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

Bhutto, Zohaib Ahmed; He, Fang; Zloh, Mire; Yang, Jing; Huang, Jinhu; Guo, Tingting; Wang, Liping

doi:10.1038/s41598-018-22354-1

Cited by 30 publications

(17 citation statements)

References 48 publications

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“…The previously reported homology model of CXR [15] was used to dock a set of small molecules and evaluate their affinity to the binding site of the ligand binding domain. The docking scores and poses agreed with the previous results, and the binding energy of −7.8 kcal/mol suggested that berberine interacts favorably with CXR (Table 4, Figure 8A).…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Homology modeling of CXR was performed following a previously described procedure [15]. The homology model for chicken P-glycoprotein (CP-gp) was produced as described previously [15], with minor modifications. Briefly, the GenPept database was used to retrieve the sequence of CP-gp (accession number NP_990225), which was submitted to the I-TASSER homology modeling server [38] to obtain a three-dimensional structure.…”

Section: Methodsmentioning

confidence: 99%

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Inhibitory Effect of Berberine on Broiler P-glycoprotein Expression and Function: In Situ and In Vitro Studies

Zhang

Guo

Huang

et al. 2019

IJMS

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Overcoming P-glycoprotein (P-gp) efflux is a strategy to improve the absorption and pharmacokinetics of its substrate drugs. Berberine inhibits P-gp and thereby increases the bioavailability of the P-gp substrate digoxin in rodents. However, the effects of berberine on P-gp in chickens are still unclear. Here, we studied the role of berberine in modulating broilers P-gp expression and function through both in situ and in vitro models. In addition, molecular docking was applied to analyze the interactions of berberine with P-gp as well as with chicken xenobiotic receptor (CXR). The results showed that the mRNA expression levels of chicken P-gp and CXR decreased in the ileum following exposure to berberine. The absorption rate constant of rhodamine 123 increased after berberine treatment, as detected using an in situ single-pass intestinal perfusion model. Efflux ratios of P-gp substrates (tilmicosin, ciprofloxacin, clindamycin, ampicillin, and enrofloxacin) decreased and the apparent permeability coefficients increased after co-incubation with berberine in MDCK-chAbcb1 cell models. Bidirectional assay results showed that berberine could be transported by chicken P-gp with a transport ratio of 4.20, and this was attenuated by verapamil (an inhibitor of P-gp), which resulted in a ratio of 1.13. Molecular docking revealed that berberine could form favorable interactions with the binding pockets of both CXR and P-gp, with docking scores of −7.8 and −9.5 kcal/mol, respectively. These results indicate that berberine is a substrate of chicken P-gp and down-regulates P-gp expression in chicken tissues, thereby increasing the absorption of P-gp substrates. Our findings suggest that berberine increases the bioavailability of other drugs and that drug-drug interactions should be considered when it is co-administered with other P-gp substrates with narrow therapeutic windows.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Inhibitory Effect of Berberine on Broiler P-glycoprotein Expression and Function: In Situ and In Vitro Studies

Zhang

Guo

Huang

et al. 2019

IJMS

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“…Homology model of the cBCRP was generated using procedure described previously [ 35 ] with some modifications. Then, model availability was validated by comparing docking scores of known BCRP substrates and inhibitors into the efflux pump site.…”

Section: Methodsmentioning

confidence: 99%

Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies

Liu

Guo

Zloh

et al. 2018

IJMS

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Florfenicol (FFC) is a valuable synthetic fluorinated derivative of thiamphenicol widely used to treat infectious diseases in food animals. The aims of the study were to investigate whether FFC is a substrate for the breast cancer resistance protein (BCRP) and whether the transporter influences oral availability of FFC. In vitro transport assays using MDCK-chAbcg2 cells were conducted to assess chicken BCRP-mediated transport of FFC, while in vivo pharmacokinetic experiments with single or combined BCRP inhibitor gefitinib were employed to study the role of BCRP in oral FFC disposition. According to U.S. Food and Drug Administration (FDA) criteria, FFC was found to be a potential BCRP substrate due to the net efflux ratio being over 2.0 (2.37) in MDCK cells stably transfected with chicken BCRP and the efflux completely reversed by a BCRP inhibitor (Gefitinib). The molecular docking results indicated that florfenicol can form favorable interactions with the binding pocket of homology modeled chicken BCRP. Pharmacokinetic studies of FFC in different aged broilers with different expression levels of BCRP showed that higher BCRP expression would cause a lower Area Under Curve (AUC) and a higher clearance of FFC. In addition, more extensive absorption of florfenicol after the co-administration with gefitinib (a BCRP inhibitor) was observed. The overall results demonstrated that florfenicol is a substrate of the chicken breast cancer resistant protein which in turn affects its pharmacokinetic behavior.

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“…Molecular docking study showed that addition of flavonoid moiety not only provided several additional interactions but also did not disturb the binding mode of the quinolone . Therefore, covalently binding an antibiotic with an efflux pump inhibitor may probably develop antibiotics effective against resistant strains …”

Section: Recent Advances Of Quinolone Antibacterial Agentsmentioning

confidence: 99%

Recent updates of fluoroquinolones as antibacterial agents

Ezelarab

Abbas

Hassan

et al. 2018

Archiv der Pharmazie

149

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Fluoroquinolones remain one of the most important kind of antibacterial agents used nowadays. The emergence of more virulent and resistant strains of bacteria by the development of either mutated DNA-binding proteins or efflux pump mechanism for drugs is considered the main problem associated with the therapeutic use of these drugs. This situation participated in pushing researchers to design new fluoroquinolone derivatives, mainly with different substituents at C-7 to withstand these resistant strains of bacteria and to obtain a wider spectrum of activity including activity against anaerobic organisms. Conjugation of fluoroquinolones with substitutions such as 1,2,4-triazoles, alkyl oximes, flavonoids, aryl furans, benzofuroxans, metronidazoles or even other antibiotics such as neomycin-B produced derivatives that have a superior and wider spectrum of activity and better resistance than the classical fluoroquinolone agents. Addition of a hydroxamic acid moiety to fluoroquinolones also increased the activity against Proteus mirabilis, which represents one of the most resistant strains of bacteria in urinary tract infections. This review aims to highlight the recent updates made for fluoroquinolones for broadening the spectrum of activity to become active not only against resistant strains of bacteria but also against anaerobic pathogens.

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

Cited by 30 publications

References 48 publications

Inhibitory Effect of Berberine on Broiler P-glycoprotein Expression and Function: In Situ and In Vitro Studies

Inhibitory Effect of Berberine on Broiler P-glycoprotein Expression and Function: In Situ and In Vitro Studies

Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies

Recent updates of fluoroquinolones as antibacterial agents

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