The lampricide 3-trifluoromethyl-4-nitrophenol causes temporary metabolic disturbances in juvenile lake sturgeon (Acipenser fulvescens): implications for sea lamprey control and fish conservation

Abstract

The pesticide 3-trifluoromethyl-4-nitrophenol (TFM) is applied to rivers and streams draining into the Laurentian Great Lakes to control populations of invasive sea lamprey (Petromyzon marinus), which are ongoing threats to fisheries during the lamprey’s hematophagous, parasitic juvenile life stage. While TFM targets larval sea lamprey during treatments, threatened populations of juvenile lake sturgeon (Acipenser fulvescens), particularly young-of-the-year (<100 mm in length), may be adversely affected by TFM when their habitats overlap with larval sea lamprey. Exposure to TFM causes marked reductions in tissue glycogen and high energy phosphagens in lamprey and rainbow trout (Oncorhynchus mykiss) by interfering with oxidative ATP production in the mitochondria. To test that environmentally relevant concentrations of TFM would similarly affect juvenile lake sturgeon, we exposed them to the larval sea lamprey minimum lethal concentration (9-h LC99.9), which mimicked concentrations of a typical lampricide application and quantified energy stores and metabolites in the carcass, liver and brain. Exposure to TFM reduced brain ATP, PCr and glycogen by 50–60%, while lactate increased by 45–50% at 6 and 9 h. A rapid and sustained depletion of liver glucose and glycogen of more than 50% was also observed, whereas the respective concentrations of ATP and glycogen were reduced by 60% and 80% after 9 h, along with higher lactate and a slight metabolic acidosis (~0.1 pH unit). We conclude that exposure to environmentally relevant concentrations of TFM causes metabolic disturbances in lake sturgeon that can lead to impaired physiological performance and, in some cases, mortality. Our observations support practices such as delaying TFM treatments to late summer/fall or using alternative TFM application strategies to mitigate non-target effects in waters where lake sturgeon are present. These actions would help to conserve this historically and culturally significant species in the Great Lakes.

Niclosamide Is a Much More Potent Toxicant of Mitochondrial Respiration than TFM in the Invasive Sea Lamprey (Petromyzon marinus)

“…The EC 50 values of TFM and the TFM–niclosamide mixture were 40-fold and 60-fold greater than that of niclosamide alone at all three temperatures (Table ). These EC 50 values are reflective of whole-animal acute toxicity studies, where the concentrations of TFM known to cause mortality in the sea lamprey and nontarget fishes (e.g., 9–96 h LC 50 or LC 99.9 values) are typically 10 to 50 times greater than that of niclosamide. ,− The broad agreement in sensitivity to lampricides at both the mitochondrial (RCR) and whole animal (mortality) levels strongly support our conclusion that the greater potency of niclosamide compared to TFM is primarily due to events occurring at the level of the mitochondria.…”

“…At the level of the whole animal, TFM impairs the aerobic metabolism and correspondingly forces a greater reliance on anaerobic ATP production pathways such as glycolysis and high-energy phosphagens. ,,, For animals that survive exposure to lampricides, the temporary draining of the ATP pool may nevertheless lead to adverse outcomes such as decreased growth . Recent studies have shown that niclosamide has similar effects in the sea lamprey, rainbow trout, and lake sturgeon (Acipenser fulvescens), including depletion of glycogen and phosphocreatine reserves, increased lactate, and pronounced reductions in muscle intracellular pH. , Taken together, niclosamide appears to have a very similar mode of action in fishes and sea lamprey to that of TFM, but the effects of niclosamide result from concentrations that are less than 2% of those of TFM. , …”

“…41,50 Taken together, niclosamide appears to have a very similar mode of action in fishes and sea lamprey to that of TFM, but the effects of niclosamide result from concentrations that are less than 2% of those of TFM. 41,50 The exact electrochemical mechanism by which lampricides exert their uncoupling effects and thereby alter the mitochondrial proton motive force remains unclear. One hypothesis suggests that they act as protonophores as the relatively acidic intermembrane space promotes the formation of the lipophilic TFM-OH (or niclosamide-OH) that can diffuse into the matrix, where it is then deprotonated to TFM-O − or niclosamide-O − .…”

“…52 Recent studies have shown that niclosamide has similar effects in the sea lamprey, rainbow trout, and lake sturgeon (Acipenser fulvescens), including depletion of glycogen and phosphocreatine reserves, increased lactate, and pronounced reductions in muscle intracellular pH. 41,50 Taken together, niclosamide appears to have a very similar mode of action in fishes and sea lamprey to that of TFM, but the effects of niclosamide result from concentrations that are less than 2% of those of TFM. 41,50 The exact electrochemical mechanism by which lampricides exert their uncoupling effects and thereby alter the mitochondrial proton motive force remains unclear.…”