CIMAR/CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, Endocrine Disruptors and Emerging Contaminants Group, University of Porto, Matosinhos, Portugal.
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
J Toxicol Environ Health A. 2020 Feb 1;83(3):113-125. doi: 10.1080/15287394.2020.1733722. Epub 2020 Mar 2.
Simvastatin (SIM), a hypocholesterolaemic drug belonging to the statins group, is a widely prescribed pharmaceutical for prevention of cardiovascular diseases. Several studies showed that lipophilic statins, as SIM, cross the blood-brain barrier and interfere with the energy metabolism of the central nervous system in humans and mammalian models. In fish and other aquatic organisms, the effects of SIM on the brain energy metabolism are unknown, particularly following exposure to low environmentally relevant concentrations. Therefore, the present study aimed at investigating the influence of SIM on gene signaling pathways involved in brain energy metabolism of adult zebrafish () following chronic exposure (90 days) to environmentally relevant SIM concentrations ranging from 8 ng/L to 1000 ng/L. Real-time PCR was used to determine the transcript levels of several genes involved in different pathways of the brain energy metabolism (, and ). The findings here reported integrated well with ecological and biochemical responses obtained in a parallel study. Data demonstrated that SIM modulates transcription of key genes involved in the mitochondrial electron transport chain, in glucose transport and metabolism, in fatty acid synthesis and β-oxidation. Further, SIM exposure led to a sex-dependent transcription profile for some of the studied genes. Overall, the present study demonstrated, for the first time, that SIM modulates gene regulation of key pathways involved in the energy metabolism in fish brain at environmentally relevant concentrations.
辛伐他汀（SIM）是一种降脂药物，属于他汀类药物，是广泛用于预防心血管疾病的处方药物。多项研究表明，亲脂性他汀类药物，如 SIM，可穿过血脑屏障并干扰人类和哺乳动物模型中枢神经系统的能量代谢。在鱼类和其他水生生物中，SIM 对大脑能量代谢的影响尚不清楚，尤其是在接触低浓度的环境相关浓度后。因此，本研究旨在研究 SIM 对慢性暴露（90 天）于环境相关 SIM 浓度（8ng/L 至 1000ng/L）后的成年斑马鱼大脑能量代谢相关基因信号通路的影响。实时 PCR 用于测定参与大脑能量代谢不同途径的几种基因的转录水平（，和）。这里报告的结果与平行研究中获得的生态和生化反应很好地整合在一起。数据表明，SIM 调节参与线粒体电子传递链、葡萄糖转运和代谢、脂肪酸合成和β-氧化的关键基因的转录。此外，SIM 暴露导致一些研究基因的转录谱出现性别依赖性。总的来说，本研究首次表明，SIM 可调节环境相关浓度下鱼类大脑中参与能量代谢的关键途径的基因调控。
