Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Archives of Gynecology and Obstetrics
Published in: Archives of Gynecology and Obstetrics 5/2010

01-05-2010 | Materno-fetal Medicine

Carrier-mediated uptake of Levofloxacin by BeWo cells, a human trophoblast cell line

Authors: Hana Polachek, Gershon Holcberg, Joseph Polachek, Mazal Rubin, Valeria Feinshtein, Eyal Sheiner, Zvi Ben-Zvi

Published in: Archives of Gynecology and Obstetrics | Issue 5/2010

Login to get access

Abstract

Objective

Placental transfer of Levofloxacin (LF), a broad spectrum fluoroquinolone antibiotic, and its inhibition was investigated in BeWo cells, a human trophoblast cell line.

Methods

The experiments of LF uptake by BeWo cells were performed after preincubation and in the presence of the P-glycoprotein inhibitors (Cyclosporin A, Verapamil and Quercetin), the organic anion/cation transporter inhibitor (Cimetidine) and the MCT substrates (lactic acid and salicylic acid).

Results

P-glycoprotein inhibitors increased the uptake of LF by BeWo cells. The increase in LF accumulation by Cyclosporin A, Verapamil and Quercetin was by 30, 90 and 80%, respectively. Cimetidine, the organic cation inhibitor, increased the transport of LF by 48%. Lactic acid and salicylic acid, the MCT substrates, initially decreased the accumulation of LF by 30% and subsequently increased the uptake of LF by 500 and 53%, respectively.

