Article
Estrogenic and AhR activities in dissolved phase and suspended solids from wastewater treatment plants.
UMR 5569 Hydrosciences Montpellier, Université Montpellier 1, Av. Charles Flahault, 34060 Montpellier, France.
Science of The Total Environment (impact factor:
3.29).
03/2010;
408(12):2608-15.
DOI:10.1016/j.scitotenv.2010.02.034
pp.2608-15
Source: PubMed
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Citations (0)
- Cited In (1)
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Article: Ivermectin induces P-glycoprotein expression and function through mRNA stabilization in murine hepatocyte cell line.
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ABSTRACT: Ivermectin is widely used in human and veterinary medicine for the control of helminth infections. Ivermectin is known to interact with P-glycoprotein (P-gp/MDR1), being a good substrate and a potent inhibitor, however, the influence of ivermectin on the expression of the transporter has not been investigated. Expression of P-glycoprotein was investigated in cultured mouse hepatocytes acutely exposed to ivermectin. The two P-glycoprotein murine isoforms, Mdr1a and Mdr1b, mRNA levels were assessed by real-time RT-PCR. Ivermectin induced a clear time- and concentration-dependent up-regulation of Mdr1a and Mdr1b mRNA levels (as early as a 12-h exposure and up to 2.5-fold at 10μM). Moreover, ivermectin-treated cells displayed enhanced cellular efflux of the P-glycoprotein substrate calcein that was inhibited by the P-glycoprotein blocker valspodar, providing evidence that the ivermectin-induced P-glycoprotein was functional. The mechanisms underlying these effects were investigated. Ivermectin-mediated Mdr1 mRNA induction was independent of the two nuclear receptors CAR and PXR, which are known to be involved in drug transporters regulation. Moreover, by using reporter cell lines that detects specific ligand-activated transcription factors, we showed that ivermectin did not displayed CAR, PXR or AhR ligand activities. However, studies with actinomycin D revealed that the half-life of Mdr1a and Mdr1b mRNA were significantly prolonged by two-fold in ivermectin-treated cells suggesting a post-transcriptional mode of ivermectin regulation. This study demonstrates for the first time that ivermectin induces P-glycoprotein overexpression through post-transcriptional mRNA stabilization, thus offering insight into the mechanism of reduced therapeutic efficacy and development of ivermectin-resistant parasites.Biochemical pharmacology 01/2012; 83(2):269-78. · 4.25 Impact Factor
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Keywords
activated sludge supplemented
AhR activities
Aryl Hydrocarbon Receptor
biofilter system
different treatment technologies
dissolved phase
environmental contamination
estrogen receptor
lowest removal efficiency
similar removal efficiency
solid phase
solids
suspended solid phase
suspended solids
TF
trickling filters
waste stabilization ponds
wastewater influents
wastewater treatment
wastewater treatment plants