The anti-lipidemic drug simvastatin modifies epigenetic biomarkers in the amphipod Gammarus locusta

• Published in: Ecotoxicology and environmental safety Vol. 209; p. 111849
• Main Authors: Alves, Nélson, Neuparth, Teresa, Barros, Susana, Santos, Miguel M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.02.2021; Elsevier
• Subjects: Adaptation; Amphipoda - drug effects; Amphipoda - physiology; Animals; Biomarkers - metabolism; CCAAT-Enhancer-Binding Proteins - metabolism; CCAAT-Enhancer-Binding Proteins - pharmacology; DNA Methylation; Emerging pollutants; Environmental Exposure; Epigenesis, Genetic; Guidelines; Pharmaceutical Preparations; Regulation; Simvastatin - toxicity; Transgenerational; Ubiquitin-Protein Ligases - metabolism; Ubiquitin-Protein Ligases - pharmacology; Ubiquitin-Specific Peptidase 7 - metabolism; Water Pollutants, Chemical - toxicity; Regulation; Transgenerational; Emerging pollutants; Adaptation; Guidelines
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2020.111849

The adverse effects of certain environmental chemicals have been recently associated with the modulation of the epigenome. Although changes in the epigenetic signature have yet to be integrated into hazard and risk assessment, they are interesting candidates to link environmental exposures and altered phenotypes, since these changes may be passed across multiple non-exposed generations. Here, we addressed the effects of simvastatin (SIM), one of the most prescribed pharmaceuticals in the world, on epigenetic regulation using the amphipod Gammarus locusta as a proxy, to support its integration into hazard and environmental risk assessment. SIM is a known modulator of the epigenome in mammalian cell lines and has been reported to impact G. locusta ecological endpoints at environmentally relevant levels. G. locusta juveniles were exposed to three SIM environmentally relevant concentrations (0.32, 1.6 and 8 µg L−1) for 15 days. Gene transcription levels of selected epigenetic regulators, i.e., dnmt1, dmap1, usp7, kat5 and uhrf1 were assessed, along with the quantification of DNA methylation levels and evaluation of key ecological endpoints: survival and growth. Exposure to 0.32 and 8 µg L−1 SIM induced significant downregulation of DNA methyltransferase 1 (dnmt1), concomitant with global DNA hypomethylation and growth impacts. Overall, this work is the first to validate the basal expression of key epigenetic regulators in a keystone marine crustacean, supporting the integration of epigenetic biomarkers into hazard assessment frameworks. •Validating new biomarkers of epigenetic modifications in the amphipod Gammarus locusta.•Simvastatin disrupted growth, transcription of key epigenetic modulators and DNA methylation.•Transcription of dnmt1, dmap1 and global DNA methylation as new biomarkers of epigenetics.•The genes involved in regulation of epigenetic machinery should be included in chemical risk assessment frameworks.