Abstract
Pravastatin, used for lowering cholesterol and further decreasing blood lipid, has been frequently detected in the contaminated freshwaters, whereas its long-term exposure effects on non-target aquatic invertebrates remains undetermined. Therefore, the purpose of this study was to evaluate the toxic effects of pravastatin (PRA) with the concentration gradients (0, 0.5, 50, 5000 μg/L) on a model water flea Daphnia magna (D. magna) over 21 d based on phenotypic and genome-wide transcriptomic analyses. After 21 d, exposure to PRA at 5000 μg/L significantly reduced the body length and increased the number of offspring. The 76, 167, and 499 differentially expressed genes (DEGs) were identified by using absolute log2 fold change < 1 and adj p < 0.05 as a cutoff in the 0.5, 50, and 5000 μg/L PRA treatment groups, respectively. Three pathways, including xenobiotic metabolism, insect hormone biosynthesis pathway, and energy metabolism were significantly (p < 0.05) enriched after exposure to PRA. These suggested that the upregulation of genes in insect biosynthetic hormone pathway increased the juvenile hormone III content, which further reduced the body length of D. magna. The positive effect of methyl farnesoate synthesis on the ovarian may result in the increased number of offspring. Furthermore, energy tended to be allocated to detoxification process and survival under stress conditions, as the amount of energy that an individual can invest in maintenance and growth is limited. Taken together, our results unraveled the toxic mechanism of cardiovascular and lipid pharmaceuticals in aquatic invertebrate.
Highlights
Statins act as cholesterol-lowering drugs that inhibit HMG-CoA reductase through binding to the enzyme’s active site, which block the substrate product transition state of the enzyme in humans [1,2]
In accordance with our hypothesis, the energy metabolism related pathways such as protein digestion and absorption and pancreatic secretion were suppressed in D. magna treated with 5000 μg/L PRA, while insect hormone biosynthesis involved in the reproductive process was up-regulated in all PRA groups (Table 1)
To sum up, chronic exposure to PRA at all treatment groups remarkably reduced the body length of D. magna, and the number of newborns increased in the high PRA group
Summary
Statins act as cholesterol-lowering drugs that inhibit HMG-CoA reductase through binding to the enzyme’s active site, which block the substrate product transition state of the enzyme in humans [1,2]. Contrary to atorvastatin and simvastatin, pravastatin (PRA) possesses the highest stability and accounts for 25% of statin use on the market [3]. PRA entering the body cannot be fully absorbed and metabolized. Since conventional sewage treatment plants are not designed to remove these emerging contaminants, the unaltered statins in effluent are released into the aquatic environment [5,6]. Occurrence of statins (e.g., simvastatin) has been reported in surface water with the maximum concentration of 1.23 μg/L [7]. Concerns over the potentially adverse effects of statins on the aquatic ecosystem have been raised, especially for invertebrates with significant roles in the food chain [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
