Environmentally relevant concentrations of aqueous atorvastatin produce alterations in cholesterol biosynthesis and gene expression patterns in Xenopus laevis

Aquat Toxicol. 2024 Feb 5;269:106856. doi: 10.1016/j.aquatox.2024.106856. Online ahead of print.ABSTRACTNumerous studies report active pharmaceutical compounds detected in both wastewater effluent and surface waters. Exposure to statin drugs in general, and atorvastatin in particular, is likely to be a concern. We hypothesized that chronic exposure to low concentrations of atorvastatin in water would result in an adverse effect on production of steroids regulating growth and development of the model amphibian Xenopus laevis. The FETAX assay was used to evaluate the effects of a range of doses of atorvastatin on developing embryos. A 60 day metamorphosis assay assessed the effects of aqueous atorvastatin exposure at environmentally concentrations on metamorphosing tadpoles. A 60 day chronic flow-through exposure evaluated the effects of chronic low concentrations of atorvastatin on adults. The purpose of the FETAX assay was to confirm that atorvastatin can reduce circulating cholesterol in X. laevis with a similar manner to that expected in humans. The results of the 60-day flow-through exposure on metamorphosing tadpoles showed significant evidence of altered cholesterol biosynthesis. The dose-dependent increase in cyp19a1 expression also indicated that the steroidogenesis pathway was affected. The RNAseq analysis confirmed that exposure to environmentally relevant concentrations of atorvastatin does cause significant alterations to global transcriptional profiles in a manner...
Source: Aquatic Toxicology - Category: Toxicology Authors: Source Type: research