Toxic effects of acute and chronic atorvastatin exposure on antioxidant systems, autophagy processes, energy metabolism and life history in Daphnia magna

Atorvastatin (ATV) is a representative for hypolipidemic pharmaceuticals and is widely detectable in aquatic environments around the world. However, there are limited studies on the potential effects of ATV on aquatic non-target organisms, especially on aquatic invertebrates. In the present study, the model organism, Daphnia magna was used to investigate the responses of antioxidant system, autophagy process and energy metabolism under the acute exposure of ATV (24 h–96 h), and the changes of physiological parameters of D. magna in response to chronic ATV exposure (21 d) was addressed as well. The results showed that ATV caused oxidative stress in D. magna and elevated activities of antioxidant enzymes (SOD, GST, GPx, and TrxR) at 48 h. However, the progressively increasing oxidative pressure eventually suppressed antioxidant capacities and triggered the transcriptional autophagy process in organism under the regulation of Sestrin as well as its regulated genes (P62, LC3, ATG1, and ATG4B). ATV also altered the expression of DNA methylation related genes. Unlike the clinical response, we found acute ATV exposure led to lipid accumulation in D. magna, affecting energy metabolism. Chronic exposure of higher concentration of ATV (50, 500 μg L⁻¹) adversely affected growth and reproduction parameters of D. magna, caused delayed molting, reduced body length, and decreased number and delayed time of neonates production. Lethal effects were observed in the 5000 μg L⁻¹ of ATV. The present study investigated the toxic effects and mechanisms of acute and chronic ATV exposure on D. magna to provide a scientific basis for evaluating the potential ecological risks of statins on aquatic invertebrates.