Ionescu R Adrian, Mitrovic Dejana, Wilkie Michael P
Department of Biology & Laurier Institute for Water Science, 75 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada.
Department of Biology & Laurier Institute for Water Science, 75 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada.
Aquat Toxicol. 2022 Jan;242:106006. doi: 10.1016/j.aquatox.2021.106006. Epub 2021 Oct 22.
Since the 1960s, chemical control of larval sea lamprey has been achieved using the pesticides 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide (Bayluscide®). Much more potent, niclosamide is often used as an adjuvant for TFM, and on its own to treat lentic habitats, rivers with high discharge and currents, and for population surveys. Yet, little is known about its mode of action or physiological effects on sea lamprey. Like TFM, niclosamide is thought to impair mitochondrial ATP production by uncoupling oxidative phosphorylation. We therefore tested the hypothesis that niclosamide would result in metabolic perturbations and disturbances to acid-base balance in larval lamprey due to their need to balance ATP supply with ATP demands. When larval sea lamprey were exposed to the nominal 9-h niclosamide LC (0.11 mg L) over 9 h, it resulted in significant decreases in brain, phosphocreatine (35 %) and glycogen (50 %), accompanied by a 5-fold increase in lactate. In carcass, there were 25-30 % decreases in glycogen, corresponding increases in pyruvate and lactate, and a pronounced 0.5 unit decrease in intracellular pH. Calculation of the NAD/NADH ratio in the carcass indicated that neither oxygen delivery nor the flux of reducing equivalents through the mitochondrial electron transport chain were impaired by niclosamide, supporting the hypothesis that niclosamide interferes with mitochondrial ATP production by uncoupling oxidative phosphorylation. Thus, greater reliance on glycogen, characterized by higher rates of glycolysis, temporarily mitigates the corresponding shortfall in ATP supply caused by niclosamide. Notably, all lamprey that survived niclosamide exposure readily restored ATP, phosphocreatine, glycogen and acid-base balance after recovery in niclosamide-free water. This resilience suggests that sea lamprey that survive or escape niclosamide treatment could compromise sea lamprey control efforts by subsequently completing their larval stage and developing into parasitic juvenile sea lamprey that could ultimately threaten Great Lake's fisheries populations.
自20世纪60年代以来，使用农药3-三氟甲基-4-硝基苯酚（TFM）和氯硝柳胺（贝螺杀®）实现了对海七鳃鳗幼体的化学控制。氯硝柳胺的效力更强，常被用作TFM的佐剂，也单独用于处理静水栖息地、流量和水流较大的河流以及进行种群调查。然而，人们对其作用方式或对海七鳃鳗的生理影响知之甚少。与TFM一样，氯硝柳胺被认为通过解偶联氧化磷酸化来损害线粒体ATP的产生。因此，我们检验了这样一个假设：由于幼体七鳃鳗需要平衡ATP供应与需求，氯硝柳胺会导致其代谢紊乱和酸碱平衡失调。当幼体海七鳃鳗在9小时内暴露于名义浓度为9小时的氯硝柳胺LC（0.11毫克/升）时，脑内磷酸肌酸（减少35%）和糖原（减少50%）显著降低，同时乳酸增加了5倍。在鱼体中，糖原减少了25%-30%，丙酮酸和乳酸相应增加，细胞内pH值明显下降了0.5个单位。对鱼体中NAD/NADH比值的计算表明，氯硝柳胺既不影响氧气输送，也不影响还原当量通过线粒体电子传递链的通量，这支持了氯硝柳胺通过解偶联氧化磷酸化干扰线粒体ATP产生的假设。因此，以更高的糖酵解速率为特征，对糖原的更大依赖暂时缓解了氯硝柳胺导致的ATP供应相应短缺。值得注意的是，所有在氯硝柳胺暴露中存活下来的七鳃鳗在无氯硝柳胺的水中恢复后，都能迅速恢复ATP、磷酸肌酸、糖原和酸碱平衡。这种恢复能力表明，在氯硝柳胺处理中存活或逃脱的海七鳃鳗随后完成幼体阶段并发育成寄生性幼体海七鳃鳗，最终可能威胁五大湖的渔业种群，从而可能破坏海七鳃鳗的控制工作。
