Cyclosporin A affects the bioavailability of ginkgolic acids via inhibition of P-gp and BCRP

Li, Li; Yao, Qingqing; Xu, Siyun; Shen, Qi; Pan, Liya; Zhou, Hui; Jiang, Huidi; Lu, Chuang; Yu, Lushan; Zeng, Su

doi:10.1016/j.ejpb.2014.06.012

Cited by 31 publications

(13 citation statements)

References 41 publications

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“…Compound concentrations were not considered to compromise cell viability if it was maintained above 85% compared with control cells (Li et al, 2014).…”

Section: Downloaded Frommentioning

confidence: 99%

Elucidation of the Impact of P-glycoprotein and Breast Cancer Resistance Protein on the Brain Distribution of Catechol-O-Methyltransferase Inhibitors

et al. 2017

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P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are clinically important efflux transporters that act cooperatively at the blood-brain barrier, limiting the entry of several drugs into the central nervous system (CNS) and affecting their pharmacokinetics, therapeutic efficacy, and safety. In the present study, the interactions of catechol--methyltransferase (COMT) inhibitors (BIA 9-1059, BIA 9-1079, entacapone, nebicapone, opicapone, and tolcapone) with P-gp and BCRP were investigated to determine the contribution of these transporters in their access to the brain. In vitro cellular accumulation and bidirectional transport assays were conducted in Madin-Darby canine kidney (MDCK) II, MDCK-MDR1, and MDCK-BCRP cells. In vivo pharmacokinetic studies were carried out for tolcapone and BIA 9-1079 in rats, with and without elacridar, a well-known P-gp and BCRP modulator. The results suggest that BIA 9-1079, nebicapone, and tolcapone inhibit BCRP in a concentration-dependent manner. Moreover, with net flux ratios higher than 2 and decreased over 50% in the presence of verapamil or Ko143, BIA 9-1079 was identified as a P-gp substrate while BIA 9-1059, entacapone, opicapone, and nebicapone were revealed to be BCRP substrates. In vivo, brain exposure was limited for tolcapone and BIA 9-1079, although tolcapone crossed the blood-brain barrier at a greater rate and to a greater extent than BIA 9-1079. The extent of brain distribution of both compounds was significantly increased in the presence of elacridar, attesting to the involvement of efflux transporters. These findings provide relevant information and improve the understanding of the mechanisms that govern the access of these COMT inhibitors to the CNS.

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“…Compound concentrations were not considered to compromise cell viability if it was maintained above 85% compared with control cells (Li et al, 2014).…”

Section: Downloaded Frommentioning

confidence: 99%

Elucidation of the Impact of P-glycoprotein and Breast Cancer Resistance Protein on the Brain Distribution of Catechol-O-Methyltransferase Inhibitors

et al. 2017

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“…Of the fi ve naturally occurring ginkgolides, B is considered the most active from the point of view of antagonizing PAF (23). Among various compounds, ginkgolic acid C 17 : 1 and ginkgolic acid C 15 : 1 are the most abundant ones extracted from Ginkgo biloba leaves (24), its antitumor effects through the modulation of several oncogenic targets including attenuation of pathways involved in lipogenesis (25), cell cycle arrest and decrease of the Bcl-2/Bax ratio (26). It was found for the fi rst time that ginkgolic acid inhibits both constitutive and inducible STAT3 (oncogenic transcription factor) activation leading to the suppression of cell proliferation and down-regulation of various gene products that prevent apoptosis and promote infl ammation and metastasis in tumor cells (27).…”

Section: Introductionmentioning

confidence: 99%

Inhibition by Egb761 of the effect of cellphone radiation on the male reproductive system

