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Effects of a common pharmaceutical, atorvastatin, on energy metabolism and detoxification mechanisms of a marine bivalve Mytilus edulis.
Aquat Toxicol. 2019 Mar; 208:47-61.AT

Abstract

Biologically active compounds from pharmaceuticals cause concern due to their common occurrence in water and sediments of urbanized coasts and potential threat to marine organisms. Atorvastatin (ATO), a globally prescribed drug, is environmentally stable and bioavailable to marine organisms; however, the physiological and toxic effects of this drug on ecologically important coastal species are yet to be elucidated. We studied the effect of ATO (˜1.2 μg L-1) on bioenergetics (including whole-organism and mitochondrial respiration, as well as tissue energy reserves and mRNA expression of genes involved in mitochondrial biogenesis and fatty acid metabolism in the gills and the digestive gland) of a keystone bivalve Mytulis edulis (the blue mussel) from the Baltic Sea. Xenobiotic detoxification systems including activity and mRNA expression of P-glycoprotein, and Phase I and II biotransformation enzymes (cytochrome P450 monooxygenase CYP1A and glutathione transferase, GST) were also assessed in the gill and digestive gland of the mussels. Exposure to ATO caused rapid uptake and biotransformation of the drug by the mussels. Standard metabolic rate of ATO-exposed mussels increased by 56% indicating higher maintenance costs, yet no changes were detected in the respiratory capacity of isolated mitochondria. ATO exposure led to ˜60% decrease in the lysosomal membrane stability of hemocytes and ˜3-fold decrease in the whole-organism P-glycoprotein-driven and diffusional efflux of xenobiotics indicating altered membrane properties. The digestive gland was a major target of ATO toxicity in the mussels. Exposure of mussels to ATO led to depletion of lipid, carbohydrate and protein pools, and suppressed transcription of key enzymes involved in mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-alpha PGC-1α) and fatty acid metabolism (acetyl-CoA carboxylase and CYP4Y1) in the digestive gland. No bioenergetic disturbances were observed in the gills of ATO-exposed mussels, and elevated GST activity indicated enhanced ATO detoxification in this tissue. These data demonstrate that ATO can act as a metabolic disruptor and chemosensitizer in keystone marine bivalves and warrant further investigations of statins as emerging pollutants of concern in coastal marine ecosystems.

Authors+Show Affiliations

Department of Marine Biology, Institute of Biological Sciences, University of Rostock, Rostock, Germany; Department of Human Health, Physical Rehabilitation and Vital Activity, Ternopil V. Hnatiuk National Pedagogical University, Ternopil, Ukraine.Leibniz Institute for Baltic Sea Research, Leibniz ScienceCampus Phosphorus Research Rostock, Warnemünde, Germany.Department of Marine Biology, Institute of Biological Sciences, University of Rostock, Rostock, Germany.Department of Industrial Chemistry, Institute of Chemistry, University of Rostock, Rostock, Germany.Department of Industrial Chemistry, Institute of Chemistry, University of Rostock, Rostock, Germany.Department of Industrial Chemistry, Institute of Chemistry, University of Rostock, Rostock, Germany.Department of Marine Biology, Institute of Biological Sciences, University of Rostock, Rostock, Germany.Department of Marine Biology, Institute of Biological Sciences, University of Rostock, Rostock, Germany.Department of Marine Biology, Institute of Biological Sciences, University of Rostock, Rostock, Germany.Department of Marine Biology, Institute of Biological Sciences, University of Rostock, Rostock, Germany; Department of Maritime Systems, Interdisciplinary Faculty, University of Rostock, Rostock, Germany. Electronic address: Inna.Sokolova@uni-rostock.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30610964

