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Evaluation of pharmaceutical activities of G-protein coupled receptor targeted pharmaceuticals in Chinese wastewater effluent
Institution:1. National and Kapodistrian University of Athens, Department of Chemistry, Laboratory of Analytical Chemistry, Panepistimiopolis 157 71, Athens, Greece;2. Hellenic Centre for Marine Research, Institute of Oceanography, 46.7 Km Athens Sounio Av., Mavro Lithari, 19013 Anavyssos, Attica, Greece;1. Wadsworth Center, New York State Department of Health, and Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Empire State Plaza, P.O. Box 509, Albany, New York 12201-0509, United States;2. Department of Marine Sciences and Convergent Technology, College of Science and Technology, Hanyang University, Ansan 426-791, Republic of Korea;3. Department of Biochemistry, Faculty of Science, and Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia;1. Department of Chemical and Petroleum Engineering, American University of Beirut, P.O. Box 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon;2. Department of Civil and Environmental Engineering, American University of Beirut, P.O. Box 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon
Abstract:The occurrence of biologically active pharmaceuticals in aquatic environments raised the potential risks to aquatic species. Among these marketed biological active pharmaceuticals, it has been estimated that 40% of them target G-protein-coupled receptors (GPCRs). We have illustrated pharmaceutical activities of GPCR targeted pharmaceuticals in English and Japanese wastewater by the in vitro transforming growth factor-α (TGFα) shedding assay. However, as the most important producer and consumer of pharmaceuticals, the occurrence of GPCR targeted pharmaceuticals in China had remained unclear. In this study, we investigated the pharmaceutical activities of GPCR targeted pharmaceuticals in secondary effluents of Chinese wastewater treatment plants. We discovered antagonistic activities against angiotensin (AT1) receptor at up to 7.2 × 102 ng-valsartan-equivalent quantity/L in Chinese wastewater for the first time as well as agonistic activities against dopamine (D2) receptor. Furthermore, in parallel with the assay, we determined concentrations of GPCR targeted pharmaceuticals in target wastewater by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Through the comparison of predicted antagonistic activities calculated by concentrations and potency values from the assay, we found that the measured antagonistic activities against AT1 receptor from the assay were higher than the predicted AT1 activities from valsartan, irbesartan, and losartan, indicating the potential existence of other unknown AT1 antagonists in wastewater.
Keywords:PCR targeted pharmaceutical  Pharmaceutical activity  Wastewater
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