MS-222, the most widely used anaesthetic in fish, has been shown to induce embryotoxic effects in zebrafish. However, the underlying molecular effects are still elusive. This study aimed to investigate the effects of MS-222 exposure during early developmental stages by evaluating biochemical and molecular changes. Embryos were exposed to 50, 100 or 150 mg L⁻¹ MS-222 for 20 min at one of three developmental stages (256-cell, 50% epiboly, or 1–4 somite stage) and oxidative-stress, cell proliferation and apoptosis-related parameters were determined at two time-points (8 and 26 hpf). Following exposure during the 256-cell stage, the biochemical redox balance was not affected. The genes associated with glutathione homeostasis (gstpi and gclc) were affected at 8 hpf, while genes associated with apoptosis (casp3a and casp6) and cellular proliferation (pcna) were found affected at 26 hpf. An inverted U-shaped response was observed at 8 hpf for catalase activity. After exposure at the 50% epiboly stage, the gclc gene associated with oxidative stress was found upregulated at 8 hpf, while gstpi was downregulated and casp6 was upregulated later on, coinciding with a decrease in glutathione peroxidase (GPx) activity and a non-monotonic elevation of protein carbonyls and casp3a. Additionally, MS-222 treated embryos showed a decrease in DCF-staining at 26 hpf. When exposure was performed at the 1–4 somite stage, a similar DCF-staining pattern was observed. The activity of GPx was also affected whereas RT-qPCR showed that caspase transcripts were dose-dependently increased (casp3a, casp6 and casp9). The pcna mRNA levels were also found to be upregulated while gclc was changed by MS-222. These results highlight the impact of MS-222 on zebrafish embryo development and its interference with the antioxidant, cell proliferation and cellular death systems by mechanisms still to be explained; however, the outcomes point to the Erk/Nrf2 signalling pathway as a target candidate.

MS-222是鱼类中使用最广泛的麻醉剂，已显示出在斑马鱼中诱导胚胎毒性作用。但是，潜在的分子效应仍然难以捉摸。这项研究旨在通过评估生化和分子变化来研究MS-222暴露在发育早期的影响。胚胎在三个发育阶段之一（256细胞，50％外表皮或1-4松果期）之一暴露于50、100或150 mg L ^-1 MS-222中，持续20分钟，氧化应激，细胞增殖和凋亡在两个时间点（8和26 hpf）确定了相关参数。在256细胞阶段暴露后，生化氧化还原平衡不受影响。与谷胱甘肽稳态相关的基因（gstpi和gclc）在8 hpf时受到影响，而与凋亡相关的基因（casp3a和casp6）和细胞增殖（pcna）在26 hpf时受到影响。在8hpf观察到过氧化氢酶活性的倒U形反应。在暴露于50％外显子期后，发现与氧化应激相关的gclc基因在8 hpf时被上调，而gstpi被下调，而casp6在以后被上调，这与谷胱甘肽过氧化物酶（GPx）活性降低和非单调蛋白羰基和casp3a的升高。此外，MS-222处理的胚胎在26 hpf时显示DCF染色降低。当在1-4步步兵阶段进行曝光时，观察到类似的DCF染色图案。GPx的活性也受到影响，而RT-qPCR显示caspase转录物呈剂量依赖性增加（casp3a，casp6和casp9）。的PCNA还发现mRNA水平被上调，而GCLC通过MS-222改变。这些结果突出了MS-222对斑马鱼胚胎发育的影响及其对抗氧化剂，细胞增殖和细胞死亡系统的干扰，其机制尚待阐明。但是，结果表明Erk / Nrf2信号通路是目标候选人。