The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
Arzu Ersöz - One of the best experts on this subject based on the ideXlab platform.
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Ligand exchange and MIP-based Paraoxon memories onto QCM sensor
Applied Physics A, 2015Co-Authors: Ebru Birlik Özkütük, Sibel Emir Diltemiz, Elif Özalp, Lokman Uzun, Arzu ErsözAbstract:In this study, we have aimed to prepare quartz crystal microbalance (QCM) sensor using Paraoxon-imprinted particles. Firstly, methacryloyl antipyrine (MAAP)-based metal–chelate-coordinated pre-complex has been prepared and used for Paraoxon templation. Then, Paraoxon-imprinted nanofilms were formed on QCM sensor after modification of the gold surfaces with allyl mercaptan. By this way, specific and selective memories, which depend on metal–chelate interactions between Eu(III) ions and template, for Paraoxon molecules have been obtained on the electrode surface. QCM sensor has characterized using AFM and ellipsometer. The detection limit and the affinity constant have found to be 0.09 μM and 5.71 × 103 M−1 for MAAP–Eu Paraoxon-based nanofilm, respectively. The specificity of the QCM sensor has shown using parathion as a competitor molecule.
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Paraoxon imprinted biopolymer based QCM sensor
Materials Chemistry and Physics, 2013Co-Authors: Ebru Birlik Özkütük, Sibel Emir Diltemiz, Elif Özalp, Tevfik Gedikbey, Arzu ErsözAbstract:Abstract In this study, a novel quartz crystal microbalance (QCM) based on the modification of Paraoxon imprinted polymer (TCM-Cd(II)-Paraoxon) film onto a quartz crystal sensor has been developed for the determination of Paraoxon. The sensor is based on a molecular imprinted polymer (MIP) which can be synthesized using Paraoxon as a template molecule, Thiourea Modified Chitosan-Cd(II) (TCM-Cd(II)) as the metal-chelate monomer, ephychlorohydrin as a crosslinking agent. The MIP particles have been characterized by FTIR measurements and QCM sensor has characterized using AFM and ellipsometer. The performance of the Paraoxon imprinted sensor has indicated that a selective and sensitive Paraoxon imprinted sensor could be fabricated. The sensor is able to discriminate Paraoxon in solution owing to the specific binding of the imprinted sites. The obtained Paraoxon imprinted sensor has 0.02–1 μM linear range and low detection limit (0.02 μM). The selectivity studies have shown that the selectivity of prepared Paraoxon imprinted sensor has found as being very high in the presence of parathion which is similar in structure with Paraoxon. The Paraoxon imprinted sensor has been repeatedly used for more than 7 months in many continuous experiments.
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Ligand exchange based Paraoxon imprınted QCM sensor.
Materials science & engineering. C Materials for biological applications, 2012Co-Authors: Ebru Birlik Özkütük, Sibel Emir Diltemiz, Elif Özalp, Rıdvan Say, Arzu ErsözAbstract:Abstract In the present work, a Paraoxon imprinted QCM sensor has been developed for the determination of Paraoxon based on the modification of Paraoxon imprinted film onto a quartz crystal combining the advantages of high selectivity of the piezoelectric microgravimetry using MIP film technique and high sensitivity of QCM detection. The Paraoxon selective memories have formed on QCM electrode surface by using a new metal–chelate interaction based on pre-organized monomer and the Paraoxon recognition activity of these molecular memories was investigated. Molecular imprinted polymer (MIP) film for the detection of Paraoxon was developed and the analytical performance of Paraoxon imprinted sensor was studied. The molecular imprinted polymer were characterized by FTIR measurements. Paraoxon imprinted sensor was characterized with AFM and ellipsometer. The study also includes the measurement of binding interaction of Paraoxon imprinted quartz crystal microbalance (QCM) sensor, selectivity experiments and analytical performance of QCM electrode. The detection limit and the affinity constant (K affinity ) were found to be 0.06 μM and 2.25 × 10 4 M − 1 for Paraoxon [MAAP–Cu(II)–Paraoxon] based thin film, respectively. Also, it has been observed that the selectivity of the prepared Paraoxon imprinted sensor is high compared to a similar chemical structure which is parathion.
