Fluazinam is a pyridinamine fungicide that induces oxidative stress and mitochondrial damage in cells, and it has been reported to exhibit neurotoxicity. To characterize the biological effects of fluazinam, we assessed mitochondrial bioenergetics, dopamine system expression, and behavior of early life staged zebrafish (0.01 μM–0.5 μM). Fluazinam at environmentally-relevant levels did not induce sub-lethal effects in larvae, but at the LC₅₀ (0.5 μM), fluazinam decreased basal and ATP-linked respiration significantly in embryos. As mitochondria are directly related to redox homeostasis and apoptosis, the expression of genes related to oxidative stress and apoptosis were measured. Superoxide dismutase 2 (sod2), heat stock protein 70 (hsp70), bcl2-associated X protein (bax), and caspase 9 (casp9) mRNA levels were up-regulated by 0.5 μM fluazinam. Taken together, there is evidence for mitochondrial dysfunction and oxidative damage, only at the highest concentration of fluazinam (0.5 μM). As there are reports for fluazinam-induced neurotoxicity in dopamine synthesizing cells, transcriptional targets in the dopamine system were assessed in the zebrafish. Tyrosine hydroxylase 1 (th1) and dopamine receptor 2a (drd2a) were suppressed by 0.5 μM fluazinam, suggesting that this fungicide may affect the dopaminergic system. To further assess the potential for fluazinam-mediated neuromodulation, the dark photokinesis response was assessed in larvae following exposure. Larvae exposed to 0.1 μM fluazinam showed hyperactivity, while larvae exposed to 0.2 and 0.3 μM showed hypo-activity. This study demonstrates that fluazinam disrupts mitochondrial bioenergetics in zebrafish, potentially leading to an oxidative stress response, and aberrant behaviors in larvae that are dose dependent.

Fluazinam是一种嘧啶胺类杀菌剂，可诱导细胞中的氧化应激和线粒体损伤，并且据报道具有神经毒性。为了表征氟喹嗪的生物学效应，我们评估了线粒体的生物能，多巴胺系统的表达以及生命早期斑马鱼（0.01 μM–0.5μM）的行为。在环境相关水平的氟齐南并没有在幼虫中诱导亚致死作用，但是在LC ₅₀（0.5μM）时，氟齐南显着降低了胚胎的基础呼吸和与ATP相关的呼吸作用。由于线粒体与氧化还原稳态和细胞凋亡直接相关，因此测量了与氧化应激和细胞凋亡相关的基因的表达。小号uperoxide氧化物歧化酶2（SOD2），热股票蛋白70（hsp70），与bcl2相关的X蛋白（bax）和半胱天冬酶9（casp9）mRNA水平被0.5μMfluazinam上调。综上所述，仅在氟喹那南的最高浓度（0.5μM）下，才有线粒体功能障碍和氧化损伤的证据。由于有报道称氟齐南对多巴胺合成细胞具有神经毒性，因此在斑马鱼中评估了多巴胺系统中的转录靶点。酪氨酸羟化酶1（th1）和多巴胺受体2a（drd2a）被0.5μM氟嗪南抑制，表明该杀菌剂可能会影响多巴胺能系统。为了进一步评估氟喹酰胺介导的神经调节的潜力，在暴露后评估幼虫的黑暗光动力反应。暴露于0.1μM氟喹嗪的幼虫表现出高活性，而暴露于0.2和0.3μM的幼虫表现出低活性。这项研究表明，氟哌西那破坏了斑马鱼中的线粒体生物能，可能导致氧化应激反应以及幼虫的异常行为，这些行为与剂量有关。