Mode of action characterization for adverse effect of propranolol in Daphnia magna based on behavior and physiology monitoring and metabolite profiling

Mode of action characterization for adverse effect of propranolol in Daphnia magna based on... Studies are underway to gather information about the mode of action (MOA) of emerging pollutants that could guide practical environmental decision making. Previously, we showed that propranolol, an active pharmaceutical ingredient, had adverse effects on Daphnia magna that were similar to its pharmaceutical action. In order to characterize the mode of action of propranolol in D. magna, which is suspected to be organ-specific pharmaceutical action or baseline toxicity, we performed time-series monitoring of behavior along with heart rate measurements and nuclear magnetic resonance (NMR) based metabolite profiling. Principle component analysis (PCA) and hierarchical clustering were used to categorize the mode of action of propranolol among 5 chemicals with different modes of action. The findings showed that the mode of action of propranolol in D. magna is organ-specific and vastly different from those of narcotics, even though metabolite regulation is similar between narcotic and non-narcotic candidates. The method applied in this study seems applicable to rapid characterization of the MOA of other cardiovascular pharmaceutical ingredients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Environmental Pollution Elsevier

Mode of action characterization for adverse effect of propranolol in Daphnia magna based on behavior and physiology monitoring and metabolite profiling

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Publisher
Elsevier
Copyright
Copyright © 2017 Elsevier Ltd
ISSN
0269-7491
D.O.I.
10.1016/j.envpol.2017.10.043
Publisher site
See Article on Publisher Site

Abstract

Studies are underway to gather information about the mode of action (MOA) of emerging pollutants that could guide practical environmental decision making. Previously, we showed that propranolol, an active pharmaceutical ingredient, had adverse effects on Daphnia magna that were similar to its pharmaceutical action. In order to characterize the mode of action of propranolol in D. magna, which is suspected to be organ-specific pharmaceutical action or baseline toxicity, we performed time-series monitoring of behavior along with heart rate measurements and nuclear magnetic resonance (NMR) based metabolite profiling. Principle component analysis (PCA) and hierarchical clustering were used to categorize the mode of action of propranolol among 5 chemicals with different modes of action. The findings showed that the mode of action of propranolol in D. magna is organ-specific and vastly different from those of narcotics, even though metabolite regulation is similar between narcotic and non-narcotic candidates. The method applied in this study seems applicable to rapid characterization of the MOA of other cardiovascular pharmaceutical ingredients.

Journal

Environmental PollutionElsevier

Published: Feb 1, 2018

References

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