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Imprinted polymer/organo-smectite nanocomposites for Paraoxon hydrolysis
Applied Clay Science, 2009Co-Authors: Murat Erdem, Rıdvan Say, Arzu Ersöz, Adil Denizli, Hayrettin TürkAbstract:Abstract We have used the imprinting technique to create a polymer/organo-smectite nanocomposite catalyst. The aim was preparing a synthetic enzyme which shows high selectivity for Paraoxon hydrolysis. Paraoxon imprinted polymer/organo-smectite composites (PIPO) and non-imprinted polymer/organo-smectite composites (NIPO) were prepared using methacryloylhistidine-Cu2+ (MAH-Cu(II)) and [2-methacryloyloxy)ethyl]dimethylhexadecylammonium bromide] (MOEDMAC16) modified smectite. These nanocomposites were applied as a catalyst in the hydrolysis of Paraoxon which is an organophosphate ester and used as a pesticide. The catalytic activity of these composites was evaluated according to the enzyme kinetics model of Michaelis–Menten. PIPO showed better catalytic activity than NIPO. In addition, the Paraoxon imprinted nanocomposite had greater catalytic activity (based on kcat/Km values) for Paraoxon hydrolysis by a factor of 391 compared to that of parathion hydrolysis.
Alireza Asgari - One of the best experts on this subject based on the ideXlab platform.
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Synaptosomal GABA uptake decreases in Paraoxon-treated rat brain
Toxicology, 2007Co-Authors: Moslem Mohammadi, Asghar Ghasemi, Ali Khoshbaten, Esmaeel Ghani, Alireza AsgariAbstract:Abstract A synaptosomal model was used to evaluate in vivo effects of Paraoxon on the uptake of [ 3 H]GABA in rat cerebral cortex and hippocampus. Male Wistar rats were given a single intraperitoneal injection of one of three doses of Paraoxon (0.1, 0.3, or 0.7 mg/kg) and acetylcholinesterase (AChE) activity in the plasma, cerebral cortex, and hippocampus was measured at 30 min, 4 h, and 18 h after exposure. [ 3 H]GABA uptake in synaptosomes was also studied in another series of animals. Paraoxon administration (0.3 and 0.7 mg/kg) caused significant inhibition of AChE activity in the plasma and both brain areas at all time points. 0.1 mg/kg Paraoxon significantly inhibited AChE activity but only in the plasma for 4 h, the activity was completely recovered at 18 h. GABA uptake was significantly ( p l -DABA, an inhibitor of neuronal GABA transporter, allowed us to conclude that the uptake was mediated primarily by neuronal GABA transporter GAT-1. In conclusion, present data suggests that GABA uptake by synaptosomes decreases probably secondary to Paraoxon-induced seizure activity.
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Forskolin potentiates the Paraoxon-induced hyperexcitability in snail neurons by blocking afterhyperpolarization.
Neurotoxicology, 2007Co-Authors: Jafar Vatanparast, Mahyar Janahmadi, Alireza AsgariAbstract:One characteristic of organophosphate poisoning is the ability to increase excitability or induce epileptiform activity in nerve cells, but underlying mechanisms are not fully understood. We have previously reported that Paraoxon, an organophosphate compound, at submicromolar concentrations effectively suppress Ca(2+) spikes and modulate the activity of snail neurons. This effect was unrelated to acetylcholinesterase (AChE) inhibition but was found to involve the direct or indirect modulation of ion channels [Vatanparast J, Janahmadi M, Asgari AR, Sepehri H, Haeri-Rohani A. Paraoxon suppresses Ca(2+) spike and afterhyperpolarization in snail neurons: relevance to the hyperexcitability induction. Brain Res 2006a;1083(1):110-7]. In the present study, the interaction of Paraoxon with cAMP formation on the modulation of Ca(2+) spikes and neuronal excitability was examined. Forskolin, the activators of adenylate cyclase, suppressed afterhyperpolarization (AHP) and increased the activity of snail neurons without any significant effect on the Ca(2+) spike duration. Pretreatment with forskolin, although attenuated the suppressing effect of Paraoxon on the duration of Ca(2+) spikes but also potentiated the Paraoxon-induced hyperexcitability by enhancing the suppressive effects of Paraoxon on AHP. Our findings support the possible involvement of cAMP formation in the Paraoxon-induced AHP suppression and neuronal hyperexcitability, although activation of cAMP pathway may attenuates some effects of Paraoxon.
