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Marine Bivalve Cellular Responses to Beta Blocker Exposures
Khan, B., R. Burgess, S. Fogg, M. Cantwell, D. Katz, AND K. Ho. Marine Bivalve Cellular Responses to Beta Blocker Exposures. Society of Environmental Toxicology and Chemistry (SETAC) North America 37th Annual Meeting, Orlando, FL, November 06 - 10, 2016.
The purpose of this research is to identify Molecular Initiating Events (MIEs) indicative of environmental exposure to two antihypertensive prescription drugs, also called β blockers, in marine bivalves. β blockers make their way to coastal habitats via waste water treatment plant discharges. Evaluation of MIEs in bioindicator species such as filter-feeding bivalves can serve to develop adverse outcome pathways (AOPs) for environmental exposure to these drugs. Cellular biomarker analyses have allowed us to determine toxic effects of β blockers on Eastern oysters, blue mussels and hard clams as well as differences in species sensitivities at environmentally relevant concentrations of these drugs.
β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent binding of agonists such as catecholamines to β adrenoceptors. In the absence of agonist induced activation of the receptor, adenylate cyclase is not activated which in turn limits cAMP production and protein kinase A activation, preventing increases in blood pressure and arrhythmias. After being taken therapeutically, commonly prescribed β blockers may make their way to coastal habitats via discharge from waste water treatment plants (WWTP) posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular responses of three commercially important marine bivalves - Eastern oysters, blue mussels and hard clams - upon exposure to two β blocker drugs, propranolol and metoprolol, and to find molecular initiating events (MIEs) indicative of the exposure. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas (HP) tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug. Tissues were bathed in 30 parts per thousand (ppt) filtered seawater, antibiotic mix, Leibovitz nutrient media, and the test drug. Exposures were conducted for 24 hours and samples were saved for cellular biomarker assays. A lysosomal destabilization assay, which is a marker of membrane damage, was also performed at the end of each exposure. EC50 values were calculated and compared across species to evaluate drug and dosage effects as well as species sensitivities. Exposed tissues had significantly higher membrane damage than controls at environmentally relevant concentrations. Differences in species sensitivities were also observed. The results suggest that propranolol is more toxic than metoprolol in all three species. Cellular damage and enzymatic markers are currently being analyzed. These studies enhance our understanding of the impacts of commonly used prescription medication on organisms in coastal ecosystems and demonstrate that filter feeders such as these marine bivalves can serve as good model organisms to examine the effects of water soluble drugs like propranolol and metoprolol. Evaluating a suite of biomarkers allows us to better define MIEs that can be used to develop adverse outcome pathways (AOPs) for environmental exposure to β blockers.