Use of quercetin in animal feed : effects on the P-gp expression and pharmacokinetics of orally administrated enrofloxacin in chicken

Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken. Absorption rate constant and apparent permeability coefficient of rhodamine 123 were decreased, reflecting efflux function of P-gp in chicken intestine increased by quercetin. Quercetin altered pharmacokinetic of enrofloxacin by decreasing area under curve, peak concentration, and time to reach peak concentration and by increasing clearance rate. Molecular docking shows quercetin can form favorable interactions with binding pocket of chicken xenobiotic receptor (CXR). Results provide convincing evidence that quercetin induced P-gp expression in tissues by possible interaction with CXR, and consequently reducing bioavailability of orally administered enrofloxacin through restricting its intestinal absorption and liver/kidney clearance in broilers. The results can be further extended to guide reasonable use of quercetin to avoid drug-feed interaction occurred with co-administered enrofloxacin or other similar antimicrobials.Peer reviewedFinal Published versio

Phenotypic and genetic variation in the response of chickens to Eimeria tenella induced coccidiosis

Background: Coccidiosis is a major contributor to losses in poultry production. With emerging constraints on the use of in-feed prophylactic anticoccidial drugs and the relatively high costs of effective vaccines, there are commercial incentives to breed chickens with greater resistance to this important production disease. To identify phenotypic biomarkers that are associated with the production impacts of coccidiosis, and to assess their covariance and heritability, 942 Cobb500 commercial broilers were subjected to a defined challenge with Eimeria tenella (Houghton). Three traits were measured: weight gain (WG) during the period of infection, caecal lesion score (CLS) post mortem, and the level of a serum biomarker of intestinal inflammation, i.e. circulating interleukin 10 (IL-10), measured at the height of the infection.Results: Phenotypic analysis of the challenged chicken cohort revealed a significant positive correlation between CLS and IL-10, with significant negative correlations of both these traits with WG. Eigenanalysis of phenotypic covariances between measured traits revealed three distinct eigenvectors. Trait weightings of the first eigenvector, (EV1, eigenvalue = 59%), were biologically interpreted as representing a response of birds that were susceptible to infection, with low WG, high CLS and high IL-10. Similarly, the second eigenvector represented infection resilience/resistance (EV2, 22%; high WG, low CLS and high IL-10), and the third eigenvector tolerance (EV3, 19%; high WG, high CLS and low IL-10), respectively. Genome-wide association studies (GWAS) identified two SNPs that were associated with WG at the suggestive level.Conclusions: Eigenanalysis separated the phenotypic impact of a defined challenge with E. tenella on WG, caecal inflammation/pathology, and production of IL-10 into three major eigenvectors, indicating that the susceptibility-resistance axis is not a single continuous quantitative trait. The SNPs identified by the GWAS for body weight were located in close proximity to two genes that are involved in innate immunity (FAM96B and RRAD)

Comparing the pharmacokinetics of a fourth generation cephalosporin in three different age groups of New Forest ponies

REASONS FOR PERFORMING STUDY To compare the pharmacokinetics of the fourth generation cephalosporin, cefquinome, in neonatal foals, 6-week-old foals and mature New Forest ponies in order to recommend appropriate dosage regimens for use of this drug. METHODS Cefquinome was administered i.v. at 1 mg/kg bwt twice a day (q. 12 h), 1 mg/kg bwt 3 times a day (q. 8 h) or 4.5 mg/kg bwt q. 12 h to each age group (n = 6). Plasma cefquinome concentrations were analysed using high-performance liquid chromatography combined with electrospray tandem mass spectrometry. RESULTS Both foal age groups had comparable pharmacokinetic data except for the volume of distribution at a steady-state (Vss), total body clearance (CIB) and mean residence time (MRT). Both ClB and MRT decreased as the age of the foals increased. Values of area under the curve increased, in a dose dependent manner, with significant increases for all age groups following administration of 4.5 mg/kg bwt q. 12 h. Total body clearance did not have comparable dose dependency. CONCLUSIONS Cefquinome can be given at a dose of 1 mg/kg bwt q. 12 h for the treatment of infections caused by susceptible pathogens with MIC <0.125 microg/ml. A higher dose of 4.5 mg/kg bwt q. 12 h is recommended for the treatment of bacterial pathogens with minimal inhibitory concentration (MIC) 0.125-0.5 microg/ml. POTENTIAL RELEVANCE Commonly used dosing regimens should be critically evaluated in neonatal foals due to the higher volume of distribution of less lipophilic drugs in this age group

Morphological and morphometrical characterization, and estimation of population of preantral ovarian follicles from senile common squirrel monkey (Saimiri sciureus)

Project No. 483439/2009-6 from CNPq, Brazil.Federal University of Pará. Laboratory of Wild Animal Biology and Medicine. Castanhal, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.Federal University of Pará. Laboratory of Wild Animal Biology and Medicine. Castanhal, PA, Brazil / Utrecht University. Faculty of Veterinary Medicine. Utrecht, The Netherlands.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.Trakia University. Faculty of Veterinary Medicine. Department of Pharmacology, Physiology of Animals and Physiological Chemistry. Stara Zagora, Bulgaria.Biokapital. Geno. Hamar, Norway.Federal University of Pará. Laboratory of Wild Animal Biology and Medicine. Castanhal, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.The experiment described the morphological and morphometrical characteristics as well as estimate the population of primordial, primary and secondary ovarian follicles from common squirrel monkey (Saimiri sciureus). Ovaries (n = 10) from five senile squirrel monkeys were collected after natural death and processed for classical histology. The mean ovarian population was estimated as 915.04 ± 78.83, 230.46 ± 20.82 and 115.88 ± 15.72 primordial, primary and secondary follicles per ovary, respectively. 73.30% were classified as primordial, 18.62% as primary, and 8.09% as secondary follicles. From all these developmental stages, the mean diameters of follicles, oocytes, oocytes nuclei and the mean number of granulosa cells were described. The number of granulosa cells surrounding normal primordial follicles (5.65 ± 0.001) was lower (P < 0.05) than the number of granulosa cells (13.17 ± 0.02) surrounding the primary follicles. Secondary follicles presented the highest (P < 0.001) number of granulosa cells surrounding each oocyte (273.73 ± 20.80). We have estimated the follicular population, as well as described the morphometric and morphological characteristics of preantral follicles from senile squirrel monkeys, which may be a valuable animal model for female ovarian aging studies