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Paraoxon inhibits GABA uptake in brain synaptosomes.
Toxicology in vitro : an international journal published in association with BIBRA, 2007Co-Authors: Asghar Ghasemi, Moslem Mohammadi, Ahmad Sadidi, Ali Khoshbaten, Alireza AsgariAbstract:Abstract To investigate possible effect of Paraoxon (10 −9 –10 −3 M) on GABA uptake, we used rat cerebral cortex synaptosomes. K m and V max of GABA uptake were determined in presence of Paraoxon (10 −3 M). Acetylcholine and its antagonists (atropine and mecamylamine) were used for evaluating cholinergic-dependency of uptake. Type of transporter involved was determined by using glial (beta-alanine) and neuronal (DABA) GABA uptake inhibitors. The results of the study showed that Paraoxon at low doses (10 −9 –10 −6 M) increased and at high doses (10 −5 –10 −3 M) decreased GABA uptake. One millimolar Paraoxon significantly decreased V max (175.2 ± 4.23 vs. 80.4 ± 2.03, P K m . DABA significantly decreased GABA uptake ( P
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FORSKOLIN ATTENUATES THE Paraoxon-INDUCED HYPEREXCITABILITY IN SNAIL NEURONS
Physiology and Pharmacology, 2006Co-Authors: Jafar Vatanparast, Mahyar Janahmadi, Houri Sepehri, Ali Haeri-rohani, Alireza AsgariAbstract:Introduction: Since organophosphorus compounds (OP) are toxic and designed to destroy insects and pest species, there are many hazards associated with their use. Although, the main target site of these compounds is acetylcholinesterase (AChE), however it has become increasingly evident that OPs have also other direct effects on cellular processes. In the present study, the effects of low concentrations of Paraoxon and its interaction with forskolin, an activator of protein kinase A (PKA), were studied on Ca 2+ spike configuration and frequency in neurons of snail Caucasotachea atrolabiata. Methods: Subesophageal ganglia neurons were recorded in current clamp mode in Na + free Ringer solution that contained voltage dependent potassium channel blockers, 4AP and TEA. Results: Paraoxon (0.3-0.6 µM) decreased the duration of spontaneous Ca 2+ spikes. This effect was seen with a suppression of single spike AHPs, leading to an increment in firing rate. Paraoxon induced hyperactivity appeared to be a consequence of decrease in Ca 2+ influx during spikes which is the main determinant of AHP duration by activating Ca 2+ dependent potassium channels. Forskolin (25 µM), in the absence of a significant change in spike duration, decreased the duration of single spike AHPs and increased the frequency of spikes. After forskolin application, Paraoxon decreased the duration of Ca 2+ spikes and AHPs, and increased the activity. However, these effects, especially on spike duration, were not as pronounced as in the absence of forskolin. Conclusion: These findings suggest that although forskolin, similar to Paraoxon, decreases the AHP and increases the frequency of spikes but it employs mechanism(s) different from Paraoxon which also oppose the effects of Paraoxon on Ca 2+ spikes configuration and frequency.
Ebru Birlik Özkütük - One of the best experts on this subject based on the ideXlab platform.
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Ligand exchange and MIP-based Paraoxon memories onto QCM sensor
Applied Physics A, 2015Co-Authors: Ebru Birlik Özkütük, Sibel Emir Diltemiz, Elif Özalp, Lokman Uzun, Arzu ErsözAbstract:In this study, we have aimed to prepare quartz crystal microbalance (QCM) sensor using Paraoxon-imprinted particles. Firstly, methacryloyl antipyrine (MAAP)-based metal–chelate-coordinated pre-complex has been prepared and used for Paraoxon templation. Then, Paraoxon-imprinted nanofilms were formed on QCM sensor after modification of the gold surfaces with allyl mercaptan. By this way, specific and selective memories, which depend on metal–chelate interactions between Eu(III) ions and template, for Paraoxon molecules have been obtained on the electrode surface. QCM sensor has characterized using AFM and ellipsometer. The detection limit and the affinity constant have found to be 0.09 μM and 5.71 × 103 M−1 for MAAP–Eu Paraoxon-based nanofilm, respectively. The specificity of the QCM sensor has shown using parathion as a competitor molecule.
