title: Transcriptional and cellular effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in experimentally exposed mussels, Mytilus galloprovincialis.
abstract: The aim of the present investigation was to provide new insights on accumulation and possible adverse effects of various non-steroidal anti-inflammatory drugs (NSAIDs) in mussels, Mytilus galloprovincialis, exposed to an environmentally realistic concentration (0.5μg/L) of individual compounds, Acetaminophen (AMP), Diclofenac (DIC), Ibuprofen (IBU), Ketoprofen (KET) or Nimesulide (NIM). The measurement of drugs in mussel tissues was integrated with both functional alterations at cellular level and transcriptomic responses. Results indicated the capability of mussels to accumulate DIC and NIM, while AMP, IBU and KET were always below detection limit. A large panel of ecotoxicological biomarkers revealed the early onset of alterations induced by tested NSAIDs on immunological responses, lipid metabolism and DNA integrity. The gene transcription analysis through DNA microarrays, supported cellular biomarker results, with clear modulation of a large number of genes involved in the arachidonic acid and lipid metabolism, immune responses, cell cycle and DNA repair. The overall results indicated an ecotoxicological concern for pharmaceuticals in M. galloprovincialis, with transcriptional responses appearing as sensitive exposure biomarkers at low levels of exposure: such changes, however, are not always paralleled by corresponding functional effects, suggesting caution when interpreting observed effects in terms of perturbed cellular pathways. Fascinating similarities can also be proposed in the mode of action of NSAIDs between bivalves and vertebrate species.
authors: Dipartimento di Scienze della Vita e dell'Ambiente (DiSVA), Università Politecnica delle Marche, Ancona, Italy.
authors: M
authors: M
authors: Mezzelani
authors: Dipartimento di Scienze della Vita e dell'Ambiente (DiSVA), Università Politecnica delle Marche, Ancona, Italy.
authors: S
authors: S
authors: Gorbi
authors: Dipartimento di Scienze della Vita e dell'Ambiente (DiSVA), Università Politecnica delle Marche, Ancona, Italy.
authors: D
authors: D
authors: Fattorini
authors: Dipartimento di Scienze della Vita e dell'Ambiente (DiSVA), Università Politecnica delle Marche, Ancona, Italy.
authors: G
authors: G
authors: d'Errico
authors: Dipartimento di Scienze della Vita e dell'Ambiente (DiSVA), Università Politecnica delle Marche, Ancona, Italy.
authors: M
authors: M
authors: Benedetti
authors: Dipartimento di Biomedicina Comparata e Alimentazione (BCA), Università di Padova, Italy.
authors: M
authors: M
authors: Milan
authors: Dipartimento di Biomedicina Comparata e Alimentazione (BCA), Università di Padova, Italy.
authors: L
authors: L
authors: Bargelloni
authors: Dipartimento di Scienze della Vita e dell'Ambiente (DiSVA), Università Politecnica delle Marche, Ancona, Italy; CoNISMa, Consorzio Interuniversitario per le Scienze del Mare, Roma, Italy. Electronic address: f.regoli@univpm.it.
authors: F
authors: F
authors: Regoli
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D049878:Mytilus / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D018675:Toxicity Tests; D059467:Transcriptome / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D014874:Water Pollutants, Chemical
keywords: Bioaccumulation; Biomarkers; DNA-microarray; Marine mussels; Non-Steroidal anti-Inflammatory drugs