Paraoxon, the main active metabolite of the organophosphorus insecticide parathion, exerted a dose-dependent inhibitory effect on the activity of pig kidney (Na+ + K+)-ATPase contained in microsomal fraction and purified from it. Substrate kinetics studies revealed the existence of two active sites with high and low affinity to ATP. The Dixon analysis of the mode of the inhibition indicated its...

Central cholinergic overstimulation results in prolonged seizures of status epilepticus in humans and experimental animals. Cellular mechanisms of underlying seizures caused by cholinergic stimulation remain uncertain, but enhanced glutamatergic transmission is a potential mechanism. Paraoxon, an organophosphate cholinesterase inhibitor, enhanced glutamatergic transmission on hippocampal granul...

The effect of competing elimination pathways on the metabolic and excretory clearance estimates was examined with tracer concentrations of [(3)H]enalapril, which was both metabolized and excreted by the rat kidney. Perturbation was achieved with use of the carboxylesterase inhibitor paraoxon, which inhibited [(3)H]enalapril metabolism to [(3)H]enalaprilat in rat renal S9 fraction. At 0.1, 0.5, ...

Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vi...

In order to develop a new strategy for the detection and discrimination of neurotoxins, the competing anti-acetylcholinesterase activities of mixtures of different neurotoxins were investigated. The combined inhibition effects in mixtures of organophosphates and carbamates (such as paraoxon/carbaryl, diisopropyl fluorophosphate (DFP)/carbaryl, paraoxon/DFP/carbaryl) were different than what was...

Cholesterol cycles between free cholesterol (unesterified) found predominantly in membranes and cholesteryl esters (CEs) stored in cytoplasmic lipid droplets. Only free cholesterol is effluxed from macrophages via ATP-binding cassette (ABC) transporters to extracellular acceptors. Carboxylesterase 1 (CES1), proposed to hydrolyze CEs, is inactivated by oxon metabolites of organophosphorus pestic...

Introduction: Paraoxon is the neurotoxic metabolite of organophosphorus (OP) insecticide parathion and causes acute toxicity by inhibition of acetylcholinesterase (AChE). AChE inhibition leads to the accumulation of acetylcholine in cholinergic synapses and hence results in an overstimulation of the cholinergic system. Reports on changes in the level of γamino butyric acid (GABA) during OP-indu...

Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+) measur...

Introduction: Paraoxon (the neurotoxic metabolite of organophosphorus (OP) insecticide, parathion) exerts acute toxicity by inhibition of acetylcholinesterase (AChE), leading to the accumulation of acetylcholine in cholinergic synapses and hence overstimulation of the cholinergic system. Since, reports on changes in the level of γ- amino butyric acid (GABA) during OP-induced convulsion have bee...

Paralysis of skeletal muscles, which can lead to paralysis of respiratory muscles and death, is one of the most toxic effects of organophosphates (OPs), and oximes are the only available antidotes that can reverse or prevent such toxic effects. In the present study, the possible reversal or preventive effect of different concentrations of obidoxime (toxogonin) on changes induced by paraoxon (as...