Niclosamide Effects on Rainbow Trout

Niclosamide (2′,5-dichloro-4′-nitrosalicylanalide) is a piscicide used to control invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes. It is also a molluscide used in tropical and sub-tropical freshwaters to control snail populations that are intermediate hosts to the blood flukes that causes schistosomiasis in humans. While the mechanism of niclosamide toxicity is known, its corresponding physiological effects on non-target fishes are not well-established. To better understand how niclosamide could adversely affect non-target fishes, rainbow trout (Oncorhynchus mykiss) were exposed to an environmentally relevant niclosamide concentration of 0.150 mg L􀀀 1 (measured = 0.12–0.18 mg L􀀀 1) over 9 h, during which tissues were collected for measurement of energy stores and metabolites. Niclosamide exposure reduced brain ATP and glycogen by ~50 %, and liver glycogen by ~40 %. Reductions of ATP, phosphocreatine and glycogen were also observed in muscle, with corresponding increases in pyruvate and lactate, plus development of a metabolic acidosis (~0.2 unit decrease in intracellular pH). These disturbances were consistent with impaired mitochondrial oxidative phosphorylation and greater reliance on anaerobic glycolysis to generate ATP. Notably, physiological homeostasis was restored in the brain, liver, and muscle within 24 h after depuration in fresh, niclosamide-free water. We conclude that nontarget fishes are susceptible to niclosamide, but at least in rainbow trout, the effects are readily reversed after exposure ceases. Similar approaches could be used to determine the susceptibility and resilience of other fishes to niclosamide in environments where it is required as a either a lampricide or a molluscicide.氯硝柳胺（Niclosamide，化学名2′,5-二氯-4′-硝基水杨酰苯胺）是一种杀鱼剂（piscicide），用于防控圣劳伦斯五大湖中的入侵性海七鳃鳗（Petromyzon marinus）。它同时也是杀软体动物剂（molluscide），在热带及亚热带淡水水域中用于控制作为人类血吸虫病中间宿主的螺类种群。尽管氯硝柳胺的毒性作用机制已明确，但其对非靶标鱼类的相应生理效应尚未得到充分阐明。 为进一步阐明氯硝柳胺对非靶标鱼类的潜在不良影响，本研究将虹鳟（Oncorhynchus mykiss）暴露于环境相关浓度（0.150 mg·L⁻¹，实测浓度为0.12–0.18 mg·L⁻¹）的氯硝柳胺溶液中9小时，期间采集组织样本以检测能量储备与代谢物水平。 结果显示，氯硝柳胺暴露使虹鳟大脑的三磷酸腺苷（adenosine triphosphate, ATP）和糖原含量降低约50%，肝脏糖原含量降低约40%。肌肉组织中同样观测到ATP、磷酸肌酸（phosphocreatine）及糖原含量的下降，伴随丙酮酸（pyruvate）与乳酸（lactate）水平升高，同时出现代谢性酸中毒（metabolic acidosis，细胞内pH降低约0.2个单位）。这些代谢紊乱与线粒体氧化磷酸化（mitochondrial oxidative phosphorylation）功能受损、机体更依赖无氧糖酵解（anaerobic glycolysis）生成ATP的现象一致。 值得注意的是，在转移至不含氯硝柳胺的新鲜水中净化（depuration）24小时后，大脑、肝脏及肌肉的生理稳态（physiological homeostasis）均得以恢复。本研究表明，非靶标鱼类对氯硝柳胺易感，但至少在虹鳟中，暴露终止后其受影响的生理状态可快速逆转。后续可采用类似研究方法，评估其他鱼类在需要将氯硝柳胺作为杀七鳃鳗剂（lampricide）或杀软体动物剂的环境中的易感性与恢复能力。