Gevrek¹,

Aydın²,

Ozsoy³

et al. 2017

BLL

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OBJECTIVES: To determine the effects of Egb761 on testicular tissues and semen parameters in rats exposed to cellphone waves. BACKGROUND: EGb761 has antioxidant properties as a free-radical scavenger. Cellphone electromagnetic radiation (EMR) induces oxidative stress in cells. METHODS: Twenty-one Wistar albino male adult rats were divided into three groups (control, experimental, treatment), including seven rats in each. The experimental and treatment groups were exposed to cellphone EMR (0.96 W/kg) for six weeks (4 hrs/day). Egb761 (100 mg/kg/day) was also added to the treatment. Testes, epididymal semen and blood plasma were used for analysis. RESULTS: Exposure to cellular phone radiation resulted in a signifi cant impairment in testicular morphometry and histological structure, reduction of total and motile sperm numbers and plasma testosterone level. Egb761 administration improved testicular damage and led to a marked increase in plasma testosterone levels and total and motile sperm numbers. CONCLUSION: Male reproductive system is susceptible to cellphone radiation. Cellphone waves induce toxic effects in testicular tissues, impair spermatogenesis and cause an imbalance in testosterone hormone levels. Egb761 ameliorated these toxic effects by reversing testicular tissue damage, restoring normal spermatogenesis and hormone levels. This suggests that Egb761 is a potential therapeutic agent against EMR-induced male reproductive toxicity (Tab. 3, Fig. 6, Ref. 45). Text in PDF www.elis.sk.

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“…However, the net ER of evogliptin was low (1.26 and 1.16 at 0.1 and 1 μ m evogliptin, respectively), which was because the ER was comparable between MDCKII‐BCRP cell and the parental cell monolayers. A net ER close to 1 indicates that evogliptin might not be a substrate of BCRP (Li et al, ). It should be noted that the high ER in MDCKII parental cells could be due to endogenous canine P‐gp, not BCRP, because a low level of native P‐gp is expressed in MDCKII parental cells (Kuteykin‐Teplyakov, Luna‐Tortós, Ambroziak, & Löscher, ).…”

Section: Resultsmentioning

confidence: 99%

“…The apparent permeability coefficient (P app ), efflux ratio (ER) and the net ER were calculated by the same equation as used in previous reports (Ishiguro et al, ; Li et al, ).…”

Section: Methodsmentioning

confidence: 99%

In vitro evaluation of potential transporter‐mediated drug interactions of evogliptin

Lee

Chae

Shim

2017

Biopharm & Drug Disp

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To date, little is known about the transporter-mediated drug-drug interaction (DDI) potential of evogliptin, a novel DPP-4 inhibitor. The objective of this study was to evaluate the DDI potential of evogliptin using various in vitro assays in transporter-expressing cell lines. After incubating evogliptin with cells overexpressing OAT1, OAT3, OCT2, OATP1B1 and OATP1B3, there was no notable cellular accumulation of evogliptin (fold accumulation, 0.41-1.86). In bidirectional transport assays using a Caco-2 cell monolayer, a high efflux ratio (ER, 522) of evogliptin was observed, which was significantly decreased (97.96%) in the presence of a potent P-gp inhibitor. In assays using MDCKII-BCRP cell monolayers, by contrast, a low net ER (1.16-1.26) was found. In similar cellular uptake and bidirectional studies with probe substrates of P-gp, BCRP, OAT1, OAT3, OCT2, OATP1B1 and OATP1B3, the active transport of the substrates was not significantly suppressed by evogliptin. These results suggest that evogliptin may be a substrate of P-gp, but not a substrate of BCRP, OAT1B1, OAT1B3, OAT1, OAT3 or OCT2, and not an inhibitor of any of these transporters. Therefore, it could be concluded that evogliptin has some DDI potential involving P-gp, but it has low potential of DDI mediated by the other transporters.

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Cyclosporin A affects the bioavailability of ginkgolic acids via inhibition of P-gp and BCRP

Cited by 31 publications

References 41 publications

Elucidation of the Impact of P-glycoprotein and Breast Cancer Resistance Protein on the Brain Distribution of Catechol-O-Methyltransferase Inhibitors

Elucidation of the Impact of P-glycoprotein and Breast Cancer Resistance Protein on the Brain Distribution of Catechol-O-Methyltransferase Inhibitors

Inhibition by Egb761 of the effect of cellphone radiation on the male reproductive system

In vitro evaluation of potential transporter‐mediated drug interactions of evogliptin

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