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Preincubation with Mipafox and Methamidofos as well as Paraoxon (used as control) did not cause inhibition of hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase. This is in contrast with the inhibition of glycolysis by other neurotoxic compounds (hexacarbons, acrylamide, carbon disulfide).This work was supported by Fondo de Investigaciones Sanitarias de la Seguridad Social (FISSS, Spain) 相似文献
23.
M A Matin 《European journal of pharmacology》1974,29(1):168-170
The effect of paraoxon on the acetylcholinesterase activity of the cerebral cortex and corpus striatum of normal and diabetic rats has been determined. Paraoxon produced significantly less inhibition of cholinesterase activity in diabetic than in normal animals. The administration of insulin along with paraoxon restored the cholinesterase-inhibiting effect to the normal level. Paraoxon in both normal and diabetic rats produced a relatively greater degree of inhibition of cholinesterase activity in the striatum than in the cerebral cortex. 相似文献
24.
The organophosphorus (OP) chemical warfare V agent O-ethyl-S-[2(di-isopropylamino)ethyl] methyl phosphonothioate (VX), is a highly toxic compound which mainly penetrates the body via percutaneous pathways. Hence, the following prerequisite: to ascertain compound absorption and percutaneous profile distribution with a view to further assessing the efficacy of topical skin protectants. We first selected the most appropriate receptor fluid to carry out in vitro VX absorption experiments, namely: Hanks's Balanced Salt Solution (HBSS). After a 24-h topical exposure time lapse, we measured altogether the percentage of applied dose unabsorbed and absorbed, penetration rate, lag time, permeability coefficient (K(p)), and dose of VXeq present in skin. To such an end, we used full-thickness and split-thickness pig-ear or human abdominal skin membranes. Further, we scrutinised the potential use of two specific molecules as suitable surrogates for VX percutaneous penetration analyses: thus, we compared the present VX toxicokinetic parameters to earlier findings from our research unit, with respect to OP insecticides demethon-S-methyl (DSM) and paraoxon (POX). Within the framework of our study, we wish to highlight the following evidence: (a) pig-ear skin proves a relevant model to predict in vitro human abdominal skin, taking into account a 2-fold higher skin permeability to VXeq; (b) both full or split-thickness skin membranes may be used indiscriminately to gauge penetration rate and absorbed dose; (c) DSM applied on full-thickness pig-ear skin is the most relevant model to mimic the in vitro VX absorption through full-thickness skin model. 相似文献
25.
Serum paraoxonase-1 (PON1) is an esterase associated with high-density lipoproteins in plasma and is involved in the detoxification of organophosphates (OP). We have previously reported a significant decrease in serum PON1 activity following Nippostrongylus brasiliensis infection in Wistar rats. In the present study we investigated the effects of decreased serum PON1 activity due to N. brasiliensis infection on acute toxicity induced by chlorpyrifos oxon (CPO) and paraoxon (PO) in rats. CPO and PO were dermally applied at doses of 8 mg/kg and 0.2 mg/kg body weight, respectively, to infected (on day 7 post-infection) and uninfected rats, after which acetylcholinesterase (AChE) activity was measured within the brain, diaphragm, plasma, and red blood cells, 4h after administration as a measure of toxicity. In addition, serum PON1 activity was measured immediately prior to administration of CPO and PO. N. brasiliensis infection significantly increased the degree of inhibition of AChE in the brain and diaphragm after treatment with CPO and PO in association with a significant reduction in PON1 activity. Likewise, similar findings were observed in the blood (plasma and RBCs) ChE activity after treatment with PO, but not CPO. These results indicate that N. brasiliensis infection makes rats more susceptible to CPO and PO toxicity, suggesting that gastrointestinal nematode infection might be a potential factor affecting OP toxicity. 相似文献
26.
目的 探讨2型对氧磷脂酶(PON2)基因311Cys/Ser多态性与2型糖尿病肾病的相关性及其与血脂的关系。方法 采用聚合酶链式反应-长度片段多态性(PCR-RFLP)技术,对78例2型糖尿病患者(其中26例单纯性2型糖尿病,52例糖尿病肾病)和30例健康对照者,PCIN2基因311Cys/Ser多态性进行检测。结果 PON2基因311Cys/Ser多态性的基因型频率和等位基因频率在2型糖尿病合并大量蛋白尿组与对照组间差异有统计学意义,Ser等位基因在2型糖尿病合并大量蛋白尿组明显增高。结论 PON2基因311Cys/Ser遗传多态性与中国甘肃地区2型糖尿病并发肾病的发病具有相关性。 相似文献
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Binding of parathion and paraoxon to bovine serum albumin (BSA) and human serum albumin (HSA) was studied by using equilibrium dialysis. The concentration of unbound organophosphate was determined from its anticholinesterase activity.Binding of parathion to BSA was shown to be reversible. The organophosphates interact with only one type of binding sites in BSA and HSA. The affinity constants at pH 7.2 and 4° C for the interaction of BSA or HSA and parathion were found to be 2.7×106 and 1.5×106 M–1, respectively. The affinity constants for the interaction of the serum albumins and paraoxon were considerably lower, 6.0×103 and 1.6×104 M–1, respectively. Lowering the pH from 7.2 to 4.8 did not significantly affect the binding parameters. The great difference of affinity of the serum albumins to parathion and paraoxon is discussed with respect to the fate of parathion in the body. 相似文献
29.
