The Effects of Aqueous Atorvastatin on Steroidogenesis of Xenopus laevis at Environmentally Relevant Concentrations
Statin drugs are a class of drug that work to reduce endogenous production of cholesterol by competitively inhibiting 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr) thus inhibiting production of mevalonic acid in the mevalonate pathway. Atorvastatin (Lipitor) is one of the most widely prescribed statin drugs and contamination of wastewater effluent is a growing environmental concern because of the potential to interfere with steroidogenesis in wildlife. Amphibians may be particularly susceptible to the effects of atorvastatin contamination because of their highly permeable integument. I used an amphibian model, Xenopus laevis to test the hypothesis that chronic exposure to low concentrations of atorvastatin in water has an adverse effect on steroid hormone levels, growth and development. This hypothesis was tested via a series of toxicity assays designed to evaluate potential endocrine disrupting effects of atorvastatin using traditional aquatic toxicology assays combined with modern molecular biology techniques to identify and report regulatory alteration of physiological pathways. Results indicated significant dose-dependent upregulation of steroidogenesis as confirmed by both qPCR and total RNA sequencing and supported by evidence of alteration of testosterone and estradiol concentrations. Such effects have the potential to significantly alter sex ratios in amphibian populations localized around wastewater effluent sites. This research provides insight into the potentially harmful effects of relatively low concentrations of aqueous atorvastatin.
atorvastatin, aquatic toxicology, xenopus laevis, Pharmacology, Toxicology and Environmental Health
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