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Pregled bibliografske jedinice broj: 625156

Identification of P-Glycoprotein Inhibitors in Contaminated Freshwater Sediments


Zaja, Roko; Terzić, Senka; Senta, Ivan; Lončar, Jovica; Popović, Marta; Ahel, Marijan; Smital, Tvrtko
Identification of P-Glycoprotein Inhibitors in Contaminated Freshwater Sediments // Environmental science & technology, 47 (2013), 9; 4813-4821 doi:10.1021/es400334t (međunarodna recenzija, članak, znanstveni)


Naslov
Identification of P-Glycoprotein Inhibitors in Contaminated Freshwater Sediments

Autori
Zaja, Roko ; Terzić, Senka ; Senta, Ivan ; Lončar, Jovica ; Popović, Marta ; Ahel, Marijan ; Smital, Tvrtko

Izvornik
Environmental science & technology (0013-936X) 47 (2013), 9; 4813-4821

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Multixenobiotic resistance ; P-glycoprotein inhibitors ; contaminated sediments ; effect-directed analysis (EDA) ; nonionic surfactants

Sažetak
P-glycoprotein (P-gp, ABCB1) is an important part of the multixenobiotic resistance (MXR) defense system in aquatic organisms. The main goal of this study was identification of P-gp inhibitors in contaminated sediments using the effect-directed analysis (EDA) approach. The samples were collected from the Gorjak creek (Zagreb, Croatia), a recipient of wastewater effluents from the pharmaceutical industry. Sediment samples were extracted and fractionated using two-tiered approach. Resulting non-polar, medium polar and polar fractions were tested on the inhibition of P-gp activity using P-gp overexpressing PLHC-1/dox cells and calcein-AM as model substrate. The obtained EC50 values - up to 757 μg/g, expressed in toxicity equivalents of model P-gp inhibitor cyclosporine A - revealed high inhibitory potential of polar fractions of investigated sediments and clearly reflected the impact of pharmaceutical wastewater. P-gp specific ATPase assay and the cytotoxicity modulation experiments with colchicine indicated that most of the observed P-gp inhibition was due to the presence of non-competitive inhibitors. A detailed chemical analysis by ultrahigh-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QToFMS) revealed nonionic surfactants, including alcohol polyethoxylates (LAEOs) and polypropylene glycols (PPGs), as the major components of the most active sub-fractions. Testing of several LAEO and PPG commercial mixtures confirmed their potential to inhibit the fish P-glycoprotein and modulate toxicity of other xenobiotics present in complex environmental samples.

Izvorni jezik
Engleski

Znanstvena područja
Geologija, Biologija



POVEZANOST RADA


Projekt / tema
098-0982934-2712 - Organski spojevi kao molekulski obilježivači antropogenog utjecaja na okoliš (Marijan Ahel, )
098-0982934-2745 - Ekotoksikološko značenje ABC transportnih proteina u vodenih organizama (Tvrtko Smital, )

Ustanove
Institut "Ruđer Bošković", Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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