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Paraoxon imprinted biopolymer based QCM sensor
Materials Chemistry and Physics, 2013Co-Authors: Ebru Birlik Özkütük, Sibel Emir Diltemiz, Elif Özalp, Tevfik Gedikbey, Arzu ErsözAbstract:Abstract In this study, a novel quartz crystal microbalance (QCM) based on the modification of Paraoxon imprinted polymer (TCM-Cd(II)-Paraoxon) film onto a quartz crystal sensor has been developed for the determination of Paraoxon. The sensor is based on a molecular imprinted polymer (MIP) which can be synthesized using Paraoxon as a template molecule, Thiourea Modified Chitosan-Cd(II) (TCM-Cd(II)) as the metal-chelate monomer, ephychlorohydrin as a crosslinking agent. The MIP particles have been characterized by FTIR measurements and QCM sensor has characterized using AFM and ellipsometer. The performance of the Paraoxon imprinted sensor has indicated that a selective and sensitive Paraoxon imprinted sensor could be fabricated. The sensor is able to discriminate Paraoxon in solution owing to the specific binding of the imprinted sites. The obtained Paraoxon imprinted sensor has 0.02–1 μM linear range and low detection limit (0.02 μM). The selectivity studies have shown that the selectivity of prepared Paraoxon imprinted sensor has found as being very high in the presence of parathion which is similar in structure with Paraoxon. The Paraoxon imprinted sensor has been repeatedly used for more than 7 months in many continuous experiments.
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Ligand exchange based Paraoxon imprınted QCM sensor.
Materials science & engineering. C Materials for biological applications, 2012Co-Authors: Ebru Birlik Özkütük, Sibel Emir Diltemiz, Elif Özalp, Rıdvan Say, Arzu ErsözAbstract:Abstract In the present work, a Paraoxon imprinted QCM sensor has been developed for the determination of Paraoxon based on the modification of Paraoxon imprinted film onto a quartz crystal combining the advantages of high selectivity of the piezoelectric microgravimetry using MIP film technique and high sensitivity of QCM detection. The Paraoxon selective memories have formed on QCM electrode surface by using a new metal–chelate interaction based on pre-organized monomer and the Paraoxon recognition activity of these molecular memories was investigated. Molecular imprinted polymer (MIP) film for the detection of Paraoxon was developed and the analytical performance of Paraoxon imprinted sensor was studied. The molecular imprinted polymer were characterized by FTIR measurements. Paraoxon imprinted sensor was characterized with AFM and ellipsometer. The study also includes the measurement of binding interaction of Paraoxon imprinted quartz crystal microbalance (QCM) sensor, selectivity experiments and analytical performance of QCM electrode. The detection limit and the affinity constant (K affinity ) were found to be 0.06 μM and 2.25 × 10 4 M − 1 for Paraoxon [MAAP–Cu(II)–Paraoxon] based thin film, respectively. Also, it has been observed that the selectivity of the prepared Paraoxon imprinted sensor is high compared to a similar chemical structure which is parathion.
Eugenio Vilanova - One of the best experts on this subject based on the ideXlab platform.
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NTE and non-NTE esterases in brain membrane: kinetic characterization with organophosphates.
Toxicology, 2012Co-Authors: Iris Mangas, Eugenio Vilanova, Jorge EstévezAbstract:Some effects of organophosphorus compounds (OPs) esters cannot be explained by action on currently recognized targets. In this work, we evaluate and characterize the interaction (inhibition, reactivation and "ongoing inhibition") of two model compounds: Paraoxon (non-neuropathy-inducer) and mipafox (neuropathy-inducer), with esterases of chicken brain membranes, an animal model, tissue and fractions, where neuropathy target esterase (NTE) was first described and isolated. Four enzymatic components were discriminated. The relative sensitivity of time-progressive inhibition differed for Paraoxon and mipafox. The most sensitive component for Paraoxon was also the most sensitive component for mipafox (EPα: 4.4-8.3% of activity), with I(50) (30 min) of 15-43 nM with Paraoxon and 29 nM with mipafox, and it spontaneously reactivated after inhibition with Paraoxon. The second most sensitive component to Paraoxon (EPβ: 38.3% of activity) had I(50) (30 min) of 1540 nM, and was practically resistant to mipafox. The third component (EPγ: 38.6-47.6% of activity) was Paraoxon-resistant and sensitive to micromolar concentrations of mipafox; this component meets the operational criteria of being NTE (target of organophosphorus-induced delayed neuropathy). It had I(50) (30 min) of 5.3-6.6 μM with mipafox. The fourth component (EPδ: 9.8-10.7% of activity) was practically resistant to both inhibitors. Two Paraoxon-resistant and mipafox-sensitive esterases were found using the sequential assay removing Paraoxon, but only one was Paraoxon-resistant and mipafox-sensitive according to the assay without removing Paraoxon. We demonstrate that this apparent discrepancy, interpreted as reversible NTE inhibition with Paraoxon, is the result of spontaneous reactivation after Paraoxon inhibition of a non-NTE component. Some of these esterases' sensitivity to OPs suggests that they may play a role in toxicity in low-level exposure to organophosphate compounds or have a protective effect related with spontaneous reactivation. The kinetic characterization of these components will facilitate further studies for isolation and molecular characterization.