Conclusions

The uptake of LF by human trophoblast cells is mediated by multiple transporters as well as passive diffusion.
Literature
1.
Fish DN, Chow AT (1997) The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet 32:101–119CrossRefPubMed
2.
Mandel GL, Petri WA Jr (2006) The quinolones. In: Brunton LL, Lazo JS, Parker KL (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York, pp 1119–1126
3.
4.
Weier N, He SM, Li XT, Wang LL, Zhou SF (2008) Placental drug disposition and its clinical implications. Curr Drug Metab 9:106–121CrossRefPubMed
5.
Holcberg G, Tsadkin M, Sapir O, Huleihel M, Mazor M, Ben Zvi Z (2003) New aspects in placental drug transfer. Isr Med Assoc J 5(12):873–876PubMed
6.
Chandorkar GA, Ampasavate C, Stobaugh JF, Audus KL (1999) Peptide transport and metabolism across the placenta. Adv Drug Deliv Rev 38:59–67CrossRefPubMed
7.
Myren M, Mose T, Mathiesen L, Knudsen LE (2007) The human placenta—an alternative for studying foetal exposure. Toxicol In Vitro 21:1332–1340CrossRefPubMed
8.
Polachek H, Holcberg G, Sapir G, Tsadkin M, Polachek J, Katz M, Ben Zvi Z (2005) Transfer of Ciprofloxacin, Ofloxacin and Levofloxacin across the perfused human placenta in vitro. Eur J Obstet Gynecol Reprod Biol 122:61–65CrossRefPubMed
9.
Pattilo RA, Gey GO, Delfs E, Mattingly RF (1968) Human hormone production in vitro. Science 159:1467–1469CrossRef
10.
Ringler GE, Strauss JF (1990) In vitro systems for the study of human placental endocrine function. Endocrinol Rev 11:105–123CrossRef
11.
Gips M, Barel S, Bridzy M, Soback S (1995) Detection of fluoroquinolone residues in milk. In: Proceedings of the third IDF international Mastitis seminar
12.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMed
13.
Young AM, Allen CE, Audus KL (2003) Efflux transporters of the human placenta. Adv Drug Deliv Rev 55:125–132CrossRefPubMed
14.
Nakamura Y, Ikeda S, Furukawa T, Sumizawa T, Tani A, Akiyama S, Nagata Y (1997) Function of P-glycoprotein expressed in placenta and mole. Biochem Biophys Res Commun 235:849–853CrossRefPubMed
15.
Gil S, Saura R, Forestier F, Farinotti R (2005) P-glycoprotein expression of the human placenta during pregnancy. Placenta 26:268–270CrossRefPubMed
16.
Lankas GR, Wise LD, Cartwright ME, Pippert T, Umbenhauer DR (1998) Placental P-glycoprotein deficiency enhances susceptibility to chemically induced birth defects in mice. Reprod Toxicol 12:457–463CrossRefPubMed
17.
Utoguchi N, Chandorkar GA, Avery M, Audus KL (2000) Functional expression of P-glycoprotein in primary cultures of human cytotrophoblast and BeWo cells. Reprod Toxicol 14:217–224CrossRefPubMed
18.
De Lange EC, Marchand S, Van Den Berg D, Van Der Sandt IC, De Boer AG, Delon A, Bouquet S, Couet W (2000) In vitro and in vivo investigations on fluoroquinolones; effects of the P-glycoprotein efflux transporter on brain distribution of sparfloxacin. Eur J Pharm Sci 12:85–93CrossRefPubMed
19.
Yamaguchi H, Yano I, Hashimoto Y, Inui KI (2000) Secretory mechanisms of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2. J Pharmacol Exp Ther 295:360–366PubMed
20.
Rabbaa L, Dautrey S, Colas-Linhart N (1996) Intestinal elimination of ofloxacin enantiomers in the rat: evidence of a carrier-mediated process. Antimicrob Agents Chemother 40:2126–2130PubMed
21.
Ito T, Yano I, Tanaka K, Inuri KI (1997) Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1. J Pharmacol Exp Ther 282:955–960PubMed
22.
Takaai M, Suzuki H, Ishida K, Tahara K, Hashimoto Y (2007) Pharmacokinetic analysis of transcellular transport of levofloxacin across LLC-PK1 and Caco-2 cell monolayers. Biol Pharm Bull 30(11):2167–2172CrossRefPubMed
23.
Hagenbuch B, Meier PJ (2004) Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Eur J Physiol 447:653–665CrossRef
24.
Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H (2001) Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol 59:1277–1286PubMed
25.
Tahara H, Kusuhara H, Endou H, Koepsell H, Imaoka T, Fuse E, Sugiyama Y (2005) A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther 15:337–345CrossRef
26.
Balkovetz DF, Leibach FH, Mahesh VB, Ganapathy V (1988) A proton gradient is the driving force for uphill transport of lactate in human placental brush-border membrane vesicles. J Biol Chem 263:13823–13830PubMed
27.
Carstensen MH, Leichtweiss HP, Schroder H (1983) Lactate carriers in the artificially perfused human term placenta. Placenta 4:165–174CrossRefPubMed
28.
Utoguchi N, Magnusson M, Audus KL (1999) Carrier-mediated transport of monocarboxylic acid in BeWo cell monolayers as a model of the human trophoblast. J Pharma Sci 88:1288–1292CrossRef
29.
Ushigome F, Takanaga H, Matsuo H, Tsukimori K, Nakano H, Ohtani H, Sawada Y (2001) Uptake mechanism of valproic acid in human placental choriocarcinoma cell line (BeWo). Eur J Pharmacol 417:169–176CrossRefPubMed
30.
Alonso-Torre SR, Serrano MA, Alvarado F, Medina JM (1991) Carrier-mediated l-lactate transport in brush border membrane vesicles from rat placenta during late gestation. Biochem J 278:535–541
Metadata
Title
Carrier-mediated uptake of Levofloxacin by BeWo cells, a human trophoblast cell line
Authors
Hana Polachek
Gershon Holcberg
Joseph Polachek
Mazal Rubin
Valeria Feinshtein
Eyal Sheiner
Zvi Ben-Zvi
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
Archives of Gynecology and Obstetrics / Issue 5/2010
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-009-1177-y

Other articles of this Issue 5/2010

Archives of Gynecology and Obstetrics 5/2010 Go to the issue

Materno-fetal Medicine

Bilateral humerus fracture in a neonate after cesarean delivery

Original Article

Splenic artery: peak systolic velocity of normal fetuses

Reproductive Medicine

A prospective randomized trial comparing the clinical and endocrinological outcome with rosiglitazone versus laparoscopic ovarian drilling in patients with polycystic ovarian disease resistant to ovulation induction with clomiphene citrate

Gynecologic Oncology

“Inflammatory” changes in breast: how to provide a better care to our patients

Original Article

Altered gene profile of placenta from women with intrahepatic cholestasis of pregnancy

General Gynecology

Management of severe cervical stenosis after conization by detention of nylon threads tied up to intrauterine contraceptive device