Citation

Falfushynska, Halina, et al. "Effects of a Common Pharmaceutical, Atorvastatin, On Energy Metabolism and Detoxification Mechanisms of a Marine Bivalve Mytilus Edulis." Aquatic Toxicology (Amsterdam, Netherlands), vol. 208, 2019, pp. 47-61.
Falfushynska H, Sokolov EP, Haider F, et al. Effects of a common pharmaceutical, atorvastatin, on energy metabolism and detoxification mechanisms of a marine bivalve Mytilus edulis. Aquat Toxicol. 2019;208:47-61.
Falfushynska, H., Sokolov, E. P., Haider, F., Oppermann, C., Kragl, U., Ruth, W., Stock, M., Glufke, S., Winkel, E. J., & Sokolova, I. M. (2019). Effects of a common pharmaceutical, atorvastatin, on energy metabolism and detoxification mechanisms of a marine bivalve Mytilus edulis. Aquatic Toxicology (Amsterdam, Netherlands), 208, 47-61. https://doi.org/10.1016/j.aquatox.2018.12.022
Falfushynska H, et al. Effects of a Common Pharmaceutical, Atorvastatin, On Energy Metabolism and Detoxification Mechanisms of a Marine Bivalve Mytilus Edulis. Aquat Toxicol. 2019;208:47-61. PubMed PMID: 30610964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of a common pharmaceutical, atorvastatin, on energy metabolism and detoxification mechanisms of a marine bivalve Mytilus edulis. AU - Falfushynska,Halina, AU - Sokolov,Eugene P, AU - Haider,Fouzia, AU - Oppermann,Christina, AU - Kragl,Udo, AU - Ruth,Wolfgang, AU - Stock,Marius, AU - Glufke,Sabrina, AU - Winkel,Eileen J, AU - Sokolova,Inna M, Y1 - 2018/12/28/ PY - 2018/11/21/received PY - 2018/12/27/revised PY - 2018/12/28/accepted PY - 2019/1/6/pubmed PY - 2019/3/9/medline PY - 2019/1/6/entrez KW - Bioenergetics KW - Biotransformation KW - Carbohydrates KW - LC–MS analysis KW - Lipids KW - Mitochondria KW - Oxygen consumption KW - Proteins KW - Statins KW - Toxicity SP - 47 EP - 61 JF - Aquatic toxicology (Amsterdam, Netherlands) JO - Aquat Toxicol VL - 208 N2 - Biologically active compounds from pharmaceuticals cause concern due to their common occurrence in water and sediments of urbanized coasts and potential threat to marine organisms. Atorvastatin (ATO), a globally prescribed drug, is environmentally stable and bioavailable to marine organisms; however, the physiological and toxic effects of this drug on ecologically important coastal species are yet to be elucidated. We studied the effect of ATO (˜1.2 μg L-1) on bioenergetics (including whole-organism and mitochondrial respiration, as well as tissue energy reserves and mRNA expression of genes involved in mitochondrial biogenesis and fatty acid metabolism in the gills and the digestive gland) of a keystone bivalve Mytulis edulis (the blue mussel) from the Baltic Sea. Xenobiotic detoxification systems including activity and mRNA expression of P-glycoprotein, and Phase I and II biotransformation enzymes (cytochrome P450 monooxygenase CYP1A and glutathione transferase, GST) were also assessed in the gill and digestive gland of the mussels. Exposure to ATO caused rapid uptake and biotransformation of the drug by the mussels. Standard metabolic rate of ATO-exposed mussels increased by 56% indicating higher maintenance costs, yet no changes were detected in the respiratory capacity of isolated mitochondria. ATO exposure led to ˜60% decrease in the lysosomal membrane stability of hemocytes and ˜3-fold decrease in the whole-organism P-glycoprotein-driven and diffusional efflux of xenobiotics indicating altered membrane properties. The digestive gland was a major target of ATO toxicity in the mussels. Exposure of mussels to ATO led to depletion of lipid, carbohydrate and protein pools, and suppressed transcription of key enzymes involved in mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-alpha PGC-1α) and fatty acid metabolism (acetyl-CoA carboxylase and CYP4Y1) in the digestive gland. No bioenergetic disturbances were observed in the gills of ATO-exposed mussels, and elevated GST activity indicated enhanced ATO detoxification in this tissue. These data demonstrate that ATO can act as a metabolic disruptor and chemosensitizer in keystone marine bivalves and warrant further investigations of statins as emerging pollutants of concern in coastal marine ecosystems. SN - 1879-1514 UR - https://www.unboundmedicine.com/medline/citation/30610964/Effects_of_a_common_pharmaceutical_atorvastatin_on_energy_metabolism_and_detoxification_mechanisms_of_a_marine_bivalve_Mytilus_edulis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-445X(18)31035-X DB - PRIME DP - Unbound Medicine ER -