Lei Yuan, Guo Jiahua, Chen Qiqi, Mo Jiezhang, Tian Yulu, Iwata Hisato, Song Jinxi
Shaanxi Key Laboratory of Earth Surface System and Environmental Carrying Capacity, College of Urban and Environmental Sciences, Northwest University, Xi'an 710127, China.
State Key Laboratory of Marine Pollution, Department of Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
Toxics. 2022 Feb 25;10(3):110. doi: 10.3390/toxics10030110.
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.
普伐他汀用于降低胆固醇和进一步降低血脂,在受污染的淡水中经常被检测到,而其对非目标水生无脊椎动物的长期暴露影响仍未确定。因此,本研究的目的是基于表型和全基因组转录组分析,评估浓度梯度为0、0.5、50、5000μg/L的普伐他汀(PRA)对模式水蚤大型溞(D. magna)在21天内的毒性作用。21天后,暴露于5000μg/L的PRA显著缩短了体长并增加了后代数量。分别在0.5、50和5000μg/L PRA处理组中,使用绝对log2倍数变化<1和校正p<0.05作为截止值,鉴定出76、167和499个差异表达基因(DEG)。暴露于PRA后,包括异源生物代谢、昆虫激素生物合成途径和能量代谢在内的三条途径显著(p<0.05)富集。这些表明,昆虫生物合成激素途径中基因的上调增加了保幼激素III的含量,这进一步缩短了大型溞的体长。法尼烯酸甲酯合成对卵巢的积极作用可能导致后代数量增加。此外,由于个体可用于维持和生长的能量有限,能量倾向于分配到解毒过程和应激条件下的生存。综上所述,我们的结果揭示了心血管和脂质药物在水生无脊椎动物中的毒性机制。