronidazole against Entamoeba histolytica and thereby elucidating their mechanism of action
2014-01-14 | E-MTAB-1763 | biostudies-arrayexpress
Project description:Antibiotic usage in animals as a growth promoter is considered as public health issue due to its negative impact on consumer health and environment. The present study aimed to evaluate effectiveness of herbal residue (ginger, Zingiber officinale, dried rhizome powder) and prebiotic (inulin) as an alternative to antibiotics by comparing fecal microflora composition using terminal restriction fragment length polymorphism. The grower pigs were offered feed containing antibiotic (tetracycline), ginger and inulin separately and un-supplemented group served as control. The study revealed significant changes in the microbial abundance based on operational taxonomic units (OTUs) among the groups. Presumptive identification of organisms was established based on the fragment length of OTUs generated with three restriction enzymes (MspI, Sau3AI and BsuRI). The abundance of OTUs representing Bacteroides intestinalis, Eubacterium oxidoreducens, Selonomonas sp., Methylobacterium sp. and Denitrobacter sp. was found significantly greater in inulin supplemented pigs. Similarly, the abundance of OTUs representing Bacteroides intestinalis, Selonomonas sp., and Phascolarcobacterium faecium was found significantly greater in ginger supplemented pigs. In contrast, the abundance of OTUs representing pathogenic microorganisms Atopostipes suicloacalis and Bartonella quintana str. Toulouse was significantly reduced in ginger and inulin supplemented pigs. The OTUs were found to be clustered under two major phylotypes; ginger-inulin and control-tetracycline. Additionally, the abundance of OTUs was similar in ginger and inulin supplemented pigs. The results suggest the potential of ginger and prebioticsto replace antibiotics in the diet of grower pig.
| S-EPMC4503616 | biostudies-literature
Project description:This study estimated the effect of exposure to propiconazole through implementation and residues in finishing pigs. We analyzed the expression of fibrosis-related genes and performed histological analysis of the blood, liver, kidney, muscle, ileum, and fat tissues. The animals were exposed for 28 d to different concentrations of propiconazole (0.09, 0.44, 0.88, 4.41, and 8.82 mg/kg bw/d). Quantitative, gene expression, and histological analyses in tissues were performed using liquid chromatography mass spectrometry, real-time PCR, and Masson's trichrome staining, respectively. Final body weight did not differ among groups. However, genes involved in fibrosis were significantly differentially regulated in response to propiconazole concentrations. Glucose, alanine aminotransferase, and total bilirubin levels were significantly increased compared with those in the control group, while alkaline phosphatase level was decreased (p<0.05) after exposure to propiconazole. The residue limits of propiconazole were increased in the finishing phase at 4.41 and 8.82 mg/kg bw/d. The liver, kidney, and ileum showed blue staining after propiconazole treatment, confirmed by Masson's trichrome staining. In conclusion, these findings suggest that propiconazole exposure disturbs the expression of fibrosis-related genes. This study on dietary propiconazole in pigs can provide a basis for determining maximum residue limits and a better understanding of metabolism in pigs and meat products.
| S-EPMC8564320 | biostudies-literature
Project description:The recently identified restriction factor tetherin/BST-2/CD317 is an interferon-inducible trans-membrane protein that restricts HIV-1 particle release in the absence of the HIV-1 countermeasure viral protein U (Vpu). It is known that Tantalus monkey CV1 cells can be rendered non-permissive to HIV-1 release upon stimulation with type 1 interferon, despite the presence of Vpu, suggesting species-specific sensitivity of tetherin proteins to viral countermeasures such as Vpu. Here we demonstrate that Tantalus monkey tetherin restricts HIV-1 by nearly two orders of magnitude, but in contrast to human tetherin the Tantalus protein is insensitive to HIV-1 Vpu. We have investigated tetherin's sensitivity to Vpu using positive selection analyses, seeking evidence for evolutionary conflict between tetherin and viral countermeasures. We provide evidence that tetherin has undergone positive selection during primate evolution. Mutation of a single amino acid (showing evidence of positive selection) in the trans-membrane cap of human tetherin to that in Tantalus monkey (T45I) substantially impacts on sensitivity to HIV-1 Vpu, but not on antiviral activity. Finally, we provide evidence that cellular steady state levels of tetherin are substantially reduced by Vpu, and that the T45I mutation abrogates this effect. This study provides evidence that tetherin is important in protecting mammals against viral infection, and that the HIV-1 Vpu-mediated countermeasure is specifically adapted to act against human tetherin. It also emphasizes the power of selection analyses to illuminate the molecular details of host-virus interactions. This work suggests that tetherin binding agents might protect it from viral encoded countermeasures and thus make powerful antivirals.
| S-EPMC2678251 | biostudies-literature
Project description:Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.
| S-EPMC2630645 | biostudies-literature
Project description:Most pharmacodynamic (PD) models of cellular response assume a time-invariant (i.e., constant) cellular disposition despite known changes in the disposition with time, such as the reticulocyte residence time in the systemic circulation during stress erythropoiesis. To account for changes in cellular disposition, a comprehensive PD model that involves endogenous erythropoietin (Epo), reticulocytes, and hemoglobin responses was developed in phlebotomized sheep that considers a time-variant reticulocyte residence time and allows for the simultaneous determination of changes in the cellular disposition and cellular production. Five sheep were phlebotomized to hemoglobin concentrations of approximately 4 g/dl. Epo concentrations, reticulocytes, and hemoglobin concentrations were frequently sampled for 5-7 days prior to and 25-30 days following the phlebotomy. Initial steady-state conditions were assumed and the time-variant reticulocyte residence time in the systemic circulation was semiparametrically represented using a constrained spline function. Hemoglobin production was modeled using a Hill function via an effect site compartment. The initial steady state reticulocyte residence time in the systemic circulation was estimated as 0.477 (0.100) (mean (SD)) days, which maximally increased 2.01- to 2.64-fold higher than the initial steady-state residence time 5.95 (0.899) days post-phlebotomy (P < 0.01). On average, the residence time returned to steady-state values 15.4 (2.36) days post-phlebotomy, which was not significantly different from the initial steady-state value (P > 0.05). The baseline hemoglobin production rate was estimated at 0.0929 (0.0472) g/kg/day and the maximum production rate under stress phlebotomy was estimated at 0.504 (0.0422) g/kg/day. These data indicate that endogenously released Epo under acute anemic conditions can increase hemoglobin production approximately 5-fold. The determined increase in reticulocyte residence time produced under stress erythropoiesis is similar to the commonly reported 2- to 3-fold increase observed in human patients.
| S-EPMC2882108 | biostudies-literature