Effects of Chlorpyrifos on Cholinesterase and Serine Lipase Activities and Lipid Metabolism in Brains of Rainbow Trout (Oncorhynchus mykiss)

Abstract

Chlorpyrifos is an organophosphorus insecticide that elicits acute toxicity through inhibition of acetylcholinesterase (AChE), leading to acetylcholine accumulation and prolonged stimulation of cholinergic receptors throughout the central and peripheral nervous systems. Previous studies have indicated that neurodevelopment may also be impaired through alternative pathways, including reduction of cyclic adenosine monophosphate (cAMP)-catalyzed downstream events. The upstream initiating events that underlie noncholinergic neurological actions of chlorpyrifos and other organophosphorus compounds remain unclear. To investigate the potential role of fatty acid signaling disruption as a mechanism of toxicity, lipid metabolism and fatty acid profiles were examined to identify alterations that may play a critical role in upstream signaling in the central nervous system (CNS). Juvenile rainbow trout were treated for 7 days with nominal chlorpyrifos concentrations previously reported to diminish olfactory responses (10, 20, and 40 μg/l). Although lethality was noted higher in doses, measured chlorpyrifos concentrations of 1.38 μg/l (nominal concentration 10 μg/l) significantly reduced the activity of AChE and two serine lipases, monoacylglycerol lipase, and fatty acid amide hydrolase in the brain. Reductions in lysophosphatidylethanolamines (16:0, 18:0, 18:1, and 22:6) derived from the phosphatidylethanolamines and free fatty acids (palmitic acid 16:0, linolenic acid 18:3, eicosadienoic acid 20:2, arachidonic acid 20:4, and docosahexaenoic acid 22:6) were also noted, suggesting that chlorpyrifos inhibited the metabolism of select phospholipid signaling precursors at sublethal concentrations. These results indicate that in addition to AChE inhibition, environmentally relevant chlorpyrifos exposure alters serine lipase activity and lipid metabolites in the trout brain, which may compromise neuronal signaling and impact neurobehavioral responses in aquatic animals.

Metabolomic Profiles in the Brains of Juvenile Steelhead (Oncorhynchus mykiss) Following Bifenthrin Treatment

“…Decreased levels of several lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) metabolites were found in steelhead exposed to the higher concentration of bifenthrin and were predicted to alter inflammatory response pathways (Figure B). Decreased concentrations of LPE (16:0) were previously reported in the brains of rainbow trout treated with 1.38 μg/L chlorpyrifos, with significant differences at nearly every carbon length. The top canonical pathway in the brains of Atlantic salmon dietarily exposed to 8 mg/kg chlorpyrifos-methyl was inflammation .…”

“…DHA makes up 40% of the polyunsaturated fatty acids (PUFAs) in the brain where it is highly concentrated in neuronal membranes . Chlorpyrifos, an organophosphorus pesticide that is a potent irreversible inhibitor of acetylcholinesterase activity in nerve cells, was reported to decrease DHA levels in the brains of exposed rainbow trout and was associated with olfactory impairment . DHA, also acting as the primary ligand for the activation of the retinoid X receptor (RXR), was a top canonical pathway predicted to be affected in chlorpyrifos-methyl-exposed Atlantic salmon (Salmo salar). − Increased RXR receptor activation may alter lipid metabolism and inflammatory responses .…”

The Use of Non-targeted Lipidomics and Histopathology to Characterize the Neurotoxicity of Bifenthrin to Juvenile Rainbow Trout (Oncorhynchus mykiss)

“…Similar reductions of TGs were observed in the brains of rainbow trout treated with 1.38 μg/L chlorpyrifos. 39 Atlantic salmon hepatocytes exposed to a mixture of chlorpyrifos-methyl, pirimiphos-methyl, and nonylphenol at a concentration of 100 μM also had a significantly reduced abundance of TGs. 40 There was an upregulation in lipase ( lipe ) mRNA expression reported in chlorpyrifos-exposed hepatocytes, which has a prominent role in the hydrolysis of TGs.…”

“… 62 Chlorpyrifos treatments (1.38 μg/L) in rainbow trout for 7 days did not have significantly altered levels of PC in brain tissue, with only a slight decrease in PE levels being reported. 39 An imbalance between levels of PE and PC in the brain is the major driver of motor neuron survival, which has implications for the incidence of neuronal disease 60 and may be a contributing factor to bifenthrin-induced neurotoxicity, as previous studies have reported that other fishes residing within the Delta, such as inland silversides ( Menidia beryllina ) and Delta smelt ( Hypomesus transpacificus ), exposed to bifenthrin have induced neurobehavioral effects, which could potentially have population-level consequences. 63 − 65 Alterations in PC and PE levels may be related to increased levels of fatty acids that are stored as TGs in lipid droplets within the cell, comprising a monolayer of phospholipids, 40 and known to be present in higher numbers in vacuole membranes.…”

In Silico Studies of Lamiaceae Diterpenes with Bioinsecticide Potential against Aphis gossypii and Drosophila melanogaster

“…Acetylcholinesterase (AChE) inhibition is the main mechanism of action of organophosphates [ 71 , 72 , 73 ]. The enzyme is essential and necessary for hydrolysis of the neurotransmitter acetylcholine (ACh), and plays a fundamental role in controlling synaptic transmission in all animals; hydrolyzing acetylcholine to end its synaptic action [ 74 , 75 , 76 ].…”