Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-11-02 , DOI: 10.1016/j.etap.2020.103522 D. Rebelo , A.T. Correia , B. Nunes
Due to their wide use, pharmaceuticals can be discarded, metabolized and excreted into the environment, potentially affecting aquatic organisms. Lipid-regulating drugs are among the most prescribed medications around the world, to control human cholesterol levels, in more than 20 million patients. Despite this massive use of lipid-regulating drugs, particularly simvastatin, the role of these drugs is not fully characterized and understood in terms of its potential toxicological effects at the environmental level. This work intended to characterize the toxicity of an acute (120 h post-fertilization) and chronic (60 days) exposure to the antihyperlipidemic drug simvastatin (in concentrations of 92.45, 184.9, 369.8, 739.6 and 1479.2 ng L−1), in the freshwater species zebrafish (Danio rerio). The concentrations hereby mentioned were implemented in both exposures, and were based on levels found in wastewater treatment plant influents (11.7 ± 3.2 μg L−1), effluents (2.65 ± 0.8 μg L−1) and Apies River (1.585 ± 0.3 μg L−1), located in Pretoria, South Africa and, particularly in the maximum levels found in effluents from wastewater treatment plants in Portugal (369.8 ng L−1). The acute effects were analysed focusing on behavioural endpoints (erratic and purposeful swimming), total distance travelled and swimming time), biomarkers of oxidative stress (the activities of the enzymes superoxide dismutase, catalase, glutathione peroxidase), biotransformation (the activity of glutathione S-transferases) and lipid peroxidation (levels of thiobarbituric acid reactive substances). Animals chronically exposed were also histologically analysed for sex determination and gonadal developmental stages identification. In terms of acute exposure, significant alterations were reported in terms of behavioural alterations (hyperactivity), followed by a general reduction in all tested biomarkers. Also, the analysis of chronically exposed fish evidenced no alterations in sex ratio and maturation stages. In addition, the analysis of chronically exposed fish evidenced no alterations in terms of sexual characteristics, suggesting that the chronic exposure of Danio rerio to simvastatin does not alter the sex ratio and maturation stages of individuals. This assumption suggests that simvastatin did not act as an endocrine disruptor. Moreover, the metabolism, neuronal interactions and the antioxidant properties of SIM seem to have modulated the hereby-mentioned results of toxicity. Results from this assay allow inferring that simvastatin can have an ecologically relevant impact in living organisms.
中文翻译:
环境实际浓度辛伐他汀在达尼奥雷里奥的急性和慢性影响:氧化变化和内分泌破坏活性的证据
由于其用途广泛,因此可以丢弃,代谢和排泄到环境中,从而可能影响水生生物。调节血脂的药物是全世界控制2000年患者胆固醇水平最高的处方药之一。尽管大量使用调脂药物,尤其是辛伐他汀,但这些药物的作用尚未得到充分表征,也无法从其在环境水平上的潜在毒理学作用来理解。这项工作旨在表征抗高血脂药物辛伐他汀(浓度为92.45、184.9、369.8、739.6和1479.2 ng L -1)急性(受精后120小时)和慢性(60天)暴露的毒性。淡水斑马鱼(Danio rerio)。此处提到的浓度在两次暴露中均已实施,并且基于废水处理厂进水(11.7± 3.2μgL -1),废水(2.65± 0.8μgL -1)和Apies River(1.585±0.3μgL -1),位于南非比勒陀利亚,尤其是葡萄牙废水处理厂的废水中发现的最高浓度(369.8 ng L -1)。分析了急性影响,重点关注行为终点(不稳定和有目的的游泳),总旅行距离和游泳时间),氧化应激的生物标志物(超氧化物歧化酶,过氧化氢酶,谷胱甘肽过氧化物酶的活性),生物转化(谷胱甘肽S的活性) -转移酶)和脂质过氧化(硫代巴比妥酸反应性物质的水平)。长期暴露的动物也进行了组织学分析,以确定性别和性腺发育阶段。就急性暴露而言,据报道在行为改变(多动性)方面有重大改变,随后所有测试的生物标志物普遍减少。而且,对长期暴露的鱼类的分析表明,性别比和成熟阶段没有改变。此外,Danio rerio到辛伐他汀不会改变个体的性别比和成熟阶段。该假设表明辛伐他汀没有充当内分泌干扰物。而且,SIM的代谢,神经元相互作用和抗氧化特性似乎已经调节了本文提到的毒性结果。该测定的结果可以推断辛伐他汀可以对活生物体产生与生态相关的影响。