Oxidative Stress and Cell Signaling Research Group, Interdisciplinary Research Center on Biotechnology - CIPBIOTEC, Universidade Federal do Pampa, São Gabriel, Brazil.
Biochemistry Post-Graduation Program, Universidade Federal do Pampa, Uruguaiana, Brazil.
Drug Chem Toxicol. 2023 May;46(3):575-587. doi: 10.1080/01480545.2022.2069802. Epub 2022 May 2.
Mancozeb (MZ), a manganese/zinc containing ethylene-bis-dithiocarbamate, is a broad-spectrum fungicide. Chronic exposure to MZ has been related to several organisms' neurological, hormonal, and developmental disorders. However, little is known about the post-natal effects of developmental exposure to MZ. In this study, was subjected to a pre-imaginal (eggs-larvae-pupae stage) model of exposure to MZ at 0.1 and 0.5 mg/mL. The emergence rate, body size, locomotor performance, sleep patterns, and molecular and biochemical parameters were evaluated in post-emerged flies. Results demonstrate that pre-imaginal exposure to MZ significantly impacted early emerged flies. Additionally, reduced progeny viability, smaller body size and delaying in emergence period, locomotor impairment, and prolonged sleep time were observed. Content of glucose, proteins, and triglycerides were altered, and the bioenergetics efficiency and oxidative phosphorylation at complex I were inhibited. mRNA stade state levels of genes responsive to stress, metabolism, and regulation of circadian cycle (Nrf2, p38, Hsp83, Akt1, GPDH, tor, per, tim, dILP2, and dILP6) were augmented, pointing out to stimulation of antioxidant defenses, insulin-dependent signaling pathway activation, and disruption of sleep regulation. These data were followed by increased lipid peroxidation and lower glutathione levels. In addition, the activity of catalase and glutathione-S-transferase were induced, whereas superoxide dismutase was inhibited. Together, these results demonstrate that developmental exposure to MZ formulation led to phenotype and behavioral alterations in young flies, possibly related to disruption of energetic metabolism, oxidative stress, and deregulation of genes implied in growth, sleep, and metabolism.
代森锰锌（MZ）是一种含有锰和锌的乙撑双二硫代氨基甲酸盐，是一种广谱杀菌剂。慢性暴露于 MZ 已与几种生物体的神经、激素和发育障碍有关。然而，对于发育过程中暴露于 MZ 的后期影响知之甚少。在这项研究中，研究人员采用了一种预蛹期（卵-幼虫-蛹期）暴露于 MZ 的模型，暴露浓度分别为 0.1 和 0.5mg/ml。在新羽化的果蝇中评估了羽化率、体型、运动表现、睡眠模式以及分子和生化参数。结果表明，预蛹期暴露于 MZ 显著影响早期羽化的果蝇。此外，还观察到子代存活率降低、体型较小、羽化期延迟、运动障碍和睡眠时间延长。葡萄糖、蛋白质和甘油三酯的含量发生改变，生物能效率和复合物 I 的氧化磷酸化受到抑制。与应激、代谢和生物钟节律调节相关的基因（Nrf2、p38、Hsp83、Akt1、GPDH、tor、per、tim、dILP2 和 dILP6）的 mRNA 水平升高，表明抗氧化防御、胰岛素依赖性信号通路激活和睡眠调节破坏。这些变化伴随着脂质过氧化增加和谷胱甘肽水平降低。此外，过氧化氢酶和谷胱甘肽-S-转移酶的活性被诱导，而超氧化物歧化酶的活性受到抑制。总之，这些结果表明，发育过程中暴露于 MZ 制剂会导致幼蝇出现表型和行为改变，这可能与能量代谢、氧化应激和与生长、睡眠和代谢相关的基因失调有关。
