Oxidative Stress and Cell Signaling Research Group, Interdisciplinary Center for Biotechnology Research - CIPBIOTEC, Campus São Gabriel, Universidade Federal do Pampa, São Gabriel, RS 97300-000, Brazil.
Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
Neurotoxicol Teratol. 2018 Jul-Aug;68:1-12. doi: 10.1016/j.ntt.2018.04.003. Epub 2018 Apr 14.
Mancozeb (MZ), a manganese/zinc-containing ethylene-bis-dithiocarbamate (EBCD) fungicide has been claimed to present low acute toxicity and short environmental persistence, however, its effects on embryogenesis in non-target organisms is unclear. Here, we used zebrafish embryos (5 hpf) to assess the potential embryotoxic effects induced by MZ (up to 72 hpf) as well as the role of reactive oxygen species (ROS) in this process by pre-treatment with a classical antioxidant (N-acetylcysteine, NAC). Markers of reactive oxygen species production (ROS), glutathione (GSH) levels and glutathione S-transferase (GST) activity were measured along with genotoxicity (comet assay), cell death (Acridine Orange) and behavioral parameters (spontaneous movement, touch stimulation and swimming response), in order to determine potential mechanisms of embryotoxicity. According to results, MZ was able to induce morphological abnormalities such as body axis distortion, DNA damage, cell death, increased ROS generation and changes in behavioral endpoints during zebrafish development. All these toxic effects were inhibited by the pre-treatment with NAC indicating a key role of redox unbalance during MZ-induced embryotoxicity. At least in our knowledge, this is the first report on the deleterious effect of MZ to the normal embryogenesis of zebrafish. In addition, the importance of ROS generation during this pathophysiological condition was highlighted.
代森锰锌（MZ）是一种含锰/锌的乙撑双二硫代氨基甲酸盐（EBCD）杀菌剂，据称其具有低急性毒性和短时间环境持久性，但它对非目标生物胚胎发生的影响尚不清楚。在这里，我们使用斑马鱼胚胎（5 hpf）来评估 MZ（直至 72 hpf）诱导的潜在胚胎毒性效应，以及通过预处理经典抗氧化剂（N-乙酰半胱氨酸，NAC）在这个过程中活性氧（ROS）的作用。我们测量了活性氧（ROS）产生的标志物、谷胱甘肽（GSH）水平和谷胱甘肽 S-转移酶（GST）活性，以及遗传毒性（彗星试验）、细胞死亡（吖啶橙）和行为参数（自发运动、触摸刺激和游泳反应），以确定胚胎毒性的潜在机制。结果表明，MZ 能够诱导斑马鱼发育过程中的形态异常，如体轴扭曲、DNA 损伤、细胞死亡、ROS 生成增加和行为终点改变。所有这些毒性作用都被 NAC 的预处理所抑制，表明在 MZ 诱导的胚胎毒性中氧化还原失衡起着关键作用。至少就我们所知，这是关于 MZ 对斑马鱼正常胚胎发生的有害影响的首次报道。此外，还强调了在这种病理生理条件下 ROS 生成的重要性。