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Serum albumin is as efficient as paraxonase in the detoxication of Paraoxon at toxicologically relevant concentrations.
Chemical research in toxicology, 2008Co-Authors: Miguel A. Sogorb, Sara Garcia-argüelles, Victoria Carrera, Eugenio VilanovaAbstract:Human serum albumin was able to hydrolyze the organophosphorus compounds Paraoxon, chlorpyrifos-oxon, and diazoxon at toxicologically relevant concentrations. Human serum displayed two Paraoxon hydrolyzing activities: the so-called Paraoxonase, which is associated with the lipoprotein fraction and is calcium dependent and EDTA sensitive, and the activity associated with albumin, which is EDTA resistant and sensitive to fatty acids. Human serum albumin hydrolyzed these compounds with the same relative efficacy as lipoproteins (chlorpyrifos-oxon > diazoxon > Paraoxon). The capability of detoxication of activity associated with human serum albumin was similar or even higher than Paraoxonase associated with lipoproteins in the case of Paraoxon at concentrations as low as those noted in an acute in vivo intoxication. However, Paraoxonase activity associated with lipoprotein was more effective than Paraoxonase activity associated with albumin at toxicologically relevant chlorpyrifos-oxon concentrations. These results explain why mice deficient in Paraoxonase associated with lipoprotein are not more sensitive to Paraoxon than wild animals.
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Properties of phenyl valerate esterase activities from chicken serum are comparable with soluble esterases of peripheral nerves in relation with organophosphorus compounds inhibition.
Toxicology letters, 2003Co-Authors: Adolfo G Garcia-pérez, Jorge Estévez, José Barril, Eugenio VilanovaAbstract:Chicken serum, the usual in vivo animal for testing organophosphorus delayed neuropathy, has long been reported not to contain a homologous activity of the neuronal neuropathy target esterase (NTE) activity when it is assayed according to standard methods as the phenyl valerate esterase (PVase) activity, which is resistant to Paraoxon and sensitive to mipafox. However, a PVase activity (1000-1500 nmol/min/ml) can be measured in serum that is extremely sensitive to both Paraoxon, a non-neuropathic organophosphorus compound and mipafox, a model neuropathy inducer. The inhibition was time progressive in both cases, suggesting a covalent phosphorilating reaction. The fixed time inhibition curves suggest at least two sensitive components. The IC50 for 30 min, at 37 degrees C are 6 and 51 nM for Paraoxon and 4 and 110 nM for mipafox, for every sensitive component. When Paraoxon was removed from a serum sample pretreated with the inhibitor, the Paraoxon sensitive PVase activity was recovered, in spite of showing a time progressive inhibition suggesting that hydrolytic dephosphorylating reaction recovered at a significant rate. The reactivation of the phosphorylated enzyme could explain that the time progressive inhibitions curves for long time with Paraoxon tend to reach a plateau depending on the inhibition concentration. However, with mipafox, the curve approached the same maximal inhibitions at all concentrations as expected for a permanent covalent irreversible phosphorylation, which is coherent with the observations that the activity remained inhibited after removing the inhibitor. Data of serum esterases described in this paper showed similar properties to those previously reported for peripheral nerve soluble phenylvalerate esterase: (1) extremely high sensitivity to Paraoxon and mipafox; (2) time progressive kinetic with two sensitive components; (3) recovery of activity after removal of Paraoxon; and (4) permanent inhibition with mipafox. These properties of serum esterases are very similar to those of soluble fraction of peripheral nerves. So, serum PVases could be considered as appropriate biomarkers, as a mirror for the neural soluble Paraoxon and mipafox sensitive soluble esterases that could be used for biomonitoring purpose.
