Statins: An undesirable class of aquatic contaminants?

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Santos, MM (Author) FCUP; Ruivo, R (Author) Other; Lopes Marques, M (Author) Other; Torres, T (Author) Other; de los Santos, CB (Author) Other; Filipe F C Castro (Author) FCUP; Neuparth, T (Author) Other

Journal

Title: Aquatic Toxicology

Vol. 174

Pages: 1-9

ISSN: 0166-445X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 58 Citations

Scopus - 64 Citations

Other information

Authenticus ID: P-00K-6M5

DOI: 10.1016/j.aquatox.2016.02.001

Abstract (EN): Emerging pollutants, such as pharmaceuticals, may pose a considerable environment risk. Hypocholesterolaemic drugs such as statins are among the most prescribed human pharmaceuticals in western European countries. In vertebrates, this therapeutic class disrupts the cholesterol synthesis by inhibiting the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), responsible for the limiting step in the mevalonate pathway. Recently, functional studies have shown that statins competitively inhibit HMGR in vertebrates and arthropods, two taxa that have diverged over 450 million years ago. Importantly, chronic simvastatin exposure disrupts crustacean reproduction and development at environmentally relevant concentrations. Hence, a fundamental question emerges: what is the taxonomic scope of statins-induced HMGR inhibition across metazoans? Here, we address this central question in a large sampling of metazoans using comparative genomics, homology modelling and molecular docking. Sequence alignment of metazoan HMGRs allowed the annotation of highly conserved catalytic, co-factor and substrate binding sites, including residues highjacked for statin binding. Furthermore, molecular docking shows that the catalytic domains of metazoan HMGRs are highly conserved regarding interactions, not only with HMG-CoA, but also with both simvastatin and atorvastatin, the top prescribed statins in Europe and USA. Hence, the data indicates that both statins are expected to competitively inhibit metazoan's HMGRs, and therefore all metazoan taxa might be at risk. The environmental relevance of these findings are discussed and research priorities established. We believe that the conceptual framework used in this study can be applied to other emerging pollutants and assist in the design of toxicity testing and risk assessment.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9