Comparative effects of parathion and chlorpyrifos on endocannabinoid and endocannabinoid-like lipid metabolites in rat striatum

Abstract

Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems. While substantial information is known about the eCBs, less is known about a number of endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N-oleoylethanolamine, OEA). We report the comparative effects of parathion and chlorpyrifos on AChE and enzymes responsible for inactivation of the eCBs, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and changes in the eCBs AEA and 2AG and eCBLs PEA and OEA, in rat striatum. Adult, male rats were treated with vehicle (peanut oil, 2 ml/kg, sc), parathion (27 mg/kg) or chlorpyrifos (280 mg/kg) 6-7 days after surgical implantation of microdialysis cannulae into the right striatum, followed by microdialysis two or four days later. Additional rats were similarly treated and sacrificed for evaluation of tissue levels of eCBs and eCBLs. Dialysates and tissue extracts were analyzed by LC-MS/MS. AChE and FAAH were extensively inhibited at both time-points (85-96%), while MAGL activity was significantly but lesser affected (37-62% inhibition) by parathion and chlorpyrifos. Signs of toxicity were noted only in parathion-treated rats. In general, chlorpyrifos increased eCB levels while parathion had no or lesser effects. Early changes in extracellular AEA, 2AG and PEA levels were significantly different between parathion and chlorpyrifos exposures. Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications.

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

“…FAAH in the brain hydrolyzes palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), 2 other PPAR agonists (Leishman et al, 2016). Inhibition of FAAH led to increased PEA and OEA in rat brain (Liu, Parsons, et al, 2015), which could further alter PPAR signaling if these metabolites are altered in trout following CPF exposure. Other studies have reported that CPF alters expression of transcription factors (AP1 and Sp-1) in the developing brain of neonatal rats, indicating that CPF interferes with brain development through transcription factors involved in cell replication and differentiation (Crumpton et al, 2000).…”

Recent Advances in Sensing Applications of Molecularly Imprinted Photonic Crystals

“…Parathion is a kind of broad-spectrum pesticide, which could be harmful to the nervous, reproductive, endocrine, and immune systems (Liu et al, 2015 ; Trinder et al, 2016 ). Zhang X. et al ( 2017 ) fabricated a gold doped imprinted inverse opal PhC (IO PC) for the fast determination of parathion as shown in Figure 3A .…”

The Use of Intracerebral Microdialysis to Elucidate Environmentally Induced Neurotoxic Mechanisms

“…These workers concluded that delayed treatment with these drugs was effective in reducing acetylcholine elevation, seizure activity, and neuropathology. Liu, Parsons, and Pope (2015) compared the effects of parathion and chlorpyrifos on striatal acetylcholinesterase and endocannabinoids using striatal microdialysis and liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. Endocannabinoids are endogenous neuromodulators that regulate presynaptic neurotransmitter release in central and peripheral neurons.…”