Disease relevance of parathion

• Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion [1].
• Polyneuropathy and exposure to parathion [2].
• Phosphotriesterase, as isolated from Pseudomonas diminuta, is capable of detoxifying widely used pesticides such as paraoxon and parathion and various mammalian acetylcholinesterase inhibitors [3].
• Parathion hydrolase specified by the Flavobacterium opd gene: relationship between the gene and protein [4].
• Purification and characterization of a secreted recombinant phosphotriesterase (parathion hydrolase) from Streptomyces lividans [5].

Psychiatry related information on parathion

• Preweanling rat pups were exposed daily to parathion (1.3 mg/kg or 1.9 mg/kg) or vehicle (corn oil) on postnatal days 5-20, a time period critical to development of behavioral and biochemical parameters of the cholinergic nervous system [6].
• However, no single measure was the most sensitive across all compounds; for example, the lowest dose of fenthion decreased motor activity by 86% but did not alter the tail-pinch response, whereas the lowest dose of parathion did not lower activity but did decrease the tail-pinch response [7].
• Water deprivation and food restriction on toxicity of parathion and paraoxon [8].
• Feeding behavior was inhibited most by exposure to DEF, 2,4-DMA, and methyl parathion [9].
• Similarly, after administration of several dose levels of parathion in the rat, durations of phases of the maximal electroshock seizure (MES) pattern were altered to the greatest extent 4 hours later, but effects disappeared at 24 hours [10].

High impact information on parathion

• A genetic polymorphism of paraoxonase (PON) activity which determines high versus low paraoxon hydrolysis in human populations, may determine sensitivity to parathion poisoning [11].
• Studies indicated that potent, reversible inhibition by ACVTP and the next required deoxynucleoside 5'-triphosphate also occurred when poly(dC)-oligo(dG) or activated calf thymus DNA were used as the template-primer [12].
• Reduction of the pyridoxal-5'-P enzyme complex in the presence or absence of a deoxynucleoside 5'-triphosphate showed that the alpha subunit possesses five reactive amino groups, one of which is essential for catalytic activity; the beta subunit has three reactive amino groups which are not involved in the deoxynucleoside binding site [13].
• The complex Rh(cod)(sulfos) (Rh(I); sulfos = (-)O(3)S(C(6)H(4))CH(2)C(CH(2)PPh(2))(3); cod = cycloocta-1,5-diene), either free or supported on silica, does not catalyze the hydrogenation of benzene in either homogeneous or heterogeneous phase [14].
• Reports of methyl parathion intoxication, usually seen only in field pesticide applicators, have increased throughout the United States as a result of unauthorized application of methyl parathion inside homes [15].

Chemical compound and disease context of parathion

• Methyl parathion is an organophosphorus (OP) insecticide with insecticidal properties derived from acetylcholinesterase (AChE) inhibition; this same property is also the root of its toxicity in humans [15].
• Since ethanol did not alter directly the P450-dependent activation or detoxification of parathion, and did not decrease NADPH levels, ethanol's antagonism of the acute toxicity of parathion may result from reduced availability of O2 [16].
• Chlorpyrifos (CPF) and parathion (PS), two common organophosphorus (OP) pesticides, exhibit higher acute toxicity in younger animals compared to adults [17].
• The toxicity of binary combinations of malathion and parathion adhered to the principles of concentration addition [18].
• Flavobacterium sp. has the organophosphorus hydrolase enzyme, which hydrolyzes the methyl parathion into detectable product p-nitrophenol [19].

Biological context of parathion

• Because thymidine kinase is under feedback regulatory control by the physiological deoxynucleoside-5'-triphosphate dTTP, we examined the effect on D4T phosphorylation and thus, potentially, on its antiviral activity, of a variety of agents that lower intracellular dTTP pools [20].
• The enzyme, which was immobilized on a carbon electrode, catalyzes the hydrolysis of parathion to form p-nitrophenol, which was detected by its anodic oxidation [21].
• Biotransformation of parathion in human liver: participation of CYP3A4 and its inactivation during microsomal parathion oxidation [22].
• Dieldrin is not in the small class of insecticides that are dangerous to man by skin absorption (such as parathion, arsenicals, DNC) and, at the area dosages needed for locust control, is not dangerous to stock [23].
• All these organisms synthesize an enzyme called parathion hydrolase, and in each case the enzyme is encoded by a gene (opd) located on a large indigenous plasmid [24].

