From Your Body to Theirs: How Exposure to Pharmaceuticals Is Altering Gene Expression in Fishes

by Natalie Sopinka—AFS Contributing Writer [email protected] California’s waterways are home to smelt, dace, suckers, sturgeon, salmon, roach, and the state fish, the California Golden Trout Oncorhynchus mykiss aguabonita. They are also home to several chemicals of emerging concern (CEC). A recent survey, led by Keith Maruya of the Southern California Coastal Water Research Project, recommended a number of chemicals for further monitoring, including the insecticide bifenthrin, the synthetic perfume additive galaxolide, and the household pharmaceutical ibuprofen (Maruya et al. 2014). One of the most commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen reduces inflammation by shutting down production of prostaglandins, compounds that cause inflammation.

Postdoctoral researcher Ken Jeffries studies how aquatic contaminants change gene expression in fishes.  Photo credit: University of California Davis.

Postdoctoral researcher Ken Jeffries studies how aquatic contaminants change gene expression in fishes.
Photo credit: University of California Davis.

Having ibuprofen on hand is helpful when you’ve just sprained your ankle. It is also taken to relieve headaches, fever, arthritis, and cramping. But 70-80% of ibuprofen is not used by our bodies, and the unmetabolized component is excreted in urine. The widespread use of this drug has contributed to its persistent detection in not only surface water but also the plasma, gills, liver, muscle, and bile of wild-caught fishes. In the lab, fish exposed to ibuprofen can have abnormal spine and fin growth (David and Pancharatna 2009) and produce fewer eggs (Ji et al. 2013). What is happening at the cellular level in fish exposed to ibuprofen? [su_members message=”This content is for members only. Please login.”

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   login_url=”/membership/member-login/” class=””] Ken Jeffries, a Delta Science postdoctoral fellow at the University of California-Davis in Richard Connon’s laboratory, is looking for the answers to this question using genomics tools.

Jeffries, in collaboration with Susanne Brander at the University of North Carolina-Wilmington, exposed larval Inland Silverside Menidia beryllina for two weeks to a range of ibuprofen concentrations. Invasive in California, Inland Silverside could be an important indicator species as populations live in areas with critically endangered native species (e.g., Delta Smelt Hypomesus transpacificus) and can be sampled as surrogates. Exposure of Inland Silverside to concentrations of ibuprofen similar to concentrations detected in wastewater effluent reduced expression of genes linked with bone and skeletal development (Jeffries et al. 2015). Expression of genes that regulate immune function and metabolism were also reduced. What do these changes in gene expression mean for California’s fishes?

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Inland Silverside Menidia beryllina. Photo credit: Richard A. King.

“Well, it means that fish in these systems may respond physiologically to exposure to this common wastewater contaminant. A common misconception is that ibuprofen in the environment is harmless, and therefore it isn’t a concern. However, these results show that chronic exposure can affect gene expression, which can potentially lead to impacts on growth and development as well as the overall health of an individual fish over time” said Jeffries. “Therefore, we need to look at the effects of exposure over the entire lifecycle of a fish to identify effects on reproductive output and growth, an approach that we have begun to use in current research projects.” Jeffries added, “Given that fish are rarely exposed to just ibuprofen in the environment, the real question becomes how do fish respond to the complex mixtures of pharmaceuticals that are detected in wastewater effluent?” REFERENCES David, A., and K. Pancharatna. 2009. Developmental anomalies induced by a non-selective COX inhibitor (ibuprofen) in zebrafish (Danio rerio). Environmental Toxicology and Pharmacology 27:390–395. Jeffries, K. M., S. M. Brander, M. T. Britton, N. A. Fangue, and R. E. Connon. 2015. Chronic exposures to low and high concentrations of ibuprofen elicit different gene response patterns in a euryhaline fish. Environmental Science and Pollution Research DOI: 10.1007/s11356-015-4227-y. Ji, K., X. Liu, S. Lee, S. Kang, Y. Kho, J. P. Giesy, and K. Choi. 2013. Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish. Journal of Hazardous Materials 254–255:242–251. Maruya, K. A., D. Schlenk, P. D. Anderson, N. D. Denslow, J. E. Drewes, A. W. Olivieri, G. I. Scott, and S. A. Snyder. 2014. An adaptive, comprehensive monitoring strategy for chemicals of emerging concern (CECs) in California’s aquatic ecosystems. Integrated Environmental Assessment and Management 10:69–77. TO CITE THIS ARTICLE Natalie Sopinka (2015) From Your Body to Theirs: How Exposure to Pharmaceuticals Is Altering Gene Expression in Fishes, Fisheries, 40:6, 292-292, DOI: 10.1080/03632415.2015.1038784 [/su_members]