Introduction: Parathion is an organophosphate compound that is frequently used as an insecticide. Paraoxon, the metabolic product of parathion, is reported to inhibit GABA uptake by rat cerebral cortex synaptosomes. The aim of this study is to investigate possible mechanism(s) underlying inhibitory effect of paraoxon on GABA uptake, in synaptosomes prepared from rat cerebral cortex.Methods: After preparation of synaptosomes kinetic studies were performed for determining the effect of paraoxon on Km and Vmax of GABA uptake. Acetylcholine and antagonists (atropine and mecamylamine) were used for evaluating cholinergic dependency of GABA uptake. Type of GABA transporter involved was determined by using glial (beta-alanine) and neuronal (L-DABA) GABA uptake inhibitors.Results: The results of the study showed that paraoxon significantly decreased Vmax (175.2±4.23 vs. 80.4±2.03 pmol/mg protein/min, P<0.001) of GABA uptake while had no effect on its Km (9.80±1.02 vs. 9.09±0.92μM in paraoxon and control groups respectively). DABA significantly decreased GABA uptake (P<0.001) while beta-alanine had no effect. Moreover, acetylcholine had no effect on GABA uptake. Furthermore, neither atropine nor mecamylamine could reverse the inhibitory effect of paraoxon on GABA uptake.Conclusion: In conclusion, present data suggests that paraoxon antagonizes kinetics of GABA uptake in nerve endings in a non-competitive manner. We also can conclude that the inhibitory effect of paraoxon on GABA uptake by rat cerebral synaptosomes is cholinergic-independent.

Introduction: The acute toxicity effect of OP is due to the inhibition of acetylcholinesterase (AChE), which occurs in the central nervous system of most animals, including humans. Investigations show that different classes of pesticides, including OPs, may induce in vitro and in vivo generation of reactive oxygen species (ROS). In physiological conditions, a balance exists between production and elimination of ROS. The purpose of this study was to evaluate post exposure oxidative stress in the brain of rat due to paraoxon.Methods: Male Wistar rats (200-250g) were randomly divided into five groups including: control, sham (corn oil), and three groups receiving different doses (0.1LD50, 0.5LD50, LD50) of paraoxon (ip injection). Four hours after injection, animals were anesthetized by ether and were decapitated. The brain was quickly removed and transferred to liquid nitrogen.Results: Paraoxon, dose dependently, induced AChE inhibition. Furthermore, paraoxon increased the activity of superoxide dismutase, catalase and decreased the level of glutathione. malondialdehyde concentration didn't change following paraoxon intoxication.Conclusion: present study shows that paraoxon induces elevation in the production of free radicals and oxidative stress. Elevation of catalase and superoxide dismutase activity and reduction in the level of glutathione indicate that first line of body defense is activated.

Diazinon is one of the most widely used organophosphates in agriculture.Toxic effects of diazinon are due to the inhibition of acetylcolinesterase, an enzyme needed for proper nervous system function. Investigates show that different classes of Ops may induce the production of free radicals and initiate lipid peroxidation leading to cell death, if the antioxidant system is impaired. The purpose of this study was to evaluate the effects of on diazinon oxidantantioxidant system in the kidney of rat.In this study, Wistar rats (150-250 g body wt.) were randomly divided into five groups including: control, sham (corn oil) and three of groups of diazinon receiving different doses (30, 50 and 100 mg/kg) by intraperitoneal injection only once. 7 rats in each group were killed after 24 hours of exposure. The kidney of each groups were removed and the enzyme activities of superoxide dismutase (SOD) and catalase (CAT) as well as glutathione (GSH) and malondialdehyde (MDA) levels were determined by biochemical methods.The results show that at concentrations higher than 30 mg/kg diazinon, the enhanced activities of CAT and SOD no change in MDA level was observed. The GSH level was significantly decreased. The data suggest that diazinon induces the production of free radicals and oxidative stress. The enhanced activity of antioxidant enzymes and depleted GSH content is indicative of oxidative tissue injury.

Organophosphate neurotoxicity is attributed both to their well-known cholinergic and non-cholinergic effects. In present study we compared enzymatic and morphologic changes in neurons exposed to paraoxon. Also we studied the effect of MK-801 as an antagonism of NMDA receptor and search for neuroprotective effect of MK-801.Hippocampal cells were obtained from rat neonates and cultured in Neurobasal/B27. Paraoxon with dose of 100μM was added and the exposure time was 48 hrs. The neurons were treat with MK-801 (1 μM) 15 min prior to paraoxon. Invert, electron microscopy and neurocytochemistery staining of Map-2 were used to study cell morphology. The MTS staining was used to measure viability.The results indicate that paraoxon reduced the viability and also reduced the neurite of cells and induced apparent blebs on the surface neurons, treatment of MK-801 15 min prior to paraoxon also indeuced more reduction in viability. The area of cells reduced after exposure to paraoxon and MK-801. Also there were not repair in blebs and cell neuritis after treatment with MK-801. In conclusion MK-801 did not represent neuro protection against paraoxon (100 μM) for 48 hrs exposure.

INTRODUCTION: PARAOXON (POX) IS AN ACTIVE METABOLITE OF THE ORGANOPHOSPHATE PESTICIDE PARATHION THAT WIDELY USED IN AGRICULTURE, INDUSTRY AND MEDICINE. LEPTIN (LP) ACTS PRIMARILY ON HYPOTHALAMIC CENTERS TO REGULATE FOOD INTAKE AND ENERGY EXPENDITURE. LEPTIN AND PARAOXON INCREASE THE GENERATION OF REACTIVE OXYGEN SPECIES (ROS)…