Anatomical context of parathion

• A similar alteration in the heme moiety of cytochrome P-450 is believed to be responsible, in part, for the loss of monooxygenase activity and cytochrome P-450 seen on incubation of parathion and other thiono-sulfur-containing compounds with hepatic microsomes or a reconstituted cytochrome P-450-containing monooxygenase system [25].
• Although the incubation of parathion (50 microM) with rat liver microsomes for 10 min led to a 16% decrease in P450 estimated spectrophotometrically, immunoblot analysis revealed no change in the microsomal content of P450 2C11 apoprotein [26].
• The sizes of cellular deoxynucleoside 5'-triphosphate pools in relation to sensitivity to electron irradiation using sensitive and resistant cell lines [27].
• Mice were pretreated s.c. with either parathion [a mixed plasma and red blood cell cholinesterase (RBCCh) inhibitor], tetraisopropyl pyrophosphoramide (a selective PCh inhibitor) or placebo, and cholinesterase activity was determined at 24 hr [28].
• In the present study, human bone marrow cells were exposed in vitro to paraoxon and malaoxon (the primary metabolites of parathion and malathion) [29].

Associations of parathion with other chemical compounds

• Plasma paraoxonase is a polymorphic enzyme that hydrolyzes paraoxon, the neurotoxic, active metabolite of the insecticide parathion [30].
• The application of the method to infant food in combination with a disposable AChE biosensor enabled detection of chlorpyrifos and parathion at concentrations down to 20 microg/kg within an overall assay time of 95 min [31].
• Radiolabeled solutions of parathion, carbaryl, and DDT were applied to previously shaved rats at the rate of 4 micrograms/cm2 [32].
• One of the four glutathione-S-transferases (GST) that is overproduced in the insecticide-resistant Cornell-R strain of the housefly (Musca domestica) produces an activity that degrades the insecticide dimethyl parathion and conjugates glutathione to lindane [33].
• Polyacrylamide gel electrophoresis of rat brain acetylcholinesterase: isoenzyme changes following parathion poisoning [34].
• Neonatal low-dose parathion exposure disrupts glucose and fat homeostasis in a persistent and sex-selective manner [35].
• Differences between the effects of parathion compared with chlorpyrifos or diazinon and the non-monotonic dose-effect relationships reinforce the conclusion that various organophosphates diverge in their effects on neurodevelopment, unrelated to their anticholinesterase actions [36].

Gene context of parathion

• During parathion oxidation CYP3A4 undergoes significant inactivation [22].
• P450 was lost during parathion biotransformation in human hepatic microsomes [22].
• This study has determined wide interindividual variations in capacity to metabolise parathion, mainly by CYP3A, which may influence its manifest toxicity [37].
• These data indicate that CYP3A4/5 and CYP2C8, which constitute up to 40% of human liver P450s, are the most significant participants in the metabolism of parathion [38].
• All the flavonoids examined except quercetin altered the ratio of activation/detoxification of parathion by mouse hepatic microsomes, but had no effect on this same ratio with human CYP1A2 [39].

Analytical, diagnostic and therapeutic context of parathion

• Determination of ethyl and methyl parathion in runoff water with high performance liquid chromatography [40].
• An amperometric enzyme biosensor for the direct measurement of parathion was developed [21].
• Using polymerase chain reaction (PCR) amplification with genomic DNA, multiple copies of the gene encoding the parathion-degrading activity (called MdGst-3) were subcloned from both the ancestral, insecticide-susceptible strain BPM and from the insecticide-resistant Cornell-R [33].
• Characterization of the degradation products by thin-layer chromatography indicated that the sulfur is bound as a polysulfide or hydrodisulfide formed by the combination of a reactive form of sulfur, released from parathion, with cysteine residues of the microsomal protein [41].
• Hemoperfusion is usually chosen to treat parathion intoxication, but carries the risk of causing hemorrhages in acute hemorrhagic pancreatitis [42].

References