Trace-level Gabapentin can induce cardiovascular developmental toxicity through apoptosis in zebrafish larvae,Environmental Pollution

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Trace-level Gabapentin can induce cardiovascular developmental toxicity through apoptosis in zebrafish larvae
Environmental Pollution ( IF 7.6 ) Pub Date : 2024-07-09 , DOI: 10.1016/j.envpol.2024.124526
Yide He ₁ , Jun Hu ₁ , Rosa Freitas ₂ , Jie Gu ₃ , Guixiang Ji ₃ , Yongjun Zhang ₁

Affiliation

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.

中文翻译：

痕量加巴喷丁可通过斑马鱼幼虫细胞凋亡诱导心血管发育毒性

加巴喷丁（GBP）是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。之前的研究结果表明GBP可能对斑马鱼的心脏发育产生潜在的毒性，但其对心血管的影响仍不清楚。在当前的研究中，斑马鱼胚胎暴露于环境相关浓度（0、0.1、10和1000μg/L）的GBP中，以评估其在斑马鱼生命早期阶段对心血管系统的影响。接触英镑会导致心率和血流量增加。血管的发育也受到影响，在10μg/L和更高浓度的GBP下，血管宽度显着减小。 GBP 暴露通过抑制相关基因（flk1、vegfr-3、gata1、vegfα 和 vegfr-2）的表达导致血管发育异常。此外，0.1 μg/L 的 GBP 会提高活性氧和抗氧化酶的水平。 p53、bad和bcl2等基因促进血管细胞凋亡。然而，这些副作用可通过抗氧化剂 N-乙酰基-L-半胱氨酸逆转，这凸显了氧化损伤在 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后果途径提供了新的视角。

更新日期：2024-07-09

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