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Properties of phenyl valerate esterase activities from chicken serum are comparable with soluble esterases of peripheral nerves in relation with organophosphorus compounds inhibition.
Toxicology Letters, 2003Co-Authors: Adolfo García-pérez, José Barril, Jorge Estévez, Eugenio VilanovaAbstract:Abstract Chicken serum, the usual in vivo animal for testing organophosphorus delayed neuropathy, has long been reported not to contain a homologous activity of the neuronal neuropathy target esterase (NTE) activity when it is assayed according to standard methods as the phenyl valerate esterase (PVase) activity, which is resistant to Paraoxon and sensitive to mipafox. However, a PVase activity (1000–1500 nmol/min/ml) can be measured in serum that is extremely sensitive to both Paraoxon, a non-neuropathic organophosphorus compound and mipafox, a model neuropathy inducer. The inhibition was time progressive in both cases, suggesting a covalent phosphorilating reaction. The fixed time inhibition curves suggest at least two sensitive components. The IC 50 for 30 min, at 37 °C are 6 and 51 nM for Paraoxon and 4 and 110 nM for mipafox, for every sensitive component. When Paraoxon was removed from a serum sample pretreated with the inhibitor, the Paraoxon sensitive PVase activity was recovered, in spite of showing a time progressive inhibition suggesting that hydrolytic dephosphorylating reaction recovered at a significant rate. The reactivation of the phosphorylated enzyme could explain that the time progressive inhibitions curves for long time with Paraoxon tend to reach a plateau depending on the inhibition concentration. However, with mipafox, the curve approached the same maximal inhibitions at all concentrations as expected for a permanent covalent irreversible phosphorylation, which is coherent with the observations that the activity remained inhibited after removing the inhibitor. Data of serum esterases described in this paper showed similar properties to those previously reported for peripheral nerve soluble phenylvalerate esterase: (1) extremely high sensitivity to Paraoxon and mipafox; (2) time progressive kinetic with two sensitive components; (3) recovery of activity after removal of Paraoxon; and (4) permanent inhibition with mipafox. These properties of serum esterases are very similar to those of soluble fraction of peripheral nerves. So, serum PVases could be considered as appropriate biomarkers, as a mirror for the neural soluble Paraoxon and mipafox sensitive soluble esterases that could be used for biomonitoring purpose.
Moslem Mohammadi - One of the best experts on this subject based on the ideXlab platform.
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Anxiolytic activity of Paraoxon is associated with alterations in rat brain glutamatergic system.
Neurotoxicology and teratology, 2018Co-Authors: Zohreh Zare, Mohsen Tehrani, Noorollah Rezaei, Babak Dana Ghalebarzand, Moslem MohammadiAbstract:Abstract Exposure to organophosphate (OP) compounds leads to behavioral alterations. To determine whether Paraoxon has effects on anxiety, anxiety-like behaviors were assessed in Paraoxon-exposed rats. Protein expression of glutamate transporters has also been measured in hippocampus and prefrontal cortex. Three doses of Paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle) were intraperitoneally injected to adult male rats. At 14 or 28 days after exposure, behavioral tests were done using elevated plus-maze (EPM) or open field tests. Thereafter, animals were sacrificed and both hippocampi and prefrontal cortices were extracted for cholinesterase assay and western blotting. Animals treated with convulsive doses of Paraoxon (0.7 and 1 mg/kg) showed an increase in percentage of time spent in open arms and percentage of open arm entries in the EPM. In the open field test, an increase in the time spent in central area was observed in rats treated with the same doses of Paraoxon. These effects of Paraoxon were independent of any changes in locomotor activity. There was an increase in both astrocytic glutamate transporter proteins (GLAST and GLT-1) in the hippocampus of animals treated with 0.7 and 1 mg/kg of Paraoxon. In the prefrontal cortex, protein levels of the GLAST and GLT-1 increased in 0.7 and decreased in 1 mg/kg groups. Only a significant decrease in EAAC1 protein was observed in the prefrontal cortex at 14 days following exposure to 1 mg/kg of Paraoxon. Collectively, this study showed that exposure to convulsive doses of Paraoxon induced anxiolytic-like behaviors in both behavioral tests. This effect may be attributed to alterations of glutamate transporter proteins in the rat hippocampus and prefrontal cortex.
