Future applications of phosphotriesterases in the prophylaxis and treatment of organophosporus insecticide and nerve agent poisonings

Sogorb, Miguel A.; Vilanova, Eugenio; Carrera, Victoria

doi:10.1016/j.toxlet.2004.01.022

Cited by 130 publications

(75 citation statements)

References 61 publications

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“…The a /b hydrolase fold also includes phosphotriesterases (such as paraoxonase), 4) cholinesterases, [5][6][7] and lipases 8) as well as a number of other enzymes. These enzymes are all defined by an eight-stranded mostly parallel a /b structure and a characteristic plastic nature of the protein fold that allows for large variations in domain size (Fig.…”

Section: -3)mentioning

confidence: 99%

Overview of Carboxylesterases and Their Role in the Metabolism of Insecticides

Shan²,

2005

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Carboxylesterases hydrolyze numerous endogenous and exogenous ester-containing compounds. They play a role in the detoxification of many agrochemicals including pyrethroids, organophosphates, and carbamates. Research on these enzymes is still developing and there are several topics that should be addressed to further investigations in this area. This paper focuses on a number of these issues including enzyme nomenclature, catalytic mechanism, substrate specificity, agrochemical metabolism, role in insecticide resistance and environmental significance. It is expected that carboxylesterase research will increase with specific emphasis on isozyme and substrate identification. Future research directions are discussed and the current state of the field is evaluated.

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Section: -3)mentioning

confidence: 99%

Overview of Carboxylesterases and Their Role in the Metabolism of Insecticides

Shan²,

2005

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“…They are widely spread on the phylogenetic scale and are strongly expressed in the serum and liver of mammals, while levels are barely detectable in birds. [71][72][73] The two best understood OP-detoxifying enzymes are the PTE paraoxonase, which hydrolyzes many Ops; 74 and diisopropylfluorophosphatase (DFPase), which acts on diisopropylfluorophosphate (DFP) and other phosphorofluoridates.…”

Section: Biochemical Aspects Of the Biotransformations Of Opsmentioning

confidence: 99%

“…In others, however, these inhibitions does not apparently cause toxic effects and such reactions must be considered as detoxication reactions since each molecule of the enzyme is capable of scavenging one molecule of OP from the media. [71][72][73] This detoxication system is much less efficient than hydrolysis by PTEs because each CarbE reacts stoichiometrically with OPs and, consequently, this is not a catalytic reaction. Others CarbEs that hydrolyses phenyl valerate have been considered as potential sites of detoxification at low exposure because they are highly sensitive to paraoxon and, also, are able to be spontaneously reactivated when inhibited by this OP.…”

Section: Biochemical Aspects Of the Biotransformations Of Opsmentioning

confidence: 99%

Neurotoxic Effects Associated with Current Uses of Organophosphorus Compounds

Mangas

Vilanova

Estévez

et al. 2016

Journal of the Brazilian Chemical Society

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Organophosphorus compounds (OPs) are a large and diverse class of chemicals that have been synthesized, since the XIX century for several purposes like chemical weapons, flame-retardants, ectoparasiticides and investigational new drugs, but mainly as agrochemicals in agriculture and indoor. Although the amount of OP pesticides being used is declining, especially in developed countries, OPs continue being one of the most important classes of insecticides and chemical warfare agents today due to its toxic effects on the enzyme acetylcholinesterase (AChE). Existing research on the toxicological effects of OPs is extensive, however, there is a lack of knowledge on the long-term effects of low levels of OPs and their exactly pathways of toxicity. Recent data prove that other molecular targets than AChE could be targeted by OPs, triggering these effects. Here these data are reviewed and it is highlighted that the current uses of OPs are producing several neurotoxic effects. It is also shown that, to protect people from possible uses and misuses of OPs, more regulations on OPs are needed. Moreover, more mechanistic studies are needed to completely understand their toxicological interactions and mechanisms of action and to identify the whole group of enzymes that interact with them.

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“…71,72 Accidental intoxications and suicide attempts with insecticides constitute a serious health problem, mainly in Third World countries: World Health Organization estimates that there occurs annually three millions of poisoning cases due to pesticides, with more than 220.000 deaths caused by them around the world. 73,74 Some OPCs are also used as flame retardants in electrical devices and as antiparasites in veterinary medicine. 72 Although less lethal than chemical weapons, organophosphorus pesticides can lead to similar deleterious effects when used in greater amounts or higher concentrations.…”

Section: Organophosphorus Compoundsmentioning

confidence: 99%

“…75 In fact, the World Health Organization reports about three million cases per year of intoxication with organophosphorus pesticides, causing about 220.000 deaths, in the world. 73,74 These intoxications usually result from wrong manipulation of pesticides and suicidal attempts. 73,76,77 Phosphorus is an extremely versatile element, located below nitrogen in Group V of the Periodic Table. Its general application in many reactions in organic chemistry results from its electronic structure (1s 2 2s 2 2p 6 3s 2 3p 3 ).…”

Section: Organophosphorus Compoundsmentioning

confidence: 99%

Organophosphorus compounds as chemical warfare agents: a review

Delfino¹,

Ribeiro²,

Figueroa‐Villar³

2009

J. Braz. Chem. Soc.

231

178

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Os agentes de guerra química constituem uma das maiores ameaças do mundo moderno. Dentre estes, destacam-se os agentes neurotóxicos, em virtude de sua alta letalidade e periculosidade. Eles são compostos organofosforados que atuam pela inibição da enzima acetilcolinesterase, a qual é fundamental no processo de transmissão de impulsos nervosos. Existem várias formas de tratamento para a intoxicação por organofosforados, mas nenhuma delas é eficaz contra todos os agentes conhecidos ou contra todos os seus efeitos. Esta revisão tem como foco o uso de compostos organofosforados como agentes neurotóxicos de guerra química. Após uma breve introdução histórica, será feita uma discussão sobre as principais características estruturais e biológicas da acetilcolinesterase, seguida por uma revisão das propriedades dos compostos organofosforados e da sua aplicação como agentes de guerra química. Por fim, serão discutidas as formas de tratamento contra estes agentes, com ênfase nas oximas usadas para reativar a acetilcolinesterase inibida.Chemical warfare agents constitute one of the greatest threats in the modern world. Among them, the neurotoxic agents are of special interest due to their high lethality and danger. Neurotoxic agents are organophosphorus compounds that act by inhibiting the enzyme acetylcholinesterase, which is fundamental for the control of transmission of nervous impulses. There are several ways of treating intoxication by organophosphorus compounds, but none of them is efficient against all the known neurotoxic agents or against all of their effects. This review focus on the use of organophosphorus compounds as neurotoxic chemical warfare agents. After a brief historical introduction, it will be done a discussion about the structural and biological characteristics of acetylcholinesterase, followed by a review of the properties of organophosphorus compounds and their application as chemical warfare agents. Finally, the ways of treatment against intoxication with these agents will be discussed, with emphasis on the oximes used for reactivating the inhibited acetylcholinesterase.

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Future applications of phosphotriesterases in the prophylaxis and treatment of organophosporus insecticide and nerve agent poisonings

Cited by 130 publications

References 61 publications

Overview of Carboxylesterases and Their Role in the Metabolism of Insecticides

Overview of Carboxylesterases and Their Role in the Metabolism of Insecticides

Neurotoxic Effects Associated with Current Uses of Organophosphorus Compounds

Organophosphorus compounds as chemical warfare agents: a review

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