PMID- 20513441
OWN - NLM
STAT- MEDLINE
DCOM- 20100727
LR  - 20181201
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 186
IP  - 3
DP  - 2010 Aug 5
TI  - Interaction of anthelmintic drugs with P-glycoprotein in recombinant 
      LLC-PK1-mdr1a cells.
PG  - 280-6
LID - 10.1016/j.cbi.2010.05.013 [doi]
AB  - Given the widespread use of formulations combining anthelmintics which are 
      possible P-glycoprotein interfering agents, the understanding of drug 
      interactions with efflux ABC transporters is of concern for improving 
      anthelmintic control. We determined the ability of 14 anthelmintics from 
      different classes to interact with abcb1a (mdr1a, P-glycoprotein, Pgp) by 
      following the intracellular accumulation of rhodamine 123 (Rho 123), a 
      fluorescent Pgp substrate, in LLC-PK1 cells overexpressing Pgp. The cytotoxicity 
      of the compounds that are able to interfere with Pgp activity was evaluated in 
      cells overexpressing Pgp and compared with parental cells using the MTS viability 
      assay. Among all the anthelmintics used, ivermectin (IVM), triclabendazole (TCZ), 
      triclabendazole sulfoxide (TCZ-SO), closantel (CLOS) and rafoxanide (RAF) 
      increased the intracellular Rho 123 in Pgp overexpressing cells, while 
      triclabendazole sulfone, albendazole, mebendazole, oxfendazole, thiabendazole, 
      nitroxynil, levamisole, praziquantel and clorsulon failed to have any effect. The 
      concentration needed to reach the maximal Rho 123 accumulation (E(max)) was 
      obtained with 10 microM for IVM, 80 microM for CLOS, 40 microM for TCZ and 
      TCZ-SO, and 80 microM for RAF. We showed that for these five drugs parental cell 
      line was more sensitive to drug toxicity compared with Pgp recombinant cell line. 
      Such in vitro approach constitutes a powerful tool to predict Pgp-drug 
      interactions when formulations combining several anthelmintics are administered 
      and may contribute to the required optimization of efficacy of anthelmintics.
CI  - Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Dupuy, Jacques
AU  - Dupuy J
AD  - INRA UR66, Laboratoire de Pharmacologie-Toxicologie, F-31027 Toulouse Cedex 3, 
      France. Jacques.Dupuy@toulouse.inra.fr
FAU - Alvinerie, Michel
AU  - Alvinerie M
FAU - Menez, Cecile
AU  - Menez C
FAU - Lespine, Anne
AU  - Lespine A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100601
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Anthelmintics)
RN  - 1N3CZ14C5O (Rhodamine 123)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/*metabolism
MH  - Animals
MH  - Anthelmintics/*pharmacology
MH  - Cell Membrane Permeability/drug effects
MH  - Cell Survival/drug effects
MH  - LLC-PK1 Cells
MH  - Rhodamine 123/*analysis/metabolism
MH  - Swine
MH  - Up-Regulation
EDAT- 2010/06/02 06:00
MHDA- 2010/07/28 06:00
CRDT- 2010/06/02 06:00
PHST- 2010/04/23 00:00 [received]
PHST- 2010/05/21 00:00 [revised]
PHST- 2010/05/24 00:00 [accepted]
PHST- 2010/06/02 06:00 [entrez]
PHST- 2010/06/02 06:00 [pubmed]
PHST- 2010/07/28 06:00 [medline]
AID - S0009-2797(10)00351-0 [pii]
AID - 10.1016/j.cbi.2010.05.013 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2010 Aug 5;186(3):280-6. doi: 10.1016/j.cbi.2010.05.013. Epub 
      2010 Jun 1.