Abstract：
Gabapentin (GBP), an antiepileptic drug to treat epilepsy and neuropathic pain, has become an emerging pollutant in aquatic environments. Previous results suggested that GBP can cause a potential toxicity on the heart development of zebrafish but its cardiovascular effects are still not clear. In the current study, zebrafish embryos were exposed to GBP at environmental relevant concentrations (0, 0.1, 10 and 1000 μg/L) to assess its impact on cardiovascular systems during the early life stage of zebrafish. GBP exposure induced an increase in heartbeat rate and blood flow. The development of blood vessels was also affected with the vascular width significantly decreased at 10 μg/L and higher concentration of GBP. GBP exposure led to an abnormal vascular development by inhibiting the expression of relevant genes (flk1, vegfr-3, gata1, vegfα, and vegfr-2). Furthermore, GBP at 0.1 μg/L elevated the levels of reactive oxygen species and antioxidant enzyme. The vascular cell apoptosis was promoted through genes like p53, bad, and bcl2. However, these adverse effects were reversible with the antioxidant N-acetyl-L-cysteine, highlighting the crucial role of oxidative damage in GBP induced vascular toxicity. This research offers new perspectives on the adverse outcome pathways of antiepileptic drugs in non-target aquatic organisms.
摘要：
加巴喷丁（GBP），一种治疗癫痫和神经性疼痛的抗癫痫药物，已成为水生环境中的新兴污染物。先前的结果表明，GBP可以对斑马鱼的心脏发育造成潜在的毒性，但其对心血管的影响尚不清楚。在目前的研究中,斑马鱼胚胎暴露于环境相关浓度（0、0.1、10和1,000μg/L）的GBP，以评估其对斑马鱼早期生命阶段心血管系统的影响。GBP暴露导致心跳速率和血流量增加。在10μg/L和更高浓度的GBP下，血管宽度显着降低，血管的发育也受到影响。GBP暴露通过抑制相关基因（flk1，vegfr-3，gata1，vegfα，和vegfr-2）。此外，0.1μg/L的GBP升高了活性氧和抗氧化酶的水平。血管细胞凋亡是通过p53、bad、和bcl2。然而,这些副作用是可逆的抗氧化剂N-乙酰-L-半胱氨酸，强调氧化损伤在GBP诱导的血管毒性中的关键作用。这项研究为抗癫痫药物在非靶标水生生物中的不良结局途径提供了新的视角。