Vjera Deljac Matej Maksimović Ljiljana Radović Dušanka Rakin Verica Markov Ivo Bregovec Zlatko Binenfeld 《Archives of toxicology》1982,49(3-4):285-291
Eleven isomeric phenylhydroxymethyl and cyclohexylhydroxymethyl derivatives of 1-(2-hydroxyiminomethyl-1-pyridinio)-3-(1-pyridinio)-2-oxapropane diiodide and 1-(4-hydroxyiminomethyl-1-pyridinio)-3-(1-pyridinio)-2-oxapropane diiodide were prepared and characterized by spectroscopic methods and pKa values. The inhibitory power (I50) of the investigated oximes was determined on purified bovine erythrocyte AChE and human erythrocyte AChE. Percentage of reactivation after 30 min was estimated after inhibition of human erythrocyte AChE by sarin, VX, and paraoxon. The in vitro protective index against inhibition by soman has been calculated using bovine erythrocyte AChE. Their I50 for human erythrocyte AChE varied in the range of 9–61 (10–4 mol · dm–3) and for purified bovine erythrocyte AChE in the range of 11–57 (10–5 mol · dm–3). With 2 × 10–5 mol · dm–3 of oximes the percent of reactivation was: 0–63% for paraoxon inhibited AChE, 12–73% for sarin inhibited AChE and 11–80% for VX inhibited AChE. With the exception of 1-(2-hydroxyiminomethyl-1-pyridinio)-3-(4-phenylhydroxymethyl-1-pyridinio)-2-oxapropane diiodide (6) the derivatives of 4-hydroxyiminomethylpyridine are by far better reactivators. None of the compounds could protect purified bovine erythrocyte AChE from inhibition by soman. 相似文献
30.
IntroductionMagnetic resonance (MR) imaging is a sensitive modality for demonstrating in vivo alterations in brain structure and function after acute organophosphate (OP) poisoning. The goals of this study were to explore early imaging findings in organophosphate-poisoned animals, to assess the efficacy of centrally acting antidotes and to find whether early MR findings can predict post-poisoning cognitive dysfunction.MethodsSprague–Dawley rats were poisoned with the agricultural OP paraoxon and were treated with immediate atropine and obidoxime (ATOX) to reduce acute mortality caused by peripheral inhibition of acetylcholinesterase. Animals were randomly divided into three groups based on the protocol of centrally acting antidotal treatment: group 1 – no central antidotal treatment (n = 10); group 2 – treated with midazolam (MID) at 30 min after poisoning (n = 9), group 3 – treated with a combination of MID and scopolamine (SCOP) at 30 min after poisoning (n = 9) and controls (n = 6). Each animal had a brain MR examination 3 and 24 h after poisoning. Each MR examination included the acquisition of a T2 map and a single-voxel 1H MR spectroscopy (localized on the thalami, to measure total creatine [Cr], N-acetyl-aspartate [NAA] and cholines [Cho] levels). Eleven days after poisoning each animal underwent a Morris water maze to assess hippocampal learning. Eighteen days after poisoning, animals were euthanized, and their brains were dissected, fixed and processed for histology.ResultsAll paraoxon poisoned animals developed generalized convulsions, starting within a few minutes following paraoxon injection. Brain edema was maximal on MR imaging 3 h after poisoning. Both MID and MID + SCOP prevented most of the cortical edema, with equivalent efficacy. Brain metabolic dysfunction, manifested as decreased NAA/Cr, appeared in all poisoned animals as early as 3 h after exposure (1.1 ± 0.07 and 1.42 ± 0.05 in ATOX and control groups, respectively) and remained lower compared to non-poisoned animals even 24 h after poisoning. MID and MID + SCOP prevented much of the 3 h NAA/Cr decrease (1.22 ± 0.05 and 1.32 ± 0.1, respectively). Significant correlations were found between imaging findings (brain edema and spectroscopic changes) and clinical outcomes (poor learning, weight loss and pathological score) with correlation coefficients of 0.4–0.75 (p < 0.05).ConclusionsMR imaging is a sensitive modality to explore organophosphate-induced brain damage. Delayed treatment with midazolam with or without scopolamine provides only transient neuroprotection with some advantage in adding scopolamine. Early imaging findings were found to correlate with clinical consequences of organophosphate poisoning and could be potentially used in the future to predict long-term prognosis of poisoned casualties. 相似文献