School of Environmental Science and Engineering, Nanjing Tech University, Jiangsu, 211816, PR China.
School of Environmental Science and Engineering, Nanjing Tech University, Jiangsu, 211816, PR China.
Environ Pollut. 2021 Oct 15;287:117649. doi: 10.1016/j.envpol.2021.117649. Epub 2021 Jun 24.
Gabapentin-lactam (GBP-L) is a transformation product (TP) of gabapentin (GBP), a widely used anti-epileptic pharmaceutical. Due to its high persistence, GBP-L has been frequently detected in the surface water. However, the effects of GBP-L on aquatic organisms have not been thoroughly investigated. In the present study, zebrafish (Danio rerio) embryos as a model organism were used to study the impacts of GBP-L in terms of embryos LC, spontaneous movement at 24 hpf (hours post fertilization), heartbeat rates at 48 hpf, and body length at 72 hpf, with the concentrations of GBP-L down to 0.01 μg/L, covering its environmental concentrations. Various biomarkers from nervous, antioxidant and immune systems of zebrafish larvae were analyzed, including acetylcholinesterase, acetylcholine, dopamine, gamma-aminobutyric acid, superoxide dismutase, catalase, glutathione S-transferase, C reactive protein, and lysozyme, to assess its toxicity on these systems. RT-qPCR was then used to further verify the results and explain the toxicological mechanism at the gene level. The results demonstrated that GBP-L is much more toxic than its parent compound, and could lead to adverse impacts on the aquatic organisms even at every low concentrations.
加巴喷丁-内酰胺(GBP-L)是加巴喷丁(GBP)的转化产物(TP),GBP 是一种广泛应用的抗癫痫药物。由于其高持久性,GBP-L 已在地表水经常被检测到。然而,GBP-L 对水生生物的影响尚未得到彻底研究。在本研究中,斑马鱼(Danio rerio)胚胎被用作模型生物,以研究 GBP-L 在胚胎 LC、24 hpf(受精后小时)自发运动、48 hpf 心率和 72 hpf 体长方面的影响,GBP-L 的浓度低至 0.01μg/L,涵盖其环境浓度。分析了来自斑马鱼幼虫神经系统、抗氧化系统和免疫系统的各种生物标志物,包括乙酰胆碱酯酶、乙酰胆碱、多巴胺、γ-氨基丁酸、超氧化物歧化酶、过氧化氢酶、谷胱甘肽 S-转移酶、C 反应蛋白和溶菌酶,以评估其对这些系统的毒性。然后使用 RT-qPCR 进一步验证结果并从基因水平解释毒理学机制。结果表明,GBP-L 比其母体化合物毒性更大,即使在每低浓度下也可能对水生生物产生不良影响。