Short communication
Transcriptomic effects of the non-steroidal anti-inflammatory drug
Ibuprofen in the marine bivalve Mytilus galloprovincialis Lam.
Vera L. Maria
a, b
,M
onica J.B. Amorim
b
, Maria Jo
~
ao Bebianno
a
, Francesco Dondero
c, *
a
CIMA, Faculty of Science and Technology, University of Algarve, 8005-139 Faro, Portugal
b
CESAM, Department of Biology, University of Aveiro, 3830-169 Aveiro, Portugal
c
Department of Science and Technological Innovation (DISIT), Universit a del Piemonte Orientale Amedeo Avogadro,15121 Alessandria, Italy
article info
Article history:
Received 28 April 2016
Received in revised form
4 May 2016
Accepted 5 May 2016
Available online 10 May 2016
Keywords:
Inflammation
Mitochondrion
Gene expression
Innate immunity
NF-kB
Chitinase
GM2 ganglioside activator
abstract
The transcriptomic effects of Ibuprofen (IBU) in the digestive gland tissue of Mytilus galloprovincialis Lam.
specimens exposed at low environmental concentrations (250 ng L
1
) are presented. Using a 1.7 K
feature cDNA microarray along with linear models and empirical Bayes statistical methods 225 differ-
entially expressed genes were identified in mussels treated with IBU across a 15-day period. Tran-
scriptional dynamics were typical of an adaptive response with a peak of gene expression change at day-
7 (177 features, representing about 11% of sequences available for analysis) and an almost full recovery at
the end of the exposure period. Functional genomics by means of Gene Ontology term analysis unraveled
typical mussel stress responses i.e. aminoglycan (chitin) metabolic processes but also more specific ef-
fects such as the regulation of NF-kB transcription factor activity.
© 2016 Elsevier Ltd. All rights reserved.
1. Introduction
Pharmaceutically-active compounds (PhACs) reach the aquatic
environment i.e. surface/ground water, rivers, lakes, effluents of
wastewater treatment plants and seawater as a result of diverse
anthropogenic actions (Richardson and Ternes, 2005). This
continuous flow of PhACs poses concerns in terms of the potential
toxicological consequences to non-target organisms (Fent et al.,
2006). The group of environmental PhACs include pain and fever
relieves, anti-inflammatory drugs, antibiotics, blood lipid regula-
tors, beta-blockers, antidepressants, antiepileptics, sex hormones
as well as anti-neoplastics and anti-tumor drugs (Gaw et al., 2014;
Richardson and Ternes, 2005). Ibuprofen (IBU) is among the most
consumed non-prescription medication worldwide (Mestre et al.,
2007). It belongs to the class termed non-steroidal anti-inflam-
matory drugs (NSAIDs) (Mestre et al., 2007). These drugs are used
to treat pain, fever and inflammation, mainly acting via the inhi-
bition of the cyclooxygenases (COX), resulting in lower levels of
prostaglandins and hence reducing the typical symptoms (Cryer
and Feldman, 1998).
The occurrence of IBU in surface waters ranges from 90 ng L
1
(river Rhine at Main, Germany) (Ternes, 1998) to 2370 ng L
1
(Tyne
estuary, England) (Thomas and Hilton, 2004) and to 2700 ng L
1
in
(Anoia river, Spain) (Ferrer et al., 2001). In waste water treatment
plant effluent it is easily found at ppm amounts (Pedrouzo et al.,
2007). More recently, a comprehensive review on the presence of
PhACs in seawater reported a IBU concentration range of
0.01e2370 ng L
1
(Gaw et al., 2014).
IBU effects in aquatic invertebrates was mainly assessed for sub-
lethal toxicity using either common ecotoxicological or biomarker
approaches (Contardo-Jara et al., 2011; Ericson et al., 2010; Fabbri
et al., 2014; Gonzalez-Rey and Bebianno, 2011, 2012; Matozzo
et al., 2012; Mezzelani et al., 2016; Parolini et al., 2009, 2011a,
2011b; Serrano et al., 2015). Nowadays, new techniques such as
transcriptomics offer a holistic viewpoint of the biological response
to environmental stressors in aquatic organisms (Waters and
Foster, 2004; Milan et al., 2013a). This technique provides a
systems-based unbiased approach for the development of bio-
markers able to respond to low realistic (environmental) contam-
inant concentrations. A transcriptomic assessment was successfully
applied in classical cellular model systems to evaluate possible
anticancer activity or cytotoxicity of IBU and/or similar drugs
* Corresponding author.
E-mail address: francesco.dondero@uniupo.it (F. Dondero).
Contents lists available at ScienceDirect
Marine Environmental Research
journal homepage: www.elsevier.com/locate/marenvrev
http://dx.doi.org/10.1016/j.marenvres.2016.05.010
0141-1136/© 2016 Elsevier Ltd. All rights reserved.
Marine Environmental Research 119 (2016) 31e39