RT Journal Article
SR Electronic
T1 Chronic environmentally relevant levels of Simvastatin induces non-monotonic responses in Zebrafish (<em>Danio rerio</em>)
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 289694
DO 10.1101/289694
A1 Susana Barros
A1 Rosa Montes
A1 José Benito Quintana
A1 Rosario Rodil
A1 Ana André
A1 Ana Capitão
A1 Joana Soares
A1 Miguel M. Santos
A1 Teresa Neuparth
YR 2018
UL http://biorxiv.org/content/early/2018/03/27/289694.abstract
AB Simvastatin (SIM), a hypocholesterolaemic compound, is among the most prescribed pharmaceuticals for cardiovascular disease prevention worldwide. Several studies have shown that acute exposure to SIM is able to produce multiple adverse effects in aquatic organisms. However, uncertainties still remain regarding the chronic effects of SIM in aquatic ecosystems. Therefore, the present study aimed to investigate the effects of SIM in the model freshwater teleost zebrafish (Danio rerio) following a chronic exposure (90 days) to environmentally relevant concentrations ranging from 8 ng/L to 1000 ng/L. This study used a multi-parametric approach integrating distinct ecological-relevant endpoints, i.e. survival, growth, reproduction and embryonic development, with biochemical markers (cholesterol and triglycerides). Furthermore, Real Time PCR was used to analyse the transcription levels of key genes involved in the mevalonate pathway (hmgcra, cyp51, and dhcr7). Globally, SIM induced several non-monotonic dose-responses; embryonic development, biochemical and molecular markers, were significantly impacted in the low-intermediate concentrations, 40 ng/L and 200 ng/L, whereas no effects were recorded for the highest tested SIM levels (1000 ng/L). Taken together, these findings expand our understanding of statins effects in teleost’s, demonstrating significant impacts at environmentally relevant concentrations. The findings highlight the importance of addressing the effects of chemicals under chronic low-level concentrations.HighlightsSeveral uncertainties exist regarding simvastatin mode of action in non-target organismsThis work integrates D. rerio multi-level responses after long-term exposure to simvastatinSimvastatin impacted cholesterol/triglycerides levels and transcript levels of genes related to mevalonate pathway.Parental exposure to simvastatin induced offspring embryonic malformations.Embryonic abnormalities, biochemical and molecular data did follow a non-monotonic curve.