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Differential expression of glutamate transporters in cerebral cortex of Paraoxon-treated rats
Neurotoxicology and teratology, 2017Co-Authors: Zohreh Zare, Mohsen Tehrani, Alireza Rafiei, Reza Valadan, Moslem MohammadiAbstract:Glutamatergic system is involved in pathological effects of organophosphorus (OP) compounds. We aimed to determine in vivo effects of Paraoxon, the bioactive metabolite of parathion, on the expression of glutamate transporters as well as Bax and Bcl2 in rat cerebral cortex. Male Wistar rats received an intraperitoneal (i.p.) injection of one of three doses of Paraoxon (0.3, 0.7, or 1mg/kg) or corn oil as vehicle (1ml/kg). After 4 or 18h, cerebral cortices were dissected out and used for quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot assays to measure mRNA and protein levels, respectively. The cortical glial glutamate transporters (GLAST and GLT-1) were up-regulated in animals treated with 0.7mg/kg of Paraoxon, but down-regulated in 1mg/kg group. Neuronal glutamate transporter (EAAC1) was unchanged in 0.7mg/kg treated rats, while reduced in 1mg/kg group. No significant difference was found in the mRNA and protein expression of EAAC1 in animals intoxicated with 0.3mg/kg of Paraoxon. Paraoxon (1mg/kg) resulted in an up-regulation of Bax and down-regulation of Bcl2 mRNA levels in the rat cerebral cortex. These results indicate that Paraoxon can differentially regulate expression of glutamate transporters at mRNA and protein levels in the cerebral cortex. Changes in the expression of glutamate transporters are closely related to Paraoxon-induced seizure activity.
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Synaptosomal GABA uptake decreases in Paraoxon-treated rat brain
Toxicology, 2007Co-Authors: Moslem Mohammadi, Asghar Ghasemi, Ali Khoshbaten, Esmaeel Ghani, Alireza AsgariAbstract:Abstract A synaptosomal model was used to evaluate in vivo effects of Paraoxon on the uptake of [ 3 H]GABA in rat cerebral cortex and hippocampus. Male Wistar rats were given a single intraperitoneal injection of one of three doses of Paraoxon (0.1, 0.3, or 0.7 mg/kg) and acetylcholinesterase (AChE) activity in the plasma, cerebral cortex, and hippocampus was measured at 30 min, 4 h, and 18 h after exposure. [ 3 H]GABA uptake in synaptosomes was also studied in another series of animals. Paraoxon administration (0.3 and 0.7 mg/kg) caused significant inhibition of AChE activity in the plasma and both brain areas at all time points. 0.1 mg/kg Paraoxon significantly inhibited AChE activity but only in the plasma for 4 h, the activity was completely recovered at 18 h. GABA uptake was significantly ( p l -DABA, an inhibitor of neuronal GABA transporter, allowed us to conclude that the uptake was mediated primarily by neuronal GABA transporter GAT-1. In conclusion, present data suggests that GABA uptake by synaptosomes decreases probably secondary to Paraoxon-induced seizure activity.
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Paraoxon inhibits GABA uptake in brain synaptosomes.
Toxicology in vitro : an international journal published in association with BIBRA, 2007Co-Authors: Asghar Ghasemi, Moslem Mohammadi, Ahmad Sadidi, Ali Khoshbaten, Alireza AsgariAbstract:Abstract To investigate possible effect of Paraoxon (10 −9 –10 −3 M) on GABA uptake, we used rat cerebral cortex synaptosomes. K m and V max of GABA uptake were determined in presence of Paraoxon (10 −3 M). Acetylcholine and its antagonists (atropine and mecamylamine) were used for evaluating cholinergic-dependency of uptake. Type of transporter involved was determined by using glial (beta-alanine) and neuronal (DABA) GABA uptake inhibitors. The results of the study showed that Paraoxon at low doses (10 −9 –10 −6 M) increased and at high doses (10 −5 –10 −3 M) decreased GABA uptake. One millimolar Paraoxon significantly decreased V max (175.2 ± 4.23 vs. 80.4 ± 2.03, P K m . DABA significantly decreased GABA uptake ( P
