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Nitrofurantoin transport by placental choriocarcinoma JAr cells: involvement of BCRP, OATP2B1 and other MDR transporters

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

To determine the role of BCRP in nitrofurantoin (NF) transport in JAr cells and the possible contribution of OATP2B1, P-gp and MRPs to this transport.

Methods

Cells were incubated with various BCRP, P-gp, MRPs, organic anion transporting polypeptide (OAT) and OATP2B1 inhibitors for 15 min, followed by incubation for 30 min with NF, with or without the inhibitors mentioned earlier. NF cytotoxicity was examined using neutral red (NR) assay. Intracellular NF levels were analyzed by HPLC.

Results

NR assay showed that incubation conditions with NF (as carried out in our experiments) were not cytotoxic. Incubation with specific inhibitors of BCRP (FTC, Chrysin and Novobiocin), showed a significant increase in NF accumulation in the cells. Inhibitors of OATP2B1 (EGCG and BSP) had no influence on NF accumulation. Specific inhibitors of P-gp and MRPs (Verapamil and Indomethacin, respectively) also had no influence on NF accumulation in JAr cells.

Conclusions

NF is probably a specific substrate of BCRP, and BCRP has a major active role in NF transport in JAr cells. For the first time, we showed, that P-gp, MRPs, and the OATP2B1, probably have a negligible contribution to NF transport in JAr cells.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Valeria Feinshtein, Noam Erez, Mazal Rubin, Hana Polachek & Zvi Ben-Zvi

  2. Division of Obstetrics and Gynecology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, 151, Beer Sheva, 84101, Israel

    Gershon Holcberg & Eyal Sheiner

  3. The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Alaa Amash

Authors
  1. Valeria Feinshtein
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  2. Gershon Holcberg
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  3. Alaa Amash
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Correspondence to Gershon Holcberg.

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G. Holcberg and Z. Ben-Zvi are equal contributors.

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Feinshtein, V., Holcberg, G., Amash, A. et al. Nitrofurantoin transport by placental choriocarcinoma JAr cells: involvement of BCRP, OATP2B1 and other MDR transporters. Arch Gynecol Obstet 281, 1037–1044 (2010). https://doi.org/10.1007/s00404-009-1286-7

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  • DOI: https://doi.org/10.1007/s00404-009-1286-7

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