Department of Biology, Wilfrid Laurier University, 75 University Avenue West, Waterloo, Ontario, N2L 3C5 Canada.
Aquat Toxicol. 2009 Oct 4;94(4):265-74. doi: 10.1016/j.aquatox.2009.07.012. Epub 2009 Jul 23.
Although the pesticide, 3-trifluoromethyl-4-nitrophenol (TFM), has been extensively used to control invasive sea lamprey (Petromyzon marinus) populations in the Great Lakes, it is surprising that its mechanism(s) of toxicity is unresolved. A better knowledge of the mode of toxicity of this pesticide is needed for predicting and improving the effectiveness of TFM treatments on lamprey, and for risk assessments regarding potential adverse effects on invertebrate and vertebrate non-target organisms. We investigated two hypotheses of TFM toxicity in larval sea lamprey. The first was that TFM interferes with oxidative ATP production by mitochondria, causing rapid depletion of energy stores in vital, metabolically active tissues such as the liver and brain. The second was that TFM toxicity resulted from disruption of gill-ion uptake, adversely affecting ion homeostasis. Exposure of larval sea lamprey to 4.6 m gl(-1) TFM (12-h LC50) caused glycogen concentrations in the brain to decrease by 80% after 12h, suggesting that the animals increased their reliance on glycolysis to generate ATP due to a shortfall in ATP supply. This conclusion was reinforced by a 9-fold increase in brain lactate concentration, a 30% decrease in brain ATP concentration, and an 80% decrease in phosphocreatine (PCr) concentration after 9 and 12h. A more pronounced trend was noted in the liver, where glycogen decreased by 85% and ATP was no longer detected after 9 and 12h. TFM led to marginal changes in whole body Na(+), Cl(-), Ca(2+) and K(+), as well as in plasma Na(+) and Cl(-), which were unlikely to have contributed to toxicity. TFM had no adverse effect on Na(+) uptake rates or gill Na(+)/K(+)-ATPase activity. We conclude that TFM toxicity in the sea lamprey is due to a mismatch between ATP consumption and ATP production rates, leading to a depletion of glycogen in the liver and brain, which ultimately leads to neural arrest and death.
尽管农药 3-三氟甲基-4-硝基苯酚（TFM）已被广泛用于控制大湖地区的入侵海七鳃鳗（Petromyzon marinus）种群，但令人惊讶的是，其毒性机制仍未得到解决。为了预测和提高 TFM 处理海七鳃鳗的效果，并评估其对无脊椎动物和脊椎动物非目标生物的潜在不利影响，我们需要更好地了解这种农药的毒性模式。我们研究了 TFM 对幼海七鳃鳗的两种毒性假说。第一种假说认为，TFM 干扰线粒体氧化型 ATP 产生，导致肝脏和大脑等重要代谢活跃组织的能量储备迅速耗尽。第二种假说认为，TFM 毒性是由于鳃离子摄取受到干扰，从而对离子稳态产生不利影响。将幼海七鳃鳗暴露于 4.6mgl(-1)TFM（12hLC50）中 12 小时后，大脑中的糖原浓度下降了 80%，这表明由于 ATP 供应不足，动物增加了对糖酵解产生 ATP 的依赖。这一结论得到了进一步证实，因为大脑中的乳酸浓度增加了 9 倍，大脑中的 ATP 浓度下降了 30%，磷酸肌酸（PCr）浓度下降了 80%，在 9 小时和 12 小时后。在肝脏中观察到更为明显的趋势，其中糖原下降了 85%，9 小时和 12 小时后不再检测到 ATP。TFM 对全身 Na(+)、Cl(-)、Ca(2+)和 K(+)以及血浆 Na(+)和 Cl(-)的浓度仅有轻微影响，这不太可能导致毒性。TFM 对 Na(+)摄取率或鳃 Na(+)/K(+)-ATP 酶活性没有不良影响。我们得出结论，TFM 对海七鳃鳗的毒性是由于 ATP 消耗与产生率之间不匹配导致的，导致肝脏和大脑中的糖原耗尽，最终导致神经阻滞和死亡。
